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.

The protocol for an observational Australian cohort study of CADASIL: The AusCADASIL study.

Introduction: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a rare genetic condition with a broad phenotypic presentation. This study aims to establish the first Australian cohort of individuals affected by CADASIL (AusCADASIL) and examine its clinical features and longitudinal course, and to investigate neuroimaging and blood biomarkers to assist in early diagnosis and identify disease progression. Methods: Participants will be recruited from six study centres across Australia for an observational study of CADASIL. We aim to recruit 150 participants with diagnosed CADASIL, family history of CADASIL or suspected CADASIL symptoms, and 150 cognitively normal NOTCH3 negative individuals as controls. Participants will complete: 1) online questionnaires on medical and family history, mental health, and wellbeing; 2) neuropsychological evaluation; 3) neurological examination and brain MRI; 4) ocular examination and 5) blood sample donation. Participants will have annual follow-up for 4 years to assess their progression and will be asked to invite a study partner to corroborate their self-reported cognitive and functional abilities.Primary outcomes include cognitive function and neuroimaging abnormalities. Secondary outcomes include investigation of genetics and blood and ocular biomarkers. Data from the cohort will contribute to an international consortium, and cohort participants will be invited to access future treatment/health intervention trials. Discussion: AusCADASIL will be the first study of an Australian cohort of individuals with CADASIL. The study will identify common pathogenic variants in this cohort, and characterise the pattern of clinical presentation and longitudinal progression, including imaging features, blood and ocular biomarkers and cognitive profile.

Exploring the link between brain topological resilience and cognitive performance in the context of aging and vascular risk factors: A cross-ethnicity population-based study.

Brain aging is typically associated with a significant decline in cognitive performance. Vascular risk factors (VRF) and subsequent atherosclerosis (AS) play a major role in this process. Brain resilience reflects the brain's ability to withstand external perturbations, but the relationship of brain resilience with cognition during the aging process remains unclear. Here, we investigated how brain topological resilience (BTR) is associated with cognitive performance in the face of aging and vascular risk factors. We used data from two cross-ethnicity community cohorts, PolyvasculaR Evaluation for Cognitive Impairment and Vascular Events (PRECISE, n = 2220) and Sydney Memory and Ageing Study (MAS, n = 246). We conducted an attack simulation on brain structural networks based on k-shell decomposition and node degree centrality. BTR was defined based on changes in the size of the largest subgroup of the network during the simulation process. Subsequently, we explored the negative correlations of BTR with age, VRF, and AS, and its positive correlation with cognitive performance. Furthermore, using structural equation modeling (SEM), we constructed path models to analyze the directional dependencies among these variables, demonstrating that aging, AS, and VRF affect cognition by disrupting BTR. Our results also indicated the specificity of this metric, independent of brain volume. Overall, these findings underscore the supportive role of BTR on cognition during aging and highlight its potential application as an imaging marker for objective assessment of brain cognitive performance.

Risk factors and cognitive correlates of white matter hyperintensities in ethnically diverse populations without dementia: The COSMIC consortium.

INTRODUCTION: White matter hyperintensities (WMHs) are an important imaging marker for cerebral small vessel diseases, but their risk factors and cognitive associations have not been well documented in populations of different ethnicities and/or from different geographical regions. METHODS: We investigated how WMHs were associated with vascular risk factors and cognition in both Whites and Asians, using data from five population-based cohorts of non-demented older individuals from Australia, Singapore, South Korea, and Sweden (N = 1946). WMH volumes (whole brain, periventricular, and deep) were quantified with UBO Detector and harmonized using the ComBat model. We also harmonized various vascular risk factors and scores for global cognition and individual cognitive domains. RESULTS: Factors associated with larger whole brain WMH volumes included diabetes, hypertension, stroke, current smoking, body mass index, higher alcohol intake, and insufficient physical activity. Hypertension and stroke had stronger associations with WMH volumes in Whites than in Asians. No associations between WMH volumes and cognitive performance were found after correction for multiple testing. CONCLUSION: The current study highlights ethnic differences in the contributions of vascular risk factors to WMHs.

Multi-omics and pathway analyses of genome-wide associations implicate regulation and immunity in verbal declarative memory performance.

