Michael Valenzuela

University of Sydney, Sydney, New South Wales, Australia

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Publications (89)265.41 Total impact

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    ABSTRACT: 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.
    Journal of the American Medical Directors Association 10/2014; · 5.30 Impact Factor
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    ABSTRACT: Domestic dogs have become a model organism for studying the extent and consequences of morphological diversity, especially in the skull. It has been demonstrated that Cephalic Index (CI, skull width/skull length) correlates with central concentration of ganglion cells in the retina and with ventral rotation of the cerebral hemispheres. These changes may be reflected in the behaviour of breeds with different skulls shapes. This study explored skull variation in the breed groups (n=7) described by the Australian National Kennel Club (ANKC) to determine if CI differed significantly among the breed groups; groups were expected to differ not least in behaviour. The CI of 12 representative dogs (females, n=6; males, n=6) of the most popular breeds (n=80; total n=960 dogs) were measured. Multivariate analysis of variance was performed to determine CI variance among the breed groups and between previously reported clusters of breeds with similar DNA, which identifies common ancestry. While CI differed significantly among some breed groups, neither the breed groupings nor the DNA clusters satisfactorily explained all the variance in CI. The results show that breed groupings and genetic clusters only partially explain CI differences. They also suggest that CI is on a continuum and that the definition of three categories of canine skull as dolichocephalic, mesocephalic and brachycephalic may be overly arbitrary.
    Journal of Veterinary Behavior Clinical Applications and Research 09/2014; · 1.65 Impact Factor
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    ABSTRACT: Cognitive decline is a major factor in lowering the quality of life in older populations, and contributes substantially to social, economic, and health costs. As humans age, cognitive function decreases differentially, and individual differences in cognitive ageing are likely attributed to a range of causes, including environmental and genetic influences. The current study included 360 participants (240 females and 120 males) aged between 50 and 79 years from the Tasmanian Healthy Brain Project. The brain-derived neurotrophic factor (BDNF) Val66Met and Catechol-O-Methyltransferase (COMT) Val158Met polymorphisms were examined for their association with visual and auditory episodic memory performance. The polymorphisms were also investigated for their association with reported life-long engagement in complex cognitive activity using a retrospective questionnaire. Relative to the demographic variables, the gene variations were found to have no association with episodic memory performance, with the exception of the COMT polymorphism on a single measure of auditory memory (RAVLT). Several other studies also demonstrated that these polymorphisms have no, small, or inconsistent effects on memory function. The BDNF Val66Met and COMT Val158Met polymorphisms were also found to be of little significance to active engagement in complex cognitive activity throughout most of the lifespan. An association was detected between BDNF Val66Met and engagement in cognitive activity in early life (p = .04, d = .23), however this did not reach significance when adjusted for multiple comparisons. The biological mechanisms that underlie engagement in cognitive activity are elusive, thus the potential relationship between BDNF Val66Met genotype and early life cognitive engagement warrants further investigation.
    Neurobiology of Learning and Memory 01/2014; 110:1-7. · 3.33 Impact Factor
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    ABSTRACT: Cognitive impairments associated with aging and dementia are major sources of burden, deterioration in life quality, and reduced psychological well-being (PWB). Preventative measures to both reduce incident disease and improve PWB in those afflicted are increasingly targeting individuals with mild cognitive impairment (MCI) at early disease stage. However, there is very limited information regarding the relationships between early cognitive changes and memory concern, and life quality and PWB in adults with MCI; furthermore, PWB outcomes are too commonly overlooked in intervention trials. The purpose of this study was therefore to empirically test a theoretical model of PWB in MCI in order to inform clinical intervention.
    Clinical Interventions in Aging 01/2014; 9:779-92. · 2.65 Impact Factor
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    ABSTRACT: The purpose of this descriptive correlational study was to explore potential gender differences in the relationship of dementia severity, age, APOE status, cognitive reserve and co-morbidity, (two potentially modifiable factors), to delirium severity in older adults. Baseline data from an ongoing clinical trial and a Poisson regression procedure were used in the analyses. Participants were 148 elderly individuals with dementia and delirium admitted to post-acute care. In women, delirium severity was related to dementia severity (p = 0.002) and co-morbidity moderated that effect (p = 0.03). In men, education was marginally associated with delirium severity (p = 0.06). Implications for research are discussed.
