Publications by authors named "Henry Brodaty"

518 Publications

Nutrition Module Design in Maintain Your Brain: An internet-based randomized controlled trial to prevent cognitive decline and dementia.

Br J Nutr 2021 Jun 3:1-28. Epub 2021 Jun 3.

Sydney School of Health Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.

The Maintain Your Brain trial (MYB) is one of the largest internet-delivered multidomain RCT designed to target modifiable risk factors for dementia. It comprises four intervention modules: physical activity, nutrition, mental health, and cognitive training. This paper explains the MYB Nutrition Module, which is a fully online intervention promoting the adoption of the 'traditional' Mediterranean Diet (MedDiet) pattern for those participants reporting dietary intake that does not indicate adherence to a Mediterranean-type cuisine or those who have chronic diseases/risk factors for dementia known to benefit from this type of diet. Participants who were eligible for the Nutrition Module were assigned to one of the three diet streams: Main, Malnutrition, and Alcohol group, according to their medical history and adherence to the MedDiet at baseline. A short dietary questionnaire was administered weekly during the first 10 weeks and then monthly during the 3-year follow-up to monitor whether participants adopted or maintained the MedDiet pattern during the intervention. As the Nutrition Module is a fully online intervention, resources that promoted self-efficacy, self-management, and process of change were important elements to be included in the module development. The Nutrition Module is unique in that it is able to individualize the dietary advice according to both the medical and dietary history of each participant; the results from this unique intervention will contribute substantively to the evidence that links the Mediterranean-type diet with cognitive function and the prevention of dementia and will increase our understanding of the benefits of a MedDiet in a Western country.
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http://dx.doi.org/10.1017/S0007114521001859DOI Listing
June 2021

Alzheimer's disease research progress in Australia: The Alzheimer's Association International Conference Satellite Symposium in Sydney.

Alzheimers Dement 2021 May 31. Epub 2021 May 31.

Departments of Neuroscience and Neurology, Center for Translational Research in Neurodegenerative Disease, Normal Fixel Center for Neurological Diseases, University of Florida College of Medicine, Gainesville, Florida, USA.

The Alzheimer's Association International Conference held its sixth Satellite Symposium in Sydney, Australia in 2019, highlighting the leadership of Australian researchers in advancing the understanding of and treatment developments for Alzheimer's disease (AD) and other dementias. This leadership includes the Australian Imaging, Biomarker, and Lifestyle Flagship Study of Ageing (AIBL), which has fueled the identification and development of many biomarkers and novel therapeutics. Two multimodal lifestyle intervention studies have been launched in Australia; and Australian researchers have played leadership roles in other global studies in diverse populations. Australian researchers have also played an instrumental role in efforts to understand mechanisms underlying vascular contributions to cognitive impairment and dementia; and through the Women's Healthy Aging Project have elucidated hormonal and other factors that contribute to the increased risk of AD in women. Alleviating the behavioral and psychological symptoms of dementia has also been a strong research and clinical focus in Australia.
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http://dx.doi.org/10.1002/alz.12380DOI Listing
May 2021

Harmonizing neuropsychological assessment for mild neurocognitive disorders in Europe.

Alzheimers Dement 2021 May 13. Epub 2021 May 13.

Department of Medicine and Surgery, Institute of Gerontology and Geriatrics, University of Perugia, Perugia, Italy.

Introduction: Harmonized neuropsychological assessment for neurocognitive disorders, an international priority for valid and reliable diagnostic procedures, has been achieved only in specific countries or research contexts.

Methods: To harmonize the assessment of mild cognitive impairment in Europe, a workshop (Geneva, May 2018) convened stakeholders, methodologists, academic, and non-academic clinicians and experts from European, US, and Australian harmonization initiatives.

Results: With formal presentations and thematic working-groups we defined a standard battery consistent with the U.S. Uniform DataSet, version 3, and homogeneous methodology to obtain consistent normative data across tests and languages. Adaptations consist of including two tests specific to typical Alzheimer's disease and behavioral variant frontotemporal dementia. The methodology for harmonized normative data includes consensus definition of cognitively normal controls, classification of confounding factors (age, sex, and education), and calculation of minimum sample sizes.

Discussion: This expert consensus allows harmonizing the diagnosis of neurocognitive disorders across European countries and possibly beyond.
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http://dx.doi.org/10.1002/alz.12365DOI Listing
May 2021

Investigating Olfactory Gene Variation and Odour Identification in Older Adults.

Genes (Basel) 2021 Apr 29;12(5). Epub 2021 Apr 29.

Centre for Healthy Brain Ageing, Faculty of Medicine, School of Psychiatry, University of New South Wales (UNSW), Sydney, NSW 2031, Australia.

