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A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): A randomised controlled trial
Abstract
Modifiable vascular and lifestyle-related risk factors have been associated with dementia risk in observational studies. In the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), a proof-of-concept randomised controlled trial, we aimed to assess a multidomain approach to prevent cognitive decline in at-risk elderly people from the general population.
In a double-blind randomised controlled trial we enrolled individuals aged 60-77 years recruited from previous national surveys. Inclusion criteria were CAIDE (Cardiovascular Risk Factors, Aging and Dementia) Dementia Risk Score of at least 6 points and cognition at mean level or slightly lower than expected for age. We randomly assigned participants in a 1:1 ratio to a 2 year multidomain intervention (diet, exercise, cognitive training, vascular risk monitoring), or a control group (general health advice). Computer-generated allocation was done in blocks of four (two individuals randomly allocated to each group) at each site. Group allocation was not actively disclosed to participants and outcome assessors were masked to group allocation. The primary outcome was change in cognition as measured through comprehensive neuropsychological test battery (NTB) Z score. Analysis was by modified intention to treat (all participants with at least one post-baseline observation). This trial is registered at ClinicalTrials.gov, number NCT01041989.
Between Sept 7, 2009, and Nov 24, 2011, we screened 2654 individuals and randomly assigned 1260 to the intervention group (n=631) or control group (n=629). 591 (94%) participants in the intervention group and 599 (95%) in the control group had at least one post-baseline assessment and were included in the modified intention-to-treat analysis. Estimated mean change in NTB total Z score at 2 years was 0·20 (SE 0·02, SD 0·51) in the intervention group and 0·16 (0·01, 0·51) in the control group. Between-group difference in the change of NTB total score per year was 0·022 (95% CI 0·002-0·042, p=0·030). 153 (12%) individuals dropped out overall. Adverse events occurred in 46 (7%) participants in the intervention group compared with six (1%) participants in the control group; the most common adverse event was musculoskeletal pain (32 [5%] individuals for intervention vs no individuals for control).
Findings from this large, long-term, randomised controlled trial suggest that a multidomain intervention could improve or maintain cognitive functioning in at-risk elderly people from the general population.
Academy of Finland, La Carita Foundation, Alzheimer Association, Alzheimer's Research and Prevention Foundation, Juho Vainio Foundation, Novo Nordisk Foundation, Finnish Social Insurance Institution, Ministry of Education and Culture, Salama bint Hamdan Al Nahyan Foundation, Axa Research Fund, EVO funding for University Hospitals of Kuopio, Oulu, and Turku and for Seinäjoki Central Hospital and Oulu City Hospital, Swedish Research Council, Swedish Research Council for Health, Working Life and Welfare, and af Jochnick Foundation.
Copyright © 2015 Elsevier Ltd. All rights reserved.
... A large literature indicates an important effect of APOE4 on lifestyle interventions aimed at mitigating the increased risk of AD. However, the literature is not consistent [16,17], and the biological pathways underlining these effects are still elusive. Diet is a key lifestyle factor that differentiates chimpanzees from humans. ...
... It could be considered that diet and lifestyle have effects not only on epigenetics but also on gene expression. Massive literature points to an important effect of APOE4 on lifestyle interventions [16,17]. However, the literature is inconsistent [16,17] on this point. ...
... Massive literature points to an important effect of APOE4 on lifestyle interventions [16,17]. However, the literature is inconsistent [16,17] on this point. Furthermore, iron is among the main drivers of oxidative stress threat in AD, and it strictly depends on diet and interacts with APOE4 and more in general lipid metabolism. ...
The emergence of conflicting reports on the natural occurrence of Alzheimer’s disease (AD) in non-human primates has prompted research on the comparison of the role of diet-associated changes in gene expression between humans and non-human primates. This article analyzes the effects of different human and chimpanzee diets and their link with apolipoproteins, lipid, and iron (Fe) metabolism, starting from available data, to find out any gap in the existing knowledge. By using a system biology approach, we have re-analyzed the liver and brain RNA seq data of mice fed with either human or chimpanzee diet for 2 weeks to look for genetic differences that may explain the differences in AD occurrence between those two classes. In liver samples of mice fed with the chimpanzee diet in comparison to the human diet, apolipoprotein A-1, ceruloplasmin, and 10 other genes were upregulated while 21 genes were downregulated. However, brain apolipoprotein E4 gene expression was not changed upon diet. Genetic, structural, and functional differences in apolipoprotein E protein, along with differences in Fe metabolisms and a longer lifespan of humans during evolution may account for the observed disparity.
... Although the development of disease-modifying drugs targeting Alzheimer's disease-the most common type of dementia-has progressed with positive results in clinical trials [6], their integration into routine clinical practice requires time. Conversely, nonpharmacological interventions, such as multi-domain intervention programmes for dementia prevention, have demonstrated promising results in suppressing cognitive decline [7]. Given the ease of implementing non-pharmacological therapies in routine clinical and community programmes, research on implementation and dissemination plays a significant role. ...
... However, interventions targeting individual dementia risks have limited effects, and in Europe, multi-domain interventions that include exercise, nutrition, and cognitive training are becoming increasingly common [11]. The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) was a pivotal multicentre randomised controlled trial that applied multi-domain intervention for dementia prevention in 1260 individuals aged ≥ 60 years at risk of developing dementia [7]. The intervention group underwent a twoyear period of dietary guidance, exercise instruction, cognitive training, and management of vascular risk factors, while the control group received general health advice. ...
... The proportion of individuals sustaining programme engagement will be calculated from the initial assessment to the six-month follow-up for those attending ≥ 60% of classes (with at least half of the classes attended). The rationale for setting the proportion is based on a study that examined the intervention effects by participants' adherence level in the FINGER study [7]. The above-mentioned study found that cognitive decline was suppressed when at least 50% of individuals participated and at least 57% of the group attended classes. ...
Background
Multi-domain interventions effectively prevent dementia in clinical settings; however, their efficacy within local communities is unclear. This study assesses the feasibility of an adapted multi-domain intervention for dementia prevention in community-dwelling older adults.
Methods
The single-arm trial enrolls 60 participants from two Obu City communities, Japan. Primary outcome: participant retention in the adapted multi-domain intervention; secondary outcomes: health and implementation outcomes. Over 12 months, a team of researchers and public health nurse oversees the study in the first half, gradually shifting the management to public health nurses in the second half. Using the Framework for Reporting Adaptations and Modifications-Enhanced, the clinical programme is adjusted for the local community. It includes a 60-minute exercise and 30-minute group sessions, targeting lifestyle, diet, and social participation.
Discussion
This pioneer study evaluates the feasibility of an adapted intervention programme for dementia prevention in a community setting. Challenges in disseminating dementia prevention programmes warrant further investigation into effective implementation as well as strategies and methods to appeal to the target population. Upon confirming this programme’s feasibility, future studies can further evaluate its broader effectiveness.
Trial registration
The protocol is registered with the Clinical Trials Registry (UMIN-CTR) of the University Hospital’s Medical Information Network, under registration number UMIN000050581.
... Multidomain interventions that include both a healthy diet and exercise appear to elicit stronger positive results for cognitive performance than each intervention in isolation. 42 Furthermore, exercise can stimulate protein synthesis 43 and enhance muscle mass and functional performance in older adults, 44 making it an attractive target for preventing undernutrition. An optimal protein MedDiet may induce additive effects on nutritional status and cognition when combined with exercise, but this has not yet been evaluated. ...
... A key strength is the inclusion of a validated neurocognitive test battery in the current study allowing a comprehensive assessment of performance in both memory and non-memory domains of cognition as used in other multidomain interventions in adults at increased dementia risk. 42 Prior studies in undernourished patients have relied on the limited MMSE global cognition to measure cognitive performance. 25 While MMSE is a validated screener for cognitive impairment, it provides limited examination of visuospatial cognitive ability, long-term memory and language functions. ...
... There are some limitations to the study design that should be considered. The optimum period for lifestyleinduced change in nutritional status is not clear, and the duration of the current study intervention is shorter than in other multidomain trials 42 ; however, improvement in MNA score in response to nutrition intervention has been observed in 12 weeks. 65 Furthermore, 6 months should be sufficient duration to detect increases in nutrient biomarkers in response to the interventions, especially in a high-risk population. ...
Introduction
Undernutrition leading to unplanned weight loss is common in older age and has been linked to increased dementia risk in later life. Weight loss can precede dementia by a decade or more, providing a unique opportunity for early intervention to correct undernutrition and potentially prevent or delay cognitive impairment. The combined effects of diet and exercise on undernutrition have not yet been evaluated. The objective of this trial is to determine the effect of a protein-enriched Mediterranean diet, with and without exercise, on nutritional status and cognitive performance in older adults at risk of undernutrition and cognitive decline.
Methods
One hundred and five participants aged 60 years and over at risk of undernutrition and with subjective cognitive decline will be recruited to participate in a 6-month, single-blind, parallel-group randomised controlled trial. Participants will be block randomised into one of three groups: group 1—PROMED-EX (diet+exercise), group 2—PROMED (diet only) and group 3—standard care (control). The primary outcome is nutritional status measured using the Mini Nutritional Assessment. Secondary outcomes include cognitive function, nutritional intake, body composition, physical function and quality of life. Mechanistic pathways for potential diet and exercise-induced change in nutritional status and cognition will be explored by measuring inflammatory, metabolic, nutritional and metabolomic biomarkers.
Ethics and dissemination
The study is approved by the UK Office for Research Ethics Committee (ref: 21/NW/0215). Written informed consent will be obtained from participants prior to recruitment. Research results will be disseminated to the public via meetings and media and the scientific community through conference presentations and publication in academic journals.
Trial registration number
ClinicalTrials.gov Registry ( NCT05166564 ).
... Finnish geriatric intervention study to prevent cognitive impairment and disability (FINGER) [150] High risk A multidomain intervention can improve or maintain cognitive status in risky elderly subjects. ...
... Many multidomain interventions for studying vascular and lifestyle risk factors are ongoing for AD prevention trials. Mainly they are Prevention of Dementia by Intensive Vascular Care trial (PreDIVA), Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) [150], Multidomain Alzheimer Preventive Trial (MAPT) and Multimodal Preventive trial for Alzheimer's disease (MIND-ADMINI) [151]. All above mentioned continuing multi-centered studies give emphasis to the significance of international alliance and regulation of trial plan. ...
Alzheimer's disease (AD) is a brain disorder which incrementally brings about mental decay which contributes to lack of memory and inability to think, as well as lack of behavioral and social skills in the aged population. The main constraint in the development of drug is unclear understanding about etiology and pathogenesis of disease. AD is portrayed by the assemblage of amyloid-beta (Aβ) peptides in amyloid plaques, the aggregation of misfolded tau proteins which leads to neurofibrillary tangles formation and neuronal degeneration. This chapter broods over the current updates and uncovering of novel therapeutic approaches such as focusing on impeding the amyloid pathway, which encompass refraining the production and assemblage, or augment the expulsion of amyloid-β, AntiTau therapies such as inhibiting Tau aggregation, Microtubule Stabilizers, Antitau Immunotherapy, Antineuroinflammatory approaches, Neuroprotective approaches in conjunction with approaches for cognitive enhancement and approaches for prevention of AD. The forthcoming of AD will confide on evolving safe, potent, and selective compounds which is curative or will have the potential to setback the augmentation of AD.
... Randomized controlled trials from the developed world have produced promising results on potential measures. 40,41 Findings from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability, a large, long-term, randomized controlled trial, suggest that a multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring could improve or maintain cognitive functioning in at-risk older adults from the general population. 40 Another study also suggested that cognitive training could result in improved cognitive abilities specific to the abilities trained, and reasoning training could result in less functional decline. ...
... 40,41 Findings from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability, a large, long-term, randomized controlled trial, suggest that a multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring could improve or maintain cognitive functioning in at-risk older adults from the general population. 40 Another study also suggested that cognitive training could result in improved cognitive abilities specific to the abilities trained, and reasoning training could result in less functional decline. 41 An early dementia prevention program also has been initiated in comparable populations such as Singapore. ...
INTRODUCTION
China has the world's largest number of older adults with cognitive impairment (CI). We aimed to examine secular trends in the prevalence of CI in China from 2002 to 2018.
METHODS
Generalized estimating equations (GEE) was used to assess changes in CI trend in 44,154 individuals (72,027 observations) aged 65 to 105 years old.
RESULTS
The prevalence of CI increased from 2002 to 2008 and then decreased until 2018. The age‐standardized prevalence increased from 25.7% in 2002, 26.1% in 2005, to 28.2% in 2008, then decreased to 26.0% in 2011, 25.3% in 2014, and 24.9% in 2018. Females and those ≥ 80 years old had greater CI prevalence.
DISCUSSION
The prevalence of CI showed an inverted U shape from early 2000s to late 2010s with a peak in 2008. Follow‐up studies are needed to confirm the decreasing trend after 2008 and examine the contributing factors and underlying mechanisms of this trend.
Highlights
Generalized estimating equations (GEE) were used to assess trends of changes in cognitive impairment (CI).
CI prevalence in China increased from 2002 to 2008 and then decreased until 2018.
