Brain-age prediction: Systematic evaluation of site effects, and sample age range and size.

Structural neuroimaging data have been used to compute an estimate of the biological age of the brain (brain-age) which has been associated with other biologically and behaviorally meaningful measures of brain development and aging. The ongoing research interest in brain-age has highlighted the need for robust and publicly available brain-age models pre-trained on data from large samples of healthy individuals. To address this need we have previously released a developmental brain-age model. Here we expand this work to develop, empirically validate, and disseminate a pre-trained brain-age model to cover most of the human lifespan. To achieve this, we selected the best-performing model after systematically examining the impact of seven site harmonization strategies, age range, and sample size on brain-age prediction in a discovery sample of brain morphometric measures from 35,683 healthy individuals (age range: 5-90 years; 53.59% female). The pre-trained models were tested for cross-dataset generalizability in an independent sample comprising 2101 healthy individuals (age range: 8-80 years; 55.35% female) and for longitudinal consistency in a further sample comprising 377 healthy individuals (age range: 9-25 years; 49.87% female). This empirical examination yielded the following findings: (1) the accuracy of age prediction from morphometry data was higher when no site harmonization was applied; (2) dividing the discovery sample into two age-bins (5-40 and 40-90 years) provided a better balance between model accuracy and explained age variance than other alternatives; (3) model accuracy for brain-age prediction plateaued at a sample size exceeding 1600 participants. These findings have been incorporated into CentileBrain (https://centilebrain.org/#/brainAGE2), an open-science, web-based platform for individualized neuroimaging metrics.

An accelerated degeneration of white matter microstructure and networks in the nondemented old-old.

The nondemented old-old over the age of 80 comprise a rapidly increasing population group; they can be regarded as exemplars of successful aging. However, our current understanding of successful aging in advanced age and its neural underpinnings is limited. In this study, we measured the microstructural and network-based topological properties of brain white matter using diffusion-weighted imaging scans of 419 community-dwelling nondemented older participants. The participants were further divided into 230 young-old (between 72 and 79, mean = 76.25 ± 2.00) and 219 old-old (between 80 and 92, mean = 83.98 ± 2.97). Results showed that white matter connectivity in microstructure and brain networks significantly declined with increased age and that the declined rates were faster in the old-old compared with young-old. Mediation models indicated that cognitive decline was in part through the age effect on the white matter connectivity in the old-old but not in the young-old. Machine learning predictive models further supported the crucial role of declines in white matter connectivity as a neural substrate of cognitive aging in the nondemented older population. Our findings shed new light on white matter connectivity in the nondemented aging brains and may contribute to uncovering the neural substrates of successful brain aging.

Associations of Osteoarthritis with Prevalence and Incidence of Cardiovascular Disease over 10 Years in Community-Dwelling Older Adults: The Sydney Memory and Ageing Study.

INTRODUCTION: The data are limited for the association between osteoarthritis (OA) and cardiovascular disease (CVD) in community-based older populations and whether there is sex difference. This study aimed to examine the relationship between OA and prevalence and incidence of CVD over 10 years in community-dwelling older adults. METHODS: Data on self-reported OA, high cholesterol, hypertension, and type 2 diabetes were collected from 1,025 community-dwelling participants aged 70-90 years in the Sydney Memory and Ageing Study. The presence of CVD at baseline was defined as self-reported presence of stroke, heart attack, transient ischaemic attack, angina, aortic aneurysm, or claudication. The incidence of CVD was defined by a combination of incident self-reported CVD or CVD mortality at different follow-up timepoints over 10 years. RESULTS: At baseline, 395 (38.5%) participants self-reported OA (252 [44.6%] women, 143 [31.1%] men). Self-reported OA was associated with increased prevalence of CVD in women (OR 1.67, 95% CI 1.12-2.47) but not men (1.26, 0.80-1.98). In the total population, self-reported OA at baseline was associated with increased incidence of CVD at 4 years (OR 1.77, 95% CI 1.10-2.83), 6 years (1.59, 1.03-2.46), 8 years (1.56, 1.02-2.38), and 10 years (1.66, 1.10-2.50), but not at 2 years (1.43, 0.79-2.57). Significant associations were observed in female participants at 4, 8, and 10 years, with no significant associations seen in male participants. CONCLUSION: OA was associated with increased prevalence at baseline and incidence of CVD over 10 years in community-based older adults, especially women. Identifying those with OA to target their cardiovascular risk factors while managing their OA has the potential to reduce the burden of CVD in older people, particularly women.