    Archives of Psychiatric Nursing. 01/2014;
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    ABSTRACT: Aims ANZMTG 01.07 WBRTMel is a phase 3 randomized trial to address the role of whole brain radiation therapy (WBRT) after local treatment of 1–3 melanoma brain metastases. Modern radiation therapy technologies can now conformally spare the hippocampus during WBRT and therefore potentially reduce the risk of neurocognitive deficit. The aims of this study were to report the prevalence of melanoma metastases within the hippocampal sparing region and to identify variables that correlate with the presence of metastases within the hippocampal sparing region. Methods The pre-local treatment MRI scans of 77 eligible WBRTMel patients were used to contour the individual metastasis and the hippocampus. The volume, location and closest distance of each metastasis to the hippocampus were recorded. Binary logistic regression was performed to assess the influence of factors on the location of a metastasis within 5 mm of the hippocampus. Results The median age was 61 and 66% were male. The distribution of the 115 metastases was frontal (50, 43.5%), parietal (23, 20.0%), temporal (13, 11.2%), occipital (18, 15.7%), cerebellum (10, 8.6%) and pineal gland (1, 1.0%). The median aggregate volume of the metastasis was 3516 mm3. None of the metastases were within the hippocampus. Four patients (5.2%) had metastases within 5 mm of the hippocampus. The median distance from metastasis to the nearest hippocampus was 37.2 mm. Only the total volume of metastases was a significant predictor for the risk of a metastasis within the hippocampal sparing region (OR 1.071, 95% CI: 1.003–1.144, p = 0.040). Conclusions This study confirmed a low incidence of melanoma metastasis in the hippocampal sparing region at diagnosis. Given the lack of randomized data on the safety and benefit of hippocampal sparing WBRT, the current WBRTMel trial provides the opportunity to explore the feasibility of this technique.
    Radiotherapy and Oncology 01/2014; · 4.52 Impact Factor
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    ABSTRACT: Many studies report an association of cognitive and social experiential factors and related traits with dementia risk. Further, many clinical-pathologic studies find a poor correspondence between levels of neuropathology and the presence of dementia and level of cognitive impairment. The poor correspondence suggests that other factors contribute to the maintenance or loss of cognitive function, with factors associated with the maintenance of function referred to as neural or cognitive reserve. This has led investigators to examine the associations of cognitive and social experiential factors with neuropathology as a first step in disentangling the complex associations between these experiential risk factors, neuropathology, and cognitive impairment. Despite the consistent associations of a range of cognitive and social lifestyle factors with cognitive decline and dementia risk, the extant clinical-pathologic data find only a single factor from one cohort, linguistic ability, related to AD pathology. Other factors, including education, harm avoidance, and emotional neglect, are associated with cerebrovascular disease. Overall, the associations are weak. Some factors, such as education, social networks, and purpose in life, modify the relation of neuropathology to cognition. Finally, some factors such as cognitive activity appear to bypass known pathologies altogether suggesting a more direct association with biologic indices that promote person-specific differences in reserve and resilience. Future work will first need to replicate findings across more studies to ensure the veracity of the existing data. Second, effort is needed to identify the molecular substrates of neural reserve as potential mediators of the association of lifestyle factors with cognition.
    Acta Neuropathologica 12/2013; · 9.73 Impact Factor
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    ABSTRACT: Objective: Physical and cognitive impairments associated with ageing and dementia are major sources of disability and lead to deterioration in the quality of life. Low quality of life is a strong predictor of adverse health outcomes such as nursing home placement and death. Therefore, with the epidemic of Alzheimer’s dementia, and the resulting push towards early diagnosis and intervention, specific understanding of psychological wellbeing (PWB) is necessary. Preventative intervention is increasingly targeting adults at early disease stage with mild cognitive impairment (MCI) however, life quality and PWB outcomes are too commonly overlooked in intervention trials. The purpose of this study was to empirically test a theoretical model of PWB in MCI to identify predictors of PWB as potential intervention targets. Methods: Participants were a convenience sample of 100 community-dwelling adults diagnosed with MCI who underwent clinical and cognitive assessment prior to randomisation. A series of regression analyses were used to develop a hierarchical model of PWB. Results: Significant predictors of PWB were subjective memory concern, cognitive function, evaluations of quality of life and negative affect, and the final model explained 61% of the variance of PWB in MCI. Conclusions: Our findings suggest that interventions targeting mood, cognitive impairment and memory concern in individuals with MCI may maintain psychological wellbeing in this cohort.
