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Cognitive reserve and the neurobiology of cognitive aging
Abstract
A hypothetical construct of "cognitive reserve" is widely used to explain how, in the face of neurodegenerative changes that are similar in nature and extent, individuals vary considerably in the severity of cognitive aging and clinical dementia. Intelligence, education and occupational level are believed to be major active components of cognitive reserve. Here, we summarize the main features of cognitive aging and their neuropathological correlates. We describe the neurobiology of cognitive aging and conclude that perturbations of neural health attributable to oxidative stress and inflammatory processes alone are insufficient to distinguish cognitive aging from Alzheimer's disease. We introduce the concept of cognitive reserve and illustrate its utility in explaining individual differences in cognitive aging. Structural and functional brain imaging studies suggest plausible neural substrates of cognitive reserve, probably involving processes that support neuroplasticity in the aging brain. The cognitive reserve hypothesis conforms with reported associations between early and mid life lifestyle choices, early education, lifelong dietary habit, leisure pursuits and the retention of late life mental ability.
... Quantitative neuroimaging studies have shown that, as a whole, the human brain volume tends to shrink with age, especially in terms of gray matter rather than white matter measures. 44,45 Structural MRI techniques have been commonly been used to reveal whether CR proxies (ie, occupation, education, leisure activities, and head circumference as a BR proxy) may correlate to anatomical brain parameters (ie, whole brain size, white matter damage, and cortical atrophy). 44,46,47 However, these findings in this field remain controversial, particularly TA B L E 2 Summary of cited articles and outcomes on neuroimaging and cognitive reserve in physiological aging. ...
... 44,45 Structural MRI techniques have been commonly been used to reveal whether CR proxies (ie, occupation, education, leisure activities, and head circumference as a BR proxy) may correlate to anatomical brain parameters (ie, whole brain size, white matter damage, and cortical atrophy). 44,46,47 However, these findings in this field remain controversial, particularly TA B L E 2 Summary of cited articles and outcomes on neuroimaging and cognitive reserve in physiological aging. due to the lack of follow-up studies with repeated MRI and combined CR proxies in the same individuals. ...
... However, these studies have limitations related to the lack of longitudinal data and potential additional features, such as genetic and cerebrovascular risk factors, which may remarkably impact the final measures. 44 Instead of focusing solely on overall brain measures, other studies investigated a possible association between CR parameters and specific brain region structure. For instance, physical activity has been found to correlate with gray matter volume in the middle frontal gyrus, while high level of engagement in daily activities has been associated with reduced hippocampal atrophy. ...
INTRODUCTION
This review examines the concept of cognitive reserve (CR) in relation to brain aging, particularly in the context of dementia and its early stages. CR refers to an individual's ability to maintain or regain cognitive function despite brain aging, damage, or disease. Various factors, including education, occupation complexity, leisure activities, and genetics are believed to influence CR.
METHODS
We revised the literature in the context of CR. A total of 842 articles were identified, then we rigorously assessed the relevance of articles based on titles and abstracts, employing a systematic approach to eliminate studies that did not align with our research objectives.
RESULTS
We evaluate—also in a critical way—the methods commonly used to define and measure CR, including sociobehavioral proxies, neuroimaging, and electrophysiological and genetic measures. The challenges and limitations of these measures are discussed, emphasizing the need for more targeted research to improve the understanding, definition, and measurement of CR.
CONCLUSIONS
The review underscores the significance of comprehending CR in the context of both normal and pathological brain aging and emphasizes the importance of further research to identify and enhance this protective factor for cognitive preservation in both healthy and neurologically impaired older individuals.
Highlights
This review examines the concept of cognitive reserve in brain aging, in the context of dementia and its early stages.
We have evaluated the methods commonly used to define and measure cognitive reserve.
Sociobehavioral proxies, neuroimaging, and electrophysiological and genetic measures are discussed.
The review emphasizes the importance of further research to identify and enhance this protective factor for cognitive preservation.
... memory), 2 and predicts educational and professional success, 3 social mobility, 4 health 5 and longevity. 6 It is thought to be a key mental capacity involved in 'active thinking', 7 Gf declines dramatically in various types of dementia 8 and reflects the degree of executive impairment in older patients with frontal involvement. 9 Despite the importance of Gf in defining human behaviour, it remains contentious whether this is a single or a cluster of cognitive abilities and the nature of its relationship with the brain. ...
... Suppression Errors in Section 2 were calculated. 78 7 the 4 easiest items (1, 7, 2, 4), 'medium group', containing the next 4 items (3, 5, 6, 10) and 'hard group', containing the 4 hardest items (12,9,8,11). We calculated each patient's score for the three variables (0-4). ...
... The underlay is the SPM152 T1 template distributed with MRIcroGL(https://www.nitrc.org/projects/mricrogl). The images are displayed in neurological convention.8 ...
Fluid intelligence is arguably the defining feature of human cognition. Yet the nature of its relationship with the brain remains a contentious topic. Influential proposals drawing primarily on functional imaging data have implicated “multiple demand” frontoparietal and more widely distributed cortical networks, but extant lesion-deficit studies with greater causal power are almost all small, methodologically constrained, and inconclusive. The task demands large samples of patients, comprehensive investigation of performance, fine-grained anatomical mapping, and robust lesion-deficit inference, yet to be brought to bear on it.
We assessed 165 healthy controls and 227 frontal or non-frontal patients with unilateral brain lesions on the best-established test of fluid intelligence, Raven’s Advanced Progressive Matrices, employing an array of lesion-deficit inferential models responsive to the potentially distributed nature of fluid intelligence. Non-parametric Bayesian stochastic block models were used to reveal the community structure of lesion deficit networks, disentangling functional from confounding pathological distributed effects.
Impaired performance was confined to patients with frontal lesions ( F (2,387) = 18.491; p < .001; frontal worse than non-frontal and healthy participants p < .01; p <.001), more marked on the right than left ( F (4,385) = 12.237; p < .001; right worse than left and healthy participants p <.01; p <.001). Patients with non-frontal lesions were indistinguishable from controls and showed no modulation by laterality. Neither the presence nor the extent of multiple demand network involvement affected performance. Both conventional network-based statistics and non-parametric Bayesian stochastic block modelling heavily implicated the right frontal lobe. Crucially, this localisation was confirmed on explicitly disentangling functional from pathology-driven effects within a layered stochastic block model, prominently highlighting a right frontal network involving middle and inferior frontal gyrus, pre- and post-central gyri, with a weak contribution from right superior parietal lobule. Similar results were obtained with standard lesion-deficit analyses.
Our study represents the first large-scale investigation of the distributed neural substrates of fluid intelligence in the focally injured brain. Combining novel graph-based lesion-deficit mapping with detailed investigation of cognitive performance in a large sample of patients provides crucial information about the neural basis of intelligence. Our findings indicate that a set of predominantly right frontal regions, rather than a more widely distributed network, is critical to the high-level functions involved in fluid intelligence. Further they suggest that Raven’s Advanced Progressive Matrices is a useful clinical index of fluid intelligence and a sensitive marker of right frontal lobe dysfunction.
... While people with lower educational attainment who developed dementia showed a steady decline in cognitive test scores, more educated people maintained their scores for longer, then declined rapidly towards the end of their life -metaphorically falling off a cliff rather than sliding down a slope. A common interpretation is that educational level contributes to cognitive reserve which enables people to compensate for the brain pathology that underlies cognitive decline [7][8][9][10]. Cognitive reserve may reduce the risk of developing a pathology, or help a person compensate for the early stages of cognitive loss and delay the clinical expression of underlying pathology [11,12]. ...
... Indeed, Alzheimer's pathology has been found on autopsy in some people who did not demonstrate cognitive impairment ante mortem, and such cases typically occur among those with more education and whose jobs involved more complexity [6,8,13]. ...
Many studies have shown a connection between education and late-life cognition, with the risk of dementia being inversely associated with educational attainment. This brief article proposes pathways through which cognitive ability in early life, subsequently reinforced by education and then by higher socioeconomic position in midlife, could confer a protective effect on cognitive decline many decades later, in late life. Taking a systems perspective, the article describes mutually reinforcing processes that operate to maintain the stability of cognitive abilities across the life course. The conclusion is that population-level interventions could be designed to enhance cognitive resiliency in our aging populations.
... A potential mechanism through which cash transfers may exert protective effects on midlife cognitive function is via promoting cognitive reserve [17]. Accrual of cognitive reserve is thought to occur over the life course through cumulative cognitively stimulating experiences from childhood through adulthood [17,49,50]. People with high cognitive reserve are thought to be able to use compensatory behavioral or neural brain mechanisms to stave off the functional impacts of ageing-related brain pathology [17,49]. ...
... Accrual of cognitive reserve is thought to occur over the life course through cumulative cognitively stimulating experiences from childhood through adulthood [17,49,50]. People with high cognitive reserve are thought to be able to use compensatory behavioral or neural brain mechanisms to stave off the functional impacts of ageing-related brain pathology [17,49]. In South Africa, CSG benefits account for nearly 40 per cent of income in the poorest recipient households and are accumulated over time in early-to mid-adulthood for mothers while they are raising children [21,23]. ...
Background
Cash transfers are a promising but understudied intervention that may protect cognitive function in adults. Although South Africa has a rapidly ageing population, little is known about the nature of association between cash transfers and cognitive function in this setting.
Objectives
We leveraged age-eligibility expansions to South Africa’s Child Support Grant (CSG) to investigate the association between duration of CSG eligibility and cognitive function of biological mothers of child beneficiaries in South Africa.
Methods
We analysed 2014/2015 baseline data from 944 women, aged 40–59 years with at least one CSG-eligible child, enrolled in the population-representative HAALSI cohort in Agincourt, South Africa. Duration of CSG eligibility for each mother was calculated based on the birth dates of all their children and the CSG age-eligibility expansion years (2003–2012). Cognitive function was measured using a cognitive battery administered at the HAALSI baseline interview. Linear regression was used to estimate the association between duration of CSG eligibility, dichotomized as low (≤10 years) and high (>10 years) eligibility, and cognitive function z-scores of the mothers.
Results
High vs. low duration of CSG eligibility, was associated with higher cognitive function z-scores in the full sample [β: 0.15 SD units; 95% CI: 0.04, 0.26; p-value = 0.01]. In mothers with one to four lifetime children, but not five or more, high vs. low duration of CSG eligibility, was associated with higher cognitive function z-scores [β: 0.19 SD units; 95% CI: 0.05, 0.34, p-value = 0.02].
Conclusion
Government cash transfers given to support raising children may confer substantial protective effects on the subsequent cognitive function of mothers. Further studies are needed to understand how parity may influence this relationship. Our findings bring evidence to policymakers for designing income supplementation programmes to promote healthy cognitive ageing in low-income settings.
... Higher education is a promising social determinant of health and robustly linked to lower dementia risk 1,2,6 yet Black-White inequities in dementia persist at the highest levels of education. 7 It is widely hypothesized that higher education delays the onset of cognitive decline by increasing cognitive reserve, [8][9][10] described as "capacity of the mature adult brain to sustain the effects of disease or injury (i.e., reduced brain integrity) sufficient to cause clinical dementia." 10 However, a recent study showed that higher years of education contributed to cognitive reserve providing protection against the adverse impact of reduced brain integrity for White adults, but not for Hispanic or Black adults. ...
... 7 It is widely hypothesized that higher education delays the onset of cognitive decline by increasing cognitive reserve, [8][9][10] described as "capacity of the mature adult brain to sustain the effects of disease or injury (i.e., reduced brain integrity) sufficient to cause clinical dementia." 10 However, a recent study showed that higher years of education contributed to cognitive reserve providing protection against the adverse impact of reduced brain integrity for White adults, but not for Hispanic or Black adults. 11 Each domain was z-standardized using the analytic sample baseline mean and standard deviation. ...
Introduction:
Black students attending predominantly White institutions (PWIs) versus historically Black colleges and universities (HBCUs) report more harmful discrimination and develop worse mental health outcomes, potentially offsetting the established benefits of college for lowering dementia incidence.
Methods:
Black participants in two cohorts (the Kaiser Healthy Aging and Diverse Life Experiences [KHANDLE] and the Study of Healthy Aging in African Americans [STAR]) who had attended college (N = 716) self-reported the college name (classified as HBCU vs. PWI) and completed three waves of executive function (EF) and verbal episodic memory (VEM) assessments. HBCU effects on cognitive level and decline were estimated using adjusted linear mixed-effects models.
Results:
HBCU (vs. PWI) attendees averaged better EF (β = 0.05 [-0.22, 0.32]) and VEM (β = 0.21 [-0.06, 0.46]) at age 70 though neither association was statistically significant. HBCU attendance was associated with slightly faster VEM decline (β = -0.03 [-0.05, 0.00]).
Discussion:
Harmonized analyses with larger studies are needed to estimate important effects of HBCU attendance.
Highlights:
Higher education is robustly linked to lower dementia risk, yet Black-White inequities persist among college-educated adults. Black students attending predominantly White institutions (PWIs) versus historically Black colleges and universities (HBCUs) report more harmful discrimination and develop worse mental health outcomes, which may offset the established benefits of college for lowering dementia incidence. HBCU (vs. non-HBCU) attendees averaged better executive function and verbal episodic memory (VEM) at average age 70, though confidence intervals were wide and associations were not statistically significant, and averaged slightly faster decline in VEM. Harmonized analyses using larger nationally representative studies are likely needed to avoid underestimating the health effects of HBCU attendance.
... memory), 2 and predicts educational and professional success, 3 social mobility, 4 health 5 and longevity. 6 It is thought to be a key mental capacity involved in 'active thinking', 7 fluid intelligence declines dramatically in various types of dementia 8 and reflects the degree of executive impairment in older patients with frontal involvement. 9 Despite the importance of fluid intelligence in defining human behaviour, it remains contentious whether this is a single or a cluster of cognitive abilities and the nature of its relationship with the brain. ...
... Based on visual inspection of the percent correct in healthy control performance, we graded the 12 items from easiest to hardest. We then formed three variables: 'easy group', containing the four easiest items (1,7,2,4), 'medium group', containing the next four items (3,5,6,10) and 'hard group', containing the four hardest items (12,9,8,11). We calculated each patient's score for the three variables (0-4). ...
Fluid intelligence is arguably the defining feature of human cognition. Yet the nature of its relationship with the brain remains a contentious topic. Influential proposals drawing primarily on functional imaging data have implicated ‘multiple demand’ frontoparietal and more widely distributed cortical networks, but extant lesion-deficit studies with greater causal power are almost all small, methodologically constrained, and inconclusive. The task demands large samples of patients, comprehensive investigation of performance, fine-grained anatomical mapping, and robust lesion-deficit inference, yet to be brought to bear on it.
We assessed 165 healthy controls and 227 frontal or non-frontal patients with unilateral brain lesions on the best-established test of fluid intelligence, Raven’s Advanced Progressive Matrices, employing an array of lesion-deficit inferential models responsive to the potentially distributed nature of fluid intelligence. Non-parametric Bayesian stochastic block models were used to reveal the community structure of lesion deficit networks, disentangling functional from confounding pathological distributed effects.
Impaired performance was confined to patients with frontal lesions [F(2,387) = 18.491; P < 0.001; frontal worse than non-frontal and healthy participants P < 0.01, P <0.001], more marked on the right than left [F(4,385) = 12.237; P < 0.001; right worse than left and healthy participants P < 0.01, P < 0.001]. Patients with non-frontal lesions were indistinguishable from controls and showed no modulation by laterality. Neither the presence nor the extent of multiple demand network involvement affected performance. Both conventional network-based statistics and non-parametric Bayesian stochastic block modelling heavily implicated the right frontal lobe. Crucially, this localization was confirmed on explicitly disentangling functional from pathology-driven effects within a layered stochastic block model, prominently highlighting a right frontal network involving middle and inferior frontal gyrus, pre- and post-central gyri, with a weak contribution from right superior parietal lobule. Similar results were obtained with standard lesion-deficit analyses.