Longitudinal alcohol-related brain changes in older adults: The Sydney Memory and Ageing Study.

Increases in harmful drinking among older adults indicate the need for a more thorough understanding of the relationship between later-life alcohol use and brain health. The current study investigated the relationships between alcohol use and progressive grey and white matter changes in older adults using longitudinal data. A total of 530 participants (aged 70 to 90 years; 46.0% male) were included. Brain outcomes assessed over 6 years included total grey and white matter volume, as well as volume of the hippocampus, thalamus, amygdala, corpus callosum, orbitofrontal cortex and insula. White matter integrity was also investigated. Average alcohol use across the study period was the main exposure of interest. Past-year binge drinking and reduction in drinking from pre-baseline were additional exposures of interest. Within the context of low-level average drinking (averaging 11.7 g per day), higher average amount of alcohol consumed was associated with less atrophy in the left (B = 7.50, pFDR = 0.010) and right (B = 5.98, pFDR = 0.004) thalamus. Past-year binge-drinking was associated with poorer white matter integrity (B = -0.013, pFDR = 0.024). Consuming alcohol more heavily in the past was associated with greater atrophy in anterior (B = -12.73, pFDR = 0.048) and posterior (B = -17.88, pFDR = 0.004) callosal volumes over time. Across alcohol exposures and neuroimaging markers, no other relationships were statistically significant. Within the context of low-level drinking, very few relationships between alcohol use and brain macrostructure were identified. Meanwhile, heavier drinking was negatively associated with white matter integrity.

The combination of olfactory dysfunction and depression increases the risk of incident dementia in older adults.

OBJECTIVES: Olfactory dysfunction and depression are common in later life, and both have been presented as risk factors for dementia. Our purpose was to investigate the associations between these two risk factors and determine if they had an additive effect on dementia risk. DESIGN: Olfactory function was assessed using the Brief Smell Identification Test (BSIT), and depression was classified using a combination of the 15-item Geriatric Depression Scale (GDS) score and current antidepressant use. Cross-sectional associations between depression and olfactory function were examined using correlations. Cox regression analyses were conducted to examine the longitudinal relationship between olfaction and depression and incident dementia across 12-years of follow-up. PARTICIPANTS: Participants were 780 older adults (aged 70-90 years; 56.5% female) from the Sydney Memory and Ageing Study (MAS) without a diagnosis of dementia at baseline. RESULTS: Partial correlation revealed a nonsignificant association between baseline depression and olfactory function after accounting for covariates (r = -.051, p = .173). Cox regression showed that depression at baseline (hazard ratio = 1.706, 95% CI 1.185-2.456, p = .004) and lower BSIT scores (HR = .845, 95%CI .789-.905, p < .001) were independently associated with a higher risk of incident dementia across 12 years. Entering both predictors together improved the overall predictive power of the model. CONCLUSIONS: Lower olfactory identification scores and depressive symptoms predict incident dementia over 12 years. The use of BSIT scores and depression in conjunction provides a greater ability to predict dementia than either used alone. Assessment of olfactory function and depression screening may provide clinical utility in the early detection of dementia.

Cognitive and physical declines and falls in older people with and without mild cognitive impairment: a 7-year longitudinal study.