    Asia Pacific Regional Conference of Alzheimer’s Disease International, Hong Kong; 12/2013
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    ABSTRACT: Objectives: Investigations of exercise and cognition have focused primarily on healthy or demented adults, while the few studies available in individuals with early cognitive changes have been equivocal. Therefore, we evaluated the effect of exercise on cognition specifically in older adults with Mild Cognitive Impairment (MCI). Design: We conducted a meta-analysis of randomized controlled trials (RCTs) of any modality or intensity of structured exercise in older adults with MCI, evaluating all available cognitive outcomes. Searches were conducted in Medline, EMBASE, CINAHL, PEDRO, SPORTSDICUS, Psych-Info, and PUBMED from inception through 2012. Participants: Adults over age 65 with MCI, operationalized as formal diagnosis of MCI by accepted criteria or Mini-Mental State Exam score 24-28 inclusive. Measurements: Study quality was assessed via PEDro scale; data on participant and intervention characteristics and outcomes were extracted, followed by meta-analysis. Results: Fourteen RCTs (1695 participants; age 65-95 yr) met inclusion criteria. Quality was modest and underpowering for small effects prevalent. Meta-analysis revealed small significant effects of exercise on verbal fluency [ES 0.17 (0.04, 0.30], but no other measures of executive function. No significant benefit was observed for memory or information processing, and overall results were inconsistent, with benefits varying across exercise types and cognitive domains. Conclusions: Exercise may improve some cognitive functions in individuals with MCI, however published research is of modest quality and inconclusive. Questions remain regarding the magnitude, generalization, persistence and mechanisms of benefits. Largescale, robust RCTs are required to determine if exercise can improve cognition or reduce progression to dementia in this cohort.
    The Gerontological Society of America's 66th Annual Scientific Meeting,, New Orleans; 11/2013
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    ABSTRACT: BACKGROUND: Physical exercise in early adulthood and mid-life improves cognitive function and enhances brain plasticity, but the effects of commencing exercise in late adulthood are not well-understood. METHOD: We investigated the effects of voluntary exercise in the restoration of place recognition memory in aged rats and examined hippocampal changes of synaptic density and neurogenesis. RESULTS: We found a highly selective age-related deficit in place recognition memory that is stable across retest sessions and correlates strongly with loss of hippocampal synapses. Additionally, 12 weeks of voluntary running at 20 months of age removed the deficit in the hippocampally dependent place recognition memory. Voluntary running restored presynaptic density in the dentate gyrus and CA3 hippocampal subregions in aged rats to levels beyond those observed in younger animals, in which exercise had no functional or synaptic effects. By contrast, hippocampal neurogenesis, a possible memory-related mechanism, increased in both young and aged rats after physical exercise but was not linked with performance in the place recognition task. We used graph-based network analysis based on synaptic covariance patterns to characterize efficient intrahippocampal connectivity. This analysis revealed that voluntary running completely reverses the profound degradation of hippocampal network efficiency that accompanies sedentary aging. Furthermore, at an individual animal level, both overall hippocampal presynaptic density and subregional connectivity independently contribute to prediction of successful place recognition memory performance. CONCLUSIONS: Our findings emphasize the unique synaptic effects of exercise on the aged brain and their specific relevance to a hippocampally based memory system for place recognition.
    Biological psychiatry 07/2013; 73(5):435-442. · 8.93 Impact Factor
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    ABSTRACT: Investigations of exercise and cognition have primarily focused on healthy or demented older adults, and results have been equivocal in individuals with mild cognitive impairment (MCI). Our aim was to evaluate efficacy of exercise on cognition in older adults with MCI. We conducted a meta-analysis of random controlled trials (RCTs) of exercise effects on cognitive outcomes in adults with MCI. Searches were conducted in Medline, EMBASE, CINAHL, PEDro, SPORTSDICUS, PsychInfo, and PubMed. Adults aged over 65 years with MCI or Mini-Mental State Exam mean score 24-28 inclusive. Study quality was assessed using the PEDro scale; data on participant and intervention characteristics and outcomes were extracted, followed by meta-analysis. Fourteen RCTs (1,695 participants; age 65-95 years) met inclusion criteria. Quality was modest and under-powering for small effects prevalent. Overall, 42% of effect sizes (ESs) were potentially clinically relevant (ES >0.20) with only 8% of cognitive outcomes statistically significant. Meta-analysis revealed negligible but significant effects of exercise on verbal fluency (ES: 0.17 [0.04, 0.30]). No significant benefit was found for additional executive measures, memory, or information processing. Overall results were inconsistent with benefits varying across exercise types and cognitive domains. There is very limited evidence that exercise improves cognitive function in individuals with MCI, although published research is of moderate quality and inconclusive due to low statistical power. Questions remain regarding the magnitude, generalization, persistence, and mechanisms of benefits. Large-scale, high-quality RCTs are required to determine if exercise improves cognition or reduces dementia incidence in those with MCI.
