Traumatic brain injury (TBI), mental health conditions (e.g., posttraumatic stress disorder [PTSD]), and vascular comorbidities (e.g., hypertension, diabetes) are highly prevalent in the Veteran population and may exacerbate age-related changes to cerebral white matter (WM). Our study examined (1) relationships between health conditions—TBI history, PTSD, and vascular risk—and cerebral WM micro- and macrostructure, and (2) associations between WM measures and cognition.

We analyzed diffusion tensor images from 183 older male Veterans (mean age = 69.18; SD = 3.61) with (n = 95) and without (n = 88) a history of TBI using tractography. Generalized linear models examined associations between health conditions and diffusion metrics. Total WM hyperintensity (WMH) volume was calculated from fluid-attenuated inversion recovery images. Robust regression examined associations between health conditions and WMH volume. Finally, elastic net regularized regression examined associations between WM measures and cognitive performance.

Veterans with and without TBI did not differ in severity of PTSD or vascular risk (p’s >0.05). TBI history, PTSD, and vascular risk were independently associated with poorer WM microstructural organization (p’s <0.5, corrected), however the effects of vascular risk were more numerous and widespread. Vascular risk was positively associated with WMH volume (p = 0.004, β=0.200, R2 = 0.034). Higher WMH volume predicted poorer processing speed (R2 = 0.052).

Relative to TBI history and PTSD, vascular risk may be more robustly associated with WM micro- and macrostructure. Furthermore, greater WMH burden is associated with poorer processing speed. Our study supports the importance of vascular health interventions in mitigating negative brain aging outcomes in Veterans.

White matter hyperintensity (WMH) volume is a neuroimaging marker of lesion load related to small vessel disease that has been associated with cognitive aging and Alzheimer’s disease (AD) risk.

The present study sought to examine whether regional WMH volume mediates the relationship between APOE ε4 status, a strong genetic risk factor for AD, and cognition and if this association is moderated by age group differences within a sample of 187 healthy older adults (APOE ε4 status [carrier/non-carrier] = 56/131).

After we controlled for sex, education, and vascular risk factors, ANCOVA analyses revealed significant age group by APOE ε4 status interactions for right parietal and left temporal WMH volumes. Within the young-old group (50-69 years), ε4 carriers had greater right parietal and left temporal WMH volumes than non-carriers. However, in the old-old group (70-89 years), right parietal and left temporal WMH volumes were comparable across APOE ε4 groups. Further, within ε4 non-carriers, old-old adults had greater right parietal and left temporal WMH volumes than young-old adults, but there were no significant differences across age groups in ε4 carriers. Follow-up moderated mediation analyses revealed that, in the young-old, but not the old-old group, there were significant indirect effects of ε4 status on memory and executive functions through left temporal WMH volume.

These findings suggest that, among healthy young-old adults, increased left temporal WMH volume, in the context of the ε4 allele, may represent an early marker of cognitive aging with the potential to lead to greater risk for AD.

To examine the prospective association between purpose in life measured at three points across middle and older adulthood and cognitive outcomes assessed 8–28 years later.

Prospective Study.

Wisconsin Longitudinal Study of Aging (WLS).

WLS participants who reported on their purpose in life at Round 4 (1992–1994; Mage = 52.58), Round 5 (2003–2007; Mage = 63.74), and/or Round 6 (2010–2012; Mage = 70.25) and were administered a cognitive battery at Round 7 (2020; Mage = 79.94) were included in the analysis (N = 4,632).

Participants completed the Ryff measure of purpose in life and were administered the telephone interview for cognitive status and measures of verbal fluency, digit ordering, and numeric reasoning.

Purpose in life measured at age 52 was related to better global cognitive function and verbal fluency but unrelated to dementia at age 80. In contrast, purpose in life at ages 63–70 was associated with lower likelihood of dementia, as well as better global cognitive function and verbal fluency at age 80. The effect sizes were modest (median Beta coefficient = .05; median odds ratio = .85). A slightly steeper decline in purpose in life between ages 52 and 70 was found for individuals with dementia at age 80.

Purpose in life is associated with healthier cognitive function measured up to 28 years later. Individuals with lower purpose, especially in their 60s or older, and with steeper declines in purpose, are more likely to have dementia at age 80.

Self- and informant-ratings of functional abilities are used to diagnose mild cognitive impairment (MCI) and are commonly measured in clinical trials. Ratings are assumed to be accurate, yet they are subject to biases. Biases in self-ratings have been found in individuals with dementia who are older and more depressed and in caregivers with higher distress, burden, and education. This study aimed to extend prior findings using an objective approach to identify determinants of bias in ratings.

Participants were 118 individuals with MCI and their informants. Three discrepancy variables were generated including the discrepancies between (1) self- and informant-rated functional status, (2) informant-rated functional status and objective cognition (in those with MCI), and (3) self-rated functional status and objective cognition. These variables served as dependent variables in forward linear regression models, with demographics, stress, burden, depression, and self-efficacy as predictors.