Our study represents the first large-scale investigation of the distributed neural substrates of fluid intelligence in the focally injured brain. Combining novel graph-based lesion-deficit mapping with detailed investigation of cognitive performance in a large sample of patients provides crucial information about the neural basis of intelligence. Our findings indicate that a set of predominantly right frontal regions, rather than a more widely distributed network, is critical to the high-level functions involved in fluid intelligence. Further they suggest that Raven’s Advanced Progressive Matrices is a useful clinical index of fluid intelligence and a sensitive marker of right frontal lobe dysfunction.
... Possibly, through the accumulation model, we may have captured arealevel processes affecting the brain's morphology during both its development in childhood and its degeneration in mid-to late adulthood. Individuals with lower personal resources across the life course, including cognitive reserve [57], were more vulnerable. Alternatively, it is also plausible that in our study, accumulated neighbourhood deprivation only affected the brain during its degeneration phase (e.g., through cumulative allostatic load [58]), with the lagged impact of early life neighbourhood deprivation 'kicking in' in later adulthood. ...
Neighbourhood disadvantage may be associated with brain health but the importance of exposure at different stages of the life course is poorly understood. Utilising the Lothian Birth Cohort 1936, we explored the relationship between residential neighbourhood deprivation from birth to late adulthood, and global and local neuroimaging measures at age 73. A total of 689 participants had at least one valid brain measures (53% male); to maximise the sample size structural equation models with full information maximum likelihood were conducted. Residing in disadvantaged neighbourhoods in mid- to late adulthood was associated with smaller total brain (β = −0.06; SE = 0.02; sample size[N] = 658; number of pairwise complete observations[n]=390), grey matter (β = −0.11; SE = 0.03; N = 658; n = 390), and normal-appearing white matter volumes (β = −0.07; SE = 0.03; N = 658; n = 390), thinner cortex (β = −0.14; SE = 0.06; N = 636; n = 379), and lower general white matter fractional anisotropy (β = −0.19; SE = 0.06; N = 665; n = 388). We also found some evidence on the accumulating impact of neighbourhood deprivation from birth to late adulthood on age 73 total brain (β = −0.06; SE = 0.02; N = 658; n = 276) and grey matter volumes (β = −0.10; SE = 0.04; N = 658; n = 276). Local analysis identified affected focal cortical areas and specific white matter tracts. Among individuals belonging to lower social classes, the brain-neighbourhood associations were particularly strong, with the impact of neighbourhood deprivation on total brain and grey matter volumes, and general white matter fractional anisotropy accumulating across the life course. Our findings suggest that living in deprived neighbourhoods across the life course, but especially in mid- to late adulthood, is associated with adverse brain morphologies, with lower social class amplifying the vulnerability.
... Discerning between normal age-related cognitive changes and more severe cognitive impairment becomes paramount in facilitating early identification and intervention [4]. Drachman [5], Greenwood [6], and Whalley et al. [7] explored a deeper neuropathological aspect and they reveal conditions like dementia and neurological disorders are intricately associated with both brain atrophy and the loss of synaptic connections. Furthermore, the vulnerability of cognitive functions associated with the prefrontal cortex to the aging process adds another layer of complexity to our understanding [8]. ...
... For instance, the dentate gyrus, a subregion of the hippocampal formation that is critical for memory formation, is a neurogenic network that can be modulated by behaviour and experience (Piatti et al., 2013). Cognitive experiential factors also promote neuroplasticity and resistance to cellular apoptosis (Whalley et al., 2004). By contrast, the phrase 'use it or lose it' summarises the result of a cognitively sedentary lifestyle, where acceleration of atrophy in various brain structures is associated with early clinical manifestations of cognitive decline (Bordignon et al., 2021). ...
... Thus, healthy older adults with high cognitive reserve show less episodic memory decline. Factors such as educational level, social and physical activities have been studied for their protective effects on episodic memory in advancing age [13]. ...
Aging is marked by a memory decline related to an executive function decline. Physical activity (PA) has beneficial effects on both executive functions and memory, especially in aging. The protective effects of PA on these two cognitive abilities have always been studied separately, despite the well-established relationship between memory and executive functions. Our objective was to explore whether the benefits of PA on memory could be explained by reduced age-related changes in executive functions.
Nineteen young adults (27.16 years old) and 25 older adults (69.64 years old) performed a resource-dependent memory task, three executive tasks and completed a PA questionnaire (measuring sports and leisure PA). Age group and PA effects on memory and executive performance were analyzed with generalized linear models. Mediation analyses were calculated using method of causal steps approach with a non-parametric bootstrapping procedure.
The results confirmed the effects of age and PA on memory and executive performance. A significant interaction confirmed the protective effect of PA on age-related cognitive performance. PA was positively correlated with performance in both memory and executive tasks, but only in the older adults. Although each predictor alone (age, executive functions and PA) significantly explained memory performance in older adults, only the effect of PA on memory performance remained significant when all the predictors were introduced in the analyses.
PA mediates the effects of age and executive functions on memory performance. This suggests that PA protects older adults against memory decline by reducing the decline in executive functioning.
... On the one hand, in line with previous findings, DT can be considered a resource and a protective factor during the aging process [63,64,77]. Subjects with higher DT tend to accumulate higher CR, which, according to a wide range of evidence, can support cognitive efficiency during both healthy [44,78] and pathological aging [79][80][81]. On the other hand, the beneficial effect of CR seems to go beyond cognitive efficiency, significantly and positively predicting some PWB facets (mainly coping and emotional competence), confirming a strict interplay between cognition and emotions during the aging process, e.g., [16,20]. ...
The maintenance of psychological well-being (PWB) in the older adult population is a pivotal goal for our rapidly aging society. PWB is a multicomponent construct that can be influenced by several factors in the lifespan. The beneficial role of divergent thinking (DT) and cognitive reserve (CR) in sustaining older subjects’ PWB has been scarcely investigated so far. The present study aims to investigate the relationships between DT, CR, and PWB in a sample of 121 healthy older adults (61 females; M age: 73.39 ± 6.66 years; M education: 11.33 ± 4.81 years). The results highlight that better DT performance predicts higher CR, which mediates an indirect positive effect of DT on emotional competence, one of the PWB factors. It follows that DT and CR can be considered protective factors in aging, and their effects go beyond cognitive functioning, revealing a positive effect even on some PWB components. The practical implications regarding targeted health interventions for prevention in the older adult population to support well-being and promote healthy aging are discussed.
... ), while on higher difficulty levels this distinction vanishes, and instead connectivity was similarly related to CANTAB measures in both groups. These results indicate an already diminished cognitive reserve in the elderly population [82], showing that a smaller mental workload already poses a significant challenge reflected in fractal connectivity dynamics that is yet absent in the young group. ...
Analysis of brain functional connectivity (FC) could provide insight in how and why cognitive functions decline even in healthy aging (HA). Despite FC being established as fluctuating over time even in the resting state (RS), dynamic functional connectivity (DFC) studies involving healthy elderly individuals and assessing how these patterns relate to cognitive performance are yet scarce. In our recent study we showed that fractal temporal scaling of functional connections in RS is not only reduced in HA, but also predicts increased response latency and reduced task solving accuracy. However, in that work we did not address changes in the dynamics of fractal connectivity (FrC) strength itself and its plausible relationship with mental capabilities. Therefore, here we analyzed RS electroencephalography recordings of the same subject cohort as previously, consisting of 24 young and 19 healthy elderly individuals, who also completed 7 different cognitive tasks after data collection. Dynamic fractal connectivity (dFrC) analysis was carried out via sliding-window detrended cross-correlation analysis (DCCA). A machine learning method based on recursive feature elimination was employed to select the subset of connections most discriminative between the two age groups, identifying 56 connections that allowed for classifying participants with an accuracy surpassing 92%. Mean of DCCA was found generally increased, while temporal variability of FrC decreased in the elderly when compared to the young group. Finally, dFrC indices expressed an elaborate pattern of associations—assessed via Spearman correlation—with cognitive performance scores in both groups, linking fractal connectivity strength and variance to increased response latency and reduced accuracy in the elderly population. Our results provide further support for the relevance of FrC dynamics in understanding age-related cognitive decline and might help to identify potential targets for future intervention strategies.
... Nevertheless, a key assumption with this model is that the degree of compensatory involvement is directly related to the degree of cognitive performance, an assumption which has been tested less frequently in studies so far. Lastly, theories of reserve typically posit the idea that fitness (similarly to other proxies for reserve) can contribute to accumulated neural reserve (structural and/or functional) which is amassed over an extended period (which may be childhood, early adulthood, or, in older age) (Tucker & Stern, 2011;Whalley et al., 2004). The accumulation of reserve is thought to act as a protective shield against age-related neural pathology. ...
Cognitive decline associated with healthy ageing is complex and multifactorial: vascular and lifestyle factors uniquely and jointly contribute to distinct neurocognitive trajectories of ageing. To evaluate existing accounts of neurocognitive ageing that propose mechanisms of compensation, maintenance or reserve, studies should explore how various known brain-based and lifestyle factors intersect to better understand cognitive decline. Here, we bring together brain function, structure, perfusion, and cardiorespiratory fitness to investigate a well-documented, prominent cognitive challenge for older adults: word-finding failures. Commonality analysis on 73 neurologically healthy older adults revealed that functional activation of language networks associated with tip-of-the-tongue states is in part determined by age and, interestingly, cardiorespiratory fitness levels. Age-associated atrophy and perfusion in regions other than those showing functional differences accounted for variance in tip-of-the-tongue states. Our findings can be interpreted in the context of the classic models of neurocognitive ageing, with mechanisms of compensation and reserve interacting with each other.
Highlights
The incidence of word-finding failures is determined by brain health and lifestyle factors
Language network activation associated with word-finding failures is determined by age and cardiorespiratory fitness levels
Distinct contribution of brain structure and perfusion also predict this decline
Brain health indices in concordance with lifestyle measures provide a holistic explanation of individual differences in age-related cognitive decline
... Research in midlife adults without DS suggests that factors related to cardiovascular health such as increased moderate-to-vigorous physical activity (MVPA), cardiorespiratory fitness, and systolic blood pressure are associated with components of cognition including attention, memory, and executive function [6,7,8]. Additionally, MVPA [9] cardiorespiratory fitness [10] and systolic blood pressure [11] at midlife are associated with a lower incidence of later life dementia, possibly by increasing cognitive reserve so that a person can better maintain cognitive performance even with neuropathologic changes related to AD [12]. ...
Introduction
Evidence in the general population suggests that predictors of cardiovascular health such as moderate to vigorous physical activity (MVPA), cardiorespiratory fitness, and systolic blood pressure are associated with cognitive function. Studies supporting these associations in adults with Down syndrome (DS) are limited. The purpose of this study was to examine the associations between systolic blood pressure, cardiorespiratory fitness, and MVPA on cognition in adults with DS.
Methods
This is a cross-sectional analysis using baseline data from a trial in adults with DS. Participants attended a laboratory visit where resting blood pressure, cardiorespiratory fitness (VO2 Peak), and cognitive function (CANTAB® DS Battery) were obtained. The cognitive battery included tests measuring multitasking, episodic memory, and reaction time. Physical activity (accelerometer) was collected over the week following the laboratory visit. Pearson correlations and linear regressions were used to measure the impact of systolic blood pressure, cardiorespiratory fitness, and MVPA on cognitive outcomes.
Results
Complete data was available for 72 adults with DS (26.8 ± 9.3 years of age, 57% female). At baseline, VO2 Peak (21.1 ± 4.2 ml/kg/min) and MVPA were low (14.4 ± 14.4 min/day), and systolic blood pressure was 118.3 ± 13.3 mmHg. VO2 Peak was correlated with simple movement time (rho = − 0.28, p = 0.03) but was not significant using a linear regression controlling for age and sex. Systolic blood pressure was significantly associated with episodic memory (first attempt memory score: β = − 0.11, p = 0.002; total errors: β = 0.58, p = 0.001) and reaction time (five-choice movement time: β = 4.11, p = 0.03; simple movement time: β = 6.14, p = 0.005) using age- and sex-adjusted linear regressions. No associations were observed between MVPA and multitasking, episodic memory, or reaction time.
Conclusion
Predictors of cardiovascular health, including cardiorespiratory fitness and systolic blood pressure, were associated with some aspects of cognition in adults with DS. While future research should examine the role of improved cardiovascular health on delaying decreases in cognitive function and dementia in adults with DS, we recommend that health care providers convey the importance of exercise and cardiovascular health to their patients with DS.
Trial registration
NCT04048759, registered on August 7, 2019.
... Cognitive aging refers to age-related impairments in cognitive functions, including slower problem-solving, reduced fluid reasoning, diminished perceptual speed, and impaired memory and spatial ability. It stands as one of the most common health concerns among older individuals [1]. It is estimated that cognitive impairment affects over 11.7% of adults aged 65 and above, with the prevalence increasing to approximately 40% among those aged 80 and older [2]. ...
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ABSTRACT
In recent years, exploring natural compounds with functional properties to ameliorate aging-associated cognitive decline has become a research priority to ensure healthy aging. In the present study, we investigated the effects of Trigonelline (TG), a plant alkaloid, on memory and spatial learning in 16-week-old senescence-accelerated mouse model SAMP8 using an integrated approach for cog-nitive and molecular biology aspects. After 30 days of oral administration of TG at the dose of 5 mg/kg/ day, the mice were trained in Morris Water Maze task. TG-treated SAMP8 mice exhibited significant improvement in the parameters of escape latency, distance moved, and annulus crossing index. Next, we performed a whole-genome transcriptome profiling of the mouse hippocampus using microarrays. Gene ontology analyses showed that a wide range of biological processes, including nervous system development , mitochondrial function, ATP synthesis, and several signaling pathways related to inflammation, autophagy, and neurotransmitter release, were significantly enriched in TG-treated SAMP8 compared to nontreated. Further, a nonlinear dimensionality reduction technique, Uniform Manifold Approximation and Projection (UMAP), was applied to identify clusters of functions that revealed TG primarily regulated pathways related to inflammation, followed by those involved in neurotransmitter release. In addition, a protein-protein interaction network analysis indicated that TG may exert its biological effects through negatively modulating Traf6-mediated NF-κB activation. Finally, ELISA test showed that TG treatment significantly decreased proinflammatory cytokines-TNFα and IL6 and increased neurotransmitters-dopamine, noradrenaline, and serotonin in mouse hippocampus. Altogether, our integrated bio-cognitive approach highlights the potential of TG in alleviating age-related memory and spatial impairment.
... The decline of brain structure and function with aging is the main cause of cognitive decline in the older adults (44). As for the relationship between educational attainment and cognitive ability, our findings indicate that older adults with a high school diploma or higher are more likely to suffer from cognitive impairment than their illiterate counterparts, which is contrary to previous research findings that individuals with a higher level of education are more resistant to the aging process, diseases associated with aging, and brain and cognitive impairment (45,46). However, recent studies also have pointed out that educational attainment is not associated with long-term rates of change in any cognitive domain, with studies stating that education is only associated with cognitive performance and not with cognitive decline (47). ...
Objective
To compare the sex differences in cognitive function and its influencing factors among Chinese older adults.
Method
We conducted a cross-sectional study by using data from the China Longitudinal Healthy Longevity Survey (CLHLS). According to the 32 provinces and 4 municipalities directly under the Central Government of China, 3–5 counties or districts were randomly selected in each province or city (except Tibet), and then 1–3 villages or streets were randomly selected in each county or district, from which the target population was sampled. Mini Mental State Examination (MMSE) was used to assess the cognitive function of 9,262 older adults aged 65 and above in China. Descriptive analysis was applied to demonstrate the participants’ demographic characteristics, health-related behaviors, social and non-social activity, disease status, mental and sleep condition. And then, univariate and multifactor analyses were performed to validate different risk factors for cognitive function, respectively in the general population, male older adults and female older adults.