    The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 07/2013; · 3.35 Impact Factor
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    ABSTRACT: Background: Cognitive lifestyle may be an important modifiable risk factor for dementia but has not yet been comprehensively studied in healthy elderly. Objective: To examine gender- and lifespan-related differences in cognitive lifestyle in a population-based cohort. Methods: 872 individuals from the second wave of the Sydney Memory and Ageing Study (MAS) cohort were invited to complete the Lifetime of Experiences Questionnaire (LEQ), a validated measure of cognitive lifestyle. Of 555 questionnaires returned (64%), 253 were excluded due to prior diagnosis of mild cognitive impairment, leaving n = 302 cognitively-intact elders (mean age 80.1 years, ±SD 4.7, 40.1% men). Results: Total LEQ was significantly higher in men (97.9 ± 20.0) than women (90.0 ± 24.5), resulting mainly from midlife LEQ differences. Men were more likely to have worked in managerial or professional jobs (73.8% versus 39.5% women), and twice as likely to have supervised large groups of workers. In late life, women were significantly more likely to be living alone (68.1% versus 25.4% men), but otherwise significantly more engaged in specific cognitive activities, including reading novels (72.3% versus 52.0% men) and incorporating volunteer work (31.9% versus 19.7% men) and socializing (59.0% versus 37.0% men) into their typical day. Over the adult lifespan, it was more common for men and women to transition between LEQ tertiles than remain the same. Conclusions: Cognitive lifestyle changes over the adult lifespan and exhibits a range of gender-based differences. While older women are more likely to be living alone they generally lead a more active current cognitive lifestyle.
    Journal of Alzheimer's disease: JAD 03/2013; · 4.17 Impact Factor
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    ABSTRACT: ABSTRACT Background: Differences in the level of cognitive compromise between individuals following brain injury are thought to arise from underlying differences in cognitive reserve. The level of cognitive reserve attained by an individual is influenced by both genetic and life experience factors such as educational attainment and occupational history. The Tasmanian Healthy Brain Project (THBP) is a world-first prospective study examining the capacity of university-level education to enhance cognitive reserve in older adults and subsequently reduce age-related cognitive decline and risk for neurodegenerative disease. Methods: Up to 1,000 adults aged 50-79 years at the time of entry into the study will be recruited to participate in the THBP. All participants will be healthy and free of significant medical, psychological, or psychiatric illness. Of the participant sample, 90% will undertake a minimum of 12 months part-time university-level study as an intervention. The remaining 10% will act as a control reference group. Participants will complete an annual comprehensive assessment of neuropsychological function, medical health, socialization, and personal well-being. Premorbid estimates of past cognitive, education, occupational, and physical function will be used to account for the mediating influence of prior life experience on outcomes. Potential contributing genetic factors will also be explored. Results: Participant results will be assessed annually. Participants displaying evidence of dementia on the comprehensive neuropsychological assessment will be referred to an independent psycho-geriatrician for screening and diagnosis. Conclusions: The THBP commenced in 2011 and is expected to run for 10-20 years duration. To date, a total of 383 participants have been recruited into the THBP.
    International Psychogeriatrics 01/2013; 25(7):1145-1155. · 2.19 Impact Factor
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    ABSTRACT: The dog (Canis lupus familiaris) displays more morphological diversity than any other species. It is a direct descendant of the gray wolf (Canis lupus), but shows remarkable behavioral and morphological differences. It has been suggested that differences in skull shape that relate to brain shape and retinal ganglion cell distribution may predict behavioral differences. The aim of this pilot study was to assess head morphology in common breeds for evidence of sexual dimorphism in head length, head width, and the ratio of the 2: cephalic index (CI). When males of 80 breeds studied were compared with females, sexual dimorphism (differences in a t-test at the level of P < 0.01) emerged for head length in 5 breeds, for head width in 10 breeds and in CI for 2 breeds. The 2 breeds that showed sexual dimorphism in CI showed no difference (at the level of P < 0.01) in either length or width. These results suggest that all 3 types of dimorphism in head morphometrics must be considered separately. Although the longer and wider heads in males may be predicted because, within a breed, they are expected to be generally bigger animals, the sexual dimorphism in CI is of interest. It may belie differences in brain shape and even predict differences in health, welfare, and behavior.
