Poor mobility and lower limb weakness are associated with three distinct depressive symptom trajectories over 6 years in older people.

OBJECTIVES: Physical decline can be associated with the onset of depressive symptoms in later life. This study aimed to identify physical and lifestyle risk factors for depressive symptom trajectories in community-dwelling older adults. METHODS: Participants were 553 people aged 70-90 years who underwent baseline physical, psychological and lifestyle assessments. Group-based trajectory analysis was used to identify patterns of depressive symptom development over 6 years of follow-up. Strengths of associations between baseline functional test performances and depressive symptom trajectories were evaluated with univariable ordinal models. Subsequently, the adjusted cumulative odds ratio for the association between identified risk factors, demographic factors and baseline anti-depressant use were measured using multivariable ordinal logistic regression. RESULTS: Three distinct depressive symptom trajectories were identified: a low-and-stable course (10% of participants), a low-and-increasing course (81%) and a moderate-and-increasing course (9%). Timed Up and Go test time was the strongest risk factor of depressive symptom trajectory, followed by Five Times Sit-to-Stand test performance, planned physical activity levels, and knee extension strength (adjusted standardised ORs 1.65, 95% CI 1.34-2.04; 1.44, 95% CI 1.16-1.77; 1.44, 95% CI 1.17-1.76 and 1.41, 95% CI 1.15-1.73 respectively). After adjusting for age, sex, body mass index and baseline anti-depressant use, Timed Up and Go test performance and knee extension strength were independently and significantly associated with depressive trajectories. CONCLUSIONS: Timed Up and Go test times, Five Times Sit-to-Stand test performance, planned physical activity levels and knee extension strength are associated with three discrete depressive symptom trajectories. These clinical tests may help identify older adults aged 70-90 years at risk of developing depressive symptoms and help guide subsequent strength and mobility interventions.

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.

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.

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.

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.

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).

Social connections and risk of incident mild cognitive impairment, dementia, and mortality in 13 longitudinal cohort studies of ageing.

INTRODUCTION: Previous meta-analyses have linked social connections and mild cognitive impairment, dementia, and mortality. However, these used aggregate data from North America and Europe and examined a limited number of social connection markers. METHODS: We used individual participant data (N = 39271, Mage  = 70.67 (40-102), 58.86% female, Meducation  = 8.43 years, Mfollow-up  = 3.22 years) from 13 longitudinal ageing studies. A two-stage meta-analysis of Cox regression models examined the association between social connection markers with our primary outcomes. RESULTS: We found associations between good social connections structure and quality and lower risk of incident mild cognitive impairment (MCI); between social structure and function and lower risk of incident dementia and mortality. Only in Asian cohorts, being married/in a relationship was associated with reduced risk of dementia, and having a confidante was associated with reduced risk of dementia and mortality. DISCUSSION: Different aspects of social connections - structure, function, and quality - are associated with benefits for healthy aging internationally. HIGHLIGHTS: Social connection structure (being married/in a relationship, weekly community group engagement, weekly family/friend interactions) and quality (never lonely) were associated with lower risk of incident MCI. Social connection structure (monthly/weekly friend/family interactions) and function (having a confidante) were associated with lower risk of incident dementia. Social connection structure (living with others, yearly/monthly/weekly community group engagement) and function (having a confidante) were associated with lower risk of mortality. Evidence from 13 longitudinal cohort studies of ageing indicates that social connections are important targets for reducing risk of incident MCI, incident dementia, and mortality. Only in Asian cohorts, being married/in a relationship was associated with reduced risk of dementia, and having a confidante was associated with reduced risk of dementia and mortality.

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.

Measuring distress in older population: Rasch analysis of the Kessler Psychological Distress Scale.