Informants with higher stress rated individuals with MCI as having worse functional abilities relative to objective cognition. Individuals with MCI with worse self-efficacy rated their functional abilities as being worse compared to objective cognition. Informant-ratings were worse than self-ratings for informants with higher stress and individuals with MCI with higher self-efficacy.

This study highlights biases in subjective ratings of functional abilities in MCI. The risk for relative underreporting of functional abilities by individuals with higher stress levels aligns with previous research. Bias in individuals with MCI with higher self-efficacy may be due to anosognosia. Findings have implications for the use of subjective ratings for diagnostic purposes and as outcome measures.

Numerous studies have shown a decrease in executive functions (EF) associated with aging. However, few investigations examined whether this decrease is similar between sexes throughout adulthood. The present study investigated if age-related decline in EF differs between men and women from early to late adulthood.

A total of 302 participants (181 women) aged between 18 and 78 years old completed four computer-based cognitive tasks at home: an arrow-based Flanker task, a letter-based Visual search task, the Trail Making Test, and the Corsi task. These tasks measured inhibition, attention, cognitive flexibility, and working memory, respectively. To investigate the potential effects of age, sex, and their interaction on specific EF and a global EF score, we divided the sample population into five age groups (i.e., 18–30, 31–44, 45–54, 55–64, 65–78) and conducted analyses of covariance (MANCOVA and ANCOVA) with education and pointing device as control variables.

Sex did not significantly affect EF performance across age groups. However, in every task, participants from the three youngest groups (< 55 y/o) outperformed the ones from the two oldest. Results from the global score also suggest that an EF decrease is distinctly noticeable from 55 years old onward.

Our results suggest that age-related decline in EF, including inhibition, attention, cognitive flexibility, and working memory, becomes apparent around the age of 55 and does not differ between sexes at any age. This study provides additional data regarding the effects of age and sex on EF across adulthood, filling a significant gap in the existing literature.

Normative neuropsychological data are essential for interpretation of test performance in the context of demographic factors. The Mayo Normative Studies (MNS) aim to provide updated normative data for neuropsychological measures administered in the Mayo Clinic Study of Aging (MCSA), a population-based study of aging that randomly samples residents of Olmsted County, Minnesota, from age- and sex-stratified groups. We examined demographic effects on neuropsychological measures and validated the regression-based norms in comparison to existing normative data developed in a similar sample.

The MNS includes cognitively unimpaired adults ≥30 years of age (n = 4,428) participating in the MCSA. Multivariable linear regressions were used to determine demographic effects on test performance. Regression-based normative formulas were developed by first converting raw scores to normalized scaled scores and then regressing on age, age2, sex, and education. Total and sex-stratified base rates of low scores (T < 40) were examined in an older adult validation sample and compared with Mayo’s Older Americans Normative Studies (MOANS) norms.

Independent linear regressions revealed variable patterns of linear and/or quadratic effects of age (r2 = 6–27% variance explained), sex (0–13%), and education (2–10%) across measures. MNS norms improved base rates of low performance in the older adult validation sample overall and in sex-specific patterns relative to MOANS.

Our results demonstrate the need for updated norms that consider complex demographic associations on test performance and that specifically exclude participants with mild cognitive impairment from the normative sample.

Neuropsychologists have difficulty detecting cognitive decline in high-functioning older adults because greater neurological change must occur before cognitive performances are low enough to indicate decline or impairment. For high-functioning older adults, early neurological changes may correspond with subjective cognitive concerns and an absence of high scores. This study compared high-functioning older adults with and without subjective cognitive concerns, hypothesizing those with cognitive concerns would have fewer high scores on neuropsychological testing and lower frontoparietal network volume, thickness, and connectivity.

Participants had high estimated premorbid functioning (e.g., estimated intelligence ≥75th percentile or college-educated) and were divided based on subjective cognitive concerns. Participants with cognitive concerns (n = 35; 74.0 ± 9.6 years old, 62.9% female, 94.3% White) and without cognitive concerns (n = 33; 71.2 ± 7.1 years old, 75.8% female, 100% White) completed a neuropsychological battery of memory and executive function tests and underwent structural and resting-state magnetic resonance imaging, calculating frontoparietal network volume, thickness, and connectivity.

Participants with and without cognitive concerns had comparable numbers of low test scores (≤16th percentile), p = .103, d = .40. Participants with cognitive concerns had fewer high scores (≥75th percentile), p = .004, d = .71, and lower mean frontoparietal network volumes (left: p = .004, d = .74; right: p = .011, d = .66) and cortical thickness (left: p = .010, d = .66; right: p = .033, d = .54), but did not differ in network connectivity.

Among high-functioning older adults, subjective cognitive decline may correspond with an absence of high scores on neuropsychological testing and underlying changes in the frontoparietal network that would not be detected by a traditional focus on low cognitive test scores.