    Journal of Veterinary Behavior Clinical Applications and Research 01/2013; · 1.65 Impact Factor
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    ABSTRACT: Dogs offer unique opportunities to study correlations between morphology and behavior because skull shapes and body shape are so diverse among breeds. Several studies have shown relationships between canine cephalic index (CI: the ratio of skull width to skull length) and neural architecture. Data on the CI of adult, show-quality dogs (six males and six females) were sourced in Australia along with existing data on the breeds' height, bodyweight and related to data on 36 behavioral traits of companion dogs (n = 8,301) of various common breeds (n = 49) collected internationally using the Canine Behavioral Assessment and Research Questionnaire (C-BARQ). Stepwise backward elimination regressions revealed that, across the breeds, 33 behavioral traits all but one of which are undesirable in companion animals correlated with either height alone (n = 14), bodyweight alone (n = 5), CI alone (n = 3), bodyweight-and-skull shape combined (n = 2), height-and-skull shape combined (n = 3) or height-and-bodyweight combined (n = 6). For example, breed average height showed strongly significant inverse relationships (p<0.001) with mounting persons or objects, touch sensitivity, urination when left alone, dog-directed fear, separation-related problems, non-social fear, defecation when left alone, owner-directed aggression, begging for food, urine marking and attachment/attention-seeking, while bodyweight showed strongly significant inverse relationships (p<0.001) with excitability and being reported as hyperactive. Apart from trainability, all regression coefficients with height were negative indicating that, across the breeds, behavior becomes more problematic as height decreases. Allogrooming increased strongly (p<0.001) with CI and inversely with height. CI alone showed a strong significant positive relationship with self-grooming (p<0.001) but a negative relationship with chasing (p = 0.020). The current study demonstrates how aspects of CI (and therefore brain shape), bodyweight and height co-vary with behavior. The biological basis for, and significance of, these associations remain to be determined.
    PLoS ONE 01/2013; 8(12):e80529. · 3.53 Impact Factor
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    ABSTRACT: Cognitive training (CT) is effective at improving cognitive outcomes in children with and without clinical impairment as well as older individuals. Yet whether CT is of any preventative health benefit to working age adults is controversial. Our objective was therefore to investigate the real-world efficacy of CT in the workplace, involving employees from across the working-age spectrum and addressing many of the design issues that have limited trials to date. 135 white collar employees of a large Australian public sector organization were randomised to either 16 weeks (20 minutes three times per week) of online CT or an active control (AC) program of equal length and structure. Cognitive, wellbeing and productivity outcome measures were analysed across three timepoints: baseline, immediately after training and 6 months post-training. CT effects on cognitive outcomes were limited, even after planned subgroup analyses of cognitive capacity and age. Unexpectedly, we found that our AC condition, which comprised viewing short documentaries about the natural world, had more impact. Compared to the CT group, 6 months after the end of training, those in the AC group experienced a significant increase in their self-reported Quality of Life (Effect Size g = .34 vs -.15; TIME×GROUP p = .003), decrease in stress levels (g = .22 vs -.19; TIME x GROUP p = .03), and overall improvement in Psychological Wellbeing (g = .32 vs -.06; TIME×GROUP p = .02). CT does not appear to positively impact cognition or wellbeing amongst white collar office workers; however, short time-out respite activities may have value in the promotion of psychological wellbeing. Given looming challenges to workplace productivity, further work-based interventional research targeting employee mental health is recommended. THIS TRIAL WAS REGISTERED WITH THE AUSTRALIAN NEW ZEALAND CLINICAL TRIALS REGISTRY: ACTRN12610000604000 (http://www.anzctr.org.au/TrialSearch.aspx).