Females and those ≥ 80 years old had greater CI prevalence.
Stroke, diabetes, and cigarette smoking were risk factors for CI.
... Early observations in the 1990s suggested that nutrients with antioxidant capacities could potentially reduce oxidative stress and inflammation, which are thought to contribute to AD (2, 3). Despite evidence from observational studies and animal studies showing that nutrients with antioxidant and anti-inflammatory capacities delayed the onset of AD and slower cognitive decline (3)(4)(5)(6), randomized controlled trials on antioxidant supplementation and cognitive function and AD risk reported mixed results (3)(4)(5)(6)(7)(8)(9)(10)(11)(12). It is crucial to consider nutrients within the context of dietary patterns and their sources (dietary vs. supplements), as they are not consumed in isolation. ...
... However, most of the current evidence comes from studies conducted in Western countries, highlighting the need for research on diverse dietary patterns globally. Additionally, there is an urgent need to improve our understanding of external factors related to diet quality as well as the effects of multimodal interventions, in line with the FINGER trial (12). In this Research Topic, "Nutrition and neurodegenerative diseases: insights and perspectives on prevention strategies, " we included topics that cover environmental and dietary factors associated with cognition. ...
... 6,7 A few randomized controlled trials have shown that multidomain and intensive lifestyle interventions as a whole could improve cognitive function and reduce the prevalence of frailty, a geriatric syndrome. 8,9 Despite the observed benefit of lifestyle interventions, the potential mechanisms explaining how healthy lifestyles contribute to the reduction of adverse health outcomes remain poorly understood. ...
... The associations of unhealthy lifestyles with CVD, cancer, and mortality observed in this study highlight the potential of multi-domain lifestyle interventions (i.e., healthy diet, no smoking, no alcohol consumption, regular exercise, and healthy BMI) in disease prevention. As the implementation of multi-domain interventions in preventing cognitive decline and frailty has been suggested to be effective, 8,9,37 it is meaningful to extend such interventions to CVD, cancer, and even aging itself. Besides, from the point of view of pharmacological intervention, many anti-aging drugs have been developed such as caloric restriction mimetics (resveratrol, rapamycin, metformin), senolytics, and synthetic sirtuin activators, which are promising to alleviate or delay age-related conditions. ...
Background
With two well‐validated aging measures capturing mortality and morbidity risk, this study examined whether and to what extent aging mediates the associations of unhealthy lifestyles with adverse health outcomes.
Methods
Data were from 405,944 adults (40–69 years) from UK Biobank (UKB) and 9972 adults (20–84 years) from the US National Health and Nutrition Examination Survey (NHANES). An unhealthy lifestyles score (range: 0–5) was constructed based on five factors (smoking, drinking, physical inactivity, unhealthy body mass index, and unhealthy diet). Two aging measures, Phenotypic Age Acceleration (PhenoAgeAccel) and Biological Age Acceleration (BioAgeAccel) were calculated using nine and seven blood biomarkers, respectively, with a higher value indicating the acceleration of aging. The outcomes included incident cardiovascular disease (CVD), incident cancer, and all‐cause mortality in UKB; CVD mortality, cancer mortality, and all‐cause mortality in NHANES. A general linear regression model, Cox proportional hazards model, and formal mediation analysis were performed.
Results
The unhealthy lifestyles score was positively associated with PhenoAgeAccel (UKB: β = 0.741; NHANES: β = 0.874, all p < 0.001). We further confirmed the respective associations of PhenoAgeAccel and unhealthy lifestyles with the outcomes in UKB and NHANES. The mediation proportion of PhenoAgeAccel in associations of unhealthy lifestyles with incident CVD, incident cancer, and all‐cause mortality were 20.0%, 17.8%, and 26.6% (all p < 0.001) in UKB, respectively. Similar results were found in NHANES. The findings were robust when using another aging measure—BioAgeAccel.
Conclusions
Accelerated aging partially mediated the associations of lifestyles with CVD, cancer, and mortality in UK and US populations. The findings reveal a novel pathway and the potential of geroprotective programs in mitigating health inequality in late life beyond lifestyle interventions.
... Currently, AD can be treated with non-pharmacologic therapy and pharmacologic therapy. Non-pharmacologic therapy consists of lifestyle changes, and multidomain interventions to prevent cognitive decline [6,7,[9][10][11]. Pharmacotherapy is focused on diseasemodifying treatments, including drugs targeting Aβ and Tau proteins, and other target classes such as proteostasis/ protein opathies, epigenetic regulators, synaptic plasticity and neuroprotection, inflammation and infection, metabolism and bioenergetics, vascular and growth factors are also of interest [1]. ...
Background
Alzheimer’s disease (AD) is a worldwide public health problem and is difficult to cure. Drugs aimed at slowing the progression of the disease have been developed, with the Food and Drug Administration (FDA) granting accelerated approval for aducanumab on June 21, 2021 and a new accelerated approval for lecanemab on January 22, 2023. We performed this systematic review and meta-analysis to assess the efficacy and safety of FDA-approved anti-amyloid-β (anti-Aβ) monoclonal antibodies (mabs) for the treatment of AD.
Method
PubMed, Embase, and Cochrane Library were systematically searched to identify relevant studies published before May 2023. Efficacy outcomes included Aβ, neuroimaging, and biomarker outcomes. Safety outcomes included amyloid-related imaging abnormalities with edema or effusions (ARIA-E) and ARIA with cerebral microhemorrhages, cerebral macrohemorrhages, or superficial siderosis (ARIA-H). Review Manager 5.4 software was used to assess the data. The standard mean differences (SMDs) or odds ratio (OR) with 95% confidence interval (95% CI) were analyzed and calculated with a random effect model or a fixed effect model.
Result
Overall, 4471 patients from 6 randomized controlled trials (RCTs), with 2190 patients in the treatment group and 2281 patients in the placebo group meeting the inclusion criteria. FDA-approved anti-Aβ mabs showed statistically significant improvements in clinical outcomes, including CDR-SB (P = 0.01), ADCS-ADL-MCI (P = 0.00003), ADCOMS (P < 0.00001), ADAS-Cog (P < 0.00001). Moreover, FDA-approved anti-Aβ mabs increased cerebrospinal fluid (CSF) Aβ1-42 (P = 0.002) and plasma Aβ42/40 ratios (P = 0.0008). They also decreased CSF P-Tau (P < 0.00001), CSF T-Tau (P < 0.00001), and plasma p-tau181 (P < 0.00001). FDA-approved anti-Aβ mabs perform neuroimaging changes in amyloid Positron Emission Tomography Standardized Uptake Value ratio (PET SUVr) (P < 0.00001). However, compared with placebo, FDA-approved anti-Aβ mabs had higher risk of ARIA-E (P < 0.00001) and ARIA-H (P < 0001).
Conclusion
FDA-approved anti-Aβ mabs have a role in slowing disease progression in patients with AD, at the cost of an increased probability of side effects.
... Dementia, characterized by progressive cognitive and functional decline, is a global health problem affecting about 57 million people worldwide [1]. With no cure so far, targeting modifiable risk and protective factors may lead to effective risk reduction 1042 S. Köhler [2], with proven modest effects on cognitive performance over time [3]. Several modifiable risk factors for dementia have been identified including diet, physical and cognitive activity, and vascular conditions [4], accounting for approximately 40% of the total risk [5]. ...
Background: Sleep disturbances have been linked with cognitive decline and a higher risk of dementia. However, there is a lack of studies with sufficient follow-up duration, a detailed neuropsychological assessment and adequate control of main confounders. Objective: To investigate the relation between self-reported sleep quality and cognitive decline over 12 years in cognitively healthy individuals from the general population. Methods: We used data from the Maastricht Aging Study (MAAS), a Dutch population-based prospective cohort study of 1,823 community-dwelling adults aged 24 to 82 years at baseline. Cognitive performance was measured at baseline, 6 and 12 years on verbal memory, executive functions, and information processing speed. Sleep quality was assessed at baseline using the sleep subscale score of the 90-item Symptom Checklist (SCL-90). Additional modifiable dementia risk factors were summarized in the LIfestyle for BRAin health (LIBRA) risk score. Weighted linear mixed models tested the association between continuous scores and tertiles of subjective sleep quality and change in cognitive performances over time. Models were adjusted for age, gender, educational level, LIBRA, and use of hypnotic (sleep) medication. Results: Worse sleep quality was associated with faster decline in processing speed. At older age (≥65 years), it was also associated with faster decline in verbal memory. Association were independent of other modifiable dementia risk factors and use of hypnotic medication. Directionally similar but non-significant associations were found between worse sleep quality and executive functions. Conclusions: In this population-based study across the adult age range, poor self-reported sleep was associated with accelerated cognitive decline.
... We also found that modifiable risk factors for dementia development such as diabetes, cardiovascular diseases, and obesity were associated with poor HR-QoL in SCD and MCI patients. This suggests that multidomain health interventions targeting these modifiable risk factors to prevent dementia development [45] may also help to maintain HR-QoL in individuals with SCD. ...
Background
Health-related quality of life (HR-QoL) is an important outcome for patients and crucial for demonstrating the value of new treatments. Health utility estimates in subjective cognitive decline (SCD) and mild cognitive impairment (MCI) are limited, especially in biomarker-confirmed populations. Besides, little is known about the longitudinal HR-QoL trajectory. This study aims to provide health utility estimates for SCD and MCI and investigate the QoL trajectory along the disease continuum.
Methods
Longitudinal data from 919 SCD and 1336 MCI patients from the MEMENTO cohort were included. SCD was defined as clinical dementia rating (CDR) = 0, and MCI as CDR = 0.5. HR-QoL was measured using the EQ-5D-3L patient-reported instrument. Linear mixed-effect models (LMM) were used to assess the longitudinal change in HR-QoL and identify predictors of these changes.
Results
Baseline health utilities were 0.84 ± 0.16 and 0.81 ± 0.18, and visual analogue scale (VAS) were 75.8 ± 14.82 and 70.26 ± 15.77 in SCD and MCI. In amyloid-confirmed cases, health utilities were 0.85 ± 0.14 and 0.86 ± 0.12 in amyloid-negative and amyloid-positive SCD, and 0.83 ± 0.17 and 0.84 ± 0.16 in amyloid-negative and amyloid-positive MCI. LMM revealed an annual decline in health utility of − 0.015 (SE = 0.006) and − 0.09 (SE = 0.04) in moderate and severe dementia (P < 0.05). There was a negative association between clinical stage and VAS where individuals with MCI, mild, moderate, and severe dementia were on average 1.695 (SE = 0.274), 4.401 (SE = 0.676), 4.999 (SE = 0.8), and 15.386 (SE = 3.142) VAS points lower than individuals with SCD (P < 0.001). Older age, female sex, higher body mass index, diabetes, cardiovascular history, depression, and functional impairment were associated with poor HR-QoL. Amyloid positivity was associated with an annual decline of − 0.011 (SE = 0.004, P < 0.05) health utility over time.
Conclusions
Health utility estimates from this study can be used in economic evaluations of interventions targeting SCD and MCI. Health utility declines over time in moderate and severe dementia, and VAS declines with advancing clinical stages. Amyloid-positive patients show a faster decline in health utility indicating the importance of considering biomarker status in HR-QoL assessments. Future research is needed to confirm the longitudinal relationship between amyloid status and HR-QoL and to examine the level at which depression and IADL contribute to HR-QoL decline in AD.
... • Higher education reduces the risk of dementia [113]. Even in later life, educational, cognitive and leisure activities can promote the cognitive reserve and reduce age-associated cognitive deterioration [116,117]. • Primary school education levels (or lower) are associated with an increased risk of dementia [24]. ...
The brain and its health are essential for our (physical mental, social, and spiritual) wellbeing, for being able to realize our potential as individuals, and also for a fair, well-functioning, and productive society. However, today the world is facing a healthcare crisis related to the very high (and increasing) burden of brain disorders. As a response to this crisis, the “Swiss Brain Health Plan” (SBHP) was conceptualized in the context of other initiatives launched to value, promote, and protect brain health over the entire life course. In the first section of this position paper, the following fundamental considerations of the SBHP are discussed: (1) the high (and increasing) burden of brain disorders in terms of prevalence (>50% of the population suffers from a brain disorder), disability, mortality, and costs; (2) the prevention of brain disorders; (3) the operational definition of brain health; (4) determinants of brain health; (5) international initiatives to promote brain (including mental) health including the World Health Organization (WHO) intersectorial global action plan on epilepsy and other neurological disorders (NDs) (IGAP) and the WHO comprehensive mental health action plan. In the second section of the paper, the five strategic objectives of the SBHP, which has the vision of promoting brain health for all across the entire life course, are presented: (1) to raise awareness; (2) strengthen cross-disciplinary and interprofessional training/educational programs for healthcare professionals; (3) foster research on brain health determinants and individualized prevention of brain disorders; (4) prioritize a holistic (non-disease-specific), integrated, person-centered public health approach to promote brain health and prevent brain disorders through collaborations across scientific, health care, commercial, societal and governmental stakeholders and insurance providers; (5) support, empower, and engage patients, caregivers, and patient organizations, and reduce the stigma and discrimination related to brain disorders. In the third section of the paper, the first (2024) steps in the implementation of the SHBP, which will be officially launched in Zurich on 22 November 2023, are presented: (1) a definition of the overall organization, governance, specific targets, and action areas of the SBHP; (2) the patronage and/or co-organization of events on such specific topics as brain research (Lausanne), dementia (Geneva), stroke (Basel), neurohumanities (Bellinzona), sleep (Lugano), and psychiatry (Zurich); (3) the conduction of a new study on the global burden of brain disorders in Switzerland; (4) the launching of an international Certificate of Advanced Studies (CAS) on Brain Health at the University of Bern. In the fourth section of the paper, there is a concise executive summary of the SBHP.