Ageing is associated with a decrease in odour identification. Additionally, deficits in olfaction have been linked to age-related disease and mortality. Heritability studies suggest genetic variation contributes to olfactory identification. The olfactory receptor (OR) gene family is the largest in the human genome and responsible for overall odour identification. In this study, we sought to find olfactory gene family variants associated with individual and overall odour identification and to examine the relationships between polygenic risk scores (PRS) for olfactory-related phenotypes and olfaction. Participants were Caucasian older adults from the Sydney Memory and Ageing Study and the Older Australian Twins Study with genome-wide genotyping data ( = 1395, mean age = 75.52 ± 6.45). The Brief-Smell Identification Test (BSIT) was administered in both cohorts. PRS were calculated from independent GWAS summary statistics for Alzheimer's disease (AD), white matter hyperintensities (WMH), Parkinson's disease (PD), hippocampal volume and smoking. Associations with olfactory receptor genes ( = 967), previously identified candidate olfaction-related SNPs ( = 36) and different PRS with BSIT scores (total and individual smells) were examined. All of the relationships were analysed using generalised linear mixed models (GLMM), adjusted for age and sex. Genes with suggestive evidence for odour identification were found for 8 of the 12 BSIT items. Thirteen out of 36 candidate SNPs previously identified from the literature were suggestively associated with several individual BSIT items but not total score. PRS for smoking, WMH and PD were negatively associated with chocolate identification. This is the first study to conduct genetic analyses with individual odorant identification, which found suggestive olfactory-related genes and genetic variants for multiple individual BSIT odours. Replication in independent and larger cohorts is needed.
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http://dx.doi.org/10.3390/genes12050669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145954PMC
April 2021

Social connectedness and dementia prevention: Pilot of the APPLE-Tree video-call intervention during the Covid-19 pandemic.

Dementia (London) 2021 Apr 29:14713012211014382. Epub 2021 Apr 29.

9747Camden and Islington NHS Foundation Trust, London, UK.

Background And Objectives: The Covid-19 pandemic reduced access to social activities and routine health care that are central to dementia prevention. We developed a group-based, video-call, cognitive well-being intervention; and investigated its acceptability and feasibility; exploring through participants' accounts how the intervention was experienced and used in the pandemic context.

Research Design And Method: We recruited adults aged 60+ years with memory concerns (without dementia). Participants completed baseline assessments and qualitative interviews/focus groups before and after the 10-week intervention. Qualitative interview data and facilitator notes were integrated in a thematic analysis.

Results: 12/17 participants approached completed baseline assessments, attended 100/120 (83.3%) intervention sessions and met 140/170 (82.4%) of goals set. Most had not used video calling before. In the thematic analysis, our overarching theme was . Three sub-themes were as follows: : social connectedness could not be at the expense of independence; : participants strived to compensate for previous social connectedness as the pandemic reduced support networks; although there were tensions, for example, between sharing of achievements feeling supportive and competitive, participants engaged with various lifestyle changes; social connections supported group attendance and implementation of lifestyle changes.

Discussion And Implications: Our intervention was acceptable and feasible to deliver by group video-call. We argue that dementia prevention is both an individual and societal concern. For more vulnerable populations, messages that lifestyle change can help memory should be communicated alongside supportive, relational approaches to enabling lifestyle changes.
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http://dx.doi.org/10.1177/14713012211014382DOI Listing
April 2021

Dementia increases mortality beyond effects of comorbid conditions: A national registry-based cohort study.

Eur J Neurol 2021 Jul 14;28(7):2174-2184. Epub 2021 May 14.

Department of Neurology, Danish Dementia Research Centre, Rigshospitalet, Copenhagen Ø, Denmark.

Background And Purpose: Mortality is known to be markedly increased in people with dementia. However, the association between multiple chronic conditions and mortality in dementia is not well clarified. The aim of this study was to investigate the impact of somatic and psychiatric diseases on mortality in dementia compared with the general elderly population.

Methods: Using a cohort study design, nationwide registry data from 2006 to 2015 on dementia and psychiatric and somatic comorbidities defined by the Charlson Comorbidity Index (CCI) were linked. Impact of chronic conditions was assessed according to mortality rate ratios (MRRs) in all Danish residents aged ≥65 years with and without dementia.

Results: Our population comprised 1,518,917 people, of whom 114,109 people were registered with dementia. The MRRs was 2.70 (95% confidence interval 2.68, 2.72) in people with dementia after adjusting for sex, age, calendar year, and comorbidities. MRRs increased with higher CCI score, and when comparing people with a similar comorbidity load, MRRs were significantly higher for people with dementia.

Conclusions: The comorbidity load was associated with increased mortality in both people with and without dementia. Mortality in dementia remained increased, even after adjusting for psychiatric and chronic somatic comorbidities. Our findings suggest that dementia disorders alone contribute to excess mortality, which may be further increased by comorbidities.
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http://dx.doi.org/10.1111/ene.14875DOI Listing
July 2021

The influence of rs53576 polymorphism in the oxytocin receptor () gene on empathy in healthy adults by subtype and ethnicity: a systematic review and meta-analysis.

Rev Neurosci 2021 Apr 23. Epub 2021 Apr 23.

Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales, Sydney, NSW 2052, Australia.