BACKGROUND: Uncovering the functional relevance underlying verbal declarative memory (VDM) genome-wide association study (GWAS) results may facilitate the development of interventions to reduce age-related memory decline and dementia. METHODS: We performed multi-omics and pathway enrichment analyses of paragraph (PAR-dr) and word list (WL-dr) delayed recall GWAS from 29,076 older non-demented individuals of European descent. We assessed the relationship between single-variant associations and expression quantitative trait loci (eQTLs) in 44 tissues and methylation quantitative trait loci (meQTLs) in the hippocampus. We determined the relationship between gene associations and transcript levels in 53 tissues, annotation as immune genes, and regulation by transcription factors (TFs) and microRNAs. To identify significant pathways, gene set enrichment was tested in each cohort and meta-analyzed across cohorts. Analyses of differential expression in brain tissues were conducted for pathway component genes. RESULTS: The single-variant associations of VDM showed significant linkage disequilibrium (LD) with eQTLs across all tissues and meQTLs within the hippocampus. Stronger WL-dr gene associations correlated with reduced expression in four brain tissues, including the hippocampus. More robust PAR-dr and/or WL-dr gene associations were intricately linked with immunity and were influenced by 31 TFs and 2 microRNAs. Six pathways, including type I diabetes, exhibited significant associations with both PAR-dr and WL-dr. These pathways included fifteen MHC genes intricately linked to VDM performance, showing diverse expression patterns based on cognitive status in brain tissues. CONCLUSIONS: VDM genetic associations influence expression regulation via eQTLs and meQTLs. The involvement of TFs, microRNAs, MHC genes, and immune-related pathways contributes to VDM performance in older individuals.

Critical periods for cognitive reserve building activities for late life global cognition and cognitive decline: the Sydney memory and aging cohort study.

Cognitive, social, and physical activities, collectively linked to cognitive reserve, are associated with better late-life cognitive outcomes. To better understand the building of cognitive reserve, we investigated which of these activities, during which stages of life, had the strongest associations with late-life cognitive performance. From the Sydney Memory and Aging Study, 546 older Australians, who were community-dwelling and without a dementia diagnosis at recruitment (Mage 80.13 years, 52.2% female), were asked about their engagement in social, physical, and cognitive activities throughout young adulthood (YA), midlife (ML), and late-life (LL). Comprehensive neuropsychological testing administered biennially over 6 years measured baseline global cognition and cognitive decline. In our study, YA, but not ML nor LL, cognitive activity was significantly associated with late-life global cognition (ß = 0.315, p < .001). A follow-up analysis pointed to the formal education component of the YA cognitive activity measure, rather than YA cognitive leisure activities, as a significant predictor of better late-life global cognition (ß = 0.146, p = .003). YA social activity and LL cognitive activity were significantly associated with less cognitive decline (ß = 0.023, p < .001, and ß = 0.016, p = .022, respectively). Physical activity was not found to be associated with global cognition or cognitive decline. Overall, YA cognitive activity was associated with better late-life cognition, and YA social and LL cognitive activities were associated with less cognitive decline. Formal education emerges as the key contributor in the association between YA cognitive activity and late-life global cognition.

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.

Risk factors and cognitive correlates of white matter hyperintensities in ethnically diverse populations without dementia: the COSMIC consortium.

INTRODUCTION: White matter hyperintensities (WMH) are an important imaging marker for cerebral small vessel diseases, but their risk factors and cognitive associations have not been well-documented in populations of different ethnicities and/or from different geographical regions. METHOD: Magnetic resonance imaging data of five population-based cohorts of non-demented older individuals from Australia, Singapore, South Korea, and Sweden (N = 1,946) were examined for WMH and their associations with vascular risk factors and cognition. RESULT: Factors associated with larger whole brain WMH volumes included diabetes, hypertension, stroke, current smoking, body mass index, higher alcohol intake and insufficient physical activity. Participants with moderate or higher physical activity had less WMH than those who never exercised, but the former two groups did not differ. Hypertension and stroke had stronger associations with WMH volumes in the White, compared to Asian subsample. DISCUSSION: The current study highlighted the ethnic differences in the contributions of vascular risk factors to WMH.

Enhancing precision of the Telephone Interview for Cognitive Status-Modified (TICS-M) using the Rasch model.