... [34] A previous randomised study of older patients with risk of developing dementia showed improvement in cognitive frailty status after a combined intervention of nutritional therapy, physical exercise, cognitive training and social activities. [35] Unfortunately, no clinical outcome measures such as mortality was reported. ...
Introduction Elderly patients with acute coronary syndrome (ACS) have a higher risk of adverse cardiovascular events and may be frail but are underrepresented in clinical trials. Previous studies have proposed that frailty assessment is a better tool than chronological age, in assessing older patients’ biological age, and may exceed conventional risk scores in predicting prognosis. Therefore, we wanted to investigate prevalence and impact on 12-month outcomes of frailty in patients ≥70 years with ACS referred for coronary angiography (CAG). Methods Patients ≥70 years with ACS referred for CAG underwent frailty scoring with the clinical frailty scale (CFS). Patients were divided into three groups depending on their CFS: Robust (1-3), Vulnerable (4) and Frail (5-9) and followed for 12 months. Results Of 455 patients, 69 (15%) patients were frail, 79 (17%) were vulnerable and 307 (68%) were robust. Frail patients were older (frail: 80.9±5.7 years, vulnerable: 78.5±5.5 years and robust 76.6±4.9 years, p<0.001) and less often treated with percutaneous coronary intervention (frail: 56.5%, vulnerable: 53.2% and robust: 68.6%, p=0.014). 12-month mortality was higher among frail patients (frail: 24.6%, vulnerable: 21.8% and robust: 6.2%, p<0.001). Frailty was associated with a higher mortality after adjustment for age, sex, comorbidities, GRACE score and revascularisation (HR 2.67, 95%CI 1.30-5.50, p=0.008). There was no difference between GRACE and CFS in predicting 12-month mortality (p=0.893). Conclusions 15% of patients ≥70 years with ACS referred for CAG are frail. Frail patients have significantly higher 12-month mortality. GRACE and CFS are similar in predicting 12-month mortality.
... Further, such multidomain interventions would also be cost-effective and easily translatable into national-level public health strategies. Of late, the importance of such multidomain, lifestyle-based interventions is being increasingly recognised, owing to large, international studies, such as the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability, 30 the Multidomain Alzheimer Preventive Trial 31 and the Prevention of Dementia by Intensive Vascular Care study. 32 However, such multimodal, lifestyle-based interventions cannot be directly translated to the Indian scenario for various reasons. ...
Objective
The burden of cardiovascular risk factors is increasing in India, which, in turn, can adversely impact cognition. Our objective was to examine the effect of cardiovascular risk factors measured by Framingham Risk Score (FRS) on cognitive performance among a cohort of healthy, ageing individuals (n=3609) aged ≥45 years from rural India.
Design
A cross-sectional analysis.
Setting
A rural community setting in southern India.
Participants
Healthy, ageing, dementia-free participants, aged 45 years and above, belonging to the villages of Srinivaspura (a rural community located around 100 km from Bangalore, India), were recruited.
Primary outcome measures
Using a locally adapted, validated, computerised cognitive test battery, we assessed cognitive performance across multiple cognitive domains: attention, memory, language, executive functioning and visuospatial ability.
Results
The median (IQR) age of the sample was 57 (50.65) and 50.5% were women. Multiple linear regression analysis showed that participants with higher FRS performed poorly in attention (visual attention (β=−0.018, p=0.041)), executive functioning (categorical fluency (β=−0.064, p<0.001)), visuospatial ability (form matching (β=−0.064, p<0.001) and visuospatial span (β=−0.020, p<0.001)), language (reading and sentence comprehension (β=−0.010, p=0.013), word comprehension (β=−0.021, p<0.001) and semantic association (β=−0.025, p<0.001)), and memory (episodic memory IR (β=−0.056, p<0.001), episodic memory DR (β=−0.076, p<0.001) and name-face association (β=−0.047, p<0.001)).
Conclusion
Increased cardiovascular risk as evidenced by FRS was associated with poorer cognitive performance in all cognitive domains among dementia-free middle-aged and older rural Indians. It is imperative to design and implement appropriate interventions (pharmacological and lifestyle-based) for cardiovascular risk reduction and thereby, prevent or mitigate accelerated cognitive impairment in ageing individuals.
... Efforts to guide the type or amount of each component of a multidimensional intervention have been established in some risk reduction and prevention trials, such as the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability study. 18 Significant progress in the development of sensitive assays to detect AD pathology (phosphorylated tau and Aβ) in plasma is pointing to promising new tools on the horizon for detecting early AD and differentiating between AD and other forms of dementia. [19][20][21] These rapid, non-invasive, and relatively inexpensive forms of assessment will represent a huge advancement in clinical trial recruitment and also in the clinical diagnosis of AD. ...
The efficient and accurate execution of clinical trials testing novel treatments for Alzheimer's disease (AD) is a critical component of the field's collective efforts to develop effective disease‐modifying treatments for AD. The lengthy and heterogeneous nature of clinical progression in AD contributes to the challenges inherent in demonstrating a clinically meaningful benefit of any potential new AD therapy. The failure of many large and expensive clinical trials to date has prompted a focus on optimizing all aspects of decision making, to not only expedite the development of new treatments, but also maximize the value of the information that each clinical trial yields, so that all future clinical trials (including those that are negative) will contribute toward advancing the field. To address this important topic the Alzheimer's Association Research Roundtable convened December 1–2, 2020. The goals focused around identifying new directions and actionable steps to enhance clinical trial decision making in planned future studies.
... Although numerous therapies have been investigated, there has been no successful trial that can modify the course of the disease. On the other hand, according to the data from epidemiologic studies and clinical trials, it has indicated that early intervention may delay the AD progression (Brookmeyer et al., 1998;Norton et al., 2014;Ngandu et al., 2015). The . ...
Alzheimer's disease (AD) is the most common cause of dementia. Accurate prediction and diagnosis of AD and its prodromal stage, i.e., mild cognitive impairment (MCI), is essential for the possible delay and early treatment for the disease. In this paper, we adopt the data from the China Longitudinal Aging Study (CLAS), which was launched in 2011, and includes a joint effort of 15 institutions all over the country. Four thousand four hundred and eleven people who are at least 60 years old participated in the project, where 3,514 people completed the baseline survey. The survey collected data including demographic information, daily lifestyle, medical history, and routine physical examination. In particular, we employ ensemble learning and feature selection methods to develop an explainable prediction model for AD and MCI. Five feature selection methods and nine machine learning classifiers are applied for comparison to find the most dominant features on AD/MCI prediction. The resulting model achieves accuracy of 89.2%, sensitivity of 87.7%, and specificity of 90.7% for MCI prediction, and accuracy of 99.2%, sensitivity of 99.7%, and specificity of 98.7% for AD prediction. We further utilize the SHapley Additive exPlanations (SHAP) algorithm to visualize the specific contribution of each feature to AD/MCI prediction at both global and individual levels. Consequently, our model not only provides the prediction outcome, but also helps to understand the relationship between lifestyle/physical disease history and cognitive function, and enables clinicians to make appropriate recommendations for the elderly. Therefore, our approach provides a new perspective for the design of a computer-aided diagnosis system for AD and MCI, and has potential high clinical application value.
... These developments within the field have led to multidomain lifestyle-intervention trials for middle-aged and older individuals. The population-based Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) was the first to show improvements in cognition (Ngandu et al., 2015). The recent initiative World Wide FINGERS aims to harmonize adapted versions of the FINGER trial worldwide, such as the Australian Maintain Your Brain and U.S. POINTER trials (Kivipelto et al., 2020). ...
Objectives
This study investigated whether the association between modifiable dementia risk and rate of cognitive decline differs across socioeconomic status (SES) strata.
Design, setting and participants
Data were used from Maastricht Aging Study, a prospective cohort study with a 12-year follow-up. The baseline sample consisted of 1023 adults over 40 years old.
Measurements
The “LIfestyle for BRAin health” (LIBRA) index was used to assess modifiable dementia risk. Cognitive performance was assessed at baseline, 6 and 12 years, and measured in the domains of information processing speed, executive functioning and verbal memory function. An SES score was calculated from equivalent income and educational level (tertiles). Linear mixed models were used to study the association between LIBRA, SES and their interaction on the rate of cognitive decline.
Results
Participants in the lowest SES tertile displayed more decline in information processing speed (vs. middle SES: X ² = 7.08, P = 0.029; vs. high SES: X ² = 9.49, P = 0.009) and verbal memory (vs. middle SES: X ² = 9.28, P < 0.001; vs. high SES: X ² = 16.68, P < 0.001) over 6 years compared to their middle- and high-SES counterparts. Higher (unhealthier) LIBRA scores were associated with more decline in information processing speed (X ² = 12.66, P = 0.002) over 12 years and verbal memory (X ² = 4.63, P = 0.032) over 6 years. No consistent effect modification by SES on the association between LIBRA and cognition was found.
Conclusions
Results suggest that lifestyle is an important determinant of cognitive decline across SES groups. Yet, people with low SES had a more unfavorable modifiable risk score suggesting more potential for lifestyle-based interventions.
... 13 Given the multifactorial aetiology of dementia, it is likely that targeting a combination of risk factors may provide more synergistic benefits compared with just targeting one risk factor. 14 15 As such, multidomain intervention trials have become increasingly prevalent in the dementia prevention space compared with single-domain or pharmacological trials, 16 with PreDIVA, 17 MAPT, 18 FINGER 19 and Body Brain Life (BBL) 20 being examples of early trials. ...
Introduction
Digital health interventions are cost-effective and easily accessible, but there is currently a lack of effective online options for dementia prevention especially for people at risk due to mild cognitive impairment (MCI) or subjective cognitive decline (SCD).
Methods and analysis
MyCOACH (COnnected Advice for Cognitive Health) is a tailored online dementia risk reduction programme for adults aged ≥65 living with MCI or SCD. The MyCOACH trial aims to evaluate the programme’s effectiveness in reducing dementia risk compared with an active control over a 64-week period (N=326). Eligible participants are randomly allocated to one of two intervention arms for 12 weeks: (1) the MyCOACH intervention programme or (2) email bulletins with general healthy ageing information (active control). The MyCOACH intervention programme provides participants with information about memory impairments and dementia, memory strategies and different lifestyle factors associated with brain ageing as well as practical support including goal setting, motivational interviewing, brain training, dietary and exercise consultations, and a 26-week post-intervention booster session. Follow-up assessments are conducted for all participants at 13, 39 and 65 weeks from baseline, with the primary outcome being exposure to dementia risk factors measured using the Australian National University-Alzheimer’s Disease Risk Index. Secondary measures include cognitive function, quality of life, functional impairment, motivation to change behaviour, self-efficacy, morale and dementia literacy.
Ethics and dissemination
Ethical approval was obtained from the University of New South Wales Human Research Ethics Committee (HC210012, 19 February 2021). The results of the study will be disseminated in peer-reviewed journals and research conferences.
Trial registration number
ACTRN12621000977875.
... The results imply that individuals with cardiometabolic multimorbidity might benefit more than others from adopting a healthy lifestyle. Several trials have also shown benefits of multidomain lifestyle interventions on improving cognitive function in older people with an elevated risk of dementia [31][32][33]. Therefore, from a public health perspective, lifestyle modification could be a feasible and effective prevention strategy that is likely to have a significant impact on dementia risk reduction in people with CMDs, particularly those with cardiometabolic multimorbidity. ...
Background
The co-occurrence of cardiometabolic diseases (CMDs) is increasingly prevalent and has been associated with an additive risk of dementia in older adults, but the extent to which this risk can be offset by a healthy lifestyle is unknown. We aimed to examine the associations of cardiometabolic multimorbidity and lifestyle with incident dementia and related brain structural changes.
Methods
This prospective study extracted health and lifestyle data from 171 538 UK Biobank participants aged 60 years or older without dementia at baseline between 2006 and 2010 and followed up until July 2021, as well as brain structural data in a nested imaging subsample of 11 972 participants. Cardiometabolic multimorbidity was defined as the presence of two or more CMDs among type 2 diabetes, coronary heart disease, stroke, and hypertension. Lifestyle patterns were determined based on 7 modifiable lifestyle factors including smoking, alcohol consumption, physical activity, diet, sleep duration, sedentary behavior, and social contact.