Empathy is essential for navigating complex social environments. Prior work has shown associations between rs53576, a single nucleotide polymorphism (SNP) located in the oxytocin receptor gene (), and generalized empathy. We undertook a systematic review and meta-analysis to assess the effects of rs53576 on subdomains of empathy, specifically cognitive empathy (CE) and affective empathy (AE), in healthy adults. Twenty cohorts of 8933 participants aged 18-98 were identified, including data from the Sydney Memory and Ageing Study, a cohort of older community adults. Meta-analyses found G homozygotes had greater generalized empathic abilities only in young to middle-aged adults. While meta-analyses of empathy subdomains yielded no significant overall effects, there were differential effects based on ethnicity. G homozygotes were associated with greater CE abilities in Asian cohorts (standardized mean difference; SMD: 0.09 [2.8·10-0.18]), and greater AE performance in European cohorts [SMD: 0.12 (0.04-0.21)]. The current literature highlights a need for further work that distinguishes between genetic and ethnocultural effects and explores effects of advanced age on this relationship.
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http://dx.doi.org/10.1515/revneuro-2021-0038DOI Listing
April 2021

Sex differences in risk factors for cognitive decline and dementia, including death as a competing risk, in individuals with diabetes: Results from the ADVANCE trial.

Diabetes Obes Metab 2021 Mar 30. Epub 2021 Mar 30.

The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia.

Aim: To estimate the associations between risk factors and cognitive decline (CD)/dementia, and the sex differences in these risk factors in individuals with type 2 diabetes, while accounting for the competing risk of death.

Materials And Methods: The Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial of 11,140 individuals with type 2 diabetes was used to estimate the odds of CD/dementia using multinomial logistic regression.

Results: During a median 5-year follow-up, 1827 participants (43.2% women) had CD/dementia (1718 with CD only; 21 with dementia only; 88 with CD and dementia), and 929 (31.0% women) died without CD/dementia. Women had lower odds of CD/dementia than men (odds ratio [OR] [95% confidence interval], 0.88 [0.77, 1.00]); older age, higher total cholesterol, HbA1c, waist circumference, waist-to-height ratio, moderately increased albumin-creatinine ratio, stroke/transient ischaemic attack and retinal disease were each associated with greater odds of CD/dementia; higher years at education completion, baseline cognitive function, taller stature and current alcohol use were inversely associated. Higher waist circumference (women-to-men ratio of ORs [ROR], 1.05 [1.00, 1.10] per 5 cm) and presence of anxiety/depression (ROR, 1.28 [1.01, 1.63]) were associated with greater ORs for CD/dementia in women than men.

Conclusions: Several risk factors were associated with CD/dementia. Higher waist circumference and mental health symptoms were more strongly associated with CD/dementia in women than men. Further studies should examine the mechanisms that underlie these sex differences.
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http://dx.doi.org/10.1111/dom.14391DOI Listing
March 2021

Translating evidence-based psychological interventions for older adults with depression and anxiety into public and private mental health settings using a stepped care framework: Study protocol.

Contemp Clin Trials 2021 May 22;104:106360. Epub 2021 Mar 22.

Older Persons' Mental Health Service, Aged Care - North Shore Ryde, Royal North Shore Hospital, Sydney 2065, Australia.

Background: With expected increases in the number of older adults worldwide, the delivery of stepped psychological care for depression and anxiety in older populations may improve both treatment and allocative efficiency for individual patients and the health system.

Design: A multisite pragmatic randomised controlled trial evaluating the clinical and cost-effectiveness of a stepped care model of care for treating depression and anxiety among older adults compared to treatment as usual (TAU) will be conducted. Eligible participants (n = 666) with clinically interfering anxiety and/or depression symptoms will be recruited from and treated within six Australian mental health services. The intervention group will complete a low intensity cognitive behavioural therapy (CBT) program: Internet-delivered or using a work-at-home book with brief therapist calls (STEP 1). Following STEP 1 a higher intensity face-to-face CBT (STEP 2) will then be offered if needed. Intention-to-treat analyses will be used to examine changes in primary outcomes (e.g. clinician-rated symptom severity changes) and secondary outcomes (e.g. self-reported symptoms severity, health related quality of life and service utilisation costs). An economic evaluation will be conducted using a cost-utility analysis to derive the incremental cost-effectiveness ratio for the stepped care intervention.

Discussion: This study will demonstrate the relative clinical and economic benefits of stepped care model of psychological care for older adults experiencing anxiety and/or depression compared to TAU. The evaluation of the intervention within existing mental health services means that results will have significant implications for the translation of evidence-based interventions in older adult services across urban and rural settings.

Trail Registration: Prospectively registered on anzctr.org.au (ACTRN12619000219189) and isrctn.com (ISRCTN37503850).
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http://dx.doi.org/10.1016/j.cct.2021.106360DOI Listing
May 2021

1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans.

Transl Psychiatry 2021 Mar 22;11(1):182. Epub 2021 Mar 22.

Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.

Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.
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http://dx.doi.org/10.1038/s41398-021-01213-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985307PMC
March 2021

A systematic review of the associations, mediators and moderators of life satisfaction, positive affect and happiness in near-centenarians and centenarians.

Aging Ment Health 2021 Mar 1:1-17. Epub 2021 Mar 1.

Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.

Objective: Results from studies investigating life satisfaction, positive affect and happiness of near-centenarians (95+) and centenarians are inconsistent. This is the first systematic review to summarise the extant literature on the subjective well-being of this unique age group.

Method: Seven electronic databases (PubMed, MEDLINE, EMBASE, PsycINFO, CINAHL, Web of Science and the Cochrane database for systematic reviews) were systematically searched. Subjective well-being was defined as life satisfaction, positive affect and happiness. A narrative synthesis of relevant articles was undertaken.

Results: Of 28 studies eligible for inclusion in this review, 20 predominantly examined life satisfaction, 11 positive affect and 4 happiness. Sex and other demographic variables were not significant predictors of subjective well-being. In contrast, greater perceived health was significantly associated with higher levels of life satisfaction and positive affect. Fatigue and visual impairment were significantly correlated with lower levels of life satisfaction and positive affect. However, there was considerable heterogeneity in the findings on physical, cognitive and social associations, mediators and moderators.

Conclusion: The large discrepancy of results in the literature may be explained by methodological differences between studies. Centenarian research needs a clearer definition of life satisfaction, positive affect and happiness as their operationalisation is inconsistent. An international consortium of centenarian studies could facilitate cross-cultural comparisons on subjective well-being. Future research should be directed towards interventions that promote subjective well-being in the oldest-old.
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http://dx.doi.org/10.1080/13607863.2021.1891197DOI Listing
March 2021

Cortical thickness across the lifespan: Data from 17,075 healthy individuals aged 3-90 years.

Hum Brain Mapp 2021 Feb 17. Epub 2021 Feb 17.

Laboratory of Psychiatric Neuroimaging, Departamento e Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.

Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.
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http://dx.doi.org/10.1002/hbm.25364DOI Listing
February 2021

Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3-90 years.

Hum Brain Mapp 2021 Feb 11. Epub 2021 Feb 11.

Department of Psychology, Center for Brain Science, Harvard University, Cambridge, Massachusetts, USA.

Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.
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http://dx.doi.org/10.1002/hbm.25320DOI Listing
February 2021

Association of Dilated Perivascular Spaces With Cognitive Decline and Incident Dementia.

Neurology 2021 03 27;96(11):e1501-e1511. Epub 2021 Jan 27.

From the Centre for Healthy Brain Ageing (CHeBA) (M.P., J.D.C., B.C.P.L., W.W., N.A.K., S.M., J.T., B.D., H.B., P.S.S.), School of Psychiatry, UNSW Medicine, University of New South Wales; Neuropsychiatric Institute (P.S.S.), The Prince of Wales Hospital (L.D., B.D., H.B.) ; and Department of Developmental Disability Neuropsychiatry, School of Psychiatry (J.T.), UNSW Sydney, Australia.

Objective: To determine whether severe perivascular space (PVS) dilation is associated with longitudinal cognitive decline and incident dementia over 4 and 8 years, respectively, we analyzed data from a prospective cohort study.

Methods: A total of 414 community-dwelling older adults aged 72-92 years were assessed at baseline and biennially for up to 8 years, with cognitive assessments, consensus dementia diagnoses, and 3T MRI. The numbers of PVS in 2 representative slices in the basal ganglia (BG) and centrum semiovale (CSO) were counted and severe PVS pathology defined as the top quartile. The effects of severe PVS pathology in either region or both regions and those with severe BG PVS and severe CSO PVS were examined. White matter hyperintensity volume, cerebral microbleed number, and lacune number were calculated.

Results: Participants with severe PVS pathology in both regions or in the CSO alone had greater decline in global cognition over 4 years, even after adjustment for the presence of other small vessel disease neuroimaging markers. The presence of severe PVS pathology in both regions was an independent predictor of dementia across 8 years (odds ratio 2.91, 95% confidence interval 1.43-5.95, = 0.003). The presence of severe PVS pathology in all groups examined was associated with greater dementia risk at either year 4 or 6.

Conclusions: Severe PVS pathology is a marker for increased risk of cognitive decline and dementia, independent of other small vessel disease markers. The differential cognitive associations for BG and CSO PVS may represent differences in their underlying pathology.
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http://dx.doi.org/10.1212/WNL.0000000000011537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032377PMC
March 2021

A slower rate of sulcal widening in the brains of the nondemented oldest old.

Neuroimage 2021 04 15;229:117740. Epub 2021 Jan 15.

Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, UNSW Sydney, NSW 2052, Australia; Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, NSW, Australia.

The relationships between aging and brain morphology have been reported in many previous structural brain studies. However, the trajectories of successful brain aging in the extremely old remain underexplored. In the limited research on the oldest old, covering individuals aged 85 years and older, there are very few studies that have focused on the cortical morphology, especially cortical sulcal features. In this paper, we measured sulcal width and depth as well as cortical thickness from T1-weighted scans of 290 nondemented community-dwelling participants aged between 76 and 103 years. We divided the participants into young old (between 76 and 84; mean = 80.35±2.44; male/female = 76/88) and oldest old (between 85 and 103; mean = 91.74±5.11; male/female = 60/66) groups. The results showed that most of the examined sulci significantly widened with increased age and that the rates of sulcal widening were lower in the oldest old. The spatial pattern of the cortical thinning partly corresponded with that of sulcal widening. Compared to females, males had significantly wider sulci, especially in the oldest old. This study builds a foundation for future investigations of neurocognitive disorders and neurodegenerative diseases in the oldest old, including centenarians.
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http://dx.doi.org/10.1016/j.neuroimage.2021.117740DOI Listing
April 2021

The effects of the COVID-19 pandemic on people with dementia.