OBJECTIVES: The 10-item Kessler Psychological Distress Scale (K-10) is a widely applied distress measure; however, its psychometric properties were not established with older populations using advanced methodology. The aim of this study was to examine psychometric properties of the K-10 through application of Rasch methodology and if possible, develop an ordinal-to-interval conversion to improve its reliability in older populations. METHOD: The Partial Credit Rasch Model was applied to analyse K-10 scores of the sample including 490 participants (56.3 % females) aged 70 to 90 years and without dementia from the Sydney Memory and Ageing Study (MAS). RESULTS: The initial analysis of the K-10 showed poor reliability and significant deviation from the expectations of the Rasch model. The best model fit was evident after correcting disordered thresholds and creating two testlet models to address local dependency between items (χ2(35) = 29.87, p = 0.71). The modified K-10 demonstrated strict unidimensionality, enhanced reliability and scale invariance across personal factors, such as sex, age, and education and permitted development of ordinal-to-interval transformation algorithms. LIMITATIONS: Ordinal-to-interval conversion can only be applied for older adults with complete data. CONCLUSIONS: The K-10 satisfied principles of fundamental measurement defined by Rasch model after minor modifications. Clinicians and researchers can transform K-10 raw scores into interval-level data using converging algorithms published here without altering the original scale response format, which increases reliability of the K-10.

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.

Sex differences in dementia risk and risk factors: Individual-participant data analysis using 21 cohorts across six continents from the COSMIC consortium.

INTRODUCTION: Sex differences in dementia risk, and risk factor (RF) associations with dementia, remain uncertain across diverse ethno-regional groups. METHODS: A total of 29,850 participants (58% women) from 21 cohorts across six continents were included in an individual participant data meta-analysis. Sex-specific hazard ratios (HRs), and women-to-men ratio of hazard ratios (RHRs) for associations between RFs and all-cause dementia were derived from mixed-effect Cox models. RESULTS: Incident dementia occurred in 2089 (66% women) participants over 4.6 years (median). Women had higher dementia risk (HR, 1.12 [1.02, 1.23]) than men, particularly in low- and lower-middle-income economies. Associations between longer education and former alcohol use with dementia risk (RHR, 1.01 [1.00, 1.03] per year, and 0.55 [0.38, 0.79], respectively) were stronger for men than women; otherwise, there were no discernible sex differences in other RFs. DISCUSSION: Dementia risk was higher in women than men, with possible variations by country-level income settings, but most RFs appear to work similarly in women and men.

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.

The Heritability of Subjective Cognitive Complaints in Older Australian Twins.

BACKGROUND: Subjective cognitive complaints (SCCs) may be a precursor to mild cognitive impairment (MCI) and dementia. OBJECTIVE: This study aimed to examine the heritability of SCCs, correlations between SCCs and memory ability, and the influence of personality and mood on these relationships. METHODS: Participants were 306 twin pairs. The heritability of SCCs and the genetic correlations between SCCs and memory performance, personality, and mood scores were determined using structural equation modelling. RESULTS: SCCs were low to moderately heritable. Memory performance, personality and mood were genetically, environmentally, and phenotypically correlated with SCCs in bivariate analysis. However, in multivariate analysis, only mood and memory performance had significant correlations with SCCs. Mood appeared to be related to SCCs by an environmental correlation, whereas memory performance was related to SCCs by a genetic correlation. The link between personality and SCCs was mediated by mood. SCCs had a significant amount of both genetic and environmental variances not explained by memory performance, personality, or mood. CONCLUSION: Our results suggest that SCCs are influenced both by a person's mood and their memory performance, and that these determinants are not mutually exclusive. While SCCs had genetic overlap with memory performance and environmental association with mood, much of the genetic and environmental components that comprised SCCs were specific to SCCs, though these specific factors are yet to be determined.

The role of dyadic cognitive report and subjective cognitive decline in early ADRD clinical research and trials: Current knowledge, gaps, and recommendations.