Results
Over a median follow-up of 12.3 years, 4479 (2.6%) participants developed dementia. The presence of CMDs was dose-dependently associated with an increased risk of dementia. Compared with participants with no CMDs and a favourable lifestyle, those with ≥ 3 CMDs and an unfavourable lifestyle had a five times greater risk of developing dementia (HR 5.33, 95% CI 4.26–6.66). A significant interaction was found between CMD status and lifestyle ( P interaction =0.001). The absolute difference in incidence rates of dementia per 1000 person years comparing favourable versus unfavourable lifestyle was − 0.65 (95% CI − 1.02 to − 0.27) among participants with no CMDs and − 5.64 (− 8.11 to − 3.17) among participants with ≥ 3 CMDs, corresponding to a HR of 0.71 (0.58–0.88) and 0.42 (0.28–0.63), respectively. In the imaging subsample, a favourable lifestyle was associated with larger total brain, grey matter, and hippocampus volumes across CMD status.
Conclusion
Our findings suggest that adherence to a healthy lifestyle might substantially attenuate dementia risk and adverse brain structural changes associated with cardiometabolic multimorbidity.
... The intervention included diet teaching, exercise, cognitive training, and vascular risk monitoring. The primary outcome was the Neuropsychological Test Battery which showed a statistically significant benefit in favor of intervention (59). Physical exercise is an example of an intervention with multi-system effects including musculoskeletal, cardiovascular, pulmonary, digestive, and cognitive functions. ...
Age is the most important risk factor for Alzheimer’s disease (AD). The acceptable age range for participation in AD clinical trials is 50 to 90, and this 40-year span incorporates enormous age-related change. Clinical trial participants tend to be younger and healthier than the general population. They are also younger than the general population of AD patients. Drug development from a geroscience perspective would take greater account of effects of aging on clinical trial outcomes. The AD clinical trial pipeline has diversified beyond the canonical targets of amyloid beta protein and tau. Many of these interventions apply to age-related disorders. Anti-inflammatory agents and bioenergetic and metabolic therapies are among the well represented classes in the pipeline and are applicable to AD and non-AD age-related conditions. Drug development strategies can be adjusted to better inform outcomes of trials regarding aged individuals. Inclusion of older individuals in the multiple ascending dose trials of Phase 1, use of geriatric-related clinical outcomes and biomarkers in Phase 2, and extension of these Phase 2 learnings to Phase 3 will result in a more comprehensive understanding of AD therapies and their relationship to aging. Clinical trials can employ a more comprehensive geriatric assessment approach and biomarkers more relevant to aging at baseline and as exploratory outcomes. Greater attention to the role of aging and its influence in AD clinical trials can result in better understanding of the generalizability of clinical trial findings to the older AD population.
... On the front of multimodal studies, the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) was the first larger (n=1260) multimodal lifestyle-based RCT to show significant benefits on cognition in at-risk older individuals from general population (16). The FINGER trial combined five different intervention domains: 1) healthy balanced nutrition, 2) physical exercise, 3) cognitive training, 4) social activities, and 5) vascular/ metabolic risk management, compared to the control arm receiving regular health advice. ...
At least 40% of all dementia has been linked to modifiable risk factors suggesting a clear potential for preventative approaches targeting these factors. Despite the recent promising findings from anti-amyloid monoclonal antibodies, a limited proportion of patients are expected to be eligible for these novel AD treatments. Given the heterogeneous nature of AD and the complex multi-level pathological processes leading to dementia (involving, e.g., shared risk factors, interaction of different pathology mechanisms, and their putative synergistic effects on cognition), targeting a single pathology may not be sufficient to halt or significantly impact disease progression. With exponentially increasing numbers of patients world-wide, in parallel to the unprecedented population ageing, new multimodal therapy approaches targeting several modifiable risk factors and disease mechanisms simultaneously are urgently required. Developing the next generation of combination therapies with lifestyle intervention and pharmacological treatments, implementing the right interventions for the right people at the right time, and defining accessible and sustainable strategies worldwide are crucial. Here, we summarize the state-of-the-art multimodal lifestyle-based approaches, especially findings and lessons learned from the FINGER trial, for prevention and risk reduction of cognitive impairment and dementia. We also discuss some emerging underlying biological mechanisms and the current development of precision prevention approaches. We present an example of a novel trial design combining healthy lifestyle changes with a repurposed putative disease-modifying drug and place this study in the context of the World-Wide FINGERS, the first interdisciplinary network of multimodal trials dedicated to the prevention and risk reduction of cognitive impairment and dementia.
... 8 Several interventional studies have tested the efficacy of prevention strategies in cognitively healthy individuals at risk of dementia (primary prevention) or to prevent further cognitive decline or progression to dementia in people with mild cognitive impairment (MCI) or other early symptoms (secondary prevention). Dementia prevention clinical trials targeting single or multiple risk factors have evaluated a range of pharmacological (cholinesterase inhibitors) and non-pharmacological interventions (e.g., exercise programs, cognitive training, multidomain 9 ). However, evidence that the treatment of these risk factors reduces the risk or progression of dementia remains weak. ...
INTRODUCTION
A wide range of modifiable risk factors for dementia have been identified. Considerable debate remains about these risk factors, possible interactions between them or with genetic risk, and causality, and how they can help in clinical trial recruitment and drug development. Artificial intelligence (AI) and machine learning (ML) may refine understanding.
METHODS
ML approaches are being developed in dementia prevention. We discuss exemplar uses and evaluate the current applications and limitations in the dementia prevention field.
RESULTS
Risk‐profiling tools may help identify high‐risk populations for clinical trials; however, their performance needs improvement. New risk‐profiling and trial‐recruitment tools underpinned by ML models may be effective in reducing costs and improving future trials. ML can inform drug‐repurposing efforts and prioritization of disease‐modifying therapeutics.
DISCUSSION
ML is not yet widely used but has considerable potential to enhance precision in dementia prevention.
Highlights
Artificial intelligence (AI) is not widely used in the dementia prevention field.
Risk‐profiling tools are not used in clinical practice.
Causal insights are needed to understand risk factors over the lifespan.
AI will help personalize risk‐management tools for dementia prevention.
AI could target specific patient groups that will benefit most for clinical trials.
... when compared to those complying to ≤ 1 healthy lifestyle factor. Previous multi-lifestyle interventions among healthy older people has proven beneficial in reducing risk for CVD and cognitive decline [35][36][37], whereas evidence from single domain lifestyle interventions are less convincing [38]. Furthermore, these studies, plus others [39], suggest that simple and effective methods for lifestyle modification may be possible among older people. ...
Background
Unhealthy lifestyle behaviours such as smoking, high alcohol consumption, poor diet or low physical activity are associated with morbidity and mortality. Public health guidelines provide recommendations for adherence to these four factors, however, their relationship to the health of older people is less certain.
Methods
The study involved 11,340 Australian participants (median age 7.39 [Interquartile Range (IQR) 71.7, 77.3]) from the ASPirin in Reducing Events in the Elderly study, followed for a median of 6.8 years (IQR: 5.7, 7.9). We investigated whether a point-based lifestyle score based on adherence to guidelines for a healthy diet, physical activity, non-smoking and moderate alcohol consumption was associated with subsequent all-cause and cause-specific mortality.
Results
In multivariable adjusted models, compared to those in the unfavourable lifestyle group, individuals in the moderate lifestyle group (Hazard Ratio (HR) 0.73 [95% CI 0.61, 0.88]) and favourable lifestyle group (HR 0.68 [95% CI 0.56, 0.83]) had lower risk of all-cause mortality. A similar pattern was observed for cardiovascular related mortality and non-cancer/non-cardiovascular related mortality. There was no association of lifestyle with cancer-related mortality.
Conclusions
In a large cohort of initially healthy older people, reported adherence to a healthy lifestyle is associated with reduced risk of all-cause and cause-specific mortality. Adherence to all four lifestyle factors resulted in the strongest protection.
There is a growing incidence of cognitive decline and dementia associated with the ageing population. Lifestyle factors such as diet, physical activity, and cognitive activities may individually or collectively be undertaken to increase one’s odds of preventing cognitive decline and future dementia. This study will examine whether clinical trials using multidomain lifestyle intervention can significantly decrease the risk of cognitive decline and therefore dementia.
This systematic literature review of multidomain lifestyle interventions for the prevention of cognitive decline and dementia followed the PRISMA guidelines. Clinical trials involving multidomain intervention (i.e., diet and physical activity, or without cognitive training) in older adults (≥ 49 years old) at higher risk of dementia were identified through 5 electronic databases (EMBASE, MEDLINE, CINAHL, Cochrane, and Scopus). A comprehensive search was performed to identify and retrieve publications until 15 November 2022. Trials were published in English.
The included studies (n=15) assessed change in cognition in response to a multidomain lifestyle intervention. However, the cognitive outcome measures used in these studies were heterogeneous. Despite this heterogeneity, two thirds of the studies showed improvement in cognition following a multidomain intervention (n=10 with a total of 9,439 participants). However, five studies reported no improvement in cognition following the multidomain intervention. The most common form of dietary intervention included higher amount of fruit and vegetable intake; whole-grain cereal products instead of refined; low fat options in milk and meat products; and limiting sucrose intake to less than 50 g/day. Most clinical trial studies were powered to examining the effects of multidomain interventions in cognition but were not designed to test the contribution of individual domains (i.e., dietary changes, increased physical activity, or increased cognitive stimulation alone).
This systematic review aimed to determine the effect of multimodal lifestyle interventions on cognitive outcomes in older adults at risk of dementia. We found that participants with conditions that may increase the risk of dementia, (e.g., hypertension, cardiovascular fragility) do benefit from multi-modal lifestyle changes including diet, physical activity, and cognitive training. Two thirds of studies using multidomain lifestyle interventions showed improvements in cognitive function. Trials with a focus on cognitive training, dietary improvement, and physical activity may prevent or delay cognitive decline in older adults including those at risk of developing dementia. Future studies should consider longer follow-up periods and adequate power to be able to examine the effects of each lifestyle component in the context of multimodal interventions.
This study investigated the impact of multimorbidity patterns on physical activity and capacity outcomes over the course of a year-long exercise intervention, and on physical activity 1 year later. Participants were 314 physically inactive community-dwelling men and women aged 70–85 years, with no contraindications for exercise at baseline. Physical activity was self-reported. Physical capacity measurements included five-time chair-stand time, 6-minute walking distance, and maximal isometric knee-extension strength. The intervention included supervised and home-based strength, balance, and walking exercises. Multimorbidity patterns comprised physician-diagnosed chronic disease conditions as a predictor cluster and body mass index as a measure of obesity. Multimorbidity patterns explained 0%–12% of baseline variance and 0%–3% of the change in outcomes. The magnitude and direction of the impact of unique conditions varied by outcome, time point, and sex. Multimorbid older adults with no contraindications for exercise may benefit from multimodal physical training.
Importance
Modifiable risk factors are hypothesized to account for 30% to 40% of dementia; yet, few trials have demonstrated that risk-reduction interventions, especially multidomain, are efficacious.
Objective
To determine if a personalized, multidomain risk reduction intervention improves cognition and dementia risk profile among older adults.
Design, Setting, and Participants
The Systematic Multi-Domain Alzheimer Risk Reduction Trial was a randomized clinical trial with a 2-year personalized, risk-reduction intervention. A total of 172 adults at elevated risk for dementia (age 70-89 years and with ≥2 of 8 targeted risk factors) were recruited from primary care clinics associated with Kaiser Permanente Washington. Data were collected from August 2018 to August 2022 and analyzed from October 2022 to September 2023.
Intervention
Participants were randomly assigned to the intervention (personalized risk-reduction goals with health coaching and nurse visits) or to a health education control.
Main Outcomes and Measures
The primary outcome was change in a composite modified Neuropsychological Test Battery; preplanned secondary outcomes were change in risk factors and quality of life (QOL). Outcomes were assessed at baseline and 6, 12, 18, and 24 months. Linear mixed models were used to compare, by intention to treat, average treatment effects (ATEs) from baseline over follow-up. The intervention and outcomes were initially in person but then, due to onset of the COVID-19 pandemic, were remote.
Results
The 172 total participants had a mean (SD) age of 75.7 (4.8) years, and 108 (62.8%) were women. After 2 years, compared with the 90 participants in the control group, the 82 participants assigned to intervention demonstrated larger improvements in the composite cognitive score (ATE of SD, 0.14; 95% CI, 0.03-0.25; P = .02; a 74% improvement compared with the change in the control group), better composite risk factor score (ATE of SD, 0.11; 95% CI, 0.01-0.20; P = .03), and improved QOL (ATE, 0.81 points; 95% CI, −0.21 to 1.84; P = .12). There were no between-group differences in serious adverse events (24 in the intervention group and 23 in the control group; P = .59), but the intervention group had greater treatment-related adverse events such as musculoskeletal pain (14 in the intervention group vs 0 in the control group; P < .001).
Conclusions and Relevance
In this randomized clinical trial, a 2-year, personalized, multidomain intervention led to modest improvements in cognition, dementia risk factors, and QOL. Modifiable risk-reduction strategies should be considered for older adults at risk for dementia.
