Associations Between Self and Study Partner Report of Cognitive Decline With Regional Tau in a Multicohort Study.

BACKGROUND AND OBJECTIVES: Self-reported cognitive decline is an early behavioral manifestation of Alzheimer disease (AD) at the preclinical stage, often believed to precede concerns reported by a study partner. Previous work shows cross-sectional associations with ß-amyloid (Aß) status and self-reported and study partner-reported cognitive decline, but less is known about their associations with tau deposition, particularly among those with preclinical AD. METHODS: This cross-sectional study included participants from the Anti-Amyloid Treatment in Asymptomatic AD/Longitudinal Evaluation of Amyloid Risk and Neurodegeneration studies (N = 444) and the Harvard Aging Brain Study and affiliated studies (N = 231), which resulted in a cognitively unimpaired (CU) sample of individuals with both nonelevated (Aß-) and elevated Aß (Aß+). All participants and study partners completed the Cognitive Function Index (CFI). Two regional tau composites were derived by averaging flortaucipir PET uptake in the medial temporal lobe (MTL) and neocortex (NEO). Global Aß PET was measured in Centiloids (CLs) with Aß+ >26 CL. We conducted multiple linear regression analyses to test associations between tau PET and CFI, covarying for amyloid, age, sex, education, and cohort. We also controlled for objective cognitive performance, measured using the Preclinical Alzheimer Cognitive Composite (PACC). RESULTS: Across 675 CU participants (age = 72.3 ± 6.6 years, female = 59%, Aß+ = 60%), greater tau was associated with greater self-CFI (MTL: ß = 0.28 [0.12, 0.44], p < 0.001, and NEO: ß = 0.26 [0.09, 0.42], p = 0.002) and study partner CFI (MTL: ß = 0.28 [0.14, 0.41], p < 0.001, and NEO: ß = 0.31 [0.17, 0.44], p < 0.001). Significant associations between both CFI measures and MTL/NEO tau PET were driven by Aß+. Continuous Aß showed an independent effect on CFI in addition to MTL and NEO tau for both self-CFI and study partner CFI. Self-CFI (ß = 0.01 [0.001, 0.02], p = 0.03), study partner CFI (ß = 0.01 [0.003, 0.02], p = 0.01), and the PACC (ß = -0.02 [-0.03, -0.01], p < 0.001) were independently associated with MTL tau, but for NEO tau, PACC (ß = -0.02 [-0.03, -0.01], p < 0.001) and study partner report (ß = 0.01 [0.004, 0.02], p = 0.002) were associated, but not self-CFI (ß = 0.01 [-0.001, 0.02], p = 0.10). DISCUSSION: Both self-report and study partner report showed associations with tau in addition to Aß. Additionally, self-report and study partner report were associated with tau above and beyond performance on a neuropsychological composite. Stratification analyses by Aß status indicate that associations between self-reported and study partner-reported cognitive concerns with regional tau are driven by those at the preclinical stage of AD, suggesting that both are useful to collect on the early AD continuum.

Recent contributions to the field of subjective cognitive decline in aging: A literature review.

Subjective cognitive decline (SCD) is defined as self-experienced, persistent concerns of decline in cognitive capacity in the context of normal performance on objective cognitive measures. Although SCD was initially thought to represent the "worried well," these concerns can be linked to subtle brain changes prior to changes in objective cognitive performance and, therefore, in some individuals, SCD may represent the early stages of an underlying neurodegenerative disease process (e.g., Alzheimer's disease). The field of SCD research has expanded rapidly over the years, and this review aims to provide an update on new advances in, and contributions to, the field of SCD in key areas and themes identified by researchers in this field as particularly important and impactful. First, we highlight recent studies examining sociodemographic and genetic risk factors for SCD, including explorations of SCD across racial and ethnic minoritized groups, and examinations of sex and gender considerations. Next, we review new findings on relationships between SCD and in vivo markers of pathophysiology, utilizing neuroimaging and biofluid data, as well as associations between SCD and objective cognitive tests and neuropsychiatric measures. Finally, we summarize recent work on interventions for SCD and areas of future growth in the field of SCD.

Subjective cognitive decline across ethnoracial groups in the A4 study.