OBJECTIVES: We examined longitudinal changes in cognitive and physical function and associations between change in function and falls in people with and without mild cognitive impairment (MCI). DESIGN: Prospective cohort study with assessments every 2 years (for up to 6 years). SETTING: Community, Sydney, Australia. PARTICIPANTS: Four hundred and eighty one people were classified into three groups: those with MCI at baseline and MCI or dementia at follow-up assessments (n = 92); those who fluctuated between cognitively normal and MCI throughout follow-up (cognitively fluctuating) (n = 157), and those who were cognitively normal at baseline and all reassessments (n = 232). MEASUREMENTS: Cognitive and physical function measured over 2-6 years follow-up. Falls in the year following participants' final assessment. RESULTS: In summary, 27.4%, 38.5%, and 34.1% of participants completed 2, 4, and 6 years follow-up of cognitive and physical performance, respectively. The MCI and cognitive fluctuating groups demonstrated cognitive decline, whereas the cognitively normal group did not. The MCI group had worse physical function than the cognitively normal group at baseline but decline over time in physical performance was similar across all groups. Decline in global cognitive function and sensorimotor performance were associated with multiple falls in the cognitively normal group and decline in mobility (timed-up-and-go test) was associated with multiple falls across the whole sample. CONCLUSIONS: Cognitive declines were not associated with falls in people with MCI and fluctuating cognition. Declines in physical function were similar between groups and decline in mobility was associated with falls in the whole sample. As exercise has multiple health benefits including maintaining physical function, it should be recommended for all older people. Programs aimed at mitigating cognitive decline should be encouraged in people with MCI.

Knowledge, attitudes and self-confidence with skills required for providing dementia care in physicians at primary healthcare settings in Vietnam.

BACKGROUND: Dementia is a global public health priority. The World Health Organization adopted a Global Action Plan on Dementia, with dementia awareness a priority. This study examined the knowledge, attitudes, and self-confidence with skills required for providing dementia care among primary health care providers in Vietnam. METHODS: A cross-sectional study was conducted with 405 primary health care providers who worked at commune health stations and district health centers in eight provinces across Vietnam. RESULTS: The results showed that primary health care providers had poor knowledge and little confidence but more positive attitudes toward dementia care and management. CONCLUSIONS: The results suggest the training needs for building capacity amongst primary health care providers, which will be critical as Vietnam's population ages.

Biomedical knowledge of dementia is not enough to counteract its stigma - quantitative research among future medical and social care staff in Poland.

OBJECTIVES: The aim is to assess the level of stigmatization and knowledge of dementia among university students of medical, rehabilitation and social faculties in Poland. Possible correlates of these concepts and group differences are also investigated. METHODS: We applied quantitative methods using an online questionnaire comprising sociodemographics, the Alzheimer's Disease Knowledge Scale, a vignette of a person with dementia and the modified Family Stigma in Alzheimer's Disease Scale. RESULTS: Students had low levels of dementia knowledge and moderate levels of stigma. Medical science students had significantly better knowledge than the other groups but did not differ in their level of stigma. Relationships between the main variables were complex. Emotional and cognitive stigmatizing attributions were negatively correlated with knowledge about communication and behaviors of people with dementia. Better knowledge on causes and characteristics, as well as on risks and health promotion of the disease also triggered fewer negative attributions toward people with dementia. CONCLUSIONS: If health-related programs are to be effective, they should provide opportunities for the acquisition of relevant knowledge and skills that also address the stigmatization of people living with dementia. Well-established biomedical knowledge on dementia must be supplemented with a person-centered approach and proper communication skills.

Moving forward with dementia: an explorative cross-country qualitative study into post-diagnostic experiences.

OBJECTIVES: This explorative cross-country qualitative study aims to describe experiences of receiving a dementia diagnosis and experiences of support following a diagnosis in Australia, Canada, the Netherlands and Poland. METHOD: Qualitative study using projective techniques during online focus groups, online and telephone interviews with people with dementia and caregivers. RESULTS: Twenty-three people with dementia and 53 caregivers participated. Qualitative content analysis revealed five themes; (1) 'Coming to terms with dementia' helped people deal with complex emotions to move forward. (3) 'The social network as a source of support' and (4) 'The challenges and realities of formal support' and impacted 'Coming to terms with dementia'. (2) 'Navigating life with dementia as a caregiver' highlights caregiver burden and was impacted by (4) 'The challenges and realities of formal support'. People were (5) 'Self-caring and preparing for tomorrow' as they focused on maintaining current health whilst planning the future. Despite differences in healthcare and post-diagnostic support systems, there were more similarities across countries than differences. CONCLUSION: Across countries, formal support and support from friends and family are crucial for people with dementia and caregivers to come to terms with dementia and maintain carer wellbeing to ultimately live well with dementia.