    PLoS ONE 01/2013; 8(3):e59982. · 3.53 Impact Factor
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    ABSTRACT: Objective Subjective memory complaint (SMC) in older adults is common, frequently associated with psychological factors such as depression as well as personality traits such as negative cognitive bias. SMC is central to Mild Cognitive Impairment (MCI) diagnosis and frequently underlies presentation to medical professionals. The relationships between SMC, cognitive decline, psychological well-being (PWB) and QoL in adults with MCI are unclear. The purpose of this investigation was therefore to test whether SMC, cognition and functional status – all diagnostic criteria for MCI – are associated with lower QoL and psychological wellbeing (PWB). Methods Community-dwelling residents near Sydney were recruited for the SMART trial. Inclusion criteria were age >55, MCI (SMC, Mini-Mental Status Examination (MMSE) score 23-29; functional independence; and no dementia [Clinical Dementia Rating (CDR) of ≤ 1.0] or unstable disease. Baseline neuropsychological tests of cognitive and memory function were entered as independent variables, with age, gender, education as covariates. The dependent variables, QoL and PWB, were measured on self-rated scales, and analysis was undertaken using linear regression models. Results 100 participants (68% women, 70 years (SD=6.62), 13years education (SD=3.56)) were enrolled. Unexpectedly, SMC and functional independence were not related to QoL or PWB. Lower capacity to complete daily memory tasks was associated with lower QoL (β=0.27; p<.001) and lower PWB (β=0.44; p<.0001). Visual, but not auditory, memory difficulties were linked to lower QoL (β=0.22; p<.04) and PWB (β=0.35; p<.002). Lower global cognitive function was related to lower QoL (β=0.24; p<.02) and PWB (β=0.31; p<.004), as was slower information processing speed (QoL β=0.25; p<.02) and PWB (β=.32; p<.004). Conclusions Traditional criteria used in MCI diagnosis are differentially associated with quality of life and wellbeing. These preliminary results suggest that SMC does not predict QoL or PWB despite previous associations between SMC and depression in non-MCI cohorts. By contrast, lower memory functioning in daily life, as well as poorer cognitive performance across several domains was related to lower QoL and PWB. Further analysis of these relationships and possible mediating factors will be undertaken. Longitudinal studies are required to determine which aspects of well-being are most susceptible to deterioration or intervention. These findings will better inform clinical management and treatment of individuals with MCI.
    Asia Pacific Geriatric Conference, Hong Kong; 10/2012
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    ABSTRACT: Cultivation of an active cognitive lifestyle, including diverse and challenging educational, occupational and cognitively-loaded leisure activities may be protective against development of dementia but the mechanisms underlying this link are not clear. We used the Lifetime Experiences Questionnaire (LEQ) to assess the structural brain correlates of cognitive lifestyle in the Sydney Memory and Aging Study, a large population-based cohort of originally 1037 non-demented elderly aged over 70years of age. After excluding those without structural Magnetic Resonance Image data or Mild Cognitive Impairment at their most recent assessment, 151 cognitively intact subjects were studied. Whole-brain voxel based morphometric analysis found that higher total Lifetime Experiences Questionnaire scores are linked with increased grey matter volume in the medial temporal lobe, especially in the hippocampus. Through a series of more specific analyses, we found that supervisory and managerial experience in midlife was the dominant contributor to this effect. Furthermore, in those with longitudinal neuroimaging data (N=91), we measured hippocampal structural changes over a 2-3year period by gold-standard manual tracing. The rate of hippocampal atrophy in late-life in those with high level supervisory experience in midlife was five-times slower than those with no midlife supervisory experience (p<0.001). Individual differences in intracranial volume, age, gender, physical activity, depressive symptoms, or apolipoprotein ε4 genetic status could not explain these findings, nor could specific lifestyle patterns in late life. For the first time, we reveal that managerial and supervisory experience during our working life is connected to hippocampal integrity after retirement, some 20-30years later. Our results stimulate several questions about the nature of work-related effects on longterm behaviour, structural neuroplasticity and neuroprotection, and may help explain differences in dementia-risk based on cognitive lifestyle.
    NeuroImage 08/2012; 63(3):1542-51. · 6.25 Impact Factor
  • Alzheimer's and Dementia 07/2012; 8(4 (Suppl. 2)):P147. · 17.47 Impact Factor

Publication Stats

2k Citations
265.41 Total Impact Points

Institutions

  • 2010–2014
    • University of Sydney
      • • Brain and Mind Research Institute
      • • Brain and Mind Research Institute (BMRI)
      • • Faculty of Veterinary Science
      Sydney, New South Wales, Australia
  • 2001–2013
    • University of New South Wales
      • • School of Psychiatry
      • • Brain and Ageing Research Program
      Kensington, New South Wales, Australia
  • 2001–2012
    • Prince of Wales Hospital and Community Health Services
      • Institute of Neurological Sciences
      Sydney, New South Wales, Australia
  • 2011
    • Pacific Neuropsychiatric Institute
      Seattle, Washington, United States
    • University of South Wales
      Понтиприте, Wales, United Kingdom
  • 2002
    • New South Wales Institute of Psychiatry
      Sydney, New South Wales, Australia