INTRODUCTION: The associations between subjective cognitive decline (SCD), cognition, and amyloid were explored across diverse participants in the A4 study. METHODS: Five thousand one hundred and fifty-one non-Hispanic White, 262 non-Hispanic Black, 179 Hispanic-White, and 225 Asian participants completed the Preclinical Alzheimer Cognitive Composite (PACC), self- and study partner-reported Cognitive Function Index (CFI). A subsample underwent amyloid positron emission tomography (18 F-florbetapir) (N = 4384). We examined self-reported CFI, PACC, amyloid, and study partner-reported CFI by ethnoracial group. RESULTS: The associations between PACC-CFI and amyloid-CFI were moderated by race. The relationships were weaker or non-significant in non-Hispanic Black and Hispanic White groups. Depression and anxiety scores were stronger predictors of CFI in these groups. Despite group differences in the types of study partners, self- and study partner-CFI were congruent across groups. DISCUSSION: SCD may not uniformly relate to cognition or AD biomarkers in different ethnoracial groups. Nonetheless, self- and study partner-SCD were congruent despite differences in study partner type. Highlights Association between SCD and objective cognition was moderated by ethnoracial group. Association between SCD and amyloid was moderated by ethnoracial group. Depression and anxiety were stronger predictors of SCD in Black and Hispanic groups. Study-partner and self-reported SCD are congruent across groups. Study-partner report was consistent despite difference in study partner types.

Pre-Morbid IQ Moderates the Relationship between Cognitive Performance and Performance-Based Functional Status in Older Adults.

Objectives: The current study sought to evaluate the relationship between cognitive performance and Instrumental Activities of Daily Living (IADL) performance in a population of community dwelling older adults, and assess to what extent this relationship is moderated by cognitive reserve (Premorbid-IQ)Methods: 123 community-dwelling older adults completed a general cognitive assessment, a word-reading based premorbid-IQ estimate (PMIQE) measure, and the performance-based Direct Assessment of Functional Status, Revised (DAFS-R). Moderated regression analysis was used to assess the influence of PMIQE on the relationship between cognitive performance and IADLs.Results: There was a significant main effect of cognitive performance on IADLs, and no main effect of PMIQE on functional IADLs. There was a significant moderating effect of PMIQE on the relationship between cognitive performance and IADLs performance, such that at higher levels of PMIQE, cognitive performance scores became slightly less predictive of weaknesses in IADLs.Conclusions: Results suggest that for individuals with high reserve, assessment of cognitive performance alone may not be robust a predictor of IADLs functioning.Clinical implications: In estimating functional abilities as a consequence of cognitive performance, consideration should be given to premorbid-IQ/cognitive reserve.

Frailty and Cognitive Function in Older Adults: A Systematic Review and Meta-Analysis of Cross-Sectional Studies.

The relationship between cognitive function and frailty among older adults is a growing area of research due to the implications of cognitive and physical decline for functional independence in late life. Multiple studies demonstrate a meaningful relationship between these two factors, which together may constitute increased risk of negative health outcomes for older adults. The current analysis was conducted to 1) systematically review current evidence for differences in cognitive performance based on frailty status among older adults and provide quantitative evidence for the magnitude of this effect, and 2) assess the influence of demographic and methodological variables on this effect. The preregistered protocol (CRD42018087138) included a search of EBSCOhost, Pubmed, and Embase online databases and reference lists to identify cross-sectional studies comparing frail and non-frail or robust older adults (60+) on cognitive performance. In total, 42 effects were retrieved from 38 studies, expressed as Hedges' g, and pooled based on a random-effects model. Results indicated an overall significant, negative effect of frailty status on cognitive function among tests of global cognitive function (g = 0.734: 95% CI = 0.601-0.867) and individual cognitive domains (g = 0.439: 95% CI = 0.342-0.535). Age, frailty assessment used, and cognitive status of the sample did not significantly moderate the overall effect. Post-hoc moderator analysis revealed that difference in mean age of frail and robust groups significantly moderated the overall effect (R2 = 0.38, ß = .0974, 95% CI = 0.0537-0.141). Implications for future research are discussed.

Physical activity moderates the association between executive function and functional connectivity in older adults.

