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Background: Aspirin as a primary preventative in healthy older adults did not prolong disability-free survival in the ASPREE randomized trial. Observational studies following randomized trials allow assessment of benefits and harms which may not appear during the trial. We describe health characteristics, physical function, and aspirin use in the ASPREE-eXTension (ASPREE-XT) observational study cohort., Methods: Descriptive statistics compared health characteristics of those consented to ASPREE-XT at their first post-trial baseline (XT01) to corresponding ASPREE baseline values, and to those not consented. Likelihood of an indication for aspirin was assessed in participants reporting aspirin use at XT01., Results: 16,317 (93%) of the remaining and eligible 17,546 ASPREE participants were consented into ASPREE-XT; 14,894 completed XT01. Mean participant age had increased from 74.9 to 80.6 years. Overall health and physical function declined from the original ASPREE baseline; more participants were living alone, there was higher prevalence of chronic kidney disease, diabetes, and frailty, grip strength was lower and gait speed slower. Those not consented into ASPREE-XT were slightly older, and had lower cognitive scores and higher prevalence of age-related conditions than those who continued. 1015/11,717 (8.7%) participants without an apparent indication for aspirin reported using aspirin at XT01., Conclusions: The ASPREE-XT cohort was slightly less healthy at the XT01 visit than at ASPREE trial initiation, and rates of aspirin use without indication were similar to ASPREE baseline. Participants will be followed long-term to investigate aspirin's potential legacy towards dementia and cancer prevention and explore determinants of healthy aging., Competing Interests: Declaration of Competing Interest All authors declare no conflicts of interest in the publication of this manuscript., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Cognitive test-retest reliability measures can be used to evaluate meaningful changes in scores., Objective: This analysis aimed to develop a comprehensive set of test-retest reliability values and minimal detectable change (MDC) values for a cognitive battery for community-dwelling older individuals in Australia and the U.S., for use in clinical practice., Methods: Cognitive scores collected at baseline and year 1, in the ASPirin in Reducing Events in the Elderly clinical trial were used to calculate intraclass correlation coefficients (ICC) for four tests: Modified Mini-Mental State examination (3MS), Hopkins Verbal Learning Test-Revised (HVLT-R), single-letter Controlled Oral Word Association Test (COWAT-F), and Symbol Digit Modalities Test (SDMT). 16,956 participants aged 70 years and over (65 years and over for U.S. minorities) were included. ICCs were used to calculate MDC values for eight education and ethno-racial subgroups., Results: All four cognitive tests had moderate (ICC > 0.5) to good (ICC > 0.7) test-retest reliability. ICCs ranged from 0.53 to 0.63 (3MS), 0.68 to 0.77 (SDMT), 0.56 to 0.64 (COWAT-F), 0.57 to 0.69 (HVLT-R total recall), and 0.57 to 0.70 (HVLT-R delayed recall) across the subgroups. MDC values ranged from 6.60 to 9.95 (3MS), 12.42 to 15.61 (SDMT), 6.34 to 8.34 (COWAT-F), 8.13 to 10.85 (HVLT-R total recall), and 4.00 to 5.62 (HVLT-R delayed recall)., Conclusion: This large cohort of older individuals provides test-retest reliability and MDC values for four widely employed tests of cognitive function. These results can aid interpretation of cognitive scores and decline instead of relying on cross-sectional normative data alone.

Brain age is a neuroimaging-based biomarker of aging. This study examined whether the difference between brain age and chronological age (brain-PAD) is associated with cognitive function at baseline and longitudinally. Participants were relatively healthy, predominantly white community-dwelling older adults (n = 531, aged ≥70 years), with high educational attainment (61% ≥12 years) and socioeconomic status (59% ≥75th percentile). Brain age was estimated from T1-weighted magnetic resonance images using an algorithm by Cole et al., 2018. After controlling for age, gender, education, depression and body mass index, brain-PAD was negatively associated with psychomotor speed (Symbol Digit Modalities Test) at baseline (Bonferroni p < 0.006), but was not associated with baseline verbal fluency (Controlled Oral Word Association Test), delayed recall (Hopkins Learning Test Revised), or general cognitive status (Mini-Mental State Examination). Baseline brain-PAD was not associated with 3-year change in cognition (Bonferroni p > 0.006). These findings indicate that even in relatively healthy older people, accelerated brain aging is associated with worse psychomotor speed, but future longitudinal research into changes in brain-PAD is needed., (Copyright © 2021. Published by Elsevier Inc.)