The Telephone Interview for Cognitive Status-modified (TICS-M) is a well-established and widely used screening instrument for dementia and assessment of global cognitive function in older people. This study aimed to evaluate the psychometric properties of the TICS-M and to enhance the accuracy of the instrument using Rasch methodology. Partial Credit Rasch model was applied to the TICS-M scores. The sample selected for Rasch analysis consisted of 432 participants aged 70-90 years (M = 78.85, SD = 4.73) including 195 males (237 females), and 132 (30.56%) of whom were diagnosed with dementia after the baseline assessment. Initial analysis indicated good reliability of the TICS-M assessment scores, but there were three misfitting items and local dependency issues. Combining locally dependent and misfitting items into super-items achieved the best Rasch model fit for the TICS-M. This modification improved reliability of the assessment scores and resulted in no misfitting items, no local dependency, strict unidimensionality, and invariance across individual factors such as participants age, sex, diagnosis, and in-person neuropsychological assessment scores. Satisfying Rasch model expectations allowed for creation of a transformation table to convert raw TICS-M scores into interval-level data, which improves precision of the instrument. In summary, the TICS-M assessment scores demonstrated excellent reliability as reflected by Person Separation Index (PSI = 0.86) and met expectations of the unidimensional Rasch model after minor adjustments. The ordinal-to-interval transformation table can be used to increase accuracy of the TICS-M without altering its current format. These findings contribute to more accurate assessments of cognitive decline in older people and screening for conditions such as dementia. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Parental history of dementia and the risk of dementia: A cross-sectional analysis of a global collaborative study.

BACKGROUND: Parental history of dementia appears to increase the risk of dementia, but there have been inconsistent results. We aimed to investigate whether the association between parental history of dementia and the risk of dementia are different by dementia subtypes and sex of parent and offspring. METHODS: For this cross-sectional study, we harmonized and pooled data for 17,194 older adults from nine population-based cohorts of eight countries. These studies conducted face-to-face diagnostic interviews, physical and neurological examinations, and neuropsychological assessments to diagnose dementia. We investigated the associations of maternal and paternal history of dementia with the risk of dementia and its subtypes in offspring. RESULTS: The mean age of the participants was 72.8 ± 7.9 years and 59.2% were female. Parental history of dementia was associated with higher risk of dementia (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.15-1.86) and Alzheimer's disease (AD) (OR = 1.72, 95% CI = 1.31-2.26), but not with the risk of non-AD. This was largely driven by maternal history of dementia, which was associated with the risk of dementia (OR = 1.51, 95% CI = 1.15-1.97) and AD (OR = 1.80, 95% CI = 1.33-2.43) whereas paternal history of dementia was not. These results remained significant when males and females were analyzed separately (OR = 2.14, 95% CI = 1.28-3.55 in males; OR = 1.68, 95% CI = 1.16-2.44 for females). CONCLUSIONS: Maternal history of dementia was associated with the risk of dementia and AD in both males and females. Maternal history of dementia may be a useful marker for identifying individuals at higher risk of AD and stratifying the risk for AD in clinical trials.

Network of mental activities, cognitive function and depression in older men and women.

BACKGROUND: Evidence suggests that lifestyle activities impact cognitive and mental health in older populations. However, how lifestyle factors are associated with one another, and which factors are most important for cognitive function and mental health has received comparatively little attention. DESIGN: Bayesian-Gaussian network analysis was used to investigate unique associations between mental activities (MA; i.e., activities involving cognitive engagement), global cognition, and depression at three time-points in a large sample of older adults (baseline, 2 years, and 4 years follow-up). SETTING: This study used longitudinal data from participants living in Australia and participating in the Sydney Memory and Ageing Study. PARTICIPANTS: The sample included 998 participants (55% female) aged between 70 and 90, without a diagnosis of dementia at baseline. MEASUREMENTS: Neuropsychological assessment of global cognition, self-reported depressive symptoms, and self-reported information about daily MA. RESULTS: Cognitive functioning was positively associated with playing tabletop games and using the internet in both sexes at all time-points. MA were differentially linked in men and women. Depression was not consistently associated with MA in men across the three time-points; women who visited artistic events consistently had lower depression scores. CONCLUSIONS: Engaging with tabletop games and using the internet was associated with better cognition in both sexes, however sex acted as a modifier for other associations. These findings are useful for future investigations that consider interactive associations between MA, cognition, and mental health in older adults, and their possible roles in promoting healthy aging.

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.

Longitudinal changes in participant and informant reports of subjective cognitive complaints are associated with dementia risk.