Result
The older adults with cognitive impairment accounted for 10.4% of the total population. There are significant differences in cognitive function between male and female older adults. The odds of cognitive impairment in older adult women was 1.291 times that of older adult men (OR = 1.291, 95%CI: 1.084–1.538). Among the male older adults, those who were older, highly educated, spouseless, had depressive symptoms, and lacked social activities were more likely to have cognitive impairment, whereas among the female older adults, those who were older, highly educated, and lacked social activities were more likely to have cognitive impairment.
Conclusion
Overall, there are subtle differences in potential influencing factors for cognitive function between the male older adults and female older adults. Attention should be paid to the different cognitive protection measures for the older adults with different sexes.
... Cognitive reserve theory describes how early life activities prevent age-associated cognitive decline. This view holds that higher levels of education, engagement in leisure activities, and innate intelligence provides cognitive reserve that contributes to less cognitive decline in aging [73] or in dementia [74]. Here we show that prior training in young and in midlife, with long intervals (2 × 6 months) of no training, is sufficient to improve cognitive function in later life. ...
Cognitive decline in spatial memory is seen in aging. Understanding affected processes in aging is vital for developing methods to improve wellbeing. Daily memory persistence can be influenced by events around the time of learning or by prior experiences in early life. Fading memories in young can last longer if a novel event is introduced around encoding, a process called behavioral tagging. Based on this principle, we asked what processes are affected in aging and if prior training can rescue them. Two groups of aged rats received training in an appetitive delayed matching-to-place task. One of the groups additionally received prior training of the same task in young and in mid-life, constituting a longitudinal study. The results showed long-term memory decline in late aging without prior training. This would reflect affected encoding and consolidation. On the other hand, short-term memory was preserved and novelty at memory reactivation and reconsolidation enabled memory maintenance in aging. Prior training improved cognition through facilitating task performance, strengthening short-term memory and intermediate memory, and enabling encoding-boosted long-term memory. Implication of these findings in understanding brain mechanisms in cognitive aging and in beneficial effects of prior training is discussed.
... Cognitive reserve is the capacity of the brain to sustain pathological changes, that with the same level of pathological change, an individual with lower cognitive reserve might have developed into dementia (Whalley et al., 2004). Even though Cajal, the father of neuroscience, claimed that the brain was mostly fixed in adulthood in the early 20 th century (Teter & Ashford, 2002), today, the neuroscience field generally agrees that the brain is a dynamic system that changes its structure and functions in response to the environment even in old age (Costandi, 2016). ...
Full text available here: https://theses.lib.polyu.edu.hk/handle/200/12383
Bilingualism has been attracting interest from the cognitive science field for years as it is suggested to be a protective factor against cognitive decline in ageing. It is often reported that bilinguals performed better than monolinguals in inhibitory control tasks. The mechanism behind the better inhibitory control was that bilinguals would have to suppress the interference from the unwanted language all the time, and such linguistic control is thought to be, at least partially, overlapped with the general inhibitory control network. However, inconsistent results have been reported. It is common for the literature to compare monolinguals with bilinguals as two homogenous groups without considering the individual variations between and among them. Moreover, as the Adaptive Control Hypothesis (Green & Abutalebi, 2013) suggested, the interaction context affects the cognitive demand in controlling the languages. Three experiments were designed to explore how different aspects of bilingualism contribute to cognition and the bilingual advantage effect.
The first experiment recruited older adults to complete a comprehensive set of cognitive tests together with questionnaires on their language and demographic profiles. Comparing the monolinguals and bilinguals, we found the classic bilingual advantage effect: bilinguals scored higher in the Montreal Cognitive Assessment (MoCA), indicating better cognitive status. Moreover, within the bilinguals, the scores in the cognitive battery were predicted with demographic and linguistic variables using linear regression analysis. We found that L2 proficiency predicts better inhibitory control and verbal ability performance in lifelong bilinguals. We propose that, because our participants are L1-dominant speakers, only the sufficiently proficient L2 would provide enough interference in the practice of linguistic inhibition control.
The second experiment investigated the cognitive changes in older foreign language learners. Older adults were recruited to study in an elementary English course for six weeks, with cognitive tests taken before and after the course. Although the statistical results between the intervention group and the active and passive control groups were not significant, the language learning-induced differences were observed in some tasks, including the accuracy of Picture Naming and the Conflicting Effect in the Attention Network Task. Correlation analysis suggested that successful language learners showed an improvement in inhibitory control and a decline in verbal fluency.
The third experiment investigated the organisation of the mental lexicon through an interesting language phenomenon in Hong Kong: dense code-switching. Whereas the literature often suggested that the comprehension of code-switching requires a switch in lexicon and is therefore challenging, we found that switching lexicon was needed only in the case of non-habitual word usage, regardless of whether it was unilingual and code-switching. From the result of this experiment, we proposed that the language input from the community had formed the bilingual prefabs, which integrated into the dominantly Cantonese lexicon.
Collectively, we suggest that the environment, language and cognition form a looping circle in that each component is interrelated. Moreover, they each affect the organisation of the bilingual mental lexicon and the retrieval of concepts from the lexicon. In view of that, we propose the Experience-based Bilingual Mental Lexicon Model, which is modified based on the Revised Hierarchical Model (Kroll & Stewart, 1994). Two critical assumptions are incorporated into the existing model: (1) the language lexicon is organised by experience but not by language origin, and (2) language dominance is dynamic. We believe the proposed model could better capture the dynamic change of language by experience. It could explain how individual differences contribute to the bilingual advantage effect.
References:
Green, D. W., & Abutalebi, J. (2013). Language control in bilinguals: The adaptive control hypothesis. Journal of Cognitive Psychology, 25(5), 515-530. https://doi.org/10.1080/20445911.2013.796377
Kroll, J. F., & Stewart, E. (1994). Category interference in translation and picture naming: Evidence for asymmetric connections between bilingual memory representations. Journal of Memory and Language, 33(2), 149-174. https://doi.org/10.1006/jmla.1994.1008
... Older adults are at increased risk for cognitive decline secondary to both age-related brain changes [1] and incipient accumulation of neuropathological burden [2]. Living with a chronic health condition often exacerbates these processes and can produce both accentuated and accelerated cognitive aging [3]. ...
Background
Modifiable lifestyle factors such as engagement with technology may be beneficial to cognition in older adults, but we know little about these relationships in older persons with chronic medical conditions.
Aims
The current study examined the association between computer use frequency and cognition in younger and older adults with and without HIV disease.
Methods
Participants included 110 older persons with HIV (pwHIV; age ≥ 50 years), 84 younger pwHIV (age ≤ 40 years), 76 older HIV−, and 66 younger HIV− adults who completed a comprehensive medical, psychiatric, and cognitive research assessment. Demographically adjusted scores were derived from a well-validated clinical battery of performance-based neuropsychological tests. Participants also completed self-reported measures of cognitive symptoms in daily life and the Brief Computer Use and Anxiety Questionnaire (BCUAQ).
Results
Older age was associated with less frequent computer use among persons with and without HIV disease. More frequent computer use was strongly and independently related to better cognitive performance, particularly in higher order domains (e.g., episodic memory and executive functions) and among the older seronegative adults. A small, univariable correlation between more frequent computer use and fewer cognitive symptoms in daily life was observed in the full sample, but that relationship was better explained by computer-related anxiety and HIV/age study group.
Discussion
These findings add to the existing literature that suggests regular engagement with digital technologies may have a beneficial impact on cognitive functioning, consistent with the technological reserve hypothesis.
... Several studies have shown that cognitive resources are reduced at high altitudes [33,34,61]. In case of reduced cognitive resources, individuals develop a series of strategies to complete tasks, such as compensation [3,55,62]. Lowering the threshold could be another strategy, especially when completing simple tasks [54]. In the DDM, a lower response threshold means that less evidence has been accumulated [63]. ...
Many studies have indicated a strong relationship between cardiac and brain activities, both of which are sensitive to high-altitude exposure. This study combined a consciousness access task and electrocardiograms (ECG) to uncover conscious awareness in response to high-altitude exposure and its relation to cardiac activity. When compared with the low-altitude groups, the behavioral results showed that the high-altitude participants shortened the time of access to visual awareness of grating orientation, which was accompanied by a faster heart rate, excluding the influence of pre-stimulus heart rate, extent of cardiac deceleration after presenting the stimulus, and task difficulty. Although there were post-stimulation cardiac deceleration and post-response acceleration at both high and low altitudes, a slight increase in heart rate after stimulation at high altitudes may indicate that participants at high altitudes could quickly readjust their attention to the target stimulus. More importantly, the drift diffusion model (DDM) was used to fit the access time distribution of all participants. These results suggest that shorter time at high altitudes might be due to the lower threshold, suggesting that less evidence in high-altitude participants was required to access visual consciousness. The participants' heart rates also negatively predicted the threshold through a hierarchical drift diffusion modeling (HDDM) regression. These findings imply that individuals with higher heart rates at high altitudes have a greater cognitive burden.
... We report that, at the baseline, the lower-educated group displayed a worse cognitive performance in the CDT with respect to the higher-educated group. This finding can be appraised within the context of the so-called cognitive reserve hypothesis by which different degrees of lifetime mental stimulation contribute to the inter-individual variability in late-life cognitive abilities and protection against the effects of ageing [15][16][17][18]. Moreover, our finding is in agreement with recent results from the FINGER study, a multidomain intervention, including cognitive training combined with physical exercise components [19]. ...
No treatment options are currently available to counteract cognitive deficits and/or delay progression towards dementia in older people with mild cognitive impairment (MCI). The 'Train the Brain' programme is a combined motor and cognitive intervention previously shown to markedly improve cognitive functions in MCI individuals compared to non-trained MCI controls, as assessed at the end of the 7-month intervention. Here, we extended the previous analyses to include the long-term effects of the intervention and performed a data disaggregation by gender, education and age of the enrolled participants. We report that the beneficial impact on cognitive functions was preserved at the 14-month follow-up, with greater effects in low-educated compared to high-educated individuals, and in women than in men.
... Additionally, the accelerated response observed due to the exposure duration via VAN and LP pathways could suggest a compensation mechanism to resist the adverse impacts of the high altitude. This mechanism is commonly employed by the brain to optimize and maximize its performance through recruitment of different brain networks or the utilization of alternative cognitive strategies to cope with brain dysfunction (Whalley et al., 2004;Stern, 2017;Alvares Pereira et al., 2021). Studies have shown that brain damage caused by aging results in under-activation of specific brain regions, leading to poorer performance in memory, cognitive control, and executive control behaviors (Grady et al., 1995;Cabeza et al., 2002;Reuter-Lorenz, 2002). ...
The psychological effects of long-term exposure to high-altitude environments have attracted great attention. These effects are usually attributed to the diminished cognitive resources due to high-altitude exposure. This study employed electroencephalography (EEG) to investigate the effects of exposure duration on awareness detection tasks. Neither reaction time nor accuracy showed the direct effects of the exposure duration, so did the model indexes obtained from drift diffusion model analysis. However, event-related potentials (ERP) analysis revealed that exposure duration was associated with changes in the visual awareness negativity (VAN) and the late positivity (LP) components, which in turn affected reaction time. Specifically, longer exposure durations were associated with lower VAN and higher LP, resulting in shorter reaction times and greater drift rate. In contrast to previous studies, the reverse relationship between VAN and LP may reflect a compensatory response to the reduced cognitive resources caused by high-altitude exposure. Additionally, increased LP and shorter reaction times with exposure duration may reflect a resistance to the high-altitude environment. We also conducted time-frequency analysis and found that theta power did not vary with exposure duration, suggesting that the reduction in cognitive resources remains stable in these individuals over time. Overall, our study provides new insights into the dynamic effects of high-altitude environments on awareness detection in the presence of reduced cognitive resources.
... This result is in line with previous studies that reported a negative association between the educational level and cognitive decline after stroke [34,35]. Education is part of the broader concept of cognitive reserve, which is the capacity of the brain to overcome an injury based on the engagement in challenging activities an individual has during their lifespan [36]. From the results of this study, we can conclude that higher cognitive reserve plays a protective role against moderate and severe stroke, leading to lower odds for SCCs 3 months after the vascular event. ...
Objective:
Cognitive deficits are commonly observed after stroke and have been associated with the cognitive decline and development of dementia in later stages. This study aimed to investigate whether cognition screened at acute stroke units could explain subjective cognitive complaints 3 months after stroke and evaluate how the severity of stroke and age could influence this association.
Methods:
In this register-based longitudinal study, data were retrieved from three Swedish registers between November 2014 and June 2019. Information on subjective cognitive complaints (SCC) was collected from the Riksstroke 3-month follow-up form, which were used to analyze the primary outcomes. Cognitive function screened using the Montreal Cognitive Assessment (MoCA) at acute stroke units was expressed as the primary independent variable.
Results:
Of the 1977 patients included in the study, 58% were males, the median age was 73 years, and 63% had a minor stroke. A total of 60% of patients had impaired cognition at acute stroke units (MoCA score, <26), of whom 40.3% reported at least 1 cognitive problem after 3 months. In adjusted binary regression analysis models, patients with normal cognitive function had lower odds for SCCs. This pattern was observed regardless of age and in patients with a minor stroke.
Conclusions:
Intact cognition early after stroke was related to decreased odds of subjective cognitive complaints at the 3-month follow-up. This study highlights the importance of both early cognitive screening after stroke and subjective cognitive complaints, which have been shown to be associated with cognitive decline. Furthermore, we suggest the importance of discussing cognitive function with patients during regular follow-up in primary care, usually 3 months after stroke.
... As people get older, their cognitive abilities also get worse [23] . Zhao [24] found that critical thinking is positively related to the cognitive ability of the elderly. ...
... Finally, when examining the neural underpinnings of EFs, we considered the role of young adult cognitive reserve, which we defined as an individual's total cognitive resources during early adulthood (Kremen et al., 2022). Theories of cognitive reserve suggest that some individuals do not exhibit the cognitive or functional deficits expected based on their brain pathology (Barulli and Stern, 2013;Stern, 2012Stern, , 2013Whalley, Deary, Appleton, & Starr, 2004), which might manifest as reduced associations between EF and white matter (and FW) in individuals with high reserve. We focus on young adulthood as a time when aging effects will have had essentially no impact on cognitive capacity. ...
Background
Studies have investigated white matter microstructure in relation to late-life cognitive impairments, with fractional anisotropy (FA) and mean diffusivity (MD) measures thought to capture demyelination and axonal degradation. However, new post-processing methods allow isolation of free water (FW), which captures extracellular fluid contributions such as atrophy and neuroinflammation, from tissue components. FW also appears to be highly relevant to late-life cognitive impairment. Here, we evaluated whether executive functions are associated with FW, and FA and MD corrected for FW (FAFWcorr and MDFWcorr).
Method
We examined 489 non-demented men in the Vietnam Era Twin Study of Aging (VETSA) at mean age 68. Two latent factors capturing ‘common executive function’ and ‘working-memory specific’ processes were estimated based on 6 tasks. Analyses focused on 11 cortical white matter tracts across three metrics: FW, FAFWcorr, and MDFWcorr.
Results
Better ‘common executive function’ was associated with lower FW across 9 of the 11 tracts. There were no significant associations with intracellular metrics after false discovery rate correction. Effects also appeared driven by individuals with MCI (13.7% of the sample). Working memory-specific tasks showed some associations with FAFWcorr, including the triangularis portion of the inferior frontal gyrus. There was no evidence that cognitive reserve (i.e., general cognitive ability assessed in early adulthood) moderated these associations between executive function and FW or FA.