Umbrella review and Delphi study on modifiable factors for dementia risk reduction.

A 2013 systematic review and Delphi consensus study identified 12 modifiable risk and protective factors for dementia, which were subsequently merged into the "LIfestyle for BRAin health" (LIBRA) score. We systematically evaluated whether LIBRA requires revision based on new evidence. To identify modifiable risk and protective factors suitable for dementia risk reduction, we combined an umbrella review of systematic reviews and meta-analyses with a two-round Delphi consensus study. The review of 608 unique primary studies and opinions of 18 experts prioritized six modifiable factors: hearing impairment, social contact, sleep, life course inequalities, atrial fibrillation, and psychological stress. Based on expert ranking, hearing impairment, social contact, and sleep were considered the most suitable candidates for inclusion in updated dementia risk scores. As such, the current study shows that dementia risk scores need systematic updates based on emerging evidence. Future studies will validate the updated LIBRA score in different cohorts. HIGHLIGHTS: An umbrella review was combined with opinions of 18 dementia experts. Various candidate targets for dementia risk reduction were identified. Experts prioritized hearing impairment, social contact, and sleep. Re-assessment of dementia risk scores is encouraged. Future work should evaluate the predictive validity of updated risk scores.

Examining the validity of the Mini-Mental State Examination (MMSE) and its domains using network analysis.

BACKGROUND: The Mini-Mental State Examination (MMSE) is the most widely used standardised screener for impairments across a range of cognitive domains. However, the degree to which its domains (orientation, registration, attention, recall, language, and visuospatial) capture cognitive functioning measured using standardised neuropsychological tests is unclear. METHOD: A longitudinal research design with four biannual assessments over a 6-year period was used with an initial sample of 1037 older adults (aged above 70 years). Participants completed MMSE and neuropsychological tests at each assessment. Network analysis was utilised to investigate unique associations among the MMSE and its domains and neuropsychological test performance at each time point. RESULTS: The total MMSE and two of its domains, language and recall, were associated with neuropsychological memory performance. The MMSE orientation, registration and visuospatial domains did not have any unique associations with neuropsychological performance. No stable internal interconnections between MMSE domains were found over time. The association of total MMSE as well as its recall domain with neuropsychological memory performance remained very similar over the 6-year period. CONCLUSIONS: The present study adds evidence to the validity of the MMSE and supports the clinical usage of the MMSE, whereby the total score is used for screening patients with or without cognitive impairments, with repeated administration to monitor cognitive changes over time, to inform intervention. However, the tool is not able to diagnose the cases for changes in specific cognitive domains and as such, should not replace a complete neuropsychological assessment.

Ensemble feature selection with data-driven thresholding for Alzheimer's disease biomarker discovery.

BACKGROUND: Feature selection is often used to identify the important features in a dataset but can produce unstable results when applied to high-dimensional data. The stability of feature selection can be improved with the use of feature selection ensembles, which aggregate the results of multiple base feature selectors. However, a threshold must be applied to the final aggregated feature set to separate the relevant features from the redundant ones. A fixed threshold, which is typically used, offers no guarantee that the final set of selected features contains only relevant features. This work examines a selection of data-driven thresholds to automatically identify the relevant features in an ensemble feature selector and evaluates their predictive accuracy and stability. Ensemble feature selection with data-driven thresholding is applied to two real-world studies of Alzheimer's disease. Alzheimer's disease is a progressive neurodegenerative disease with no known cure, that begins at least 2-3 decades before overt symptoms appear, presenting an opportunity for researchers to identify early biomarkers that might identify patients at risk of developing Alzheimer's disease. RESULTS: The ensemble feature selectors, combined with data-driven thresholds, produced more stable results, on the whole, than the equivalent individual feature selectors, showing an improvement in stability of up to 34%. The most successful data-driven thresholds were the robust rank aggregation threshold and the threshold algorithm threshold from the field of information retrieval. The features identified by applying these methods to datasets from Alzheimer's disease studies reflect current findings in the AD literature. CONCLUSIONS: Data-driven thresholds applied to ensemble feature selectors provide more stable, and therefore more reproducible, selections of features than individual feature selectors, without loss of performance. The use of a data-driven threshold eliminates the need to choose a fixed threshold a-priori and can select a more meaningful set of features. A reliable and compact set of features can produce more interpretable models by identifying the factors that are important in understanding a disease.