Efficient identification of cognitive decline and Alzheimer's disease (AD) risk in early stages of the AD disease continuum is a critical unmet need. Subjective cognitive decline is increasingly recognized as an early symptomatic stage of AD. Dyadic cognitive report, including subjective cognitive complaints (SCC) from a participant and an informant/study partner who knows the participant well, represents an accurate, reliable, and efficient source of data for assessing risk. However, the separate and combined contributions of self- and study partner report, and the dynamic relationship between the two, remains unclear. The Subjective Cognitive Decline Professional Interest Area within the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment convened a working group focused on dyadic patterns of subjective report. Group members identified aspects of dyadic-report information important to the AD research field, gaps in knowledge, and recommendations. By reviewing existing data on this topic, we found evidence that dyadic measures are associated with objective measures of cognition and provide unique information in preclinical and prodromal AD about disease stage and progression and AD biomarker status. External factors including dyad (participant-study partner pair) relationship and sociocultural factors contribute to these associations. We recommend greater dyad report use in research settings to identify AD risk. Priority areas for future research include (1) elucidation of the contributions of demographic and sociocultural factors, dyad type, and dyad relationship to dyad report; (2) exploration of agreement and discordance between self- and study partner report across the AD syndromic and disease continuum; (3) identification of domains (e.g., memory, executive function, neuropsychiatric) that predict AD risk outcomes and differentiate cognitive impairment due to AD from other impairment; (4) development of best practices for study partner engagement; (5) exploration of study partner report as AD clinical trial endpoints; (6) continued development, validation, and optimization, of study partner report instruments tailored to the goals of the research and population.

Associations between social connections and cognition: a global collaborative individual participant data meta-analysis.

BACKGROUND: Poor social connections (eg, small networks, infrequent interactions, and loneliness) are modifiable risk factors for cognitive decline. Existing meta-analyses are limited by reporting aggregate responses, a focus on global cognition, and combining social measures into single constructs. We aimed to investigate the association between social connection markers and the rate of annual change in cognition (ie, global and domain-specific), as well as sex differences, using an individual participant data meta-analysis. METHODS: We harmonised data from 13 longitudinal cohort studies of ageing in North America, South America, Europe, Africa, Asia, and Australia. Studies were eligible for inclusion if they had baseline data for social connection markers and at least two waves of cognitive scores. Follow-up periods ranged from 0 years to 15 years across cohorts. We included participants with cognitive data for at least two waves and social connection data for at least one wave. We then identified and excluded people with dementia at baseline. Primary outcomes were annual rates of change in global cognition and cognitive domain scores over time until final follow-up within each cohort study analysed by use of an individual participant data meta-analysis. Linear mixed models within cohorts used baseline social connection markers as predictors of the primary outcomes. Effects were pooled in two stages using random-effects meta-analyses. We assessed the primary outcomes in the main (partially adjusted) and fully adjusted models. Partially adjusted models controlled for age, sex, and education; fully adjusted models additionally controlled for diabetes, hypertension, smoking, cardiovascular risk, and depression. FINDINGS: Of the 40 006 participants in the 13 cohort studies, we excluded 1392 people with dementia at baseline. 38 614 individual participants were included in our analyses. For the main models, being in a relationship or married predicted slower global cognitive decline (b=0·010, 95% CI 0·000-0·019) than did being single or never married; living with others predicted slower global cognitive (b=0·007, 0·002-0·012), memory (b=0·017, 0·006-0·028), and language (b=0·008, 0·000-0·015) decline than did living alone; and weekly interactions with family and friends (b=0·016, 0·006-0·026) and weekly community group engagement (b=0·030, 0·007-0·052) predicted slower memory decline than did no interactions and no engagement. Never feeling lonely predicted slower global cognitive (b=0·047, 95% CI 0·018-0·075) and executive function (b=0·047, 0·017-0·077) decline than did often feeling lonely. Degree of social support, having a confidante, and relationship satisfaction did not predict cognitive decline across global cognition or cognitive domains. Heterogeneity was low (I2=0·00-15·11%) for all but two of the significant findings (association between slower memory decline and living with others [I2=58·33%] and community group engagement, I2=37·54-72·19%), suggesting robust results across studies. INTERPRETATION: Good social connections (ie, living with others, weekly community group engagement, interacting weekly with family and friends, and never feeling lonely) are associated with slower cognitive decline. FUNDING: EU Joint Programme-Neurodegenerative Disease Research grant, funded by the National Health and Medical Research Council Australia, and the US National Institute on Aging of the US National Institutes of Health.

Instrumental Activities of Daily Living by Subjective and Objective Measures: The Impact of Depression and Personality.