Discussion
Executive function abilities in early old age are associated primarily with extracellular fluid (FW) as opposed to white matter (FAFWcorr or MDFWcorr). Moderation analyses suggested cognitive reserve does not play a strong role in these associations, at least in this sample of non-demented men.
... The process of healthy aging itself is linked to cognitive decline, most frequently impacting the executive functioning, memory, and attentional domains (Whalley et al., 2004). Life quality is affected by cognitive decline with age (Abrahamson et al., 2012). ...
Cognitive brain aging can either be healthy or degenerative in nature. Multiple alterations occur in brain networks with healthy aging. Much of this has yet to be investigated. This study seeks to understand the typical healthy human brain’s developmental stages using a publicly available dataset from the human connectome project. As the human brain’s developmental stage varies, we also intend to identify a pattern of reorganization in the resting state functional connectivity of several brain networks. The results are specifically presented based on the resting state BOLD signals of 1096 healthy volunteers between the age group of 7-89 years. The k-means clustering method has been used to determine the various human brain developmental stages. Using the t-SNE technique, the clusters are visually separated. BrainNet Viewer is used to study the changes in resting state functional connectivity of the entire brain as the human brain developmental stages vary. The age-related pattern of change in the resting state functional connectivity of six Dosenbasch brain networks that were grouped using the k-means elbow approach has been additionally presented. For performance evaluation, three metrics of brain network connection including network segregation, between network connectivity, and within-network connectivity are used. As the age cohort changes, a consistent pattern in the variance of these connection indices is seen for different Dosenbasch brain networks. Thus, the study’s findings suggest that healthy aging causes a functional reorganization of the resting state brain network connections.
... A higher level education in early life is usually associated with a significant reduction in prevalence and incidence of dementia (8). Education may influence the course and outcome of cognitive decline and protect against the onset of dementia, the so-called cognitive reserve hypothesis (8)(9)(10)(11). The interaction between the effect of education on cognitive reserve and the joint effect of cardiac and arterial aging on cognitive decline remains poorly understood (12). ...
Background
Lower cardiac index (CI) in elders has been associated with incident dementia, and higher CI has protectively effect with brain aging. In the present study, we investigated the modulating effects of education level and arterial stiffness on the association between CI and cognitive function among older adults.MethodsA total of 723 elders (≥60 years, 50.1% women) with normal left ventricular ejection fraction (≥50%) were identified from the Cardiovascular Diseases Risk Factor Two-Township Study. CI was calculated from the Doppler-derived stroke volume. We evaluated arterial stiffness by measuring carotid-femoral pulse wave velocity (CFPWV) and global cognitive function by using the Mini-Mental Short Examination (MMSE). Education level was determined by years of formal education.ResultsIn linear regression analysis adjusting for age, sex, formal years of education, and CFPWV, CI was significantly positively associated with MMSE (BETA=0.344±0.130, P = 0.0082). In logistic regression analysis adjusting for age, sex, formal years of education, and CFPWV, subjects with a CI≥75 percentile had a significantly lower risk of low MMSE (<26) (OR = 0.495, 95% CI = 0.274–0.896, P = 0.02). In subgroup analysis, higher CI was significantly associated with higher MMSE and lower risk of low MMSE only in elders with ≤ 9 years of formal education. Causal mediation analysis suggests that higher CI maintains higher MMSE in elders with lower education levels whereas higher CFPWV causes lower MMSE in all the elders.Conclusion
In elders with normal ejection fraction, a higher CI was associated with a lower risk of cognitive function impairment, independent of arterial stiffness, mainly in subjects with a lower education level and possibly a smaller cognitive reserve.
... Cognitive aging is a normal component of advancing in age, which involves changes in cognitive abilities (Rush et al., 2006). During the aging process, modifications in the structure of the brain lead to these cognitive changes (Whalley et al., 2004), with certain functions being more sensitive to cognitive aging, such as executive functioning (Murman, 2015) and processing speed (Salthouse, 1996). Cognitive changes do not occur in a homogeneous manner. ...
We used data from the Comprehensive cohort of the Canadian Longitudinal Study on Aging to compare the cognitive performance of retirees and workers (n = 1442), 45–85 years of age at baseline. Speed processing and executive functioning were assessed using standardized assessment tools at baseline and at follow-up, measured 3 years later. Retirees and workers were matched for age, sex, and education using the nearest neighbor propensity score method with a caliper of 0.02. Mixed ANOVA and post hoc analyses were conducted separately for the English- and French-speaking samples. Results for the English-speaking sample showed a significant decline on both the Stroop and the Mental Alternation tasks for retirees compared to workers from baseline to follow-up. These results support previous cross-sectional studies that have demonstrated a negative effect of retirement on executive functioning. The absence of significant results in the French-speaking sample are discussed in terms of sample size and professional occupation.
... Age-related decreases in cognitive performance have been associated with numerous neural substrates (Hedden et al., 2016;MacDonald & Pike, 2021;Whalley et al., 2004) including age-related differences in the brain network configuration (for reviews, see, Damoiseaux, 2017;Salat, 2011;Sporns, 2013;Wig, 2017;Zuo et al., 2017). Brain networks comprise sets of brain regions (nodes) and their connections (edges) which together are associated with solving specific behavioral tasks (Schaefer et al., 2018;Smith et al., 2009;Yeo et al., 2011). ...
In the normal aging process, the functional connectome restructures and shows a shift from more segregated to more integrated brain networks, which manifests itself in highly different cognitive performances in older adults. Underpinnings of this reorganization are not fully understood, but may be related to age-related differences in structural connectivity, the underlying scaffold for information exchange between regions. The structure-function relationship might be a promising factor to understand the neurobiological sources of interindividual cognitive variability, but remain unclear in older adults. Here, we used diffusion weighted and resting-state functional magnetic resonance imaging as well as cognitive performance data of 573 older subjects from the 1000BRAINS cohort (55-85 years, 287 males) and performed a partial least square regression on 400 regional functional and structural connectivity (FC and SC, respectively) estimates comprising seven resting-state networks. Our aim was to identify FC and SC patterns that are, together with cognitive performance, characteristic of the older adults aging process. Results revealed three different aging profiles prevalent in older adults. FC was found to behave differently depending on the severity of age-related SC deteriorations. A functionally highly interconnected system is associated with a structural connectome that shows only minor age-related decreases. Because this connectivity profile was associated with the most severe age-related cognitive decline, a more interconnected FC system in older adults points to a process of dedifferentiation. Thus, functional network integration appears to increase primarily when SC begins to decline, but this does not appear to mitigate the decline in cognitive performance.
... 31 This oxidative cellular stress is linked to early pathogenesis of ADRD through neuro-and/or vascular-inflammatory pathways. 32 Although stress-related factors might be expected to diminish the returns to education for Black cohort members, we found no evidence of this. Our analyses indicate that the advantage in late-life cognition potentially offered by educational attainment is equal to or greater for Black than White individuals. ...
Background:
Higher education consistently predicts improved late-life cognition. Racial differences in educational attainment likely contribute to inequities in dementia risk. However, few studies of education and cognition have controlled for prospectively measured early-life confounders or evaluated whether the education late-life cognition association is modified by race/ethnicity.
Methods:
Among 2343 Black and White Project Talent Aging Study participants who completed telephone cognitive assessments, we evaluated whether the association between years of education and cognition (verbal fluency, memory/recall, attention, and a composite cognitive measure) differed by race, and whether these differences persisted when adjusting for childhood factors, including the cognitive ability.
Results:
In fully adjusted linear regression models, each additional year of education was associated with higher composite cognitive scores for Black [β=0.137; 95% confidence interval (CI)=0.068, 0.206] and White respondents (β=0.056; CI=0.034, 0.078) with an interaction with race (P=0.03). Associations between education and memory/recall among Black adults (β=0.036; CI=-0.037, 0.109) and attention among White adults (β=0.022; CI=-0.002, 0.046) were nonsignificant. However, there were significant race-education interactions for the composite (P=0.03) and attention measures (P<0.001) but not verbal fluency (P=0.61) or memory/recall (P=0.95).
Conclusion:
Education predicted better overall cognition for both Black and White adults, even with stringent control for prospectively measured early-life confounders.
... The process of healthy aging itself is linked to cognitive decline, most frequently impacting the executive functioning, memory, and attentional domains (Whalley et al., 2004). Life quality is affected by cognitive decline with age (Abrahamson et al., 2012). ...
The human brain is liable to undergo substantial alterations, anatomically and functionally with aging. Cognitive brain aging can either be healthy or degenerative in nature. Such degeneration of cognitive ability can lead to disorders such as Alzheimer's disease, dementia, schizophrenia, and multiple sclerosis. Furthermore, the brain network goes through various changes during healthy aging, and it is an active area of research. In this study, we have investigated the rs-functional connectivity of participants (in the age group of 7-89 years) using a publicly available HCP dataset. We have also explored how different brain networks are clustered using K-means clustering methods which have been further validated by the t-SNE algorithm. The changes in overall resting-state brain functional connectivity with changes in brain developmental stages have also been explored using BrainNet Viewer. Then, specifically within-cluster network and between-cluster network changes with increasing age have been studied using linear regression which ultimately shows a pattern of increase/decrease in the mean segregation of brain networks with healthy aging. Brain networks like Default Mode Network, Cingulo opercular Network, Sensory Motor Network, and Cerebellum Network have shown decreased segregation whereas Frontal Parietal Network and Occipital Network show increased segregation with healthy aging. Our results strongly suggest that the brain has four brain developmental stages and brain networks reorganize their functional connectivity during these brain developmental stages.
... As expected, both intrinsic and extrinsic factors proved crucial. Specifically, the missing person's age, which relates to the person's cognitive [1][2][3][4]39] or global health [11] state, or the missing person's sex, which relates to the reason for going missing [40] or the type of behaviors in which the person engages during the missingness, was important. Similarly, the date of missingness or the size of the municipality in which the missingness occurred was relevant, as they are indirectly associated with the structure and organization of the physical and social environment that surrounds the missingness. ...
Person missingness is an enigmatic and frequent phenomenon that can bring about negative consequences for the missing person, their family, and society in general. Age-related cognitive changes and a higher vulnerability to dementia can increase the propensity of older adults to go missing. Thus, it is necessary to better understand the phenomenon of missingness in older adults. The present study sought to identify individual and environmental factors that might predict whether an older adult reported missing will be found. Supervised machine learning models were used based on the missing person cases open data of Colombia between 1930 and June 2021 ( n = 7855). Classification algorithms were trained to predict whether an older adult who went missing would eventually be found. The classification models with the best performance in the test data were those based on gradient boosting. Particularly, the Gradient Boosting Classifier and the Light Gradient Boosting Machine algorithms showed, respectively, 10% and 9% greater area under the curve (AUC) of the receiver operating characteristic (ROC) curve than a data-driven, reference model based on the mean of the reported time elapsed since the missingness observed in the training data. The features with the greatest contribution to the classification were the time since the missingness, the place where it occurred, and the age and sex of the missing person. The present results shed light on the societal phenomenon of person missingness while setting the ground for the application of machine learning models in cases of missing older persons.
Background and aims: The concept of “reserve” has been used to explain the difference between individuals in their capacity to cope with or compensate for pathology. Brain reserve refers to structural aspects of the brain, such as brain size and synapse count. Cognitive reserve is the ability to optimize and maximize performance through two mechanisms: recruitment of brain networks, and/or compensation by alternative cognitive strategies. The aim of the present research was to devise an instrument for comprehensive assessment and measurement of the quantity of cognitive reserve accumulated by individuals throughout their lifespan. Methods: A new approach using the Cognitive Reserve Index questionnaire (CRIq) was developed and tested in a sample of 588 healthy individuals, from 18 to 102 years old, stratified by age (Young, Adults, Elderly) and gender. The CRIq includes demographic data and items grouped into three sections: education, working activity and leisure time, each of which returns a subscore. The WAIS Vocabulary test and TIB were also administered. Results: The main descriptive features and some inferential results are described. Intelligence was only moderately correlated with cognitive reserve, stressing the distinction between these two concepts. Age and gender significantly affected CRIq scores, whereas no effect emerged from their interaction. Adults showed a higher score than Young and Elderly. Conclusions: This study provides a new instrument for a standardized measure of the cognitive reserve accumulated by individuals through their lifespan. The potential use of the CRIq in both experimental research and clinical practice is discussed.
Introduction: Unraveling the network pathobiology in neurodegenerative disorders is a popular and promising field in research. We use a relatively newer network measure of assortativity in metabolic connectivity to understand network differences in patients with Alzheimer's Disease (AD), compared with those with mild cognitive impairment (MCI). Methods: Eighty-three demographically matched patients with dementia (56 AD and 27 MCI) who underwent positron emission tomography-magnetic resonance imaging (PET-MRI) study were recruited for this exploratory study. Global and nodal network measures obtained using the BRain Analysis using graPH theory toolbox were used to derive group-level differences (corrected p < 0.05). The methods were validated in age, and gender-matched 23 cognitively normal, 25 MCI, and 53 AD patients from the publicly available Alzheimer's Disease Neuroimaging Initiative (ADNI) data. Regions that revealed significant differences were correlated with the Addenbrooke's Cognitive Examination-III (ACE-III) scores. Results: Patients with AD revealed significantly increased global assortativity compared with the MCI group. In addition, they also revealed increased modularity and decreased participation coefficient. These findings were validated in the ADNI data. We also found that the regional standard uptake values of the right superior parietal and left superior temporal lobes were proportional to the ACE-III memory subdomain scores. Conclusion: Global errors associated with network assortativity are found in patients with AD, making the networks more regular and less resilient. Since the regional measures of these network errors were proportional to memory deficits, these measures could be useful in understanding the network pathobiology in AD.
Introduction
Cognitive phenotyping is a widely used approach to characterize the heterogeneity of deficits in patients with a range of neurological disorders but has only recently been applied to patients with epilepsy. In this study, we identify cognitive phenotypes in older adults with late-onset epilepsy (LOE) and examine their demographic, clinical, and vascular profiles. Further, we examine whether specific phenotypes pose an increased risk for progressive cognitive decline.
Methods
Participants were part of the Atherosclerosis Risk in Communities Study (ARIC), a prospective longitudinal community-based cohort study of 15,792 individuals initially enrolled in 1987–1989. LOE was identified from linked Centers for Medicare and Medicaid Services claims data. Ninety-one participants with LOE completed comprehensive testing either prior to or after seizure onset as part of a larger cohort in the ARIC Neurocognitive Study in either 2011–2013 or 2016–2017 (follow-up mean = 4.9 years). Cognitive phenotypes in individuals with LOE were derived by calculating test-level impairments for each participant (i.e., ≤1 SD below cognitively normal participants on measures of language, memory, and executive function/processing speed); and then assigning participants to phenotypes if they were impaired on at least two tests within a domain. The total number of impaired domains was used to determine the cognitive phenotypes (i.e., Minimal/No Impairment, Single Domain, or Multidomain).
Results
At our baseline (Visit 5), 36.3% met criteria for Minimal/No Impairment, 35% for Single Domain Impairment (with executive functioning/ processing speed impaired in 53.6%), and 28.7% for Multidomain Impairment. The Minimal/No Impairment group had higher education and occupational complexity. There were no differences in clinical or vascular risk factors across phenotypes. Of those participants with longitudinal data (Visit 6; n = 24), 62.5% declined (i.e., progressed to a more impaired phenotype) and 37.5% remained stable. Those who remained stable were more highly educated compared to those that declined.
Discussion
Our results demonstrate the presence of identifiable cognitive phenotypes in older adults with LOE. These results also highlight the high prevalence of cognitive impairments across domains, with deficits in executive function/processing speed the most common isolated impairment. We also demonstrate that higher education was associated with a Minimal/No Impairment phenotype and lower risk for cognitive decline over time.