Using network analysis to validate domains of the modified telephone interview for cognitive status.

BACKGROUND: The modified Telephone Interview for Cognitive Status (TICS-M) is a widely used tool for assessing global cognitive functions and screening for cognitive impairments. The tool was conceptualised to capture various cognitive domains, but the validity of such domains has not been investigated against comprehensive neuropsychological assessments tools. Therefore, this study aimed to explore the associations between the TICS-M domains and neuropsychological domains to evaluate the validity of the TICS-M domains using network analysis. MATERIALS AND METHODS: A longitudinal research design was used with a large sample of older adults (aged above 70 years; n = 1037 at the baseline assessment) who completed the TICS-M and comprehensive neuropsychological assessments biennially. We applied network analysis to identify unique links between the TICS-M domains and neuropsychological test scores. RESULTS: At baseline, there were weak internal links between the TICS-M domains. The TICS-M memory and language domains were significantly related to their corresponding neuropsychological domains. The TICS-M attention domain had significant associations with executive function and visuospatial abilities. The TICS-M orientation domain was not significantly associated with any of the five neuropsychological domains. Despite an attrition of almost 50% at wave four, weak internal links between the TICS-M domains and most associations between TICS-M and neuropsychological domains that were found initially, remained stable at least over two waves within the 6-year period. CONCLUSIONS: This study supports the overall structural validity of the TICS-M screener in assessing enduring global cognitive function. However, separate TICS-M cognitive domains should not be considered equivalent to the analogous neuropsychological domains.

Defining exceptional cognition in older adults: A systematic review of cognitive super-ageing.

OBJECTIVE: A consistent approach to defining cognitive super-ageing is needed to increase the value of research insights that may be gained from studying this population including ageing well and preventing and treating neurodegenerative conditions. This review aims to evaluate the existing definitions of 'super-ageing' with a focus on cognition. METHODS: A systematic literature search was conducted across PubMed, Embase, Web of Science, Scopus, PsycINFO and Google Scholar from inception to 24 July 2023. RESULTS: Of 44 English language studies that defined super-ageing from a cognitive perspective in older adults (60-97 years), most (n = 33) were based on preserved verbal episodic memory performance comparable to that of younger adult in age range 16-65 years. Eleven studies defined super-agers as the top cognitive performers for their age group based upon standard deviations or percentiles above the population mean. Only nine studies included longitudinal cognitive performance in their definitions. CONCLUSIONS: Equivalent cognitive abilities to younger adults, exceptional cognition for age and a lack of cognitive deterioration over time are all meaningful constructs and may provide different insights into cognitive ageing. Using these criteria in combination or individually to define super-agers, with a clear rationale for which elements have been selected, could be fit for purpose depending on the research question. However, major discrepancies including the age range of super-agers and comparator groups and the choice of cognitive domains assessed should be addressed to reach some consensus in the field.

Experiences of people with dementia and informal caregivers with post-diagnostic support: Data from the international COGNISANCE study.

OBJECTIVES: The study aims to describe people with dementia and informal caregivers' respective experiences of support after diagnosis and compares these experiences. Additionally, we determine how people with dementia and informal caregivers who are satisfied with support differ from those dissatisfied. METHODS: A cross-sectional survey study in Australia, Canada, the Netherlands, Poland, and United Kingdom was carried out to examine people with dementia and informal caregivers experience with support (satisfaction with information, access to care, health literacy, and confidence in ability to live well with dementia). The separate surveys contained closed questions. Analysis consisted of descriptive statistics and Chi-square tests. RESULTS: Ninety people with dementia and 300 informal caregivers participated, and 69% of people with dementia and 67% of informal caregivers said support after diagnosis helped them deal more efficiently with their concerns. Up to one-third of people with dementia and informal caregivers were dissatisfied with information about management, prognosis, and strategies for living positively. Few people with dementia (22%) and informal caregivers (35%) received a care plan. People with dementia were more often satisfied with information, had more often confidence in their ability to live well with dementia, and were less often satisfied with access to care compared to informal caregivers. Informal caregivers who were satisfied with support were more satisfied with information and access to care compared to informal caregivers not satisfied with support. CONCLUSIONS: Experience of dementia support can be improved and people with dementia and informal caregiver differ in their experiences of support.