Background: Individuals with subjective cognitive complaints (SCCs) are at an increased risk of dementia. Questions remain about participant-reported versus informant-reported SCCs as indicators of future dementia and about longitudinal changes in participant-and informant-reported SCCs and risk of incident dementia. Method: Participants were 873 older adults (M = 78.65-years; 55% female) and 849 informants from the Sydney Memory and Ageing Study. Comprehensive assessments occurred biennially, and clinical diagnoses were made by expert consensus for 10-years. SCCs were participants' and informants' responses to a single binary question concerning their/the participant's memory decline (Yes/No) over the first 6-years. Categorical latent growth curve analyses, using the logit transformation, were used to model SCC change over time. Associations of initial propensity to report SCCs at baseline, and change in propensity to report SCCs over time, with dementia risk were examined using Cox regression. Results: 70% of participants reported SCCs at baseline, with a proportional increase in the odds of reporting by 11% for each additional year in the study. In contrast, 22% of informants reported SCCs at baseline, with a proportional increase by 30% in the odds of reporting per year. Participants' initial level of (p = 0.007), but not change in SCC reporting (p = 0.179), was associated with risk of dementia controlling for all covariates. Both informants' initial level of (p < 0.001), and change in (p < 0.001), SCCs significantly predicted incident dementia. When modelled together, informants' initial level of, and change in, SCCs were still independently associated with increased dementia risk (p's < 0.001). Conclusion: These data suggest that informants' initial impressions, and increased reporting, of SCCs appear to be uniquely prognostic of future dementia compared to participants', even based on a single SCC question.

Correlates of Gait Speed Among Older Adults From 6 Countries: Findings From the COSMIC Collaboration.

BACKGROUND: Few studies have compared gait speed and its correlates among different ethnogeographic regions. The goals of this study were to describe usual and rapid gait speed, and identify their correlates across Australian, Asian, and African countries. METHODS: We used data from 6 population-based cohorts of adults aged 65+ from 6 countries and 3 continents (N = 6 472), with samples ranging from 231 to 1 913. All cohorts are members of the Cohort Studies of Memory in an International Consortium collaboration. We investigated whether clinical (body mass index [BMI], hypertension, stroke, apolipoprotein status), psychological (cognition, mood, general health), and behavioral factors (smoking, drinking, physical activity) correlated with usual (N = 4 cohorts) and rapid gait speed (N = 3 cohorts) similarly across cohorts. Regression models were controlled for age, sex, and education, and were sex-stratified. RESULTS: Age- and sex-standardized usual gait speed means ranged from 0.61 to 1.06 m/s and rapid gait speed means ranged from 1.16 to 1.64 m/s. Lower BMI and better cognitive function consistently correlated with faster gait speed in all cohorts. Less consistently, not having hypertension and greater physical activity engagement were associated with faster gait speed. Associations with mood, smoking, and drinking were largely nonsignificant. These patterns were not attenuated by demographics. There was limited evidence that the associations differed by sex, except physical activity, where the greater intensity was associated with usual gait among men but not women. CONCLUSIONS: This study is among the first to describe the usual and rapid gait speeds across older adults in Africa, Asia, and Australia.

Establishing conversion of the 16-item Informant Questionnaire on Cognitive Decline in the Elderly scores into interval-level data across multiple samples using Rasch methodology.

BACKGROUND: The 16-item Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE-16) is a well-validated and widely-used measure of cognitive changes (CCs) among older adults. This study aimed to use Rasch methodology to establish psychometric properties of the IQCODE-16 and validate the existing ordinal-to-interval transformation algorithms across multiple large samples. METHODS: A Partial Credit Rasch model was employed to examine psychometric properties of the IQCODE-16 using data (n = 918) from two longitudinal studies of participants aged 57-99 years: the Older Australian Twins Study (n = 450) and the Canberra Longitudinal Study (n = 468), and reusing the Sydney Memory and Ageing Study (MAS) sample (n = 400). RESULTS: Initial analyses indicated good reliability for the IQCODE-16 (Person Separation Index range: 0.82-0.90). However, local dependency was identified between items, with several items showing misfit to the model. Replicating the existing Rasch solution could not reproduce the best Rasch model fit for all samples. Combining locally dependent items into three testlets resolved all misfit and local dependency issues and resulted in the best Rasch model fit for all samples with evidence of unidimensionality, strong reliability, and invariance across person factors. Accordingly, new ordinal-to-interval transformation algorithms were produced to convert the IQCODE-16 ordinal scores into interval data to improve the accuracy of its scores. CONCLUSIONS: The findings of this study support the reliability and validity of the IQCODE-16 in measuring CCs among older adults. New ordinal-to-interval conversion tables generated using samples from multiple independent datasets are more generalizable and can be used to enhance the precision of the IQCODE-16 without changing its original format. An easy-to-use converter has been made available for clinical and research use.

Prospective Memory Function Predicts Future Cognitive Decline and Incident Dementia.