INTRODUCTION
We compared gender disparities in later‐life memory, overall and by education, in India and the United States (US).
METHODS
Data (N = 7443) were from harmonized cognitive assessment protocols (HCAPs) in the Longitudinal Aging Study of India‐Diagnostic Assessment of Dementia (LASI‐DAD; N = 4096; 2017‐19) and US Health and Retirement Study HCAP (HRS‐HCAP; N = 3347; 2016‐17). We derived harmonized memory factors from each study using confirmatory factor analysis. We used multivariable‐adjusted linear regression to compare gender disparities in memory function between countries, overall and by education.
RESULTS
In the United States, older women had better memory than older men (0.28 SD‐unit difference; 95% CI: 0.22, 0.35). In India, older women had worse memory than older men (−0.15 SD‐unit difference; 95% CI: −0.20, −0.10), which attenuated with increasing education and literacy.
CONCLUSION
We observed gender disparities in memory in India that were not present in the United States, and which dissipated with education and literacy.
Introduction:
Middle-aged and older adults who develop cancer experience memory loss following diagnosis, but memory decline in the years before and after cancer diagnosis is slower compared to their cancer-free counterparts. Educational attainment strongly predicts memory function during aging, but it is unclear whether education protects against memory loss related to cancer incidence or modifies long-term memory trajectories in middle-aged and older cancer survivors.
Materials and methods:
Data were from 14,449 adults (3,248 with incident cancer, excluding non-melanoma skin cancer) aged 50+ in the population-based US Health and Retirement Study from 1998 to 2016. Memory was assessed every two years as a composite of immediate and delayed word recall tests and proxy assessments for impaired individuals. Memory scores all time points were standardized at to the baseline distribution. Using multivariate-adjusted linear mixed-effects models, we estimated rates of memory decline in the years before cancer diagnosis, shortly after diagnosis, and in the years after diagnosis. We compared rates of memory decline between incident cancer cases and age-matched cancer-free adults, overall and according to level of education (<12 years, "low"; 12 to <16 years, "intermediate"; ≥16 years, "high").
Results:
Incident cancer diagnoses were followed by short-term declines in memory averaging 0.06 standard deviation (SD) units (95% confidence interval [CI]: -0.084, -0.036). Those with low education experienced the strongest magnitude of short-term decline in memory after diagnosis (-0.10 SD units, 95% CI: -0.15, -0.05), but this estimate was not statistically significantly different from the short-term decline in memory experienced by those with high education (-0.04 SD units, 95% CI: -0.08, 0.01; p-value for education as an effect modifier = 0.15). In the years prior to and following an incident cancer diagnosis, higher educational attainment was associated with better memory, but it did not modify the difference in rate of long-term memory decline between cancer survivors and those who remained cancer-free.
Discussion:
Education was associated with better memory function over time among both cancer survivors and cancer-free adults aged 50 and over. Low education may be associated with a stronger short-term decline in memory after a cancer diagnosis.
Individuals with more complex jobs experience better cognitive function in old age and a lower risk of dementia, yet complexity has multiple dimensions. Drawing on the Social Networks in Alzheimer Disease study, we examine the association between occupational complexity and cognition in a sample of older adults (N = 355). A standard deviation (SD) increase in complex work with people is associated with a 9% to 12% reduction in the probability of mild cognitive impairment or dementia, a 0.14-0.19 SD increase in episodic memory, and a 0.18-0.25 SD increase in brain reserve, defined as the gap (residual) between global cognitive function and magnetic resonance imaging (MRI) indicators of brain atrophy. In contrast, complexity with data or things is rarely associated with cognitive outcomes. We discuss the clinical and methodological implications of these findings, including the need to complement data-centered activities (e.g., Sudoku puzzles) with person-centered interventions that increase social complexity.
Introduction: The world’s population is aging, increasing the prevalence of dementia. Recently, foreign language learning in later life has been suggested to improve cognition and thus support healthy cognitive aging. To date, however, there are only a few studies with conflicting findings. Therefore, the purpose of this study was to examine whether learning a foreign language can improve executive attention and executive functions in healthy older adults. Additionally, we sought to identify factors affecting cognitive change in foreign language learners, such as cognitive reserve, previous foreign knowledge and usage, and global cognition at baseline.
Methods: In a randomized-controlled trial, we assigned 34 monolinguals between the ages of 65 and 80 to a language learning or a waiting list control group. The participants enrolled in a Spanish course for beginners that met five days a week for 1.5 h for a total of 3 weeks. The waiting list control group received no intervention but had the opportunity to join the language training at the end of the study. All participants underwent an assessment of executive attention (primary outcome), executive functions, verbal fluency, and attention (secondary outcomes) before, immediately after the course, or after a waiting period of 3 weeks for the control group and 3 months after the course or the waiting period.
Results: Foreign language learning did not significantly improve primary or secondary outcomes, neither immediately nor 3 months after the course. However, moderation analyses revealed that participants with lower global baseline cognition tended to improve more on response inhibition than individuals with higher baseline cognition. This relationship was not evident in the waiting list control group.
Discussion: Our results suggest that studying a foreign language does not generally improve executive attention or executive functioning. Nevertheless, individuals with poorer baseline cognition may benefit cognitively from foreign language learning in response inhibition, a domain particularly affected by cognitive aging. Our findings highlight the need of focusing dementia prevention efforts on groups that are more vulnerable to cognitive decline. Additionally, more individualized approaches, including utilizing technology-assisted learning, might enable participants to practice at their performance level, increasing the likelihood of discernible cognitive gains.
The role of socioeconomic status (SES) across the life course in late-life cognition is unclear. We tested the hypotheses that: 1) high SES in childhood, young adulthood, mid-life, and late-life have independent causal effects on higher cognition level and slower cognitive decline; 2) Compared to stable low SES (referent), stable high SES has the largest estimated effect for higher cognition level and slower decline among life course SES combinations. The Rush Memory and Aging Project enrolled 1,940 dementia-free older adults in 1997-2018. We utilized inverse probability weighted marginal structural models to estimate the joint and independent effect of each life course SES on global and domain-specific cognition. A total of 1,746 participants had 6 years average follow-up. High SES at each life course stage starting in young adulthood had a protective estimated effect on global and domain-specific cognition intercepts. Compared to consistently low SES, consistently high SES (β = 0.64, 95% CI: 0.48, 0.93), and high SES beyond childhood (β = 0.64, 95% CI: 0.47, 0.83) had the largest benefit for global cognition intercepts. None of the life course SES measures influenced rate of global or domain specific decline. Additional understanding of life course SES components influencing cognitive level is warranted.
For decades, the literature was skeptical about the feasibility of motor rehabilitation and its impact, as well as that of physical activity (PA), in subjects with major neurocognitive disorders (MNCD), including Alzheimer's disease. Now, authors report several benefits of PA, both physical and cognitive, by promoting brain perfusion, neurogenesis and synaptic plasticity, as well as decreasing oxidative stress and inflammation. PA should be recommended in cases of TNCM.
Background:
Cognitive reserve (CR) has been postulated to contribute to the variation observed between neuropathology and clinical outcomes in Alzheimer's disease (AD).
Objective:
We investigated the effect of an education-occupation derived CR proxy on biological properties of white matter tracts in patients with amnestic mild cognitive impairment (aMCI) and healthy elders (HC).
Methods:
Educational attainment and occupational complexity ratings (complexity with data, people, and things) from thirty-five patients with aMCI and twenty-eight HC were used to generate composite CR scores. Quantitative magnetic resonance imaging (qMRI) and multi-shell diffusion MRI were used to extract macromolecular tissue volume (MTV) across major white matter tracts.
Results:
We observed significant differences in the association between CR and white matter tract MTV in aMCI versus HC when age, gender, intracranial volume, and memory ability were held constant. Particularly, in aMCI, higher CR was associated with worse tract pathology (lower MTV) in the left and right dorsal cingulum, callosum forceps major, right inferior fronto-occipital fasciculus, and right superior longitudinal fasciculus (SLF) tracts. Conversely higher CR was associated with higher MTV in the right parahippocampal cingulum and left SLF in HC.
Conclusion:
Our results support compensatory CR mechanisms in aMCI and neuroprotective mechanisms in HC and suggest differential roles for CR on white matter macromolecular properties in healthy elders versus prodromal AD patients.
Mental rotation is the ability to rotate objects in one’s mind. Large age-related decreases in accuracy and processing time are often found in studies using paper-and-pencil or computerized mental rotation tests. For older participants, these tests are often too difficult. In the present study, real models consisting of cube figures were used to assess the mental rotation performance of middle and older aged adults. It should be investigated whether these tests were comparable to paper-and-pencil or chronometric tests and if very old participants were able to solve them. Eighty-four participants (49 females) between 40 and 90 years took part and were divided into middle (40–68 years) and older aged (69–90 years) and groups with higher (with college degree) and lower education (without college degree). For accuracy, main effects of gender and age group as well as interactions of age group and education were found. Younger participants outperformed older ones only in the group with lower education. For processing time, a main effect of age group as well as an interaction of age group and education was found. The age-related cognitive decline in the higher educated group was moderate, while a large effect appeared for the group without college degree. Age and gender effects of our new test with real objects were comparable to paper–pencil and computerized tests. Furthermore, a protective effect of education on the cognitive decline in mental rotation performance is discussed.
Dementia is a global health priority, with huge human and financial costs. Over 50 million people worldwide live with dementia, a figure which is set to rise to 130 million by 2050. The current cost of dementia to the global economy is a staggering $1 trillion per year.
Around 60% of people with dementia live in low- and middle-income countries (LMICs), countries in which population ageing is occurring at the most rapid rate and which already have the least capacity to cope. Key challenges in these regions include limited reliable epidemiological data, poor public understanding of dementia, inadequate health and social care systems and a lack of coherent, national or transnational dementia strategies. These challenges require concerted effort towards innovative, collaborative and technology-driven solutions involving clinicians, academics, engineers, economists and policymakers.
LMICs also present new opportunities for globally relevant dementia research: for example, the study of novel genetic and environmental factors that modify vulnerability and resilience to disease, as well as innovative approaches to dementia diagnosis and care in resource-poor situations. Whilst some established institutions in the developing world are already engaged in exploring these research opportunities, there is enormous potential for benefit from greater international exposure and collaboration.
The 2015 World Health Organization First Ministerial Conference on dementia concluded that “A sustained global effort is required to promote action on dementia and address the challenges posed by dementia and its impacts. No single country, sector or organization can tackle these challenges alone.” The aim of this Research Topic is to bring together, in one volume, research addressing problems that specifically relate to the impact of dementia in the developing world. In doing so, we hope to identify new challenges for future investigation.
We welcome submissions from a broad range of disciplines and are particularly interested in work that illustrates the collaborative coming together of disciplines and centers. Topics that will be considered include, but are not restricted to, epidemiology, diagnosis (clinical, neuropsychology, biomarkers, imaging), genetics, modifiable risk factors, treatment, diversity and under-represented populations, health economics, social science and public policy. Whilst submissions covering the full range of article types are encouraged, we are particularly interested in Original Research on dementia that specifically addresses issues relating to the LMIC context.
Background
Cannabis legalization and use are outpacing our understanding of its long-term effects on brain and behavior, which is fundamental for effective policy and health practices. Existing studies are limited by small samples, cross-sectional measures, failure to separate long-term from recreational use, and inadequate control for other substance use. Here, we address these limitations by determining the structural brain integrity of long-term cannabis users in the Dunedin Study, a longitudinal investigation of a population-representative birth cohort followed to midlife.
Methods
We leveraged prospective measures of cannabis, alcohol, tobacco, and other illicit drug use, in addition to structural neuroimaging in 875 Study members at age 45 to test for differences in both global and regional grey and white matter integrity between long-term cannabis users and lifelong non-users. We additionally tested for dose-response associations between continuous measures of cannabis use and brain structure, including careful adjustments for use of other substances.
Results
Long-term cannabis users had a thinner cortex, smaller subcortical grey matter volumes, and higher machine-learning-predicted brain age than non-users. However, these differences in structural brain integrity were explained by the propensity of long-term cannabis users to engage in polysubstance use, especially with alcohol and tobacco.
Conclusions
These findings suggest that diminished midlife structural brain integrity in long-term cannabis users reflects a broader pattern of polysubstance use, underlining the importance of understanding comorbid substance use in efforts to curb the negative effects of cannabis on brain and behavior as well as establish more effective policy and health practices.
Current neuropsychological models propose that some age-related cognitive changes are due to frontal-lobe deterioration. However, these models have not considered the possible subdivision of the frontal lobes into the dorsolateral and ventromedial regions. This study assessed the age effects on 3 tasks of executive function and working memory, tasks dependent on dorsolateral prefrontal dysfunction; and 3 tasks of emotion and social decision making, tasks dependent on ventromedial prefrontal dysfunction. Age-related differences in performance were found on all tasks dependent on dorsolateral prefrontal dysfunction. In contrast, age-related differences were not found on the majority of the tasks dependent on ventromedial prefrontal dysfunction. The results support a specific dorsolateral prefrontal theory of cognitive changes with age, rather than a global decline in frontal-lobe function.
This commentary calls attention to the value of combining genetic and epidemiologic methods in studies to understand the determinants of two crucial aspects of aging: ages at which certain outcomes (e.g., disease, mortality) occur and rates of change with age of individual's characteristics (e.g., physiologic functions, disease risk factors). Inclusion of age in the specification of traits in genetic epidemiologic studies could lead to improved strategies to increase healthy life expectancy and evaluate individuals' risk for age-related morbidity. Special issues that make genetic epidemiologic approaches important for studies of age-specified phenomena as well as opportunities and challenges for such studies are discussed, including study designs, sampling frames, databases, analytic tools, and related methodological issues. This commentary is based on a report prepared by the Aging and Genetic Epidemiology Working Group, convened by the National Institute on Aging to review opportunities for research on the genetic epidemiology of aging-related outcomes. The report, which contains more extensive discussion, literature review, and references, is available on the World Wide Web at http://www.nih.gov/nia/conferences/GenetReport111199.htm. Am J Epidemiol 2000;152;1003-8.
Replies to comments by R. J. Sternberg (1997) and D. A. Washburn and D. M. Rumbaugh (1997) on the authors' (I. J. Deary and C. Stough, see record 83-29472) article regarding the use of inspection time as a measure of intelligence. The authors focus their responses on Sternberg's criticisms of their work, and reiterate their position that inspection time is unique with regard to its combination of level of correlation, simplicity, and theoretical tractability. (PsycINFO Database Record (c) 2012 APA, all rights reserved)
A theory is proposed to account for some of the age-related differences reported in measures of Type A or fluid cognition. The central hypothesis in the theory is that increased age in adulthood is associated with a decrease in the speed with which many processing operations can be executed and that this reduction in speed leads to impairments in cognitive functioning because of what are termed the limited time mechanism and the simultaneity mechanism. That is, cognitive performance is degraded when processing is slow because relevant operations cannot be successfully executed (limited time) and because the products of early processing may no longer be available when later processing is complete (simultaneity). Several types of evidence, such as the discovery of considerable shared age-related variance across various measures of speed and large attenuation of the age-related influences on cognitive measures after statistical control of measures of speed, are consistent with this theory.
To determine the relationship of brain infarction to the clinical expression of Alzheimer disease (AD).
Cognitive function and the prevalence of dementia were determined for participants in the Nun Study who later died. At autopsy, lacunar and larger brain infarcts were identified, and senile plaques and neurofibrillary tangles in the neocortex were quantitated. Participants with abundant senile plaques and some neurofibrillary tangles in the neocortex were classified as having met the neuropathologic criteria for AD.
Convents in the Midwestern, Eastern, and Southern United States.
A total of 102 college-educated women aged 76 to 100 years.
Cognitive function assessed by standard tests and dementia and AD assessed by clinical and neuropathologic criteria.