Objective: Previous research shows that depression and personality are independently associated with self- and informant-reports of the ability to perform instrumental activities of daily living (IADLs). However, less is known about the association between depression and personality and performance-based measures of IADLs. We aimed to determine how depression and personality predict self-and informant-reports of IADL compared to performance-based measures of IADLs in a sample of older adults with normal cognition (NC) and Mild Cognitive Impairment (MCI). Methods: Participants consisted of 385 older adults with NC (n = 235), or a diagnosis of MCI (n = 150), aged between 76 and 99-years from the Sydney Memory and Ageing Study. Participants underwent comprehensive neuropsychological and clinical assessments to determine global cognition and clinical diagnoses. Personality traits were measured by the NEO Five-Factor Inventory (NEO-FFI) and depression by the Geriatric Depression Scale (GDS). Subjective IADLs were self- and informant-reported Bayer Activities of Daily Living (B-ADL) scales and objective IADL was the Sydney Test of Activities of Daily Living in Memory Disorders (STAM). Linear regressions examined the relationship between depression and personality and the three types of IADL measures, controlling for all covariates and global cognition. Results: Participant-reported IADL, although associated with global cognition, was more strongly associated with GDS and NEO-FFI scores (conscientiousness and neuroticism). Informant-reported IADL was strongly associated with both global cognition and participants' GDS scores. STAM scores were not associated with participants' GDS or NEO-FFI scores; instead, they were predicted by demographics and global cognition. Conclusion: These results suggest that performance-based measures of IADL may provide more objective and reliable insight into an individual's underlying functional ability and are less impacted by the participants' mood and personality compared to subjectively reported IADL. We argue that performance-based IADL measures are preferable when trying to accurately assess everyday functional ability and its relationship to cognitive status. Where performance-based measures are not available (e.g., in some clinical settings), informant ratings should be sought as they are less influenced by the participant's personality and mood compared to self-reports.

Polygenic resilience scores capture protective genetic effects for Alzheimer's disease.

Polygenic risk scores (PRSs) can boost risk prediction in late-onset Alzheimer's disease (LOAD) beyond apolipoprotein E (APOE) but have not been leveraged to identify genetic resilience factors. Here, we sought to identify resilience-conferring common genetic variants in (1) unaffected individuals having high PRSs for LOAD, and (2) unaffected APOE-ε4 carriers also having high PRSs for LOAD. We used genome-wide association study (GWAS) to contrast "resilient" unaffected individuals at the highest genetic risk for LOAD with LOAD cases at comparable risk. From GWAS results, we constructed polygenic resilience scores to aggregate the addictive contributions of risk-orthogonal common variants that promote resilience to LOAD. Replication of resilience scores was undertaken in eight independent studies. We successfully replicated two polygenic resilience scores that reduce genetic risk penetrance for LOAD. We also showed that polygenic resilience scores positively correlate with polygenic risk scores in unaffected individuals, perhaps aiding in staving off disease. Our findings align with the hypothesis that a combination of risk-independent common variants mediates resilience to LOAD by moderating genetic disease risk.

Networks of inflammation, depression, and cognition in aging males and females.

BACKGROUND: Prioritizing the maintenance of healthy cognitive aging and personalizing preventive interventions to enhance their effectiveness is crucial as the global population ages. Systemic inflammation and depression in older people have been associated with decreased levels of cognition but results have been inconsistent. AIMS: To explore the interactive network of inflammation, depression and cognition by sex in older people. METHODS: We used novel network analysis to explore the unique associations between inflammatory biomarkers, depression, cognition, and somatic, genetic, and lifestyle risk factors in an older (aged 70-90 years), non-demented, community-dwelling sample from the longitudinal Sydney Memory and Aging Study (N = 916) at baseline and at a two-year follow-up. RESULTS: The networks of biomarkers, depression, cognition, and relevant covariates were significantly different between males and females. A stable negative link between depression and cognition was found in females only; a stable positive association between biomarker interleukin-6 and depression was found in females only; and a stable positive association between biomarker interleukin-8 and alcohol was found in females only. For both males and females, a stable, positive relationship was found between the presence of APOE-ε4 gene and biomarker C-reactive protein; between education and cognition; and between biomarker interleukin-6 and all other biomarkers. CONCLUSIONS: These findings suggest different psychophysiological mechanisms underlie the interactive network of biomarkers, depression and cognition in males and females that should be considered when designing personalized preventive interventions to maintain cognitively healthy aging.