Background: Cognitive impairment is common after stroke, and a large proportion of stroke patients will develop dementia. However, there have been few large prospective studies which have assessed cognition both prior to and after stroke. This study aims to determine the extent to which incident stroke impacts different domains of cognitive function in a longitudinal cohort of older community-dwelling individuals. Methods: 19,114 older individuals without cardiovascular disease or major cognitive impairment were recruited and followed over a maximum 11 years. Stroke included ischaemic and haemorrhagic stroke and was adjudicated by experts. Cognitive function was assessed regularly using Modified Mini-Mental State Examination (3MS), Hopkins Verbal Learning Test–Revised (HVLT-R), Symbol Digit Modalities Test (SDMT), and Controlled Oral Word Association Test (COWAT). Linear mixed models were used to investigate the change in cognition at the time of stroke and decline in cognitive trajectories following incident stroke. Results: During a median follow-up period of 8.4 [IQR: 7.2, 9.6] years, 815 (4.3%) participants experienced a stroke. Over this time, there was a general decline observed in 3MS, HVLT-R delayed recall, and SDMT scores across participants. However, for individuals who experienced a stroke, there was a significantly greater decline across all cognitive domains immediately after the event immediately after the event (3MS: -1.03 [95%CI: -1.45, -0.60]; HVLT-R: -0.47 [-0.70, -0.24]; SDMT: -2.82 [-3.57, -2.08]; COWAT: -0.67 [-1.04, -0.29]) and a steeper long-term decline for three of these domains (3MS -0.62 [-0.88, -0.35]; COWAT: -0.30 [-0.46, -0.14]); HVLT-R: -0.12 [95%CI, -0.70, -0.24]). However individuals with stroke experienced no longer-term decline in SDMT compared to the rest of the participants. Conclusions: These findings highlight the need for comprehensive neuropsychology assessments for ongoing monitoring of cognition following incident stroke; and potential early intervention. [ABSTRACT FROM AUTHOR]

Study Objective: What is the association between anticholinergic burden and specific domains of cognitive function in older adults who are initially without major cognitive impairment? Design: Post‐hoc analysis of longitudinal observational data from the ASPirin in Reducing Events in the Elderly (ASPREE) study. Patients: 19,114 participants from Australia and the United States aged 70 years and older (65 years and older for US minorities) were recruited and followed for a median of 4.7 years. At enrollment, participants were free of known cardiovascular disease, major physical disability, or dementia. Measurements: Cognitive assessments administered at baseline and biennially at follow‐up visits included the Modified Mini‐Mental State examination (3MS), Hopkins Verbal Learning Test–Revised (HVLT‐R) delayed recall, Controlled Oral Word Association Test (COWAT), and Symbol Digit Modalities Test (SDMT). Anticholinergic burden was calculated at baseline using the Anticholinergic Cognitive Burden (ACB) scale and grouped as scores of 0 (no burden), 1‐2 (low to moderate), or 3+ (high). Main Results: Linear mixed effects models were used to assess the relationship between ACB score and cognition over time. After adjusting for sex, age, education, minority status, smoking status, hypertension, diabetes, depression, chronic kidney disease, country, and frailty, participants with a high ACB score had worse performance over time for 3MS (Adjusted [Adj] B=‐0.092, P=0.034), HVLT‐R delayed recall (Adj B=‐0.104, P<0.001), COWAT (Adj B=‐0.151, P<0.001), and SDMT (Adj B=‐0.129, P=0.026), than participants with an ACB score of 0. A low to moderate ACB score was also associated with worse performance over time for HVLT‐R delayed recall (Adj B=‐0.037, P=0.007) and COWAT (Adj B=‐0.065, P=0.003), compared to those with no ACB. Conclusions: Anticholinergic burden predicts worse cognitive function over time in initially dementia‐free older adults, particularly for executive function (COWAT) and episodic memory (HVLT‐R). [ABSTRACT FROM AUTHOR]

Background: Poor social health is prevalent in older adults and may be associated with worse cognition, and increased dementia risk. The aim of this study was to determine whether social isolation, social support and loneliness are independently associated with cognitive function and incident dementia over 5 years in older adults, and to investigate potential gender differences.Methods: Participants were 11,498 community-dwelling relatively healthy Australians aged 70-94, in the ASPREE Longitudinal Study of Older Persons (ALSOP). Social isolation, social support, loneliness and cognitive function were assessed through self-report. Outcomes examined were cognitive decline (>1.5 SD decline in cognitive performance since baseline) and incident dementia (adjudicated according to DSM-IV criteria).Results: Most participants self-reported good social health (92%) with very few socially isolated (2%), with low social support (2%) or lonely (5%). Among women, social isolation and low social support were consistently associated with lower cognitive function (e.g., social support and cognition β = -1.17, p < 0.001). No consistent longitudinal associations were observed between baseline social health and cognitive decline (over median 3.1 years) or incident dementia (over median 4.4 years; social isolation: HR = 1.00, p = 0.99; low social support: HR = 1.79, p = 0.11; loneliness: HR = 0.72, p = 0.34 among women and men).Conclusion: Our study provides evidence that social isolation and a low social support are associated with worse cognitive function in women, but not men. Social health did not predict incident cognitive decline or dementia, but we lacked power to stratify dementia analyses by gender. [ABSTRACT FROM AUTHOR]