Among 61 participants who met the neuropathologic criteria for AD, those with brain infarcts had poorer cognitive function and a higher prevalence of dementia than those without infarcts. Participants with lacunar infarcts in the basal ganglia, thalamus, or deep white matter had an especially high prevalence of dementia, compared with those without infarcts (the odds ratio [OR] for dementia was 20.7, 95% confidence interval [95% CI], 1.5-288.0). Fewer neuropathologic lesions of AD appeared to result in dementia in those with lacunar infarcts in the basal ganglia, thalamus, or deep white matter than in those without infarcts. In contrast, among 41 participants who did not meet the neuropathologic criteria for AD, brain infarcts were only weakly associated with poor cognitive function and dementia. Among all 102 participants, atherosclerosis of the circle of Willis was strongly associated with lacunar and large brain infarcts.
These findings suggest that cerebrovascular disease may play an important role in determining the presence and severity of the clinical symptoms of AD.
To investigate the risk of AD associated with a family history of dementia, female gender, low levels of education, smoking, and head trauma.
These putative factors have been identified in cross-sectional studies. However, those studies are prone to bias due to systematic differences between patients and control subjects regarding survival and how risk factors are recalled.
The authors performed a pooled analysis of four European population-based prospective studies of individuals 65 years and older, with 528 incident dementia patients and 28,768 person-years of follow-up. Patients were detected by screening the total cohort with brief cognitive tests, followed by a diagnostic assessment of those who failed the screening tests. Dementia was diagnosed with the Diagnostic and Statistical Manual of Mental Disorders, 3rd ed. (revised), and AD was diagnosed according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria. Incident rates and relative risk (95% CI) express the association of a risk factor for dementia.
Incident rates for dementia and AD were similar across studies. The incidence of AD increased with age. At 90 years of age and older the incidence was 63.5 (95% CI, 49.7 to 81.0) per 1,000 person-years. Female gender, current smoking (more strongly in men), and low levels of education (more strongly in women) increased the risk of AD significantly. A history of head trauma with unconsciousness and family history of dementia did not increase risk significantly.
Contrary to previous reports, head trauma was not a risk factor for AD, and smoking did not protect against AD. The association of family history with the risk of AD is weaker than previously estimated on the basis of cross-sectional studies. Female gender may modify the risk of AD, whether it be via biological or behavioral factors.
To examine the cognitive function in a large, ongoing cohort study of older men, and to identify associations with social and lifestyle factors.
A cross sectional study of cognitive function was conducted within the Caerphilly Prospective Study of Heart Disease and stroke.
The Caerphilly Study was originally set up in 1979-83 when the men were 45-59 years of age. Extensive data are available on a wide range of lifestyle and other factors of possible relevance to cognitive decline. Associations between some of these and cognitive function are reported.
A representative sample of 1870 men aged 55-69 years.
Age, social class, medication, and mood were found to be powerful determinants of performance. Self report data on the involvement of the men in leisure pursuits were examined by factor analysis. This indicated that the more intellectual leisure pursuits are the most strongly linked with performance. A measure of social contact showed a weak positive association with the test scores. Current cigarette smokers gave lower test cognitive function scores than either men who had never smoked, or ex-smokers. There was however no evidence of any gradient in function with the total lifetime consumption of tobacco. The disparity between these two data sets suggests that there had been prior selection of men who had originally started to smoke, but more particularly selection of those who later quit smoking. There was no significant association between alcohol consumption and cognitive function, though ex-drinkers had markedly lower test scores than either current drinkers or men who had never drunk alcohol. This seemed probably to be a consequence of an high prevalence of illness among the ex-drinkers.
Age and social class show strong associations with cognitive function. Leisure persuits and social contact are also both positively associated. Neither tobacco smoking nor the drinking of alcohol seem to be associated with cognitive function, though there is evidence suggestive of self selection of both men who had never smoked and ex-smokers.
In primates, prefrontal, inferior temporal, and posterior parietal cortex are important for cognitive function. It is shown
that in adult macaques, new neurons are added to these three neocortical association areas, but not to a primary sensory area
(striate cortex). The new neurons appeared to originate in the subventricular zone and to migrate through the white matter
to the neocortex, where they extended axons. These new neurons, which are continually added in adulthood, may play a role
in the functions of association neocortex.
To explore volume changes of the entorhinal cortex (ERC) and hippocampus in mild cognitive impairment (MCI) and Alzheimer's disease (AD) compared with normal cognition (NC); to determine the powers of the ERC and the hippocampus for discrimination between these groups.
This study included 40 subjects with NC, 36 patients with MCI, and 29 patients with AD. Volumes of the ERC and hippocampus were manually measured based on coronal T1 weighted MR images. Global cerebral changes were assessed using semiautomatic image segmentation.
Both ERC and hippocampal volumes were reduced in MCI (ERC 13%, hippocampus 11%, p<0.05) and AD (ERC 39%, hippocampus 27%, p<0.01) compared with NC. Furthermore, AD showed greater volume losses in the ERC than in the hippocampus (p<0.01). In addition, AD and MCI also had cortical grey matter loss (p< 0.01) and ventricular enlargement (p<0.01) when compared with NC. There was a significant correlation between ERC and hippocampal volumes in MCI and AD (both p<0.001), but not in NC. Using ERC and hippocampus together improved discrimination between AD and CN but did not improve discrimination between MCI and NC. The ERC was better than the hippocampus for distinguishing MCI from AD. In addition, loss of cortical grey matter significantly contributed to the hippocampus for discriminating MCI and AD from NC.
Volume reductions in the ERC and hippocampus may be early signs of AD pathology that can be measured using MRI.
In this review we summarize the progress that has been made in the research on attentional and executive deficits in Alzheimer's disease. Like memory, attention is now recognized as consisting of subtypes that differ in their function and anatomical basis. We base our review upon a classification of three subtypes of attention: selective, sustained and divided. This model derives from lesion studies, animal electrophysiological recordings and functional imaging. We examine how these sub-components of attention can be reconciled with neuropsychological models of attentional control, particularly the Supervisory Attentional System and the Central Executive System of Shallice and Baddeley, respectively. We also discuss the relationship of attention to the concept of executive function. Current evidence suggests that after an initial amnesic stage in Alzheimer's disease, attention is the first non-memory domain to be affected, before deficits in language and visuospatial functions. This is consistent with the possibility that
There is an increasing amount of experimental evidence that oxidative stress is a causal, or at least an ancillary, factor in the neuropathology of several adult neurodegenerative disorders, as well as in stroke, trauma, and seizures. At the same time, excessive or persistent activation of glutamate-gated ion channels may cause neuronal degeneration in these same conditions. Glutamate and related acidic amino acids are thought to be the major excitatory neurotransmitters in brain and may be utilized by 40 percent of the synapses. Thus, two broad mechanisms--oxidative stress and excessive activation of glutamate receptors--are converging and represent sequential as well as interacting processes that provide a final common pathway for cell vulnerability in the brain. The broad distribution in brain of the processes regulating oxidative stress and mediating glutamatergic neurotransmission may explain the wide range of disorders in which both have been implicated. Yet differential expression of components of the processes in particular neuronal systems may account for selective neurodegeneration in certain disorders.
Background
We have undertaken a large unselected, community-based neuropathology study in an elderly (70–103 years) UK population in relation to prospectively evaluated dementia status. The study tests the assumption that dementing disorders as defined by current diagnostic protocols underlie this syndrome in the community at large.
Methods
Respondents in the Medical Research Council Cognitive Function and Ageing Study were approached for consent to examine the brain at necropsy. Dementia status was assigned by use of the automated geriatric examination for computer-assisted taxonomy algorithm. Neuropathological features were standardised by use of the protocol of the Consortium to Establish a Registry of Alzheimer's Disease, which assesses the severity and distribution of Alzheimer-type pathology, vascular lesions, and other potential causes of dementia. A statistical model of dementia risk related predominantly to Alzheimer-type and vascular pathology was developed by multivariate logistic regression.
Findings
We report on the first 209 individuals who have come to necropsy. The median age at death was 85 years for men, and 86 years for women. Cerebrovascular (78%) and Alzheimer-type (70%) pathology were common. Dementia was present in 100 (48%), of whom 64% had features indicating probable or definite Alzheimer's disease. However, 33% of the 109 non-demented people had equivalent densities of neocortical neuritic plaques. Some degree of neocortical neurofibrillary pathology was found in 61% of demented and 34% of non-demented individuals. Vascular lesions were equally common in both groups, although the proportion with multiple vascular pathology was higher in the demented group (46% vs 33%).
Interpretation
Alzheimer-type and vascular pathology were the major pathological correlates of cognitive decline in this elderly sample, as expected, but most patients had mixed disease. There were no clear thresholds of these features that predicted dementia status. The findings therefore challenge conventional dementia diagnostic criteria in this setting. Additional factors must determine whether moderate burdens of cerebral Alzheimer-type pathology and vascular lesions are associated with cognitive failure.
Background We have undertaken a large unselected, community-based neuropathology study in an elderly (70-103 years) UK population in relation to prospectively evaluated dementia status. The study tests the assumption that dementing disorders as defined by current diagnostic protocols underlie this syndrome in the community at large. Methods Respondents in the Medical Research Council Cognitive Function and Ageing Study were approached for consent to examine the brain at necropsy. Dementia status was assigned by use of the automated geriatric examination for computer-assisted taxonomy algorithm. Neuropathological features were standardised by use of the protocol of the Consortium to Establish a Registry of Alzheimer's Disease, which assesses the severity and distribution of Alzheimer-type pathology, vascular lesions, and other potential causes of dementia. A statistical model of dementia risk related predominantly to Alzheimer-type and vascular pathology was developed by multivariate logistic regression. Findings We report on the first 209 individuals who have come to necropsy. The median age at death was 85 years for men, and 86 years for women. Cerebrovascular (78%) and Alzheimer-type (70%) pathology were common. Dementia was present in 100 (48%), of whom 64% had features indicating probable or definite Alzheimer's disease. However, 33% of the 109 non-demented people had equivalent densities of neocortical neuritic plaques. Some degree of neocortical neurofibrillary pathology was found in 61% of demented and 34% of non-demented individuals. Vascular lesions were equally common in both groups, although the proportion with multiple vascular pathology was higher in the demented group (46% vs 33%). Interpretation Alzheimer-type and Vascular pathology were the major pathological correlates of cognitive decline in this elderly sample, as expected, but most patients had mixed disease. There were no clear thresholds of these features that predicted dementia status. The findings therefore challenge conventional dementia diagnostic criteria in this setting. Additional factors must determine whether moderate burdens of cerebral Alzheimer-type pathology and vascular lesions are associated with cognitive failure.
In this study, the authors evaluated whether the association between low educational level and increased risk of Alzheimer's disease (AD) and dementia may be explained by occupation-based socioeconomic status (SES). A cohort of 931 nondemented subjects aged ≥75 years from the Kungsholmen Project, Stockholm, Sweden, was followed for 3 years between 1987 and 1993. A total of 101 incident cases of dementia, 76 involving AD, were detected. Less-educated subjects had an adjusted relative risk of developing AD of 3.4 (95% confidence interval: 2.0, 6.0), and subjects with lower SES had an adjusted relative risk of 1.6 (95% confidence interval: 1.0, 2.5). When both education and SES were introduced into the same model, only education remained significantly associated with AD. Combinations of low education with low or high SES were associated with similar increased risks of AD, but well-educated subjects with low SES were not at high risk. Low SES at 20 years of age, even when SES was high at age 40 or 60 years, was associated with increased risk; however, this increase disappeared when education was entered into the model. In conclusion, the association between low education and increased AD risk was not mediated by adult SES or socioeconomic mobility. This suggests that early life factors may be relevant.
Objective.
—To determine the relationship of brain infarction to the clinical expression of Alzheimer disease (AD).
Design.
—Cognitive function and the prevalence of dementia were determined for participants in the Nun Study who later died. At autopsy, lacunar and larger brain infarcts were identified, and senile plaques and neurofibrillary tangles in the neocortex were quantitated. Participants with abundant senile plaques and some neurofibrillary tangles in the neocortex were classified as having met the neuropathologic criteria for AD.
Setting.
—Convents in the Midwestern, Eastern, and Southern United States.
Participants.
—A total of 102 college-educated women aged 76 to 100 years.
Main Outcome Measures.
—Cognitive function assessed by standard tests and dementia and AD assessed by clinical and neuropathologic criteria.
Results.
—Among 61 participants who met the neuropathologic criteria for AD, those with brain infarcts had poorer cognitive function and a higher prevalence of dementia than those without infarcts. Participants with lacunar infarcts in the basal ganglia, thalamus, or deep white matter had an especially high prevalence of dementia, compared with those without infarcts (the odds ratio [OR] for dementia was 20.7,95% confidence interval [95% CI], 1.5-288.0). Fewer neuropathologic lesions of AD appeared to result in dementia in those with lacunar infarcts in the basal ganglia, thalamus, or deep white matter than in those without infarcts. In contrast, among 41 participants who did not meet the neuropathologic criteria for AD, brain infarcts were only weakly associated with poor cognitive function and dementia. Among all 102 participants, atherosclerosis of the circle of Willis was strongly associated with lacunar and large brain infarcts.
Conclusion.
—These findings suggest that cerebrovascular disease may play an important role in determining the presence and severity of the clinical symptoms of AD.
Objective:
To investigate the risk of AD associated with a family history of dementia, female gender, low levels of education, smoking, and head trauma.
Background:
These putative factors have been identified in cross-sectional studies. However, those studies are prone to bias due to systematic differences between patients and control subjects regarding survival and how risk factors are recalled.
Methods:
The authors performed a pooled analysis of four European population-based prospective studies of individuals 65 years and older, with 528 incident dementia patients and 28,768 person-years of follow-up. Patients were detected by screening the total cohort with brief cognitive tests, followed by a diagnostic assessment of those who failed the screening tests. Dementia was diagnosed with the Diagnostic and Statistical Manual of Mental Disorders, 3rd ed. (revised), and AD was diagnosed according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria. Incident rates and relative risk (95% CI) express the association of a risk factor for dementia.
Results:
Incident rates for dementia and AD were similar across studies. The incidence of AD increased with age. At 90 years of age and older the incidence was 63.5 (95% CI, 49.7 to 81.0) per 1,000 person-years. Female gender, current smoking (more strongly in men), and low levels of education (more strongly in women) increased the risk of AD significantly. A history of head trauma with unconsciousness and family history of dementia did not increase risk significantly.
Conclusion:
Contrary to previous reports, head trauma was not a risk factor for AD, and smoking did not protect against AD. The association of family history with the risk of AD is weaker than previously estimated on the basis of cross-sectional studies. Female gender may modify the risk of AD, whether it be via biological or behavioral factors.
In this paper, we review the key pathologic events in human hippocampus and neocortex that underlie Alzheimer's disease, and contrast these events with those of normal aging in these same brain regions of animal models. Alzheimer's disease is characterized by senile plaque and neurofibrillary tangle formation, and more importantly, extensive yet selective neuron death and synapse loss in the hippocampus and neocortex. Particular subsets of pyramidal cells and their projections, such as the connection between entorhinal cortex and hippocampus and corticocortical interconnections in neocortex, are particularly vulnerable. The extensive degeneration of these circuits leads directly to dementia. Normal aging can be accompanied by a more modest disruption of memory, yet neuron death is unlikely to be a significant contributor to age-associated memory impairment. While the death of neurons is minimal in normal aging, the same hippocampal and neocortical circuits that die in Alzheimer's disease are vulnerable to sublethal age-related shifts in morphology, neurochemical phenotype and synaptic alterations that might impair function. The response of these circuits to circulating estrogen levels is also discussed, since the critical interactions between reproductive senescence and brain aging may affect excitatory synaptic transmission in the hippocampus as well. Thus, subtle changes in the aging spine and synapse may be the key to age-related memory decline, whereas degeneration of entire circuits is the more prominent substrate for functional decline in Alzheimer's disease.