Trial Registration
ClinicalTrials.gov Identifier: NCT03683394
Introduction
African Americans are two to three times more likely to be diagnosed with Alzheimer’s disease (AD) compared to White Americans. Exercise is a lifestyle behavior associated with neuroprotection and decreased AD risk, although most African Americans, especially older adults, perform less than the recommended 150 min/week of moderate-to-vigorous intensity exercise. This article describes the protocol for a Phase III randomized controlled trial that will examine the effects of cardio-dance aerobic exercise on novel AD cognitive and neural markers of hippocampal-dependent function (Aims #1 and #2) and whether exercise-induced neuroprotective benefits may be modulated by an AD genetic risk factor, ABCA7 rs3764650 (Aim #3). We will also explore the effects of exercise on blood-based biomarkers for AD.
Methods and analysis
This 6-month trial will include 280 African Americans (≥ 60 years), who will be randomly assigned to 3 days/week of either: (1) a moderate-to-vigorous cardio-dance fitness condition or (2) a low-intensity strength, flexibility, and balance condition for 60 min/session. Participants will complete health and behavioral surveys, neuropsychological testing, saliva and venipuncture, aerobic fitness, anthropometrics and resting-state structural and functional neuroimaging at study entry and 6 months.
Discussion
Results from this investigation will inform future exercise trials and the development of prescribed interventions that aim to reduce the risk of AD in African Americans.
Obesity is associated with systemic inflammation, comorbidities like diabetes, cardiovascular disease and several cancers, cognitive decline and structural and functional brain changes. To treat, or potentially prevent these related comorbidities, individuals with obesity must achieve long-term sustainable weight loss. Often life style interventions, such as dieting and increased physical activity are not successful in achieving long-term weight loss. Meanwhile bariatric surgery has emerged as a safe and effective procedure to treat obesity. Bariatric surgery causes changes in physiological processes, but it is still not fully understood which exact mechanisms are involved. The successful weight loss after bariatric surgery might depend on changes in various energy regulating hormones, such as ghrelin, glucagon-like peptide-1 and peptide YY. Moreover, changes in microbiota composition and white adipose tissue functionality might play a role. Here, we review the effect of obesity on neuroendocrine effects, microbiota composition and adipose tissue and how these may affect inflammation, brain structure and cognition. Finally, we will discuss how these obesity-related changes may improve after bariatric surgery.
Background
Per cent slowing of decline is frequently used as a metric of outcome in Alzheimer’s disease (AD) clinical trials, but it may be misleading. Our objective was to determine whether per cent slowing of decline or Cohen’s d is the more valid and informative measure of efficacy.
Methods
Outcome measures of interest were per cent slowing of decline; Cohen’s d effect size and number-needed-to-treat (NNT). Data from a graphic were used to model the inter-relationships among Cohen’s d, placebo decline in raw score units and per cent slowing of decline with active treatment. NNTs were computed based on different magnitudes of d. Last, we tabulated recent AD anti-amyloid clinical trials that reported per cent slowing and for which we computed their respective d’s and NNTs.
Results
We demonstrated that d and per cent slowing were potentially independent. While per cent slowing of decline was dependent on placebo decline and did not include variance in its computation, d was dependent on both group mean difference and pooled SD. We next showed that d was a critical determinant of NNT, such that NNT was uniformly smaller when d was larger. In recent AD associated trials including those focused on anti-amyloid biologics, d’s were below 0.23 and thus considered small, while per cent slowing was in the 22–29% range and NNTs ranged from 14 to 18.
Conclusions
Standardised effect size is a more meaningful outcome than per cent slowing of decline because it determines group overlap, which can directly influence NNT computations, and yield information on the likelihood of minimum clinically important differences. In AD, greater use of effect sizes, NNTs, rather than relative per cent slowing, will improve the ability to interpret clinical trial results and evaluate the clinical meaningfulness of statistically significant results.
Alzheimer's disease (AD) is the major cause of dementia that is now threatening the lives of billions of elderly people on the globe, and recent progress in the elucidation of the pathomechanism of AD is now opening venue to tackle the disease by developing and implementing “disease-modifying therapies” that directly act on the pathophysiology and slow down the progression of neurodegeneration. A recent example is the success of clinical trials of anti-amyloid b antibody drugs, whereas other therapeutic targets, e.g., inflammation and tau, are being actively investigated. In this dual perspective session, we plan to have speakers from leading pharmas in the field representing distinct investments in the AD space, which will be followed by the comment from scientific leadership of the Alzheimer's Association who will speak on behalf of all stakeholders. Neuroscientists participating in the Society for Neuroscience may be able to gain insights into the cutting edge of the therapeutic approaches to AD and neurodegenerative disorders, and discuss future contribution of neuroscience to this field.
The article discusses the possibilities of pharmacotherapy of moderate vascular cognitive impairment in different age groups. The results of a double-blind randomized clinical trial «MEMO» using the antioxidant and antihypoxic drug Mexidol are presented. On the basis of cognitive scales, when using a sequential course of parenteral and oral administration of mexidol, its reliable effectiveness was shown in each of the three analyzed groups: 40-60 years old, 61-75 years old and 76-90 years old. Mexidol showed an optimal safety profile in all age groups.
As a progressive and cognitively debilitating disease, Alzheimer’s disease ranks the third cause of death for older people, right after cancer and heart disease. Despite the far-reaching understanding of its pathogenicity, the current FDA-approved drugs can only partially inhibit the disease progression. Options from alternative therapies target overcoming present therapies’ inadequate efficacy, adverse effects, and poor patient compliance. Significant leads have emerged from scientific studies of phytoconstituents of Ayurvedic herbs, Siddha medicines, and homeopathic formulations. These therapeutic interventions aim toward the prevention and postponement of Alzheimer’s disease onset, and many are already in different phases of clinical trials. Traditional medicine has been practiced since time immemorial, despite little understanding of the mechanism of their action. However, current scientific leads are consistently reporting anti-inflammatory, anti-amyloidogenic, anti-cholinesterase, hypolipidemic, and antioxidant activities in the herbal phytoconstituents, i.e., lignans, flavonoids, tannins, polyphenols, triterpenes, sterols, and alkaloids. This review aims to collectively present the scientific evidence of the vast potential of Ayurvedic medicinal plants; medicinal plants from the Siddha system; and homeopathic plant remedies in the prevention and treatment of Alzheimer’s disease. Information was collected from scientific databases like PubMed, Semantic Scholar, and Google Scholar, along with reports by government bodies and documentation. Following a comprehensive literature search, the author provides a review encompassing (1) Ayurvedic, Siddha, and homeopathy holistic approaches to manage dementia and AD and (2) phytoconstituents of traditional herbs in Siddha, Ayurveda, and homeopathic formulations effective in AD with references to their current clinical uses and future prospects.
Background
Primary care clinicians (PCCs) are typically the first practitioners to detect cognitive impairment in their patients, including those with Alzheimer’s disease or related dementias (ADRD). However, conversations around cognitive changes can be challenging for patients, family members, and clinicians to initiate, with all groups reporting barriers to open dialogue. With the expanding array of evidence-based interventions for ADRD, from multidomain care management to novel biotherapeutics for early-stage AD, incorporating conversations about brain health into routine healthcare should become a standard of care. We conducted a systematic review to identify barriers to and facilitators of brain health conversations in primary care settings.
Methods
We systematically searched PubMed, Scopus, Web of Science, and the Cochrane Library for qualitative or quantitative studies conducted in the US between January 2000 and October 2022 that evaluated perceptions of cognition and provider-patient brain health conversations prior to formal screening for, or diagnosis of, mild cognitive impairment or ADRD. We assessed the quality of the included studies using the Mixed Methods Appraisal Tool.
Results
In total, 5547 unique abstracts were screened and 22 articles describing 19 studies were included. The studies explored perceptions of cognition among laypersons or clinicians, or provider-patient interactions in the context of a patient’s cognitive concerns. We identified 4 main themes: (1) PCCs are hesitant to discuss brain health and cognitive concerns; (2) patients are hesitant to raise cognitive concerns; (3) evidence to guide clinicians in developing treatment plans that address cognitive decline is often poorly communicated; and (4) social and cultural context influence perceptions of brain health and cognition, and therefore affect clinical engagement.
Conclusions
Early conversations about brain health between PCCs and their patients are rare, and effective tools, processes, and strategies are needed to make these vital conversations routine.
Background
The SoUth Korean study to PrEvent cognitive impaiRment and protect BRAIN health through lifestyle intervention in at-risk elderly people (SUPERBRAIN) is a part of the World-Wide Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (WW-FINGERS) network. This study aimed to demonstrate the effects of the SUPERBRAIN-based multidomain intervention with nutritional supplements in amyloid positive emission tomography (PET) proven early symptomatic Alzheimer’s disease patients.
Methods
Forty-six participants who were diagnosed with mild cognitive impairment or mild dementia and were positive in the amyloid PET study randomized into three groups: group A, the multidomain intervention with nutritional supplements; group B, nutritional supplements only; and a control group. The primary outcome was a change in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total scale index score after an 8-week intervention. Secondary outcomes, including gut microbiome data, were also analyzed.
Results
The RBANS total scale index score improved significantly in group A compared with group B ( p < 0.032) and compared with the control group ( p < 0.001). After intervention, beta diversity of the gut microbiome between group A and the control group increased, and patients in group A were more enriched with Bifidobacterium .
Conclusion
SUPERBRAIN-based multidomain intervention with nutritional supplements improves cognition and gut microbiota in patients with early symptomatic Alzheimer’s disease who were amyloid-positive by PET.
Objective
As the global population ages, disability among the elderly presents unprecedented challenges for healthcare systems. However, limited research has examined whether dietary interventions like tea consumption may alleviate and prevent disability in older adults. As an important dietary therapy, the health benefits of tea drinking have gained recognition across research disciplines. Therefore, this study aimed to investigate the association between tea drinking habits and disability levels in the elderly Chinese population.
Methods
Leveraging data from the 2008 to 2018 waves of the Chinese Longitudinal Healthy Longevity Survey, we disaggregated tea drinking frequency and activities of daily living (ADL) measures and deployed fixed-effect ordered logit models to examine the tea-disability association for the first time. We statistically adjusted for potential confounders and conducted stratified analyses to assess heterogeneity across subpopulations.
Results
Multivariable fixed-effect ordered logistic regression suggested tea drinking has protective effects against ADL disability. However, only daily tea drinking was associated with lower risks of basic activities of daily living (BADL) disability [odds ratio (OR) = 0.61; 95% confidence interval (CI), 0.41–0.92] and lower levels of instrumental activities of daily living (IADL) disability (OR = 0.78; 95% CI, 0.64–0.95). Stratified analyses indicated heterogeneous effects across age and income groups. Daily tea drinking protected against BADL (OR = 0.26 and OR = 0.28) and IADL disability (OR = 0.48 and OR = 0.45) for adults over 83 years old and high-income households, respectively.
Conclusion
We found that drinking tea almost daily was protective against disability in elderly people, warranting further research into optimal dosages. Future studies should utilize more rigorous causal inference methods and control for confounders.
Existing evidence points to substantial gaps in detecting mild cognitive impairment in primary care but is based on limited or self-reported data. The recent emergence of disease-modifying treatments for the Alzheimer’s disease, the most common etiology of mild cognitive impairment, calls for a systematic assessment of detection rates in primary care.
The current study aims to examine detection rates for mild cognitive impairment among primary care clinicians and practices in the United States using Medicare claims and encounter data.
Observational study.
Medicare administrative data.
The study sample includes a total of 226,756 primary care clinicians and 54,597 practices that had at least 25 patients aged 65 or older, who were enrolled in Medicare fee-for-service or a Medicare Advantage plan between 2017 and 2019.
The detection rate for mild cognitive impairment is assessed as the ratio between the observed diagnosis rate of a clinician or practice as documented in the data, and the expected rate based on a predictive model.
The average detection rates for mild cognitive impairment is 0.08 (interquartile range=0.00–0.02) for both clinicians and practices, suggesting that only about 8% of expected cases were diagnosed on average. Only 0.1% of clinicians and practices had diagnosis rates within the expected range.
Mild cognitive impairment is vastly underdiagnosed, pointing to an urgent need to improve early detection in primary care.
Background
As exercise exerts neurobiological and immunomodulatory effects, it might also act as a disease-modifying intervention in MS. However, a clear mechanistic link between exercise and disease-modifying effects in MS has yet to be established.
Objective
Establish recommendations for future mechanistic exercise studies in MS.
Methods
In regular meetings, members of the mechanisms of action group within the MoXFo (Moving eXercise research Forward in MS) initiative evaluated gaps of knowledge and discussed unmet needs in mechanistic MS research.
Results
We concluded that biomarkers assessed in translational studies in humans and animals are essential to decipher the underlying mechanisms of exercise in MS. Consequently, we defined clear definitions of different types of biomarkers examined in MS exercise studies and operationalized their use to align with the research question and optimal testing time points. Furthermore, we provide key considerations to improve the rigor of translational studies and defined minimal reporting criteria for animal studies.
Conclusion
The resulting recommendations are intended to improve the quality of future mechanistic exercise studies in MS and consequently lead to a better understanding of therapeutic approaches.