Nat Rev Neurol 2021 02;17(2):69-70

CHeBA (Centre for Healthy Brain Ageing), School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia.

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http://dx.doi.org/10.1038/s41582-020-00450-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786184PMC
February 2021

Preserving and enhancing social health in neurocognitive disorders.

Curr Opin Psychiatry 2021 03;34(2):157-164

Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, UNSW Medicine and Health, UNSW Sydney, Sydney, Australia.

Purpose Of Review: The WHO updated concept of health includes social health alongside physical and mental health. No existing reviews have examined the evidence for preserving or enhancing social health in people living with neurocognitive disorders, such as mild cognitive impairment and dementia. The present review examines recent epidemiological studies and interventions with social health outcome measures, including interventions across multiple modalities and settings, from communities to assisted living facilities.

Recent Findings: Epidemiological evidence shows that neurocognitive disorders are associated with poorer social support, and greater social isolation and loneliness. This highlights the importance of maintaining and enhancing social health in people living with neurocognitive disorders. Group activities involving dance or music have emerging evidence indicating improvements in social health in communities and assisted living facilities. More quantitative research is required on the social health benefits of cognitive/multicomponent interventions, community social groups, exercise groups and other interventions. Several socially assistive robots are being developed to help foster social participation and require further research.

Summary: There is evidence that group music or dance interventions can improve social health for people living with neurocognitive disorders. Larger trials with multiple social health outcome measures are required to investigate the social health benefits of exercise, cognitive/multicomponent and community social group interventions.
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http://dx.doi.org/10.1097/YCO.0000000000000683DOI Listing
March 2021

Hearing loss, cognition, and risk of neurocognitive disorder: evidence from a longitudinal cohort study of older adult Australians.

Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 2020 Dec 28:1-18. Epub 2020 Dec 28.

Centre for Healthy Brain Ageing, University of New South Wales, Sydney, Australia.

Addressing midlife hearing loss could prevent up to 9% of new cases of dementia, the highest of any potentially modifiable risk factor identified in the 2017 commissioned report in The Lancet. In Australia, hearing loss is the second-most common chronic health condition in older people, affecting 74% of people aged over 70. Estimates indicate that people with severe hearing loss are up to 5-times more likely to develop dementia, but these estimates vary between studies due to methodological limitations. Using data from the Sydney Memory and Aging Study, in which 1,037 Australian men and women aged between 70 and 90 years were enrolled and completed biennial assessments from 2005-2017, investigations between hearing loss and baseline cognitive performance as well as longitudinal risk of neurocognitive disorder were undertaken. Individuals who reported moderate-to-severe hearing difficulties had poorer cognitive performances in the domains of Attention/Processing Speed and Visuospatial Ability, and on an overall index of Global Cognition, and had a 1.5-times greater risk for the neurocognitive disorder during 6-years' follow-up. Hearing loss independently predicted risk for MCI but not dementia. The presence of hearing loss is an important consideration for neuropsychological case formulation in older adults with cognitive impairment. Hearing loss may increase cognitive load, resulting in observable cognitive impairment on neuropsychological testing. Individuals with hearing loss who demonstrate impairment in non-amnestic domains may experience benefits from the provision of hearing devices; This study provides support for a randomized control trial of hearing devices for improvement of cognitive function in this group.
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http://dx.doi.org/10.1080/13825585.2020.1857328DOI Listing
December 2020

Is Healthy Neuroticism Associated with Health Behaviors? A Coordinated Integrative Data Analysis.

Collabra Psychol 2020 21;6(1). Epub 2020 Jul 21.

Humboldt University, Berlin Germany, Department of Psychology.

Current literature suggests that neuroticism is positively associated with maladaptive life choices, likelihood of disease, and mortality. However, recent research has identified circumstances under which neuroticism is associated with positive outcomes. The current project examined whether "healthy neuroticism", defined as the interaction of neuroticism and conscientiousness, was associated with the following health behaviors: smoking, alcohol consumption, and physical activity. Using a pre-registered multi-study coordinated integrative data analysis (IDA) approach, we investigated whether "healthy neuroticism" predicted the odds of engaging in each of the aforementioned activities. Each study estimated identical models, using the same covariates and data transformations, enabling optimal comparability of results. These results were then meta-analyzed in order to estimate an average (N-weighted) effect and to ascertain the extent of heterogeneity in the effects. Overall, these results suggest that neuroticism alone was not related to health behaviors, while individuals higher in conscientiousness were less likely to be smokers or drinkers, and more likely to engage in physical activity. In terms of the healthy neuroticism interaction of neuroticism and conscientiousness, significant interactions for smoking and physical activity suggest that the association between neuroticism and health behaviors was smaller among those high in conscientiousness. These findings lend credence to the idea that healthy neuroticism may be linked to certain health behaviors and that these effects are generalizable across several heterogeneous samples.
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http://dx.doi.org/10.1525/collabra.266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751766PMC
July 2020

Is Healthy Neuroticism Associated with Longevity? A Coordinated Integrative Data Analysis.