Social Health and Change in Cognitive Capability among Older Adults: Findings from Four European Longitudinal Studies.

INTRODUCTION: In this study, we examine whether social health markers measured at baseline are associated with differences in cognitive capability and the rate of cognitive decline over an 11-to-18-year period among older adults and compare results across studies. METHODS: We applied an integrated data analysis approach to 16,858 participants (mean age 65 years; 56% female) from the National Survey for Health and Development (NSHD), the English Longitudinal Study of Aging (ELSA), the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), and the Rotterdam Study. We used multilevel models to examine social health in relation to cognitive capability and the rate of cognitive decline. RESULTS: Pooled estimates show distinct relationships between markers of social health and cognitive domains, e.g., a large network size (≥6 people vs. none) was associated with higher executive function (0.17 standard deviation [SD] [95% CI: 0.00, 0.34], I2 = 27%) but not with memory (0.08 SD [95% CI: -0.02, 0.18], I2 = 19%). We also observed pooled associations between being married or cohabiting, having a large network size, and participating in social activities with slower decline in cognitive capability. However, estimates were close to zero, e.g., 0.01 SD/year (95% CI: 0.01, 0.02) I2 = 19% for marital status and executive function. There were clear study-specific differences: results for average processing speed were the most homogenous, and results for average memory were the most heterogeneous. CONCLUSION: Overall, markers of good social health have a positive association with cognitive capability. However, we found differential associations between specific markers of social health and cognitive domains and differences between studies. These findings highlight the importance of examining between-study differences and considering the context specificity of findings in developing and deploying interventions.

Apathy and depression in mild cognitive impairment: distinct longitudinal trajectories and clinical outcomes.

OBJECTIVES: Apathy is a common symptom in mild cognitive impairment (MCI) and may predict progression to dementia. Little research, however, has investigated the longitudinal trajectory of apathy in patients with MCI or controlled for depression, which can mimic apathy, when examining its clinical correlates. The current study sought to address these issues. DESIGN: A prospective longitudinal study was conducted over 3 years. SETTING: Nine memory clinics around Australia. PARTICIPANTS: One hundred and eighty-five patients with MCI at baseline. MEASUREMENTS: Measures of cognition, function, neuropsychiatric symptoms, caregiver burden, and medication use were completed annually with additional assessments at 3 and 6 months. Patients were also assessed for dementia by expert clinicians at these time points. RESULTS: Of 164 patients who completed measures of neuropsychiatric symptoms, 59 (36.0%) had apathy and 61 (37.2%) had depression. The proportion affected by apathy and overall apathy scores increased over time, in contrast to measures of depression, which remained relatively stable. Apathy was associated with incident dementia and worse cognition, function, neuropsychiatric symptoms, and caregiver burden independent of both depression and incident dementia. Depression was associated with worse function, albeit to lesser degree than apathy, and neuropsychiatric symptoms. CONCLUSIONS: Apathy increases in MCI and is associated with worse clinical outcomes. These findings provide further evidence for apathy as a marker of clinical decline in older people and poorer outcomes across neurocognitive disorders.

Views of people living with dementia and their families/care partners: helpful and unhelpful responses to behavioral changes.