OBJECTIVES: This study aimed to test whether prospective memory (PM) was an early cognitive marker of future cognitive decline and incident dementia using longitudinal data spanning 8 years from the Sydney Memory and Ageing Study. METHODS: At baseline, 121 participants aged 72-91 years were tested in PM using a validated PM task, Virtual Week, which included time- and event-based tasks presented with varying regularity. Responses were scored "Correct" if completed accurately and "Missed" if the target was not remembered at any time. Measures of cognition were taken at baseline and 2-year intervals over 8 years. Dementia diagnoses were made by expert consensus panels using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria. Linear mixed models and Cox proportional hazards regression models were used to analyze the data, controlling for potential confounds. RESULTS: Both decreased PM accuracy and missed PM responses were associated with rate of cognitive decline measured by Mini-Mental State Examination over 8 years and global cognitive decline over 4 years. Risk of incident dementia increased with poorer baseline PM ability and missed responses. These effects remained significant after controlling for baseline cognition and were strongest for event-based and regular PM tasks. DISCUSSION: PM is a sensitive early marker of future cognitive decline and risk of incident dementia. PM tasks supported by spontaneous retrieval (event-based) and those with lower retrospective memory demands (regular tasks) function as particularly sensitive predictors. In other words, deficits in performing less effortful PM tasks best predicted cognitive decline. These findings may encourage clinicians to incorporate PM tasks in clinical assessments.

Aging Is Associated With Multidirectional Changes in Social Cognition: Findings From an Adult Life-Span Sample Ranging From 18 to 101 Years.

OBJECTIVES: Normal adult aging is associated with changes in social cognition. Although 4 social cognitive domains have been identified (social perception, theory of mind [ToM], affective empathy, and social behavior), no study has tested all 4 domains concurrently in a life-span sample, limiting understanding of the relative magnitude of age-related changes across domains. This study addresses this gap by providing the first assessment of all 4 social cognitive domains in an adult life-span sample. METHODS: Three hundred and seventy-two participants ranging from 18 to 101 years of age took part in this study. Participants completed a testing battery that assessed social perception, ToM, affective empathy, and social behavior, as well as broader cognitive function and well-being. RESULTS: The results showed that adult aging is associated with multidirectional changes in social cognitive abilities, with ToM and social perception showing nonlinear decline across much of the life-span, and affective empathy and social behavior showing improvement. Age remained a significant predictor of all 4 social cognitive domains, even after accounting for broader cognitive function. Weak associations emerged between some of the social cognitive abilities and and indices of broader well-being. DISCUSSION: These findings provide novel and important evidence that normative aging is associated with both gains and losses in social cognition that occur at distinct points of the adult life-span, and that are at least partially independent of general age-related cognitive decline.

Cognition, function, and prevalent dementia in centenarians and near-centenarians: An individual participant data (IPD) meta-analysis of 18 studies.

INTRODUCTION: There are limited data on prevalence of dementia in centenarians and near-centenarians (C/NC), its determinants, and whether the risk of dementia continues to rise beyond 100. METHODS: Participant-level data were obtained from 18 community-based studies (N = 4427) in 11 countries that included individuals ≥95 years. A harmonization protocol was applied to cognitive and functional impairments, and a meta-analysis was performed. RESULTS: The mean age was 98.3 years (SD = 2.67); 79% were women. After adjusting for age, sex, and education, dementia prevalence was 53.2% in women and 45.5% in men, with risk continuing to increase with age. Education (OR 0.95;0.92-0.98) was protective, as was hypertension (odds ratio [OR] 0.51;0.35-0.74) in five studies. Dementia was not associated with diabetes, vision and hearing impairments, smoking, and body mass index (BMI). DISCUSSION: Among the exceptional old, dementia prevalence remains higher in the older participants. Education was protective against dementia, but other factors for dementia-free survival in C/NC remain to be understood.

Measuring Empathy Across the Adult Lifespan: A Comparison of Three Assessment Types.

Empathy is a core component of social cognition that can be indexed via behavioral, informant-report, or self-report methods of assessment. However, concerns have been raised regarding the lack of convergence between these assessment approaches for cognitive empathy. Here, we provided the first comparison of all three measurement approaches for cognitive and affective empathy in a large adult sample (N = 371) aged 18 to 101 years. We found that poor convergence was more of a problem for cognitive empathy than affective empathy. While none of the cognitive empathy measures correlated with each other, for affective empathy, self-report was significantly associated with both behavioral and informant-report assessments. However, for both cognitive and affective empathy, there was evidence for poor discriminant validity within the measures. Out of the three assessment approaches, only the informant-report measures were consistently associated with indices of social functioning. Importantly, age did not moderate any of the tested relationships, indicating that both the strengths and the limitations of these different types of assessment do not appear to vary as a function of age. These findings highlight the variation that exists among empathy measures and are discussed in relation to their practical implications for the assessment of empathy.

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.