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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 (M age 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 ( β = 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 ( β = 0.146, p  = .003). YA social activity and LL cognitive activity were significantly associated with less cognitive decline ( β = 0.023, p  < .001, and β =  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.

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 (χ 2 (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., Competing Interests: Conflict of interest The authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

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.

BackgroundWith no effective treatments for cognitive decline or dementia, improving the evidence base for modifiable risk factors is a research priority. This study investigated associations between risk factors and late-life cognitive decline on a global scale, including comparisons between ethno-regional groups.Methods and findingsWe harmonized longitudinal data from 20 population-based cohorts from 15 countries over 5 continents, including 48,522 individuals (58.4% women) aged 54-105 (mean = 72.7) years and without dementia at baseline. Studies had 2-15 years of follow-up. The risk factors investigated were age, sex, education, alcohol consumption, anxiety, apolipoprotein E ε4 allele (APOE*4) status, atrial fibrillation, blood pressure and pulse pressure, body mass index, cardiovascular disease, depression, diabetes, self-rated health, high cholesterol, hypertension, peripheral vascular disease, physical activity, smoking, and history of stroke. Associations with risk factors were determined for a global cognitive composite outcome (memory, language, processing speed, and executive functioning tests) and Mini-Mental State Examination score. Individual participant data meta-analyses of multivariable linear mixed model results pooled across cohorts revealed that for at least 1 cognitive outcome, age (B = -0.1, SE = 0.01), APOE*4 carriage (B = -0.31, SE = 0.11), depression (B = -0.11, SE = 0.06), diabetes (B = -0.23, SE = 0.10), current smoking (B = -0.20, SE = 0.08), and history of stroke (B = -0.22, SE = 0.09) were independently associated with poorer cognitive performance (p < 0.05 for all), and higher levels of education (B = 0.12, SE = 0.02) and vigorous physical activity (B = 0.17, SE = 0.06) were associated with better performance (p < 0.01 for both). Age (B = -0.07, SE = 0.01), APOE*4 carriage (B = -0.41, SE = 0.18), and diabetes (B = -0.18, SE = 0.10) were independently associated with faster cognitive decline (p < 0.05 for all). Different effects between Asian people and white people included stronger associations for Asian people between ever smoking and poorer cognition (group by risk factor interaction: B = -0.24, SE = 0.12), and between diabetes and cognitive decline (B = -0.66, SE = 0.27; p < 0.05 for both). Limitations of our study include a loss or distortion of risk factor data with harmonization, and not investigating factors at midlife.ConclusionsThese results suggest that education, smoking, physical activity, diabetes, and stroke are all modifiable factors associated with cognitive decline. If these factors are determined to be causal, controlling them could minimize worldwide levels of cognitive decline. However, any global prevention strategy may need to consider ethno-regional differences.

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. [ABSTRACT FROM AUTHOR]

Background: While midlife hypertension is deleterious, late-life hypertension has been associated with better cognitive outcomes in several studies. Many questions remain, including the relative benefit or harm of a blood pressure (BP) target and antihypertensive therapy of <120 in very old individuals. Methods: The Sydney Memory and Aging Study (n = 1015) comprises a cohort of 70- to 90-year-olds, who were followed biennially for 8 years. Global cognition was assessed with a battery of 10 neuropsychological tests. Blood pressure was measured at Waves 1 and 2 and classified into 3 systolic groupings: group 1 (≤120 mmHg), group 2 (121–140 mmHg), and group 3 (>140 mmHg). Multiple regression, linear mixed modeling, and Cox regression examined the effect of BP and antihypertensives. Results: There were no overall significant differences in global cognition or dementia between the disparate BP groups. However, in those not taking antihypertensives, the systolic BP (SBP) > 140 mmHg group had a significantly worse global cognitive trajectory compared to SBP ≤ 120 mmHg (b = −0.067, 95% CI [−0.129, −0.006], p = .030). Within the SBP ≤ 120 mmHg group those taking antihypertensives had significantly worse global cognition trajectories compared to those not taking antihypertensives even when controlling for past history of hypertension (b = −0.077, 95% CI [−0.147, −0.007], p = .030). Conclusions: Untreated hypertension in old age is related to worse global cognitive decline. However, ongoing treatment at new recommendations of lower SBP targets may be related to poorer cognitive decline and should be considered carefully in older populations. [ABSTRACT FROM AUTHOR]

Background: The Reading the Mind in the Eyes test (RMET) is a 36-item assessment for theory of mind (ToM) performance. While this measure has been shown to be sensitive to age-related ToM difficulties, there are no established cutoffs or guidelines currently available that are specific to older adults. This article seeks to validate a short-form version of the RMET appropriate for use in such populations.Methods: Cross-sectional data from 295 participants (mean age 86 years) from the Sydney Memory and Ageing Study, a longitudinal community observational cohort. Participants underwent an assessment battery that included the RMET. Individuals who scored >1SD below the RMET scores of cognitively normal participants were deemed to have below average RMET scores. Various model-building methods were used to generate short-form solutions of the RMET, which were compared with previously validated versions in their predictive power for below average full RMET performance.Results: Individuals with below average RMET performance tended to be older and have poorer global cognition. Of the eight short-form solutions, the 21-item version generated using genetic algorithm exhibited the best classification performance with an area under the receiver operating curve (AUROC) of 0.98 and had 93.2% accuracy in classifying individuals with below average ToM. A shorter 10-item solution derived by ant colony optimization also had acceptable performance.Conclusion: We recommend the 21-item version of the RMET for use in older adult populations for identifying individuals with impaired ToM. Where an even shorter version is needed with a trade-off of slightly reduced performance, the 10-item version is acceptable. [ABSTRACT FROM AUTHOR]

Identifying individuals at risk of developing dementia may be aided by early detection of functional impairments. The aims of the present study were to examine differences in informant-reported and performance-based measures of instrumental activities of daily living (IADL) and to assess whether a performance-based IADL measure contributes additional unique variance over informant reports in predicting incident dementia over 4 years. Prospective cohort study (Sydney Memory and Ageing Study). Eastern Suburbs, Sydney, Australia. 307 community-dwelling individuals (60.6% female) aged between 76 and 96 years with normal cognition (NC; n = 190) or mild cognitive impairment (MCI; n = 117). IADL ability was assessed with the performance-based Sydney Test of Activities of Daily Living in Memory Disorders (STAM) and the Bayer-Activities of Daily Living (B-ADL) informant report, at baseline and 4-year follow-up. Covariates included age, sex, education, Mini-Mental State Examination and Geriatric Depression Scale scores, arthritis, vision impairment, cardiovascular risk, and number of medications. Logistic regressions were conducted to examine the longitudinal association between the 2 types of IADL measures and incident dementia. Logistic regressions showed that performance-based IADL impairment at baseline [odds ratio (OR) = 0.83, 95% confidence interval (CI) 0.77, 0.90; P <.001] and decline in performance-based IADL function (OR = 0.82, 95% CI 0.73, 0.91; P <.001) were associated with incident dementia over 4 years, with the association provided by the STAM being statistically significant over and above the B-ADL. Performance-based measures of IADL can predict progression to dementia over 4 years beyond that provided by an informant report of IADL. Performance-based IADL measures are promising tools for clinical practice to identify individuals at greater risk of developing dementia. [ABSTRACT FROM AUTHOR]