Recent evidence suggests that physical activity may influence the functional connectivity of the aging brain. The purpose of this study was to examine the influence of physical activity on the association between executive function and functional connectivity of key brain networks and graph theory metrics in community-dwelling older adults. Participants were 47 older adults (M = 73 years; SD = 5.92) who participated in neuropsychological testing, physical activity measurements, and magnetic resonance imaging (MRI). Seed-to-voxel moderation analyses and graph theory analyses were conducted. Physical activity was significantly positively associated with default mode network functional connectivity (DMN FC; Posterior Cingulate Gyrus, p-FDR = 0.005; Frontal Pole (L), p-FDR = 0.005; Posterior Cingulate Gyrus, p-FDR = 0.006; Superior Frontal Gyrus (L), p-FDR = 0.016) and dorsal attention network functional connectivity (DAN FC; Inferior Frontal Gyrus Pars Opercularis (R), p-FDR = 0.044). The interaction between physical activity and executive function on the DMN FC and DAN FC was analyzed. The interaction between executive function and physical activity was significantly associated with DMN FC. When this significant interaction was probed, the association between physical activity and DMN FC differed between levels of high and low executive function such that the association was only significant at levels of high executive function. These results suggest that greater physical activity in later life is associated with greater DMN and DAN FC and provides evidence for the importance of physical activity in cognitively healthy older adults.

The Relations Between Physical Activity Level, Executive Function, and White Matter Microstructure in Older Adults.

The population of older adults is increasing, indicating a need to examine factors that may prevent or mitigate age-related cognitive decline. The current study examined whether microstructural white matter characteristics mediated the relation between physical activity and executive function in older adults without any self-reported psychiatric and neurological disorders or cognitive impairment (N = 43, mean age = 73 y). Physical activity was measured by average intensity and number of steps via accelerometry. Diffusion tensor imaging was used to examine microstructural white matter characteristics, and neuropsychological testing was used to examine executive functioning. Parallel mediation models were analyzed using microstructural white matter regions of interest as mediators of the association between physical activity and executive function. Results indicated that average steps was significantly related to executive function (ß = 0.0003, t = 2.829, P = .007), while moderate to vigorous physical activity was not (ß = 0.0007, t = 1.772, P = .08). White matter metrics did not mediate any associations. This suggests that microstructural white matter characteristics alone may not be the mechanism by which physical activity impacts executive function in aging.

Exercise interventions do not impact brain volume change in older adults: a systematic review and meta-analysis.

Exercise interventions have been shown to positively impact cognitive function in older adults, but the mechanisms underlying the neuroprotective effects of exercise on the brain are not well understood. Here, we aimed to synthesize and quantitatively analyze the current literature on exercise interventions and brain volume change in older adults and to examine the impact of key demographic and intervention features as well as study quality. This study was pre-registered with PROSPERO (CRD42018091866). EBSCOhost, Cochrane Library, Embase, and reference lists were searched to identify randomized-controlled trials (RCTs) of exercise interventions for healthy older adults and older adults (60+) with mild cognitive impairment (MCI). A total of 69 effects from 14 studies were pooled and expressed as Hedge's g using a random-effects model. Results indicated that there was no significant difference in brain volume outcomes for older adults that completed an exercise intervention compared to older adults in control groups (g = 0.012, p = 0.728, 95% CI = -0.055, .078). These results were confirmed using multilevel analysis to account for nesting of effects within studies (g = 0.009, p = 0.826, 95% CI = -0.072, 0.090) and using conservative post-hoc models to address possible non-independence of multiple outcome domains and sample nonindependence. No significant heterogeneity was detected, limiting moderator analyses. The implications for future research are discussed.

A Multi-method Investigation of the Personality Correlates of Functional Ability in Older Adults.

OBJECTIVES: This study evaluated the role of personality in predicting functional ability (FA) in older adults using self-report, collateral report, and performance-based measures of FA. METHODS: Participants included older adults (N = 131) who completed a personality measure (NEO-FFI), a self-report of FA (OARS ADL), and participated in a performance-based assessment of FA (DAFS-R). In addition, each participant had a collateral complete a collateral report of FA (OARS ADL). Bivariate correlations were computed to assess how Five Factor Model traits were related to self-report, collateral, and performance-based measures of FA. RESULTS: Neuroticism was negatively related to self-reported FA (r = - .27) and collateral-reported FA (r = - .18) and Conscientiousness was positively related to self-reported FA (r = .25). None of the traits were significantly related to the performance-based measure of FA. CONCLUSIONS: These results suggest that personality traits can impact self-reported FA in older adults and underscore the importance of assessing FA in older adults using multiple methods, particularly performance-based measures. CLINICAL IMPLICATIONS: Clinicians should consider how personality may impact FA in older adults and multiple methods of FA performance should be examined to better tailor recommendations.