Importance
Motoric cognitive risk (MCR) is a novel predementia syndrome; however, whether it can estimate dementia in a nationwide population or has additive estimation validity over cognitive or motoric components alone remains unknown.
Objective
To examine whether modified MCR, which incorporates the timed-up-and-go and one-leg-standing tests, improves estimation validity for incident dementia over using cognitive or motoric components alone.
Design, Setting, and Participants
This nationwide cohort study evaluated data from individuals aged 66 years who participated in the National Screening Program for Transitional Ages in Korea from January 1, 2009, to December 31, 2013, and examined the association between MCR and incident dementia using Cox proportional hazards regression analysis. Data were collected from the index date (the date on which the participant had the screening) until dementia onset, death, or the end of the follow-up period, whichever came first. The 2 subtypes were defined as subjective cognitive declines with timed-up-and-go impairment or one-leg-standing impairment. The data set was generated with permission from the Korean National Health Insurance Service, and data analysis was conducted from August 2, 2021, to January 31, 2022. Individuals diagnosed with dementia or psychotic disorders or those who had a documented history of dementia medication use before the index date were excluded.
Main Outcomes and Measures
The main outcome was incidence of dementia, defined as an individual receiving their first dementia medication with the relevant International Statistical Classification of Diseases and Related Health Problems, Tenth Revision , codes after the index date.
Results
Among the 1 137 530 participants (53.7% women), 15 380 (1.4%) met the MCR criteria for the timed-up-and-go subtype, and 32 910 (2.9%) met the criteria for the one-leg-standing subtype. The mean (SD) follow-up period was 7.02 (1.38) years. Participants with MCR demonstrated an approximately 2-fold higher risk of incident dementia than those without MCR (timed-up-and-go subtype, adjusted hazard ratio, 2.03; 95% CI, 1.94-2.13; one-leg-standing subtype, adjusted hazard ratio, 2.05; 95% CI, 1.98-2.12).
Conclusions and Relevance
In this cohort study of participants aged 66 years of the National Screening Program for Transitional Ages, modified motoric cognitive risk had higher adjusted hazard ratios of incident dementia than individual cognitive or motoric components. Motoric cognitive risk may be a practical screening tool for estimating dementia among individuals in their mid-60s ; however, further investigation of the clinical and neurobiological aspects is necessary.
Background:
Comprehensive treatment of Alzheimer's disease and related dementias (ADRD) requires not only pharmacologic treatment but also management of existing medical conditions and lifestyle modifications including diet, cognitive training, and exercise. Personalized, multimodal therapies are needed to best prevent and treat Alzheimer's disease (AD).
Objective:
The Coaching for Cognition in Alzheimer's (COCOA) trial was a prospective randomized controlled trial to test the hypothesis that a remotely coached multimodal lifestyle intervention would improve early-stage AD.
Methods:
Participants with early-stage AD were randomized into two arms. Arm 1 (N = 24) received standard of care. Arm 2 (N = 31) additionally received telephonic personalized coaching for multiple lifestyle interventions. The primary outcome was a test of the hypothesis that the Memory Performance Index (MPI) change over time would be better in the intervention arm than in the control arm. The Functional Assessment Staging Test was assessed for a secondary outcome. COCOA collected psychometric, clinical, lifestyle, genomic, proteomic, metabolomic, and microbiome data at multiple timepoints (dynamic dense data) across two years for each participant.
Results:
The intervention arm ameliorated 2.1 [1.0] MPI points (mean [SD], p = 0.016) compared to the control over the two-year intervention. No important adverse events or side effects were observed.
Conclusion:
Multimodal lifestyle interventions are effective for ameliorating cognitive decline and have a larger effect size than pharmacological interventions. Dietary changes and exercise are likely to be beneficial components of multimodal interventions in many individuals. Remote coaching is an effective intervention for early stage ADRD. Remote interventions were effective during the COVID pandemic.
The neurodegenerative disease field has enjoyed extremely limited success in the development of effective therapeutics. One potential reason is the lack of disease models that yield accurate predictions and optimal therapeutic targets. Standard clinical trials have pre-determined a single treatment modality, which may be unrelated to the primary drivers of neurodegeneration. Recent proof-of-concept clinical trials using a precision medicine approach suggest a new model of Alzheimer’s disease (AD) as a chronic innate encephalitis that creates a network insufficiency. Identifying and addressing the multiple potential contributors to cognitive decline for each patient may represent a more effective strategy. Here we review the rationale for a precision medicine approach in prevention and treatment of cognitive decline associated with AD. Results and implications from recent proof-of-concept clinical trials are presented. Randomized controlled trials, with much larger patient numbers, are likely to be significant to establishing precision medicine protocols as a standard of care for prevention and treatment of cognitive decline. Furthermore, combining this approach with the pharmaceutical approach offers the potential for enhanced outcomes. However, incorporating precision medicine approaches into everyday evaluation and care, as well as future clinical trials, would require fundamental changes in trial design, IRB considerations, funding considerations, laboratory evaluation, personalized treatment plans, treatment teams, and ultimately in reimbursement guidelines. Nonetheless, precision medicine approaches to AD, based on a novel model of AD pathophysiology, offer promise that has not been realized to date with monotherapeutic approaches.
Background:
New effective interventions to attenuate age-related cognitive decline are a global priority. Computerized cognitive training (CCT) is believed to be safe and can be inexpensive, but neither its efficacy in enhancing cognitive performance in healthy older adults nor the impact of design factors on such efficacy has been systematically analyzed. Our aim therefore was to quantitatively assess whether CCT programs can enhance cognition in healthy older adults, discriminate responsive from nonresponsive cognitive domains, and identify the most salient design factors.
Methods and findings:
We systematically searched Medline, Embase, and PsycINFO for relevant studies from the databases' inception to 9 July 2014. Eligible studies were randomized controlled trials investigating the effects of ≥ 4 h of CCT on performance in neuropsychological tests in older adults without dementia or other cognitive impairment. Fifty-two studies encompassing 4,885 participants were eligible. Intervention designs varied considerably, but after removal of one outlier, heterogeneity across studies was small (I(2) = 29.92%). There was no systematic evidence of publication bias. The overall effect size (Hedges' g, random effects model) for CCT versus control was small and statistically significant, g = 0.22 (95% CI 0.15 to 0.29). Small to moderate effect sizes were found for nonverbal memory, g = 0.24 (95% CI 0.09 to 0.38); verbal memory, g = 0.08 (95% CI 0.01 to 0.15); working memory (WM), g = 0.22 (95% CI 0.09 to 0.35); processing speed, g = 0.31 (95% CI 0.11 to 0.50); and visuospatial skills, g = 0.30 (95% CI 0.07 to 0.54). No significant effects were found for executive functions and attention. Moderator analyses revealed that home-based administration was ineffective compared to group-based training, and that more than three training sessions per week was ineffective versus three or fewer. There was no evidence for the effectiveness of WM training, and only weak evidence for sessions less than 30 min. These results are limited to healthy older adults, and do not address the durability of training effects.
Conclusions:
CCT is modestly effective at improving cognitive performance in healthy older adults, but efficacy varies across cognitive domains and is largely determined by design choices. Unsupervised at-home training and training more than three times per week are specifically ineffective. Further research is required to enhance efficacy of the intervention. Please see later in the article for the Editors' Summary.
Our aim is to describe the study recruitment and baseline characteristics of the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) study population. Potential study participants (age 60-77 years, the dementia risk score ≥6) were identified from previous population-based survey cohorts and invited to the screening visit. To be eligible, cognitive performance measured at the screening visit had to be at the mean level or slightly lower than expected for age. Of those invited (n = 5496), 48% (n = 2654) attended the screening visit, and finally 1260 eligible participants were randomized to the intervention and control groups (1:1). The screening visit non-attendees were slightly older, less educated, and had more vascular risk factors and diseases present. The mean (SD) age of the randomized participants was 69.4 (4.7) years, Mini-Mental State Examination 26.7 (2.0) points, systolic blood pressure 140.1 (16.2) mmHg, total serum cholesterol 5.2 (1.0) mmol/L for, and fasting glucose 6.1 (0.9) mmol/L for, with no difference between intervention and control groups. Several modifiable risk factors were present at baseline indicating an opportunity for the intervention. The FINGER study will provide important information on the effect of lifestyle intervention to prevent cognitive impairment among at risk persons.
Human cognitive aging differs between and is malleable within individuals. In the absence of a strong genetic program, it
is open to a host of hazards, such as vascular conditions, metabolic syndrome, and chronic stress, but also open to protective
and enhancing factors, such as experience-dependent cognitive plasticity. Longitudinal studies suggest that leading an intellectually
challenging, physically active, and socially engaged life may mitigate losses and consolidate gains. Interventions help to
identify contexts and mechanisms of successful cognitive aging and give science and society a hint about what would be possible
if conditions were different.
Background
Mild cognitive impairment (MCI) increases dementia risk with no pharmacologic treatment available.
Methods
The Study of Mental and Resistance Training was a randomized, double-blind, double-sham controlled trial of adults with MCI. Participants were randomized to 2 supervised interventions: active or sham physical training (high intensity progressive resistance training vs seated calisthenics) plus active or sham cognitive training (computerized, multidomain cognitive training vs watching videos/quizzes), 2–3 days/week for 6 months with 18-month follow-up. Primary outcomes were global cognitive function (Alzheimer's Disease Assessment Scale-cognitive subscale; ADAS-Cog) and functional independence (Bayer Activities of Daily Living). Secondary outcomes included executive function, memory, and speed/attention tests, and cognitive domain scores.
Results
One hundred adults with MCI [70.1 (6.7) years; 68% women] were enrolled and analyzed. Resistance training significantly improved the primary outcome ADAS-Cog; [relative effect size (95% confidence interval) −0.33 (−0.73, 0.06); P < .05] at 6 months and executive function (Wechsler Adult Intelligence Scale Matrices; P = .016) across 18 months. Normal ADAS-Cog scores occurred in 48% (24/49) after resistance training vs 27% (14/51) without resistance training [P < .03; odds ratio (95% confidence interval) 3.50 (1.18, 10.48)]. Cognitive training only attenuated decline in Memory Domain at 6 months (P < .02). Resistance training 18-month benefit was 74% higher (P = .02) for Executive Domain compared with combined training [z-score change = 0.42 (0.22, 0.63) resistance training vs 0.11 (−0.60, 0.28) combined] and 48% higher (P < .04) for Global Domain [z-score change = .0.45 (0.29, 0.61) resistance training vs 0.23 (0.10, 0.36) combined].
Conclusions
Resistance training significantly improved global cognitive function, with maintenance of executive and global benefits over 18 months.
The evaluation of cognitive functions by using CERAD (Consortium to Establish a Registry for Alzheimer's Disease) is recommended as a tool in basic health care for screening of memory diseases. The reliability of this method, adopted in Finland in 1999, has been impaired by the fact that there have been no comprehensive Finnish norms to serve as the basis for the cut-off limits of the test tasks. This article presents the new, revised cut-off values for the CERAD procedure, based on the comparison of Finnish population-based normative data with those of persons having very mild or mild Alzheimer's disease.
To assess the effects of aerobic exercise training on neurocognitive performance. Although the effects of exercise on neurocognition have been the subject of several previous reviews and meta-analyses, they have been hampered by methodological shortcomings and are now outdated as a result of the recent publication of several large-scale, randomized, controlled trials (RCTs).
We conducted a systematic literature review of RCTs examining the association between aerobic exercise training on neurocognitive performance between January 1966 and July 2009. Suitable studies were selected for inclusion according to the following criteria: randomized treatment allocation; mean age > or =18 years of age; duration of treatment >1 month; incorporated aerobic exercise components; supervised exercise training; the presence of a nonaerobic-exercise control group; and sufficient information to derive effect size data.
Twenty-nine studies met inclusion criteria and were included in our analyses, representing data from 2049 participants and 234 effect sizes. Individuals randomly assigned to receive aerobic exercise training demonstrated modest improvements in attention and processing speed (g = 0.158; 95% confidence interval [CI]; 0.055-0.260; p = .003), executive function (g = 0.123; 95% CI, 0.021-0.225; p = .018), and memory (g = 0.128; 95% CI, 0.015-0.241; p = .026).
Aerobic exercise training is associated with modest improvements in attention and processing speed, executive function, and memory, although the effects of exercise on working memory are less consistent. Rigorous RCTs are needed with larger samples, appropriate controls, and longer follow-up periods.
In the late 1960s, coronary heart disease (CHD) mortality among Finnish men was the highest in the world. From 1972 to 2007, risk factor surveys have been carried out to monitor risk factor trends and assess their contribution to declining mortality in Finland.
The first risk factor survey was carried out in the North Karelia and Kuopio provinces in 1972 as the basis for the evaluation of the North Karelia Project. Since then, up to five geographical areas have been included in the surveys. The target population has been persons aged 25-74 years, except in the first two surveys where the sample was drawn from a population aged 30-59 years. Risk factor contribution on mortality change was assessed by a logistic regression model.