OBJECTIVES: This study investigated the views of people living with dementia and their families/care partners on (i) what they find helpful or unhelpful regarding behavioral changes, i.e. which coping strategies they used for themselves and/or which responses from others, and (ii) what they consider to be appropriate terminology to describe behavioral changes. DESIGN & SETTING: One-on-one semi-structured interviews were conducted with people living with dementia and families/care partners face to face, online, or over the telephone. MEASUREMENTS: Data from open-ended questions were analyzed inductively. Common themes were derived from the data using an iterative approach. RESULTS: Twenty-one people living with dementia and 20 family members/care partners were interviewed. Four main themes were derived for helpful responses, and three main themes for unhelpful responses. Helpful responses included providing clear professional support pathways and supportive environments where people living with dementia can engage in physical, cognitive, social, and spiritual activities. Unhelpful responses included discriminatory treatment from others and use of medicalized terminology. Views toward terminology varied; people with lived experience most favored using "changed behaviors" over other terminology. Areas for improvement included targeting dementia stigma, societal education on dementia, and building confidence in people living with dementia by focusing on living well with dementia. CONCLUSION: Knowledge of the views of people living with dementia may assist healthcare professionals to provide more appropriate care for people living with dementia.

Frequency of cognitive "super-aging" in three Australian samples using different diagnostic criteria.

OBJECTIVES: To investigate the frequency of exceptional cognition (cognitive super-aging) in Australian older adults using different published definitions, agreement between definitions, and the relationship of super-aging status with function, brain imaging markers, and incident dementia. DESIGN: Three longitudinal cohort studies. SETTING: Participants recruited from the electoral roll, Australian Twins Registry, and community advertisements. PARTICIPANTS: Older adults (aged 65-106) without dementia from the Sydney Memory and Ageing Study (n = 1037; median age 78), Older Australian Twins Study (n = 361; median age 68), and Sydney Centenarian Study (n = 217; median age 97). MEASUREMENTS: Frequency of super-aging was assessed using nine super-aging definitions based on performance on neuropsychological testing. Levels of agreement between definitions were calculated, and associations between super-aging status for each definition and functioning (Bayer ADL score), structural brain imaging measures, and incident dementia were explored. RESULTS: Frequency of super-aging varied between 2.9 and 43.4 percent with more stringent definitions associated with lower frequency. Agreement between different criteria varied from poor (K = 0.04, AC1 = .24) to very good (K = 0.83, AC1 = .91) with better agreement between definitions using similar tests and cutoffs. Super-aging was associated with better functional performance (4.7-11%) and lower rates of incident dementia (hazard ratios 0.08-0.48) for most definitions. Super-aging status was associated with a lower burden of white matter hyperintensities (3.8-33.2%) for all definitions. CONCLUSIONS: The frequency of super-aging is strongly affected by the demographic and neuropsychological testing parameters used. Greater consistency in defining super-aging would enable better characterization of this exceptional minority.

Genetic and environmental influences on fruit and vegetable consumption and depression in older adults.

BACKGROUND: Prior work suggests that higher fruit and vegetable consumption may protect against depression in older adults. Better understanding of the influence of genetic and environmental factors on fruit and vegetable intakes may lead to the design of more effective dietary strategies to increase intakes. In turn this may reduce the occurrence of depression in older adults. OBJECTIVES: The primary aim of this study is to estimate the genetic and environmental influences on the consumption of fruit and vegetables in older adults. The secondary aim is an exploratory analysis into possible shared genetic influences on fruit and vegetable intakes and depression. METHODS: Analysis of observational data from 374 twins (67.1% female; 208 monozygotic (MZ); 166 dizygotic (DZ)) aged ≥ 65 years drawn from the Older Australian Twins Study. Dietary data were obtained using a validated food frequency questionnaire and depressive symptoms were measured using the 15-item short form Geriatric Depression Scale. The contribution of genetic and environmental influences on fruit and vegetable intake were estimated by comparing MZ and DZ twin intakes using structural equation modelling. A tri-variate twin model was used to estimate the genetic and environmental correlation between total fruit and vegetable intakes and depression. RESULTS: In this study, vegetable intake was moderately influenced by genetics (0.39 95%CI 0.22, 0.54). Heritability was highest for brassica vegetables (0.40 95%CI 0.24, 0.54). Overall fruit intake was not significantly heritable. No significant genetic correlations were detected between fruit and vegetable intake and depressive symptoms. CONCLUSIONS: Vegetable consumption, particularly bitter tasting brassica vegetables, was significantly influenced by genetics, although environmental influences were also apparent. Consumption of fruit was only influenced by the environment, with no genetic influence detected, suggesting strategies targeting the food environment may be particularly effective for encouraging fruit consumption.