ObjectiveTo evaluate the risk of Alzheimer’s disease-related neuropathology burden at autopsy given older adults’ current cognitive state.MethodParticipants included 1,303 individuals who enrolled in the Religious Orders Study (ROS) and 1,789 who enrolled in the Rush Memory and Aging Project (MAP). Cognitive status was evaluated via standardized assessments of global cognition and episodic memory. At the time of analyses, about 50% of participants were deceased with the remaining numbers right censored. Using multi-state Cox proportional hazard models, we compared the cognitive status of all subjects alive at a given age and estimated future risk of dying with different AD-related neuropathologies. Endpoints considered were Braak Stages (0–2, 3–4, 5–6), CERAD (0, 1, 2, 3), and TDP-43 (0, 1, 2, 3) level.ResultsFor all three pathological groupings (Braak, CERAD, TDP-43), we found that a cognitive test score one standard deviation below average put individuals at up to three times the risk for being diagnosed with late stage AD at autopsy according to pathological designations. The effect remained significant after adjusting for sex, APOE-e4 status, smoking status, education level, and vascular health scores.ConclusionApplying multi-state modeling techniques, we were able to identify those at risk of exhibiting specific levels of neuropathology based on current cognitive test performance. This approach presents new and approachable possibilities in clinical settings for diagnosis and treatment development programs.

Objectives: Lack of social support and high levels of stress represent potentially modifiable risk factors for cognitive aging. In this study we examined the relationships between these two risk factors and response time inconsistency (RTI), or trial-to-trial variability in choice response time tasks. RTI is an early indicator of declining cognitive health, and examining the influence of modifiable psychosocial risk factors on RTI is important for understanding and promoting cognitive health during adulthood and old age.

Methods: Using data from a community sample study (n = 317; M_age = 49, range = 19-83), we examined the effects of social support, including size of network and satisfaction with support, global perceived stress, and their interactions on RTI.

Results: Neither size of network nor satisfaction with support was associated with RTI independent of perceived stress. Stress was positively associated with increased RTI on all tasks, independent of social support. Perceived stress did not interact with either dimension of social support to predict RTI, and perceived stress effects were invariant across age and sex.

Conclusion: Perceived stress, but not social support, may be a unique and modifiable risk factor for normal and pathological cognitive aging. Discussion focuses on the importance of perceived stress and its impact on RTI in supporting cognitive health in adulthood and old age.

Background Measures based on DNA methylation, epigenetic clocks, have recently gained attraction as predictors of mortality and age-related pathologies. However, the origins of variation in these measures are not well understood. Methods In a pooled sample of 104 Swedish and Danish twin pairs, we estimated, at the mean age of 70 (baseline) and 79 years (follow-up), the genetic and environmental influences on the Horvath and Levine clocks. Findings A model incorporating additive genetic (A) and person-specific environmental (E) influences best explained the variation in both clocks. Heritability was estimated at 55% at baseline and at 51% at follow-up for the Horvath clock and 34% at baseline and 41% at follow-up for the Levine clock. For the Horvath clock, new sources of A influences emerged at follow-up, whereas for the Levine clock, the same A influences accounted for the genetic variance at both measurement occasions. The cross-time phenotypic correlations, 0·52 for the Horvath clock and 0·36 for the Levine clock, were mediated primarily by genetic factors, whereas the person-specific environmental factors were completely different at the two measurement occasions. Interpretation For both clocks, new sources of person-specific environmental influences emerge with age. The epigenetic clocks might thus be responsive to new environmental stimuli even at old age. Fund NIH (R01;AG04563;AG10175;AG028555) the MacArthur Foundation Research Network on Successful Aging, FAS/FORTE (97:0147:1B;2009-0795), Swedish Research Council (825-2007-7460;825-2009-6141;521-2013-8689;2015-03255;2015-06796;2018-02077), FORTE (2013-2292), the Strategic Research Program in Epidemiology at KI, VELUX FOUNDATION, NIA (P01-AG08761), the EU (FP7/2007-2011;259679) and The Danish National Program for Research Infrastructure 2007 (9-063256).

Mobile technologies are increasingly used to measure cognitive function outside of traditional clinic and laboratory settings. Although ambulatory assessments of cognitive function conducted in people’s natural environments offer potential advantages over traditional assessment approaches, the psychometrics of cognitive assessment procedures have been understudied. We evaluated the reliability and construct validity of ambulatory assessments of working memory and perceptual speed administered via smartphones as part of an ecological momentary assessment protocol in a diverse adult sample (N = 219). Results indicated excellent between-person reliability (≥0.97) for average scores, and evidence of reliable within-person variability across measurement occasions (0.41-0.53). The ambulatory tasks also exhibited construct validity, as evidence by their loadings on working memory and perceptual speed factors defined by the in-lab assessments. Our findings demonstrate that averaging across brief cognitive assessments made in uncontrolled naturalistic settings provide measurements that are comparable in reliability to assessments made in controlled laboratory environments.