A remarkable decline in serum cholesterol levels was observed between 1972 and 2007. Blood pressure declined among both men and women until 2002 but levelled off during the last 5 years. Prevalence of smoking decreased among men. Among women, smoking increased throughout the survey years until 2002 but did not increase between 2002 and 2007. Body mass index (BMI) has continuously increased among men. Among women, BMI decreased until 1982, but since then an increasing trend has been observed. Risk factor changes explained a 60% reduction in coronary mortality in middle-aged men while the observed reduction was 80%.
The 80% decline in coronary mortality in Finland mainly reflects a great reduction of the risk factor levels; these in turn have been associated with long-term comprehensive chronic disease prevention and health promotion interventions.
Type 2 diabetes mellitus is increasingly common, primarily because of increases in the prevalence of a sedentary lifestyle and obesity. Whether type 2 diabetes can be prevented by interventions that affect the lifestyles of subjects at high risk for the disease is not known.
We randomly assigned 522 middle-aged, overweight subjects (172 men and 350 women; mean age, 55 years; mean body-mass index [weight in kilograms divided by the square of the height in meters], 31) with impaired glucose tolerance to either the intervention group or the control group. Each subject in the intervention group received individualized counseling aimed at reducing weight, total intake of fat, and intake of saturated fat and increasing intake of fiber and physical activity. An oral glucose-tolerance test was performed annually; the diagnosis of diabetes was confirmed by a second test. The mean duration of follow-up was 3.2 years.
The mean (+/-SD) amount of weight lost between base line and the end of year 1 was 4.2+/-5.1 kg in the intervention group and 0.8+/-3.7 kg in the control group; the net loss by the end of year 2 was 3.5+/-5.5 kg in the intervention group and 0.8+/-4.4 kg in the control group (P<0.001 for both comparisons between the groups). The cumulative incidence of diabetes after four years was 11 percent (95 percent confidence interval, 6 to 15 percent) in the intervention group and 23 percent (95 percent confidence interval, 17 to 29 percent) in the control group. During the trial, the risk of diabetes was reduced by 58 percent (P<0.001) in the intervention group. The reduction in the incidence of diabetes was directly associated with changes in lifestyle.
Type 2 diabetes can be prevented by changes in the lifestyles of high-risk subjects.
Cognitive training has been shown to improve cognitive abilities in older adults but the effects of cognitive training on everyday function have not been demonstrated.
To determine the effects of cognitive training on daily function and durability of training on cognitive abilities.
Five-year follow-up of a randomized controlled single-blind trial with 4 treatment groups. A volunteer sample of 2832 persons (mean age, 73.6 years; 26% black), living independently in 6 US cities, was recruited from senior housing, community centers, and hospitals and clinics. The study was conducted between April 1998 and December 2004. Five-year follow-up was completed in 67% of the sample.
Ten-session training for memory (verbal episodic memory), reasoning (inductive reasoning), or speed of processing (visual search and identification); 4-session booster training at 11 and 35 months after training in a random sample of those who completed training.
Self-reported and performance-based measures of daily function and cognitive abilities.
The reasoning group reported significantly less difficulty in the instrumental activities of daily living (IADL) than the control group (effect size, 0.29; 99% confidence interval [CI], 0.03-0.55). Neither speed of processing training (effect size, 0.26; 99% CI, -0.002 to 0.51) nor memory training (effect size, 0.20; 99% CI, -0.06 to 0.46) had a significant effect on IADL. The booster training for the speed of processing group, but not for the other 2 groups, showed a significant effect on the performance-based functional measure of everyday speed of processing (effect size, 0.30; 99% CI, 0.08-0.52). No booster effects were seen for any of the groups for everyday problem-solving or self-reported difficulty in IADL. Each intervention maintained effects on its specific targeted cognitive ability through 5 years (memory: effect size, 0.23 [99% CI, 0.11-0.35]; reasoning: effect size, 0.26 [99% CI, 0.17-0.35]; speed of processing: effect size, 0.76 [99% CI, 0.62-0.90]). Booster training produced additional improvement with the reasoning intervention for reasoning performance (effect size, 0.28; 99% CI, 0.12-0.43) and the speed of processing intervention for speed of processing performance (effect size, 0.85; 99% CI, 0.61-1.09).
Reasoning training resulted in less functional decline in self-reported IADL. Compared with the control group, cognitive training resulted in improved cognitive abilities specific to the abilities trained that continued 5 years after the initiation of the intervention.
clinicaltrials.gov Identifier: NCT00298558.
Current evidence shows that type 2 diabetes (T2D) can be prevented by life-style changes and medication. To meet the menacing diabetes epidemic, there is an urgent need to translate the scientific evidence regarding prevention of T2D into daily clinical practice and public health. In Finland, a national programme for the prevention of T2D has been launched. The programme comprises 3 concurrent strategies for prevention: the population strategy, the high-risk strategy and the strategy of early diagnosis and management. The article describes the implementation strategy for the prevention programme for T2D.
The implementation project, FIN-D2D, is being conducted in 5 hospital districts, covering a population of 1.5 million, during the years 2003-2007. The main actors in the FIN-D2D are primary and occupational health care providers.
The goals of the project are (1) to reduce the incidence and prevalence of T2D and prevalence of cardiovascular risk factor levels; (2) to identify individuals who are unaware of their T2D; (3) to generate regional and local models and programmes for the prevention of T2D; (4) to evaluate the effectiveness, feasibility and costs of the programme; and (5) to increase the awareness of T2D and its risk factors in the population and to support the population strategy of the diabetes prevention programme. The feasibility, effectiveness and costs of the programme will be evaluated according to a specific evaluation plan.
Current research evidence shows that the type 2 diabetes can be effectively prevented in high-risk subjects by life-style changes, which include increased physical activity and weight reduction. FIN-D2D explores ways to implement these methods on a national level.
Intensified multifactorial intervention - with tight glucose regulation and the use of renin-angiotensin system blockers, aspirin, and lipid-lowering agents - has been shown to reduce the risk of nonfatal cardiovascular disease among patients with type 2 diabetes mellitus and microalbuminuria. We evaluated whether this approach would have an effect on the rates of death from any cause and from cardiovascular causes.
In the Steno-2 Study, we randomly assigned 160 patients with type 2 diabetes and persistent microalbuminuria to receive either intensive therapy or conventional therapy; the mean treatment period was 7.8 years. Patients were subsequently followed observationally for a mean of 5.5 years, until December 31, 2006. The primary end point at 13.3 years of follow-up was the time to death from any cause.
Twenty-four patients in the intensive-therapy group died, as compared with 40 in the conventional-therapy group (hazard ratio, 0.54; 95% confidence interval [CI], 0.32 to 0.89; P=0.02). Intensive therapy was associated with a lower risk of death from cardiovascular causes (hazard ratio, 0.43; 95% CI, 0.19 to 0.94; P=0.04) and of cardiovascular events (hazard ratio, 0.41; 95% CI, 0.25 to 0.67; P<0.001). One patient in the intensive-therapy group had progression to end-stage renal disease, as compared with six patients in the conventional-therapy group (P=0.04). Fewer patients in the intensive-therapy group required retinal photocoagulation (relative risk, 0.45; 95% CI, 0.23 to 0.86; P=0.02). Few major side effects were reported.
In at-risk patients with type 2 diabetes, intensive intervention with multiple drug combinations and behavior modification had sustained beneficial effects with respect to vascular complications and on rates of death from any cause and from cardiovascular causes. (ClinicalTrials.gov number, NCT00320008.)
Process-specific training can improve performance on untrained tasks, but the magnitude of gain is variable and often there is no transfer at all. We demonstrate transfer to a 3-back test of working memory after 5 weeks of training in updating. The transfer effect was based on a joint training-related activity increase for the criterion (letter memory) and transfer tasks in a striatal region that also was recruited pretraining. No transfer was observed to a task that did not engage updating and striatal regions, and age-related striatal changes imposed constraints on transfer. These findings indicate that transfer can occur if the criterion and transfer tasks engage specific overlapping processing components and brain regions.
OBJECTIVE: To issue a recommendation on the types and amounts of physical activity needed to improve and maintain health in older adults. PARTICIPANTS: A panel of scientists with expertise in public health, behavioral science, epidemiology, exercise science, medicine, and gerontology. EVIDENCE: The expert panel reviewed existing consensus statements and relevant evidence from primary research articles and reviews of the literature. Process: After drafting a recommendation for the older adult population and reviewing drafts of the Updated Recommendation from the American College of Sports Medicine (ACSM) and the American Heart Association (AHA) for Adults, the panel issued a final recommendation on physical activity for older adults. SUMMARY: The recommendation for older adults is similar to the updated ACSM/AHA recommendation for adults, but has several important differences including: the recommended intensity of aerobic activity takes into account the older adult's aerobic fitness; activities that maintain or increase flexibility are recommended; and balance exercises are recommended for older adults at risk of falls. In addition, older adults should have an activity plan for achieving recommended physical activity that integrates preventive and therapeutic recommendations. The promotion of physical activity in older adults should emphasize moderate-intensity aerobic activity, muscle-strengthening activity, reducing sedentary behavior, and risk management. Language: en
Importance
Assessing the ability of Alzheimer disease neuroimaging markers to predict short-term cognitive decline among clinically normal (CN) individuals is critical for upcoming secondary prevention trials using cognitive outcomes.Objective
To determine whether neuroimaging markers of β-amyloid (Aβ) and neurodegeneration (ND) are independently or synergistically associated with longitudinal cognitive decline in CN individuals.Design, Setting, and Participants
Academic medical center longitudinal natural history study among 166 CN individuals (median age, 74 years; 92 women).Main Outcomes and Measures
The Aβ status was determined with Pittsburgh Compound B–positron emission tomography, while ND was assessed using 2 a priori measures, hippocampus volume (magnetic resonance imaging) and glucose metabolism (positron emission tomography with fludeoxyglucose F 18), extracted from Alzheimer disease–vulnerable regions. Based on imaging markers, CN individuals were categorized into the following preclinical Alzheimer disease stages: stage 0 (Aβ−/ND−), stage 1 (Aβ+/ND−), stage 2 (Aβ+/ND+), and suspected non–Alzheimer disease pathology (Aβ−/ND+). Cognition was assessed with a composite of neuropsychological tests administered annually.Results
The Aβ+ CN individuals were more likely to be classified as ND+: 59.6% of Aβ+ CN individuals were ND+, whereas 31.9% of Aβ− CN individuals were ND+ (odds ratio, 3.14; 95% CI, 1.44-7.02; P = .004). In assessing longitudinal cognitive performance, practice effects were evident in CN individuals negative for both Aβ and ND, whereas diminished practice effects were observed in CN individuals positive for either Aβ or ND. Decline over time was observed only in CN individuals positive for both Aβ and ND, and decline in this group was significantly greater than that in all other groups (P < .001 for all). A significant interaction term between Aβ and ND confirmed that this decline was greater than the additive contributions of Aβ and ND (P = .04).Conclusions and Relevance
The co-occurrence of Aβ and ND accelerates cognitive decline in CN individuals. Therefore, both factors are important to consider in upcoming secondary prevention trials targeting CN individuals at high risk for progression to the symptomatic stages of Alzheimer disease.
Objective:
Investigate time-related age differences in cognitive functioning without influences of prior test experience.
Methods:
Cognitive scores were compared in different individuals from the same birth years who were tested in different years, when they were at different ages. These types of quasi-longitudinal comparisons were carried out on data from three large projects: the Seattle Longitudinal Study [Schaie, K. W. (2013). Developmental influences on adult intelligence: The Seattle Longitudinal Study (2nd ed.). New York, NY: Oxford University Press], the Betula Project [Ronnlund, M., & Nilsson, L-G. (2008). The magnitude, generality, and determinants of Flynn effects on forms of declarative memory and visuospatial ability: Time-sequential analyses of data from a Swedish cohort study. Intelligence, 36, 192-209], and the Virginia Cognitive Aging Project (this study).
Results:
In each data set, the results revealed that the estimates of cognitive change with no prior test experience closely resembled the estimates of age relations based on cross-sectional comparisons. Furthermore, longitudinal comparisons revealed positive changes at young ages that gradually became more negative with increased age, whereas all of the estimates of change without prior test experience were negative except those for measures of vocabulary.
Discussion:
The current results suggest that retest effects can distort the mean age trends in longitudinal comparisons that are not adjusted for experience. Furthermore, the findings can be considered robust because the patterns were similar across three data sets involving different samples of participants and cognitive tests, and across different methods of controlling experience effects in the new data set.
Background
Recent estimates suggesting that over half of Alzheimer's disease burden worldwide might be attributed to potentially modifiable risk factors do not take into account risk-factor non-independence. We aimed to provide specific estimates of preventive potential by accounting for the association between risk factors.
Methods
Using relative risks from existing meta-analyses, we estimated the population-attributable risk (PAR) of Alzheimer's disease worldwide and in the USA, Europe, and the UK for seven potentially modifiable risk factors that have consistent evidence of an association with the disease (diabetes, midlife hypertension, midlife obesity, physical inactivity, depression, smoking, and low educational attainment). The combined PAR associated with the risk factors was calculated using data from the Health Survey for England 2006 to estimate and adjust for the association between risk factors. The potential of risk factor reduction was assessed by examining the combined effect of relative reductions of 10% and 20% per decade for each of the seven risk factors on projections for Alzheimer's disease cases to 2050.