In the ageing process, neural areas¹,² and cognitive processes³,⁴ do not degrade uniformly. Executive control processes and the prefrontal and frontal brain regions that support them show large and disproportionate changes with age. Studies of adult animals indicate that metabolic⁵ and neurochemical⁶ functions improve with aerobic fitness. We therefore investigated whether greater aerobic fitness in adults would result in selective improvements in executive control processes, such as planning, scheduling, inhibition and working memory. Over a period of six months, we studied 124 previously sedentary adults, 60 to 75 years old, who were randomly assigned to either aerobic (walking) or anaerobic (stretching and toning) exercise. We found that those who received aerobic training showed substantial improvements in performance on tasks requiring executive control compared with anaerobically trained subjects.
The brain is not only immunologically active of its own accord, but also has complex peripheral immune interactions. Given the central role of cytokines in neuroimmmunoendocrine processes, it is hypothesized that these molecules influence cognition via diverse mechanisms. Peripheral cytokines penetrate the blood-brain barrier directly via active transport mechanisms or indirectly via vagal nerve stimulation. Peripheral administration of certain cytokines as biological response modifiers produces adverse cognitive effects in animals and humans. There is abundant evidence that inflammatory mechanisms within the central nervous system (CNS) contribute to cognitive impairment via cytokine-mediated interactions between neurons and glial cells. Cytokines mediate cellular mechanisms subserving cognition (e.g., cholinergic and dopaminergic pathways) and can modulate neuronal and glial cell function to facilitate neuronal regeneration or neurodegeneration. As such, there is a growing appreciation of the role of cytokine-mediated inflammatory processes in neurodegenerative diseases such as Alzheimer's disease and vascular dementia. Consistent with their involvement as mediators of bidirectional communication between the CNS and the peripheral immune system, cytokines play a key role in the hypothalamic-pituitary-adrenal axis activation seen in stress and depression. In addition, complex cognitive systems such as those that underlie religious beliefs, can modulate the effects of stress on the immune system. Indirect means by which peripheral or central cytokine dysregulation could affect cognition include impaired sleep regulation, micronutrient deficiency induced by appetite suppression, and an array of endocrine interactions. Given the multiple levels at which cytokines are capable of influencing cognition it is plausible that peripheral cytokine dysregulation with advancing age interacts with cognitive aging.
MRI-based measurements of hippocampal atrophy are a sensitive indicator of the early pathologic degeneration of the medial temporal lobe in AD. However, AD pathology appears first in the transentorhinal/entorhinal cortex, not the hippocampus. The authors tested the hypothesis that MRI-based measurements of the entorhinal cortex are more sensitive than measurements of hippocampal volume in discriminating among three clinical groups; controls, patients with a mild cognitive impairment (MCI), and patients with mild probable AD.
The authors studied 30 controls, 30 patients with MCI, and 30 patients with AD who were matched among clinical groups on age, gender, and education. All underwent a standardized MRI protocol from which the authors made measurements of hippocampal volume, entorhinal cortex volume, and the cumulative length of the medial border of the entorhinal cortex.
Pairwise intergroup differences (p < 0.01) were found for all MRI measurements with the exception of the cumulative length of the entorhinal cortex, which did not differentiate controls from MCI patients. Whereas the hippocampal and entorhinal cortex volume measurements provided slightly better intergroup discrimination than the entorhinal distance measurement, overall differences in discriminating ability among the three MRI measurements were minor.
Despite the theoretical rationale for the superiority of entorhinal measurements in early AD, the authors found MRI measurements of the hippocampus and entorhinal cortex were approximately equivalent at intergroup discrimination. Measurements of the hippocampus may be preferable because MRI depiction of the boundaries of the entorhinal cortex can be obscured by anatomic ambiguity, image artifact, or both.
C-reactive protein (CRP) is a plasma acute-phase protein, normally not found in the brain. Previous studies have demonstrated the presence of CRP in the senile plaques of Alzheimer's disease (AD). In this study, the presence of CRP-like immunoreactivity in AD neurofibrillary tangles (NFT) was demonstrated following pre-treatment of tissue sections with formic acid. CRP-like immunoreactivity was observed in both extracellular and intracellular NFT and was co-localized with the NFT marker PHF-1 and the amyloid P component (AP). The CRP-like immunoreactive NFT were less numerous and more limited in their distribution than PHF-1 or AP-immunoreactive NFT. The present results further support an involvement of inflammatory processes in the etiology of AD.
All Scottish children born in 1921 and attending school on June 1, 1932 (N=87,498) undertook a validated test of psychometric intelligence, The Moray House Test. We followed up 101 of these people at age 77 and re-administered the same mental ability test. Concurrent validity data are provided for the Moray House Test at age 11 (n=1,000) and age 77 years (n=97). The correlation between Moray House Test scores at age 11 and age 77 was 0.63, which adjusted to 0.73 when corrected for attenuation of ability range within the re-tested sample. This, the longest follow-up study of psychometric intelligence reported to date, shows that mental ability differences show substantial stability from childhood to late life.
In order to explore the relationships between the involvement of specific neuronal populations and cognitive deterioration, and to compare the hierarchical patterns of cortical involvement in normal brain aging and Alzheimer's disease, over 1200 brains from elderly subjects without cognitive deficits, as well as from patients with age-associated memory impairment and Alzheimer's disease, were examined. Our results suggest that the neuropathological changes associated with normal brain aging and Alzheimer's disease affect select cortical circuits at different points in time. Extensive hippocampal alterations are correlated with age-associated memory impairment, whereas substantial neurofibrillary tangle formation in neocortical association areas of the temporal lobe is a prerequisite for the development of Alzheimer's disease. Despite several lines of evidence involving amyloid deposit in the pathogenesis of Alzheimer's disease and Down's syndrome, our observations indicate that there is no correlation between senile plaque densities and degree of dementia in both disorders. In contrast to younger elderly cases, in the ninth and tenth decades of life, there is a differential cortical involvement in that parietal and cingulate areas are early affected in the course of Alzheimer's disease, and neocortical senile plaques densities are strongly correlated with the severity of dementia. Moreover, Alzheimer's disease symptomatology is characterized in these very old patients by high neurofibrillary tangle densities in the anterior CA1 field, but not in the entorhinal cortex and inferior temporal cortex. These observations are discussed in the light of the hypothesis of global corticocortical disconnection and with respect to the notion of selective neuronal vulnerability in Alzheimer's disease.
The formation of neurofibrillary tangles in Alzheimer's disease shows a preferential involvement of certain cytoarchitecturally defined cortical areas suggesting systematic differences in regional neuronal vulnerability. The cellular and molecular nature of this selective neuronal vulnerability that follows a certain hierarchy of structural brain organization is largely unknown. In the present study, we compared the regional pattern of tangle density in Alzheimer's disease with systematic regional differences in neuronal plasticity that can be observed both during ageing and in Alzheimer's disease. Changes in dendritic length and arborization of Golgi-impregnated pyramidal neurons were analysed after three-dimensional reconstruction in 12 cortical areas. The intensity of dendritic remodelling that was observed during ageing as well as in Alzheimer's disease was regionally different and decreased in the following order: transentorhinal region > limbic areas (entorhinal region, hippocampus) > non-primary association areas (37, 40, 46) > primary sensory association areas (7, 18, 22) > primary sensory and motor cortex (17, 41, 4). These regional differences of neuronal plasticity follow the same pattern as the regional vulnerability to tangle formation in Alzheimer's disease. The results of the present study provide evidence that a high degree of structural neuronal plasticity might predispose neurons to tangle formation.
This commentary calls attention to the value of combining genetic and epidemiologic methods in studies to understand the determinants of two crucial aspects of aging: ages at which certain outcomes (e.g., disease, mortality) occur and rates of change with age of individual's characteristics (e.g., physiologic functions, disease risk factors). Inclusion of age in the specification of traits in genetic epidemiologic studies could lead to improved strategies to increase healthy life expectancy and evaluate individuals' risk for age-related morbidity. Special issues that make genetic epidemiologic approaches important for studies of age-specified phenomena as well as opportunities and challenges for such studies are discussed, including study designs, sampling frames, databases, analytic tools, and related methodological issues. This commentary is based on a report prepared by the Aging and Genetic Epidemiology Working Group, convened by the National Institute on Aging to review opportunities for research on the genetic epidemiology of aging-related outcomes. The report, which contains more extensive discussion, literature review, and references, is available on the World Wide Web at http://www.nih.gov/nia/conferences/GeneticReport111199.htm .
We report the prevalence rates for dementia and Alzheimer's disease (AD) obtained from a probability sample survey of 5,055 noninstitutionalized older persons in Shanghai, China. A two-stage procedure was used for case finding and case identification. A Chinese version of the Mini-Mental State Examination was used to determine cases of possible dementia. Three different cutoff points on this mental status test were used depending on the respondent's level of education. Clinical evaluations, based on functional assessments and psychiatric interview, medical and neurological examinations, three standardized mental status tests, and a selected group of psychometric tests, were made in the second stage of the study to ascertain the clinical diagnosis of dementia and AD utilizing the Diagnostic and Statistical Manual for Mental Disorders, edition 3 and National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria, respectively. The prevalence rate of dementia in persons 65 years and older was 4.6%. Clinically diagnosed AD accounted for 65% of the subjects with dementia. These findings indicate that the prevalence of dementia in Shanghai is very much higher than figures published earlier for China and Japan, and at the lower part of the range of values reported for community residents in the United States and other Western countries, but less than half of that reported in the recently published survey of the elderly in East Boston. Increasing age, gender (female), and low education are each highly significant and independent risk factors for dementia. One hypothesis to explain the increased prevalence in elderly women who had received no formal education invokes the possibility of an effect of early deprivation, perhaps lowering brain "reserve," allowing the symptoms of dementia to appear at an earlier date during disease progression.
This review is an account of recent experimental studies of memory deficits at the early stages of Alzheimer-type dementia, evaluating these studies in relation to current theories of memory functioning in humans. Whilst memory deficits are found to be widespread, some aspects are more resilient to impairment than others. For example, the processes associated with articulatory rehearsal in working memory are unimpaired despite a reduction in performance on most tests of primary memory. The “implicit” aspects of secondary memory appear to remain unimpaired, in contrast to a marked decline in “explicit” or “episodic” memory. In addition, there is evidence that the rate of forgetting from secondary memory is normal. Some aspects of episodic and semantic memory are found to be impaired as a consequence of a decline in the efficient organisation and processing of verbal material at encoding or retrieval. It is concluded that the deficits share particular features found in organic amnesia, but with additional deficits which relate to impairments in other domains of functioning.
There is an increasing amount of experimental evidence that oxidative stress is a causal, or at least an ancillary, factor
in the neuropathology of several adult neurodegenerative disorders, as well as in stroke, trauma, and seizures. At the same
time, excessive or persistent activation of glutamate-gated ion channels may cause neuronal degeneration in these same conditions.
Glutamate and related acidic amino acids are thought to be the major excitatory neurotransmitters in brain and may be utilized
by 40 percent of the synapses. Thus, two broad mechanisms--oxidative stress and excessive activation of glutamate receptors--are
converging and represent sequential as well as interacting processes that provide a final common pathway for cell vulnerability
in the brain. The broad distribution in brain of the processes regulating oxidative stress and mediating glutamatergic neurotransmission
may explain the wide range of disorders in which both have been implicated. Yet differential expression of components of the
processes in particular neuronal systems may account for selective neurodegeneration in certain disorders.
A group of 52 male, 2-year-old Ico:WIST rats were tested on the spatial reference memory version of the Morris water maze. Their performance was rated by comparisons with the performance of 2.5-month-old control rats. Unbiased stereological estimates were made of the number of neurons in the major subdivisions of the hippocampus proper and the subiculum of the 5 aged rats with the most impaired performance, the 5 aged rats with the best performance, and 5 young control rats. There were no significant differences between the mean numbers of neurons in the various subdivisions of the hippocampal region of the impaired and nonimpaired aged groups and similarly no decreases in neuron numbers in the pooled group of aged rats relative to the control rats. The results indicate that, in rats, the structural correlates of age-related deficits in spatial memory are to be found in parameters other than the number of neurons in the hippocampus proper and the subiculum.
Clinical heterogeneity in Alzheimer's disease has been widely observed. One factor that may influence the expression of dementia in Alzheimer's disease is premorbid intellectual ability. It has been hypothesized that premorbid ability, as measured by educational experience, reflects a cognitive reserve that can affect the clinical expression of Alzheimer's disease. The authors investigated the relation between estimates of premorbid intellectual function and cerebral glucose metabolism in patients with Alzheimer's disease to test the effect of differing levels of premorbid ability on neurophysiological dysfunction.
In a resting state with eyes closed and ears occluded, 46 patients with Alzheimer's disease were evaluated with positron emission tomography and [18F]-2-fluoro-2-deoxy-D-glucose to determine cerebral metabolism. Premorbid intellectual ability was assessed by a demographics-based IQ estimate and performance on a measure of word-reading ability.
After the authors controlled for demographic characteristics and dementia severity, both estimates of premorbid intellectual ability were inversely correlated with cerebral metabolism in the prefrontal, pre-motor, and left superior parietal association regions. In addition, the performance-based estimate (i.e., reading ability) was inversely correlated with metabolism in the anterior cingulate, paracentral, right orbitofrontal, and left thalamic regions, after demographic and clinical variables were controlled for.
The results suggest that higher levels of premorbid ability are associated with greater pathophysiological effects of Alzheimer's disease among patients of similar dementia severity levels. These findings provide support for a cognitive reserve that can alter the clinical expression of dementia and influence the neurophysiological heterogeneity observed in Alzheimer's disease.
New evidence indicates that neural activity regulates the expression of trophic factors in the brain but regulation of these molecules by select aspects of behaviour remains solely a fascinating possibility. We report that following training in the Morris water maze, a spatial memory task, the hippocampus and cerebellum of learning rats exhibited an increase in basic fibroblast growth factor messenger RNA. Basic fibroblast growth factor messenger RNA levels were higher during the learning of the task and decreased once asymptotic performance was reached, suggesting an involvement of basic fibroblast growth factor in learning/memory. An active control group, which exercised for the same time as the learning group but the spatial learning component of the task was minimized, exhibited a minor increase in basic fibroblast growth factor messenger RNA. The intensification of the physical activity component of the task by massed or intensive training resulted in greater increases in basic fibroblast growth factor messenger RNA for both learning and yoked groups, but levels of basic fibroblast growth factor messenger RNA in the learning group remained higher than yoked only in the cerebellum. Changes in basic fibroblast growth factor were accompanied by an increase in astrocyte density in the hippocampus in agreement with described roles of basic fibroblast growth factor in astrocyte proliferation/reactivity. Results suggest that learning potentiates the effects of physical activity on trophic factor induction in select brain regions. Trophic factor involvement in behaviour may provide a molecular basis for the enhanced cognitive function associated with active lifestyles, and guide development of strategies to improve rehabilitation and successful ageing.
The histopathologic changes distinguishing early Alzheimer disease (AD) from normal or pathologic aging are not clearly defined. This report describes the autopsy findings of 59 elderly, well-educated, volunteers. They were examined longitudinally with mental status testing, some for up to 8 years, as part of our normal aging study. This study reveals that (1) the brains of many subjects who did not show cognitive impairment on neuropsychologic testing contain abundant senile plaques (SP) and/or neurofibrillary tangles (NFT); (2) 29 subjects met Khachaturian criteria for AD, 15 met CERAD and 7 met National Institute on Aging-Reagan Institute guidelines; (3) Braak and Braak staging method included 9 in stage IV subjects, 4 in stage V, and 1 in stage VI; (4) there was a progression of NFT from entorhinal cortex to hippocampus and amygdala as a function of age; (5) 2 subjects met criteria for a diagnosis of dementia with Lewy bodies but were not demented; (6) cerebral amyloid angiopathy was present in leptomeningeal vessels in 75% of subjects and in parenchymal vessels in 62% of subjects; (7) only 10 of 59 subjects (17%) had no or few degenerative brain changes. Our study demonstrates that the brains of a large percentage of cognitively normal, relatively well-educated individuals contain numerous degenerative changes and only a small percentage are relatively free of these changes.