Rationale Neighborhood characteristics may influence health and well-being outcomes through stressors in daily life. Objectives This study tested whether a varied set of perceived characteristics of neighborhood (i.e., social cohesion, safety, aesthetic quality, violence) predicted stressor frequency and severity as well as negative emotional responses to stressors. We predicted greater reported cohesion and safety and less violence would be associated with less frequent stressor exposure and severity and less intense negative affect following stressors; we conducted subsequent tests of neighborhood aesthetic quality as a predictor. Methods Participants (n = 233, age 25–65 years) were residents in a socio-economically, racially, and ethnically diverse zip code in Bronx, New York, most who participated in the Effects of Stress on Cognitive Aging, Physiology and Emotion study between 2012 and 2013. They provided demographic information and neighborhood ratings, then participated in the EMA protocol in which they completed brief smartphone surveys of current negative affect and stressor exposure, severity, and recency, five times daily for 14 days. Results No coded neighborhood characteristic was related to the frequency of stressors. Individuals who reported greater neighborhood violence, however, rated their stressors as more severe. Individuals rating their neighborhood lower in safety or aesthetic quality, or higher in violence, had greater negative affect following stressors. Conclusion Even among people living within the same zip code, individual differences in perceptions of neighborhood predict how stressful they appraised stressors in daily life to be and how much negative affect they reported following stressors.

Background: Older adults with subjective cognitive impairment (SCI) experience increased affective symptoms, reduced engagement in a range of activities, as well as more functional problems when compared to those without SCI. These associations suggest that SCI may be detrimental to older adults’ quality of life (QoL). The purpose of this paper is to advance understanding of the SCI–QoL relationship through a comprehensive review of the empirical literature relating SCI and QoL. Methods: A systematic literature review was conducted in CINAHL, PsycINFO, and PubMed per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. Eligible articles were appraised using the weight of evidence (WoE) framework to evaluate methodological quality, methodological relevance, and topic relevance. A narrative synthesis of results was conducted, based on conceptual definitions of QoL. Results: Eleven articles were identified that met eligibility criteria. WoE ratings ranged from low to high scores. Studies reviewed reported that the presence, greater frequency, or greater severity of SCI is associated with lower QoL regardless of methodological quality rating, sample characteristics (e.g. geographic location, clinical vs. community settings), study design (e.g. cross-sectional vs. longitudinal), and operationalization of SCI or QoL. Conclusion: Across studies, QoL was negatively associated with SCI. However, a frequent limitation of the reviewed literature was the mismatch between the conceptual and operational definitions of SCI and QoL. Similarly, SCI measures varied in quality across the reviewed literature. This suggests future empirical work should focus on the appropriate strategies for conceptually and operationally defining these constructs.

Objective To determine (1) whether delirium severity was associated with Apolipoprotein E (APOE) genotype status and occupational complexity, a measure of cognitive reserve, in individuals with delirium superimposed on dementia; and (2) whether decline in delirium severity was associated with these same factors over a post-acute care (PAC) stay. Methods Control group data (n = 142) from a completed randomized clinical trial were used to address the aims of the study. Delirium severity was calculated by combining items from the Confusion Assessment Method and the Montreal Cognitive Assessment. APOE ε4 carriers versus non-carriers were considered. Occupational complexity, a measure of cognitive reserve, was derived from the Lifetime of Experiences Questionnaire. Covariates examined included age, gender, education, Clinical Dementia Rating Scale, and the Charlson comorbidity score. Data were nested (i.e., days nested within persons) and analyzed using multilevel models. Results The presence of an APOE ε4 allele and higher Clinical Dementia Rating Scale were associated with greater delirium severity at baseline. The presence of an APOE ε4 allele was also associated with greater delirium severity averaged across the PAC stay. Occupational complexity was not associated with baseline delirium severity or average daily delirium severity; however, individuals with low occupational complexity showed a significant decreased in delirium severity during the course of their PAC stay. Conclusions Individual differences, including genetic factors and level of cognitive reserve, contribute to the severity of delirium in older adults with dementia. Copyright © 2016 John Wiley & Sons, Ltd.

AbstractPurpose of Study:. Subjective cognitive impairment (SCI) has been argued to reflect affective symptoms (i.e., depression and anxiety) rather than actua

Despite evidence that psychological stress is an important risk factor for age-related cognitive loss, little research has directly evaluated psychological and physiological mediators of the relationship between stressful experiences and cognitive function. A key objective of the ESCAPE (Effects of Stress on Cognitive Aging, Physiology, and Emotion) project is to evaluate whether engaging in stress-related unconstructive repetitive thought (URT) is a pathway through which stressful experiences negatively affect cognitive health over the short- and long-term. Over the short-term, we hypothesize that engaging in URT will deplete attentional resources and result in worse cognitive performance in daily life. Over the long-term, we expect that the effects of chronic stress, from repeated exposure to stressors and regular engagement in URT, will be apparent in dysregulated hypothalamic-pituitary-adrenal (HPA) axis function and inflammation. Over time, stress-related physiological dysregulation will result in accelerated cognitive decline.

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Although research has established a negative association between trait neuroticism and cognition, little is known about the mechanisms that underlie this relationship. We examined the tendency to experience intrusive thoughts and negative affect as potential mediators of the relationship between neuroticism and cognitive performance. We hypothesized that the tendency to experience intrusive thoughts reflects ineffective attentional control and would account for the relationship between neuroticism and cognitive performance over and above the mediating effect of negative affect. Three hundred seventeen adults (Mage=49.43) completed a series of attention-demanding cognitive tasks as well as self-report measures of intrusive thoughts, negative affect, and neuroticism. Intrusive thoughts mediated the association between trait neuroticism and cognitive performance beyond negative affect. These findings are consistent with the hypothesis that the tendency to experience intrusive thoughts is a mechanism through which trait neuroticism influences cognitive performance.