Education Differentially Buffers Cognitive Performance in Black and White Older Adults.

OBJECTIVES: Given that black American older adults are more likely to have lower educational attainment and perform worse on cognitive tests than white Americans, we examined whether increased education would confer greater cognitive advantage to black Americans on measures of global and specific domains of cognitive function. METHODS: The sample included 522 community-dwelling older adults from a larger study. An analysis of covariance was conducted with race and education as between-participant factors and global cognition as the dependent variable. A multivariate analysis of covariance was conducted with five cognitive domains (immediate memory, visuospatial/constructional ability, language, attention, and delayed memory) as the dependent variables. RESULTS: Significant main effects indicated that black Americans, F(1,516) = 29.18, p < .001, and individuals with less education, F(1,516) = 44.93, p < .001, evidenced lower cognitive functioning, controlling for age and overall health status, and the interaction term reached statistical significance, F(1,516) = 7.95, p = .005. The impact of education on global cognitive function for black participants was more than twice as large (Cohen's d = 1.30) than for white participants (Cohen's d = .52). There was a significant race × education interaction for the cognitive domain of attention (p < .001) and a composite measure of non-memory domains (i.e., language, visuospatial/constructional, and attention; p < .001). DISCUSSION: Our findings suggest that educational attainment is particularly important for black Americans with respect to global cognitive function, attention, and non-memory domains.

Body mass index and its relation to neuropsychological functioning and brain volume in healthy older adults.

Obesity is a growing concern worldwide because of its adverse health effects, including its negative impact on cognitive functioning. This concern is especially relevant for older adults, who are already likely to experience some cognitive decline and loss of brain volume due to aging, (Gea et al., 2002). However, there is some evidence that higher body mass index (BMI) may actually be protective in later life (Hughes et al., 2009; Luchsinger et al., 2007; Nilsson and Nilsson, 2009; Sturman et al., 2008). Therefore, the purpose of the current study was to assess the relationship between BMI and neuropsychological functioning in older adults, and concurrently the relationship between BMI and brain volume. Older adults (N = 88) reported height and weight to determine BMI (M = 26.5) based on Centers for Disease Control and Prevention (CDC) guidelines. Cognitive function was assessed with the Repeatable Battery for Assessment of Neuropsychological Status (RBANS). Brain volume measurements were evaluated via structural MRI. Results indicated no association between BMI and neuropsychological functioning. There was a significant association between BMI and total grey matter volume while controlling for age and years of education (ß = 0.208, p = .026, ΔR2 = 0.043), indicating that as BMI increased, brain volume in these areas modestly increased. However, these results did not survive multiple comparison corrections and were further attenuated to near significance when sex was explicitly added as an additional covariate. Nevertheless, while replication is clearly needed, these results suggest that moderately greater BMI in later life may modestly attenuate concomitant grey matter volume decline.

Lutein and Zeaxanthin Are Positively Associated with Visual-Spatial Functioning in Older Adults: An fMRI Study.

Lutein (L) and zeaxanthin (Z) are two xanthophyll carotenoids that have antioxidant and anti-inflammatory properties. Previous work has demonstrated their importance for eye health and preventing diseases such as age-related macular degeneration. An emerging literature base has also demonstrated the importance of L and Z in cognition, neural structure, and neural efficiency. The present study aimed to better understand the mechanisms by which L and Z relate to cognition, in particular, visual-spatial processing and decision-making in older adults. We hypothesized that markers of higher levels of L and Z would be associated with better neural efficiency during a visual-spatial processing task. L and Z were assessed via standard measurement of blood serum and retinal concentrations. Visual-spatial processing and decision-making were assessed via a judgment of line orientation task (JLO) completed during a functional magnetic resonance imaging (fMRI) scan. The results demonstrated that individuals with higher concentrations of L and Z showed a decreased blood-oxygen-level dependent (BOLD) signal during task performance (i.e., "neural efficiency") in key areas associated with visual-spatial perception, processing, decision-making, and motor coordination, including the lateral occipital cortex, occipital pole, superior and middle temporal gyri, superior parietal lobule, superior and middle frontal gyri, and pre- and post-central gyri. To our knowledge, this is the first investigation of the relationship of L and Z to visual-spatial processing at a neural level using in vivo methodology. Our findings suggest that L and Z may impact brain health and cognition in older adults by enhancing neurobiological efficiency in a variety of regions that support visual perception and decision-making.