Findings
Worldwide, the highest estimated PAR was for low educational attainment (19·1%, 95% CI 12·3–25·6). The highest estimated PAR was for physical inactivity in the USA (21·0%, 95% CI 5·8–36·6), Europe (20·3%, 5·6–35·6), and the UK (21·8%, 6·1–37·7). Assuming independence, the combined worldwide PAR for the seven risk factors was 49·4% (95% CI 25·7–68·4), which equates to 16·8 million attributable cases (95% CI 8·7–23·2 million) of 33·9 million cases. However, after adjustment for the association between the risk factors, the estimate reduced to 28·2% (95% CI 14·2–41·5), which equates to 9·6 million attributable cases (95% CI 4·8–14·1 million) of 33·9 million cases. Combined PAR estimates were about 30% for the USA, Europe, and the UK. Assuming a causal relation and intervention at the correct age for prevention, relative reductions of 10% per decade in the prevalence of each of the seven risk factors could reduce the prevalence of Alzheimer's disease in 2050 by 8·3% worldwide.
Interpretation
After accounting for non-independence between risk factors, around a third of Alzheimer's diseases cases worldwide might be attributable to potentially modifiable risk factors. Alzheimer's disease incidence might be reduced through improved access to education and use of effective methods targeted at reducing the prevalence of vascular risk factors (eg, physical inactivity, smoking, midlife hypertension, midlife obesity, and diabetes) and depression.
Funding
National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care for Cambridgeshire and Peterborough.
Background
Observational studies suggest that higher levels of physical activity and cardiorespiratory fitness associate with improved cognition. However, evidence from randomised controlled trials (RCT) is limited. We hypothesised that increased regular exercise improves cognition in older individuals. The trial is registered: ISRCTN45977199 (http://isrctn.org).
Background:
Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) is a multi-center, randomized, controlled trial ongoing in Finland.
Materials:
Participants (1200 individuals at risk of cognitive decline) are recruited from previous population-based non-intervention studies. Inclusion criteria are CAIDE Dementia Risk Score ≥6 and cognitive performance at the mean level or slightly lower than expected for age (but not substantial impairment) assessed with the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery. The 2-year multidomain intervention consists of: nutritional guidance; exercise; cognitive training and social activity; and management of metabolic and vascular risk factors. Persons in the control group receive regular health advice. The primary outcome is cognitive performance as measured by the modified Neuropsychological Test Battery, Stroop test, and Trail Making Test. Main secondary outcomes are: dementia (after extended follow-up); disability; depressive symptoms; vascular risk factors and outcomes; quality of life; utilization of health resources; and neuroimaging measures.
Results:
Screening began in September 2009 and was completed in December 2011. All 1200 persons are enrolled and the intervention is ongoing as planned. Baseline clinical characteristics indicate that several vascular risk factors and unhealthy lifestyle-related factors are present, creating a window of opportunity for prevention. The intervention will be completed during 2014.
Conclusions:
The FINGER is at the forefront of international collaborative efforts to solve the clinical and public health problems of early identification of individuals at increased risk of late-life cognitive impairment, and of developing intervention strategies to prevent or delay the onset of cognitive impairment and dementia.
Practice effects on cognitive tests have been shown to further characterize patients with amnestic mild cognitive impairment (aMCI) and may provide predictive information about cognitive change across time. We tested the hypothesis that a loss of practice effects would portend a worse prognosis in aMCI.
Longitudinal, observational design following participants across 1 year.
Community-based cohort.
Three groups of older adults: 1) cognitively intact (n = 57), 2) aMCI with large practice effects across 1 week (MCI + PE, n = 25), and 3) aMCI with minimal practice effects across 1 week (MCI - PE, n = 26).
Neuropsychological tests.
After controlling for age and baseline cognitive differences, the MCI - PE group performed significantly worse than the other groups after 1 year on measures of immediate memory, delayed memory, language, and overall cognition.
Although these results need to be replicated in larger samples, the loss of short-term practice effects portends a worse prognosis in patients with aMCI.
The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) has developed brief, comprehensive, and reliable batteries of clinical and neuropsychological tests for assessment of patients with the clinical diagnosis of Alzheimer's disease (AD). We administered these batteries in a standardized manner to more than 350 subjects with a diagnosis of AD and 275 control subjects who were enrolled in a nationwide registry by a consortium of 16 university medical centers. The tests selected for this study measured the primary cognitive manifestations of AD across a range of severity of the disorder, and discriminated between normal subjects and those with mild and moderate dementia. The batteries also detected deterioration of language, memory, praxis, and general intellectual status in subjects returning for reassessment 1 year later. Interrater and test-retest reliabilities were substantial. Long-term observations of this cohort are in progress in an effort to validate the clinical and neuropsychological assessments and to confirm the diagnosis by postmortem examinations. Although information on validation is limited thus far, the CERAD batteries appear to fill a need for a standardized, easily administered, and reliable instrument for evaluating persons with AD in multicenter research studies as well as in clinical practice.
The goal of this study was to project the future prevalence and incidence of Alzheimer's disease in the United States and the potential impact of interventions to delay disease onset.
The numbers of individuals in the United States with Alzheimer's disease and the numbers of newly diagnosed cases that can be expected over the next 50 years were estimated from a model that used age-specific incidence rates summarized from several epidemiological studies, US mortality rates, and US Bureau of the Census projections.
in 1997, the prevalence of Alzheimer's disease in the United States was 2.32 million (range: 1.09 to 4.58 million); of these individuals, 68% were female. It is projected that the prevalence will nearly quadruple in the next 50 years, by which time approximately 1 in 45 Americans will be afflicted with the disease. Currently, the annual number of new incident cases in 360,000. If interventions could delay onset of the disease by 2 years, after 50 years there would be nearly 2 million fewer cases than projected; if onset could be delayed by 1 year, there would be nearly 800,000 fewer prevalent cases.
As the US population ages, Alzheimer's disease will become an enormous public health problem. interventions that could delay disease onset even modestly would have a major public health impact.
A meta-analytic study was conducted to examine the hypothesis that aerobic fitness training enhances the cognitive vitality of healthy but sedentary older adults. Eighteen intervention studies published between 1966 and 2001 were entered into the analysis. Several theoretically and practically important results were obtained. Most important fitness training was found to have robust but selective benefits for cognition, with the largest fitness-induced benefits occurring for executive-control processes. The magnitude of fitness effects on cognition was also moderated by a number of programmatic and methodological factors, including the length of the fitness-training intervention, the type of the intervention, the duration of training sessions, and the gender of the study participants. The results are discussed in terms of recent neuroscientific and psychological data that indicate cognitive and neural plasticity is maintained throughout the life span.
Several vascular risk factors are associated with dementia. We sought to develop a simple method for the prediction of the risk of late-life dementia in people of middle age on the basis of their risk profiles.
Data were used from the population-based CAIDE study, which included 1409 individuals who were studied in midlife and re-examined 20 years later for signs of dementia. Several midlife vascular risk factors were studied to create the scoring tool. The score values were estimated on the basis of beta coefficients and the dementia risk score was the sum of these individual scores (range 0-15).
Occurrence of dementia during the 20 years of follow-up was 4%. Future dementia was significantly predicted by high age (> or = 47 years), low education (< 10 years), hypertension, hypercholesterolaemia, and obesity. The dementia risk score predicted dementia well (area under curve 0.77; 95% CI 0.71-0.83). The risk of dementia according to the categories of the dementia risk score was 1.0% for those with a score of 0-5, 1.9% for a score of 6-7, 4.2% for a score of 8-9, 7.4% for a score of 10-11, and 16.4% for a score of 12-15. When the cut-off of 9 points or more was applied the sensitivity was 0.77, the specificity was 0.63, and the negative predictive value was 0.98.
The dementia risk score is a novel approach for the prediction of dementia risk, but should be validated and further improved to increase its predictive value. This approach highlights the role of vascular factors in the development of dementia and could help to identify individuals who might benefit from intensive lifestyle consultations and pharmacological interventions.
To issue a recommendation on the types and amounts of physical activity needed to improve and maintain health in older adults.
A panel of scientists with expertise in public health, behavioral science, epidemiology, exercise science, medicine, and gerontology.
The expert panel reviewed existing consensus statements and relevant evidence from primary research articles and reviews of the literature.
After drafting a recommendation for the older adult population and reviewing drafts of the Updated Recommendation from the American College of Sports Medicine (ACSM) and the American Heart Association (AHA) for Adults, the panel issued a final recommendation on physical activity for older adults.
The recommendation for older adults is similar to the updated ACSM/AHA recommendation for adults, but has several important differences including: the recommended intensity of aerobic activity takes into account the older adult's aerobic fitness; activities that maintain or increase flexibility are recommended; and balance exercises are recommended for older adults at risk of falls. In addition, older adults should have an activity plan for achieving recommended physical activity that integrates preventive and therapeutic recommendations. The promotion of physical activity in older adults should emphasize moderate-intensity aerobic activity, muscle-strengthening activity, reducing sedentary behavior, and risk management.
To report the psychometric properties of an alternative instrument to the cognitive subscale of the Alzheimer's Disease Assessment Scale, a neuropsychological test battery (NTB) for measuring drug efficacy in Alzheimer disease clinical trials.
The NTB was evaluated in a randomized, double-blind, placebo-controlled trial of AN1792(QS-21) (synthetic beta-amyloid plus an adjuvant) (300 patients) and isotonic sodium chloride solution (72 patients). The test-retest reliability of the NTB was examined, and the NTB was correlated with other cognitive (cognitive subscale of the Alzheimer's Disease Assessment Scale and Mini-Mental State Examination) and functional (Disability Assessment Scale for Dementia and Clinical Dementia Rating Sum of Boxes) measures. In addition, a factor analysis was performed on NTB components. Finally, the sensitivity of the NTB to change was assessed as a function of Mini-Mental State Examination performance.
The NTB had high test-retest reliability at 6 (Pearson product moment correlation [r] = 0.92) and 12 (r = 0.88) months. Internal consistency was high (Cronbach alpha = 0.84). The correlations between the NTB z score and scores on traditional measures of cognition and function were significantly different from 0 (P < .001). A factor analysis yielded "memory" and "executive function" factors. The NTB z score declined linearly over 1 year in patients receiving placebo and, in contrast to the Alzheimer's Disease Assessment Scale cognitive subscale, demonstrated similar declines in patients with high (21-26) and low (15-20) Mini-Mental State Examination scores at baseline.
The NTB exhibits excellent psychometric properties and seems to be a reliable and sensitive measure of cognitive change in patients with mild to moderate Alzheimer disease. The psychometric properties of the NTB suggest that it may have particular utility in evaluating drug efficacy in clinical trials in which patients with mild Alzheimer disease are included.
Harmful consequences in health status caused by disease are referred to as outcomes, and in clinical studies the measures of these outcomes are called endpoints. A major challenge when deciding on endpoints is to represent the outcomes of interest accurately, and the accuracy of such representation is assessed through validation. Complex diseases like Alzheimer's disease have many different and interdependent outcomes. We present a consensus for endpoints to be used in clinical trials in Alzheimer's disease, agreed by a European task force under the auspices of the European Alzheimer Disease Consortium. We suggest suitable endpoints for primary and secondary prevention trials, for symptomatic and disease-modifying trials in very early, mild, and moderate Alzheimer's disease, and for trials in severe Alzheimer's disease. A clear and consensual definition of endpoints is crucial for the success of further clinical trials in the field and will allow comparison of data across studies.
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Preventing Alzheimer's disease and cognitive decline Evidence report/technology assessment No. 193. (Prepared by the Duke Evidence-based Practice Center under Contract No. HHSA 290-2007-10066-I.) AHRQ Publication No. 10-E005
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Williams J, Plassman B, Burke J, Holsinger T, Benjamin S.
Preventing Alzheimer's disease and cognitive decline. Evidence
report/technology assessment No. 193. (Prepared by the Duke
Evidence-based Practice Center under Contract No. HHSA
290-2007-10066-I.) AHRQ Publication No. 10-E005. Rockville, MD:
Agency for Healthcare Research and Quality, 2010.
Geneva: World Health Organization—Alzheimer's Disease International http://www. who.int/mental_health/publications/dementia_report_2012/en/ (accessed Sept 29, 2014). 2 G8 dementia summit declaration. https://www.gov.uk/government/ publications/g8-dementia-summit-agreements
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Evidence report/technology assessment No. 193. (Prepared by the Duke Evidence-based Practice Center under Contract No. HHSA 290-2007-10066-I.) AHRQ Publication No. 10-E005
- J Williams
- B Plassman
- J Burke
- T Holsinger
- S Benjamin
Williams J, Plassman B, Burke J, Holsinger T, Benjamin S.
Preventing Alzheimer's disease and cognitive decline. Evidence
report/technology assessment No. 193. (Prepared by the Duke
Evidence-based Practice Center under Contract No. HHSA
290-2007-10066-I.) AHRQ Publication No. 10-E005. Rockville, MD:
Agency for Healthcare Research and Quality, 2010.