Collabra Psychol 2020 21;6(1). Epub 2020 Jul 21.

Northwestern University, Department of Medical Social Sciences, Chicago, IL, USA.

Individual differences in the Big Five personality traits have emerged as predictors of health and longevity. Although there are robust protective effects for higher levels of conscientiousness, results are mixed for other personality traits. In particular, higher levels of neuroticism have significantly predicted an increased risk of mortality, no-risk at all, and even a reduced risk of dying. The current study hypothesizes that one potential reason for the discrepancy in these findings for neuroticism is that interactions among neuroticism and other key personality traits have largely been ignored. Thus, in the current study we focus on testing whether the personality traits neuroticism and conscientiousness interact to predict mortality. Specifically, we borrow from recent evidence of "healthy neuroticism" to explore whether higher levels of neuroticism are only a risk factor for increased mortality risk when conscientiousness levels are low. We conducted a pre-registered integrative data analysis using 12 different cohort studies (total = 44,702). Although a consistent pattern emerged of higher levels of conscientiousness predicting a reduced hazard of dying, neuroticism did not show a consistent pattern of prediction. Moreover, no study provided statistical evidence of a neuroticism by conscientiousness interaction. The current findings do not support the idea that the combination of high conscientiousness and high neuroticism can be protective for longevity. Future work is needed to explore different protective factors that may buffer the negative effects of higher levels of neuroticism on health, as well as other behaviors and outcomes that may support the construct of healthy neuroticism.
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http://dx.doi.org/10.1525/collabra.268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751763PMC
July 2020

Estimating prevalence of subjective cognitive decline in and across international cohort studies of aging: a COSMIC study.

Alzheimers Res Ther 2020 12 18;12(1):167. Epub 2020 Dec 18.

Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

Background: Subjective cognitive decline (SCD) is recognized as a risk stage for Alzheimer's disease (AD) and other dementias, but its prevalence is not well known. We aimed to use uniform criteria to better estimate SCD prevalence across international cohorts.

Methods: We combined individual participant data for 16 cohorts from 15 countries (members of the COSMIC consortium) and used qualitative and quantitative (Item Response Theory/IRT) harmonization techniques to estimate SCD prevalence.

Results: The sample comprised 39,387 cognitively unimpaired individuals above age 60. The prevalence of SCD across studies was around one quarter with both qualitative harmonization/QH (23.8%, 95%CI = 23.3-24.4%) and IRT (25.6%, 95%CI = 25.1-26.1%); however, prevalence estimates varied largely between studies (QH 6.1%, 95%CI = 5.1-7.0%, to 52.7%, 95%CI = 47.4-58.0%; IRT: 7.8%, 95%CI = 6.8-8.9%, to 52.7%, 95%CI = 47.4-58.0%). Across studies, SCD prevalence was higher in men than women, in lower levels of education, in Asian and Black African people compared to White people, in lower- and middle-income countries compared to high-income countries, and in studies conducted in later decades.

Conclusions: SCD is frequent in old age. Having a quarter of older individuals with SCD warrants further investigation of its significance, as a risk stage for AD and other dementias, and of ways to help individuals with SCD who seek medical advice. Moreover, a standardized instrument to measure SCD is needed to overcome the measurement variability currently dominant in the field.
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http://dx.doi.org/10.1186/s13195-020-00734-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7749505PMC
December 2020

Sex differences in risk factors for white matter hyperintensities in non-demented older individuals.

Neurobiol Aging 2021 02 10;98:197-204. Epub 2020 Nov 10.

Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.

White matter hyperintensities (WMH) are generally considered to be associated with cerebral small vessel disease, especially, in older age. Although significant sex differences have been reported in the severity of WMH, it is not yet known if the risk factors for WMH differ in men and women. In this study, magnetic resonance imaging brain scans from 2 Australian cohorts were analyzed to extract WMH volumes. The objective of this study is to examine the moderation effect by sex in the association between known risk factors and WMH. The burden of WMH was significantly higher in women compared to men, especially in the deep WMH (DWMH). In the generalized linear model that included the interaction between sex and body mass index (BMI), there was a differential association of BMI with DWMH in men and women in the exploratory sample, that is, the Sydney Memory and Aging Study, n = 432, aged between 70 and 90. The finding of a higher BMI associated with a higher DWMH in men compared to women was replicated in the Older Australian Twins Study sample, n = 179, aged between 65 and 90. The risk factors of WMH pathology are suggested to have a different impact on the aging brains of men and women.
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http://dx.doi.org/10.1016/j.neurobiolaging.2020.11.001DOI Listing
February 2021

Cerebral small vessel disease genomics and its implications across the lifespan.