Cerebrovascular disease and Alzheimer's disease commonly occur together in the elderly and each may contribute to dementia. Here we present evidence that cerebrovascular disease significantly worsens cognitive performance in the earliest stages of Alzheimer's disease.
To determine whether the rate of decline in performance on a memory test is more rapid in AD patients with higher versus lower educational and occupational attainment.
Epidemiologic and imaging studies have suggested that, given comparable clinical severity of dementia, AD pathology is more advanced in patients with higher educational and occupational attainment. Because educational and occupational attainment should not influence the progression of AD pathology, and because severe AD pathology will eventually produce a mortality-causing condition, people with higher attainment might experience clinical AD for a shorter time and have a more rapid clinical progression.
A total of 177 AD patients were tested yearly for up to four study visits with the Selective Reminding Test (a memory test). Analysis of prospective change in the total recall score was performed by applying generalized estimating equations to regression analyses with repeated measures.
At the initial visit, scores were comparable in the high- and low-education and the high- and low-occupation groups. Overall, memory scores declined by approximately 1 point yearly (p<0.01). There was a more rapid decline in memory scores in patients with higher educational (p<0.057) and higher occupational attainment (p<0.02). The authors then stratified patients based on their initial memory scores. The more rapid decline in memory scores associated with higher educational and occupational attainment was noted only in the group with low initial scores (p<0.05 for both). The full group and stratified group analyses were also repeated controlling for other potentially relevant variables including age, gender, race, ethnicity, and the presence of extrapyramidal signs, stroke, or at least one apolipoprotein E-epsilon4 allele. The results remained unchanged.
Memory declined more rapidly in AD patients with higher educational and occupational attainment. This adds support to the idea that the discontinuity between the degree of AD pathology and the observed clinical severity of AD is mediated through some form of reserve.
To describe the relationship between neuropathologic aging and longitudinal measures of cognitive function in healthy oldest old individuals.
Nondemented individuals without cardiovascular or other age-associated diseases of age > or =85 years were followed until death. Regional postmortem measures of senile plaque (SP) and neurofibrillary tangle (NFT) severity were examined in relationship to clinical status, cognitive measures, and rate of cognitive change.
Among 19 healthy individuals, 10 became demented or had incipient dementia develop. Clinical status and rate of change in cognitive scores correlated with increasing brain lesion burden, particularly in neocortical regions. Compared to demented individuals, nondemented individuals had few or no neocortical NFT (p = 0.009) or SP (p = 0.001). There was a strong correlation between rate of cognitive change on Mini-Mental State Examination (MMSE) and neocortical NFT (r = 0.859, p = 0.001). The few NFT and SP in nondemented patients had a predilection for limbic areas.
These results support a continuum in which AD is infrequent in the healthy, cognitively stable, oldest old. The minimal abnormalities in cognitively stable individuals are consistent with the notion that preclinical pathologic AD precedes obvious cognitive impairment. Longitudinal cognitive testing shows an increased burden of neuropathologic changes in those who have cognitive decline but are not functionally impaired and do not meet criteria for the diagnosis of dementia. The strong relationship between cumulative pathologic changes and rate of cognitive decline suggests that these lesions may have clinical consequences at any age and are not likely to be benign senescent changes.
Neural stem cells exist not only in the developing mammalian nervous system but also in the adult nervous system of all mammalian
organisms, including humans. Neural stem cells can also be derived from more primitive embryonic stem cells. The location
of the adult stem cells and the brain regions to which their progeny migrate in order to differentiate remain unresolved,
although the number of viable locations is limited in the adult. The mechanisms that regulate endogenous stem cells are poorly
understood. Potential uses of stem cells in repair include transplantation to repair missing cells and the activation of endogenous
cells to provide “self-repair.” Before the full potential of neural stem cells can be realized, we need to learn what controls
their proliferation, as well as the various pathways of differentiation available to their daughter cells.
Several studies have demonstrated a good correlation between clinical severity and Braak's neuropathological staging in Alzheimer's disease (AD). However, nonagenarians and centenarians display a different pattern of cortical vulnerability to the neurodegenerative process compared to younger elderly, and it is not known whether correlations between clinical severity and neuropathological stages remain valid in this age group. To address this issue we compared Clinical Dementia Rating scale (CDR) scores and Braak stages in 116 patients over 90 years of age with either no cognitive impairment or very mild to severe AD. There is a strong positive correlation between CDR scores and Braak staging (Spearman coefficient = 0.66; P < 0.01). However, neuropathological staging does not distinguish cases with normal cognition (CDR 0) from those with mild cognitive changes (CDR 0.5). Unlike younger cohorts, Braak stages I and II are frequently associated with questionable dementia in this age group. Braak stage III overlaps with all CDR levels and correlates poorly with cognitive function. Braak stages IV or greater are consistently associated with at least mild dementia. Consistent with our previous neuropathological analyses of nonagenarians and centenarians, the present data suggest that the substantial involvement of the hippocampus which characterizes Braak stage IV is a key step in the development of overt clinical signs of dementia in the oldest-old. Moreover, they indicate that Braak staging represents a broad concept of the evolution of neurofibrillary tangles rather than a precise hierarchical model associated with a stepwise deterioration of cognitive abilities near the upper limit of life.
To classify neuropathologic alterations in the brains of nondemented older adults using current sets of criteria for AD.
AD neuropathologic alterations are found in the brains of some nondemented elderly subjects and suggest the possibility of presymptomatic AD. Three sets of guidelines have been developed to classify AD using senile plaques, neuritic plaques, and neurofibrillary tangles (NFT).
Neuropathologic changes in 59 older adults followed longitudinally with a standard battery of mental status measures were investigated using Khachaturian, Consortium to Establish a Registry for Alzheimer's Disease (CERAD), and National Institute on Aging-Reagan Institute (NIA-RI) guidelines. AD neuropathologic markers were evaluated in neocortical and allocortical regions. Cases were categorized as neuropathologically "normal" or "AD-like" and compared for possible mental status differences.
Between 11 and 49% of cases met one or more of the three classifications of AD. With adjustments for multiple comparisons, only NFT in hippocampal CA1 region were associated with autopsy age, suggesting that this may represent a pathologic process associated with normal brain aging. Using the NIA-RI guidelines, subjects in the AD-like group performed less well on the immediate paragraph recall and word-list delayed recall than their counterparts who did not meet these guidelines.
These data indicate that the prevalence of "preclinical" AD in our population is relatively low based on the NIA-RI classification. Although many subjects had AD-like changes based on CERAD and Khachaturian guidelines, they exhibited no differences in mental performance, suggesting that the aging brain may be able to withstand such structural changes without meaningful impact on mental functioning.
Dementia is an important cause of disability in the elderly. There is evidence that cognitive impairment in dementia is on a continuum with cognitive impairment in the non-demented elderly. In order to investigate this possibility, we need detailed knowledge about the population distribution of cognitive function and change in cognitive function. The aim of this study is to describe the change in different domains of cognitive function over 4 years in a population-based sample of non-demented elderly people, and to investigate the effect of sociodemographic variables and baseline cognitive function on change in each of the cognitive domains. Respondents from two group general practice lists (n = 503) were interviewed using the Cambridge Cognitive Examination (CAMCOG) at the incidence wave of the Cambridge City Over-75 Cohort Study and after a mean time period of 3.9 years. One hundred and thirty five of 212 non-demented subjects seen at follow-up completed the CAMCOG at both interviews. The annual rate of change in total CAMCOG score was -1.6 points per year (p < 0.001). There was statistically significant decline in all of the CAMCOG subscales. Greater decline in the Memory subscale was associated with less education (p = 0.03). Greater decline in the Attention/Calculation subscale was associated with manual social class (p = 0.05). Greater decline in the Perception subscale was associated with older age (p = 0.03). Decline in specific cognitive domains may indicate a reversible phase of cognitive impairment and deserves further investigation.
To examine links between childhood mental ability and dementia using data from a 1932 survey of the mental ability of the 1921 Scottish birth cohort.
Patients with dementia from the 1921 Scottish birth cohort were located in 1) a national survey of early-onset dementia (1974-1988), 2) local mental health services, and 3) a survey of 264 of 519 surviving Aberdeen residents who took the 1932 test. Control subjects were identified in the 1932 Scottish Mental Survey.
Mean 1932 ability score for the Scottish 1921 cohort did not differ from early-onset dementia. Early-onset dementia was not associated with lower childhood mental ability when compared with matched control subjects. In Aberdeen, mental ability scores were significantly lower in children who eventually developed late-onset dementia when compared with other Aberdeen children tested in 1932. This difference was also detected between cases and tested subjects (controls) alive in 1994.
Late-onset dementia is associated with lower mental ability scores in childhood. Early-onset dementia mental ability scores did not differ from locally matched control subjects or from late-onset dementia. Mechanisms that account for the link between lower mental ability and late-onset dementia are probably not relevant to early-onset dementia.
The sensitivity of MRI volumetric measures to detect cognitive dysfunction is examined in 39 participants of an epidemiological field study (age 75-85, MMSE 19-30). According to Clinical dementia rating (CDR), 17 subjects had normal cognition (CDR 0), 12 had questionable (CDR 0.5) and 10 mild dementia (CDR 1). Discriminant analysis based on four hippocampal measures resulted in a correct classification of 76.9% of all subjects. Left-sided and posterior hippocampal measures were more responsible for group discrimination than right-sided and anterior measures. In CDR 0.5, a significant hippocampal volume reduction of 14.3% vs.11.3% (left vs. right) relative to normal was found. The right hippocampus was significantly greater than the left in CDR 0 and CDR 0.5, but not in CDR 1. The magnitude of non-directional hippocampal asymmetry increased with decreasing cognitive state. We conclude that hippocampal atrophy is sensitive to detect cognitive dysfunction and subjects at risk for Alzheimer's disease in the elderly population.
Mental function has as its cerebral basis a specific dynamic structure. In particular, cortical and limbic areas involved in “higher brain functions” such as learning, memory, perception, self-awareness and consciousness continously need to be self-adjusted even after development is completed. By this lifelong self-optimization process, the cognitive, behavioural and emotional reactivity of an individual is stepwise remodelled to meet the environmental demands. While the presence of rigid synaptic connections ensures the stability of the principal characteristics of function, the variable configuration of the flexible synaptic connections determines the unique, non-repeatable character of an experienced mental act. With the increasing need during evolution to organize brain structures of increasing complexity, this process of selective dynamic stabilization and destabilization of synaptic connections becomes more and more important. These mechanisms of structural stabilization and labilization underlying a lifelong synaptic remodelling according to experience, are accompanied, however, by increasing inherent possibilities of failure and may, thus, not only allow for the evolutionary aquisition of “higher brain function” but at the same time provide the basis for a variety of neuropsychiatric disorders.
Early diagnosis and monitoring of the progression of Alzheimer's disease is important for the development of therapeutic strategies. To detect the earliest structural brain changes, individuals need to be studied before symptom onset. We used an imaging technique known as voxel-compression mapping to localise progressive atrophy in patients with preclinical Alzheimer's disease.
Four symptom-free individuals from families with early-onset Alzheimer's disease with known autosomal dominant mutations underwent serial magnetic resonance imaging (MRI) over 5-8 years. All four became symptomatic during follow-up. 20 individuals with a clinical diagnosis of probable Alzheimer's disease and 20 control participants also underwent serial MR imaging. A non-linear fluid matching algorithm was applied to register repeat scans onto baseline imaging. Jacobian determinants were used to create the voxel-compression maps.
Progressive atrophy was revealed in presymptomatic individuals, with posterior cingulate and neocortical temporoparietal cortical losses, and medial temporal-lobe atrophy. In patients with known Alzheimer's disease, atrophy was widespread apart from in the primary motor and sensory cortices and cerebellum, reflecting the clinical phenomenology.
Voxel-compression maps confirmed early involvement of the medial temporal lobes, but also showed posterior cingulate and temporoparietal cortical losses at presymptomatic stage. This technique could be applied diagnostically and used to monitor the effects of therapeutic intervention.
Activated microglia have a key role in the brain's immune response to neuronal degeneration. The transition of microglia from the normal resting state to the activated state is associated with an increased expression of receptors known as peripheral benzodiazepine binding sites, which are abundant on cells of mononuclear phagocyte lineage. We used brain imaging to study expression of these sites in healthy individuals and patients with Alzheimer's disease.
We studied 15 normal individuals (age 32-80 years), eight patients with Alzheimer's disease, and one patient with minimal cognitive impairment. Quantitative in-vivo measurements of glial activation were obtained with positron emission tomography (PET) and carbon-11-labelled (R)-PK11195, a specific ligand for the peripheral benzodiazepine binding site.
In normal individuals, regional [11C](R)-PK11195 binding did not significantly change with age, except in the thalamus, where an age-dependent increase was found. By contrast, patients with Alzheimer's disease showed significantly increased regional [11C](R)-PK11195 binding in the entorhinal, temporoparietal, and cingulate cortex.
In-vivo detection of increased [11C](R)-PK11195 binding in Alzheimer-type dementia, including mild and early forms, suggests that microglial activation is an early event in the pathogenesis of the disease.
In Alzheimer's disease (AD) inflammatory processes occur in pathologically vulnerable brain regions. The objective of this study is to compare both the release and the presence of microvessel-associated cytokines in vessels isolated from the brains of AD patients to microvessels from control brains. Microvessels are isolated from the cortices of AD patients and age-matched controls, without evidence of neurodegenerative disease. Inflammatory factors in the media are quantitated by ELISA and microvessel-associated mediators assessed by Western blot. Our results demonstrate that unstimulated AD microvessels release significantly higher levels of interleukin-1beta-(IL-1beta), IL-6, and tumor necrosis factor alpha (TNF-alpha) compared to non-AD microvessels. Levels of microvessel-associated monocyte chemoattractant protein (MCP-1) and IL-1beta are high in AD-derived microvessels, but not detectable in non-AD microvessels. These results suggest that the cerebral microcirculation contributes inflammatory mediators to the milieu of the AD brain and may be involved in the pathogenesis of neuronal injury and death in this disorder.
To determine whether leisure activities modify the risk for incident dementia.
Although high educational and occupational attainments have been associated with reduced risk of incident dementia, the relation between leisure activities and dementia risk has not been adequately investigated.
A total of 1,772 nondemented individuals aged 65 years or older, living in northern Manhattan, New York, were identified and followed longitudinally in a community-based cohort incidence study. Subjects' leisure activities at baseline were assessed, annual examinations with the same standardized neurologic and neuropsychological measures were performed for up to 7 years (mean 2.9 years), and incident dementia was assessed as the main outcome measure. Cox proportional hazards models, adjusting for age, ethnic group, education, and occupation, were used to estimate the relative risk (RR) of incident dementia associated with high leisure activities.
Of the 1,772 subjects, 207 became demented. The risk of dementia was decreased in subjects with high leisure activities (RR, 0.62; 95% CI 0.46 to 0.83). The association of high leisure with decreased RR of incident dementia was present even when baseline cognitive performance, health limitations interfering with desired leisure activities, cerebrovascular disease, and depression were considered.
The data suggest that engagement in leisure activities may reduce the risk of incident dementia, possibly by providing a reserve that delays the onset of clinical manifestations of the disease.