Nat Commun 2020 12 8;11(1):6285. Epub 2020 Dec 8.

University of Alabama at Birmingham School of Medicine, Birmingham, AL, 35233, USA.

White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.
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http://dx.doi.org/10.1038/s41467-020-19111-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7722866PMC
December 2020

The impact of dementia on aged care service transitions in the last five years of life.

Age Ageing 2020 Dec 4. Epub 2020 Dec 4.

Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia.

Objective: To investigate the impact of dementia on aged care service use at end-of-life.

Methods: Our retrospective data linkage study in New South Wales, Australia, used survey data from participants in the 45 and Up Study who died between July 2011-June 2014 linked to routinely collected administrative data for 2006-2014. We investigated movement between aged care "states" (No Services, Home Care including Home Support and Low-and High-Level Home Care and Residential Care) in the last five years of life. The dementia cohort comprised decedents with a dementia diagnosis recorded in hospital records, death certificates or who had claims for dementia-specific medicines prior to death (n = 2,230). The comparison cohort were decedents with no dementia diagnosis, matched 1:1 on age-at-death, sex, income and location.

Results: Compared to those without dementia, people with dementia were more likely to: use home care (67 versus 60%, P < 0.001), enter residential care (72 versus 30%, P < 0.001) and stay longer in residential care (median 17.9 versus 12.7 months, P < 0.001). Five years before death, more people with dementia were within residential care (6 versus 4%; RR = 1.61, 95%CI = 1.23-2.10) and these rates diverged at the end-of-life (69 versus 28%, RR = 2.48, 95%CI = 2.30-2.66). Use of home-based care was higher among people with dementia five years from death (20 versus 17%; RR = 1.15, 95%CI = 1.02-1.30) but lower at end-of-life (13 versus 24%, RR = 0.55, 95%CI = 0.49-0.63).

Conclusion: Dementia-specific aged care trajectories were dominated by residential care. Home care use declined towards end-of-life for people with dementia and may not be meeting their needs.
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http://dx.doi.org/10.1093/ageing/afaa254DOI Listing
December 2020

Sensorimotor, Cognitive, and Affective Functions Contribute to the Prediction of Falls in Old Age and Neurologic Disorders: An Observational Study.

Arch Phys Med Rehabil 2021 05 27;102(5):874-880. Epub 2020 Nov 27.

Falls, Balance and Injury Research Centre, Neuroscience Research Australia, University of New South Wales, Sydney, Australia; School of Public Health and Community Medicine, University of New South Wales, Sydney, Australia. Electronic address:

Objective: To determine whether impairments across cognitive and affective domains provide additional information to sensorimotor deficits for fall prediction among various populations.

Design: We pooled data from 5 studies for this observational analysis of prospective falls.

Setting: Community or low-level care facility.

Participants: Older people (N=1090; 74.0±9.4y; 579 female); 500 neurologically intact (NI) older people and 3 groups with neurologic disorders (cognitive impairment, n=174; multiple sclerosis (MS), n=111; Parkinson disease, n=305).

Interventions: None.

Main Outcome Measures: Sensorimotor function was assessed with the Physiological Profile Assessment, cognitive function with tests of executive function, affect with questionnaires of depression, and concern about falling with falls efficacy questionnaires. These variables were associated with fall incidence rates, obtained prospectively over 6-12 months.

Results: Poorer sensorimotor function was associated with falls (incidence rate ratio [95% CI], 1.46 [1.28-1.66]). Impaired executive function was the strongest predictor of falls overall (2.91 [2.27-3.73]), followed by depressive symptoms (2.07 [1.56-2.75]) and concern about falling (2.02 [1.61-2.55]). Associations were similar among groups, except for a weaker relationship with executive impairment in NI persons and a stronger relationship with concern about falling in persons with MS. Multivariable analyses showed that executive impairment, poorer sensorimotor performance, depressive symptoms, and concern about falling were independently associated with falls.

Conclusions: Deficits in cognition (executive function) and affect (depressive symptoms) and concern about falling are as important as sensorimotor function for fall prediction. These domains should be included in fall risk assessments for older people and clinical groups.
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http://dx.doi.org/10.1016/j.apmr.2020.10.134DOI Listing
May 2021

A comparison of machine learning methods for survival analysis of high-dimensional clinical data for dementia prediction.

Sci Rep 2020 11 23;10(1):20410. Epub 2020 Nov 23.

School of Psychiatry, UNSW Sydney, Sydney, Australia.

Data collected from clinical trials and cohort studies, such as dementia studies, are often high-dimensional, censored, heterogeneous and contain missing information, presenting challenges to traditional statistical analysis. There is an urgent need for methods that can overcome these challenges to model this complex data. At present there is no cure for dementia and no treatment that can successfully change the course of the disease. Machine learning models that can predict the time until a patient develops dementia are important tools in helping understand dementia risks and can give more accurate results than traditional statistical methods when modelling high-dimensional, heterogeneous, clinical data. This work compares the performance and stability of ten machine learning algorithms, combined with eight feature selection methods, capable of performing survival analysis of high-dimensional, heterogeneous, clinical data. We developed models that predict survival to dementia using baseline data from two different studies. The Sydney Memory and Ageing Study (MAS) is a longitudinal cohort study of 1037 participants, aged 70-90 years, that aims to determine the effects of ageing on cognition. The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a longitudinal study aimed at identifying biomarkers for the early detection and tracking of Alzheimer's disease. Using the concordance index as a measure of performance, our models achieve maximum performance values of 0.82 for MAS and 0.93 For ADNI.
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http://dx.doi.org/10.1038/s41598-020-77220-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683682PMC
November 2020

Does Antihypertensive Use Moderate the Effect of Blood Pressure on Cognitive Decline in Older People?

J Gerontol A Biol Sci Med Sci 2021 Apr;76(5):859-866

Faculty of Medicine, University of New South Wales, Sydney, Australia.

Background: While midlife hypertension is deleterious, late-life hypertension has been associated with better cognitive outcomes in several studies. Many questions remain, including the relative benefit or harm of a blood pressure (BP) target and antihypertensive therapy of <120 in very old individuals.

Methods: The Sydney Memory and Aging Study (n = 1015) comprises a cohort of 70- to 90-year-olds, who were followed biennially for 8 years. Global cognition was assessed with a battery of 10 neuropsychological tests. Blood pressure was measured at Waves 1 and 2 and classified into 3 systolic groupings: group 1 (≤120 mmHg), group 2 (121-140 mmHg), and group 3 (>140 mmHg). Multiple regression, linear mixed modeling, and Cox regression examined the effect of BP and antihypertensives.

Results: There were no overall significant differences in global cognition or dementia between the disparate BP groups. However, in those not taking antihypertensives, the systolic BP (SBP) > 140 mmHg group had a significantly worse global cognitive trajectory compared to SBP ≤ 120 mmHg (b = -0.067, 95% CI [-0.129, -0.006], p = .030). Within the SBP ≤ 120 mmHg group those taking antihypertensives had significantly worse global cognition trajectories compared to those not taking antihypertensives even when controlling for past history of hypertension (b = -0.077, 95% CI [-0.147, -0.007], p = .030).

Conclusions: Untreated hypertension in old age is related to worse global cognitive decline. However, ongoing treatment at new recommendations of lower SBP targets may be related to poorer cognitive decline and should be considered carefully in older populations.
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http://dx.doi.org/10.1093/gerona/glaa232DOI Listing
April 2021

Toward a theory-based specification of non-pharmacological treatments in aging and dementia: Focused reviews and methodological recommendations.

Alzheimers Dement 2021 02 20;17(2):255-270. Epub 2020 Nov 20.

Faculty of Fine Arts and Music, University of Melbourne, Melbourne, Victoria, Australia.

Introduction: Non-pharmacological treatments (NPTs) have the potential to improve meaningful outcomes for older people at risk of, or living with dementia, but research often lacks methodological rigor and continues to produce mixed results.

Methods: In the current position paper, experts in NPT research have specified treatment targets, aims, and ingredients using an umbrella framework, the Rehabilitation Treatment Specification System.

Results: Experts provided a snapshot and an authoritative summary of the evidence for different NPTs based on the best synthesis efforts, identified main gaps in knowledge and relevant barriers, and provided directions for future research. Experts in trial methodology provide best practice principles and recommendations for those working in this area, underscoring the importance of prespecified protocols.

Discussion: We conclude that the evidence strongly supports various NPTs in relation to their primary targets, and discuss opportunities and challenges associated with a unifying theoretical framework to guide future efforts in this area.
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http://dx.doi.org/10.1002/alz.12188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970750PMC
February 2021

CCCDTD5: Individual and community-based psychosocial and other non-pharmacological interventions to support persons living with dementia and their caregivers.

Alzheimers Dement (N Y) 2020 11;6(1):e12086. Epub 2020 Nov 11.

Alzheimer Society of Canada Toronto Ontario Canada.

Introduction: Current pharmacological therapies for dementia have limited efficacy. Thus it is important to provide recommendations on individual and community-based psychosocial and non-pharmacological interventions for persons living with dementia (PLWDs) and their caregivers.

Methods: Phase 1: A systematic review for developing recommendations on psychosocial and non-pharmacological interventions at the individual and community level for PLWDs and their caregivers. Phase 2: Rating of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines. Phase 3: Delphi process (>50 dementia experts) for approving recommendations by the 5 Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCCDTD5).

Results: The CCCDTD5 approved the following recommendations: Exercise (1B) and group cognitive stimulation for PLWDs (2B), psychosocial and psychoeducational interventions for caregivers (2C), development of dementia friendly organization and communities (2C), and case management for PLWDs (2B).

Discussion: The CCCDTD5 provides for the first time, evidence-based recommendations on psychosocial and non-pharmacological interventions for PLWDs and their caregivers that can inform evidence-based policies for PLWDs in Canada.
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http://dx.doi.org/10.1002/trc2.12086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7657138PMC
November 2020