Physical and recreational activities are behaviors that may modify risk of late-life cognitive decline. We sought to examine the role of retrospectively self-reported midlife (age 40) physical and recreational activity engagement – and self-reported change in these activities from age 40 to initial study visit – in predicting late-life cognition.

Data were obtained from 898 participants in a longitudinal study of cognitive aging in demographically and cognitively diverse older adults (Age: range = 49–93 years, M = 75, SD = 7.19). Self-reported physical and recreational activity participation at age 40 and at the initial study visit were quantified using the Life Experiences Assessment Form. Change in activities was modeled using latent change scores. Cognitive outcomes were obtained annually (range = 2–17 years) using the Spanish and English Neuropsychological Assessment Scales, which measure verbal episodic memory, semantic memory, visuospatial processing, and executive functioning.

Physical activity engagement at age 40 was strongly associated with cognitive performance in all four domains at the initial visit and with global cognitive slope. However, change in physical activities after age 40 was not associated with cognitive outcomes. In contrast, recreational activity engagement – both at age 40 and change after 40 – was predictive of cognitive intercepts and slope.

Retrospectively self-reported midlife physical and recreational activity engagement were strongly associated with late-life cognition – both level of performance and rate of future decline. However, the data suggest that maintenance of recreational activity engagement (e.g., writing, taking classes, reading) after age 40 is more strongly associated with late-life cognition than continued maintenance of physical activity levels.

Adverse childhood experiences (ACEs) may be a risk factor for later-life cognitive disorders such as dementia; however, few studies have investigated underlying mechanisms, such as cardiovascular health and depressive symptoms, in a health disparities framework.

418 community-dwelling adults (50% nonHispanic Black, 50% nonHispanic White) aged 55+ from the Michigan Cognitive Aging Project retrospectively reported on nine ACEs. Baseline global cognition was a z-score composite of five factor scores from a comprehensive neuropsychological battery. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale. Cardiovascular health was operationalized through systolic blood pressure. A mediation model controlling for sociodemographics, childhood health, and childhood socioeconomic status estimated indirect effects of ACEs on global cognition via depressive symptoms and blood pressure. Racial differences were probed via t-tests and stratified models.

A negative indirect effect of ACEs on cognition was observed through depressive symptoms [β = −.040, 95% CI (−.067, −.017)], but not blood pressure, for the whole sample. Black participants reported more ACEs (Cohen’s d = .21), reported more depressive symptoms (Cohen’s d = .35), higher blood pressure (Cohen’s d = .41), and lower cognitive scores (Cohen’s d = 1.35) compared to White participants. In stratified models, there was a negative indirect effect through depressive symptoms for Black participants [β = −.074, 95% CI (−.128, −.029)] but not for White participants.

These results highlight the need to consider racially patterned contextual factors across the life course. Such factors could exacerbate the negative impact of ACEs and related mental health consequences and contribute to racial disparities in cognitive aging.

Adverse childhood experiences (ACEs) have been associated with worse cognitive health in older adulthood. This study aimed to extend findings on the specificity, persistence, and pathways of associations between two ACEs and cognition by using a comprehensive neuropsychological battery and a time-lagged mediation design.

Participants were 3304 older adults in the Health and Retirement Study Harmonized Cognitive Assessment Protocol. Participants retrospectively reported whether they were exposed to parental substance abuse or experienced parental physical abuse before age 18. Factor scores derived from a battery of 13 neuropsychological tests indexed cognitive domains of episodic memory, executive functioning, processing speed, language, and visuospatial function. Structural equation models examined self-reported years of education and stroke as mediators, controlling for sociodemographics and childhood socioeconomic status.

Parental substance abuse in childhood was associated with worse later-life cognitive function across all domains, in part via pathways involving educational attainment and stroke. Parental physical abuse was associated with worse cognitive outcomes via stroke independent of education.

This national longitudinal study in the United States provides evidence for broad and persistent indirect associations between two ACEs and cognitive aging via differential pathways involving educational attainment and stroke. Future research should examine additional ACEs and mechanisms as well as moderators of these associations to better understand points of intervention.

Subjective cognitive decline (SCD) is a potential early risk marker for Alzheimer’s disease (AD), but its utility may vary across individuals. We investigated the relationship of SCD severity with memory function and cerebral blood flow (CBF) in areas of the middle temporal lobe (MTL) in a cognitively normal and overall healthy sample of older adults. Exploratory analyses examined if the association of SCD severity with memory and MTL CBF was different in those with lower and higher cardiovascular disease (CVD) risk status.

Fifty-two community-dwelling older adults underwent magnetic resonance imaging, neuropsychological testing, and were administered the Everyday Cognition Scale (ECog) to measure SCD. Regression models investigated whether ECog scores were associated with memory performance and MTL CBF, followed by similar exploratory regressions stratified by CVD risk status (i.e., lower vs higher stroke risk).

Higher ECog scores were associated with lower objective memory performance and lower entorhinal cortex CBF after adjusting for demographics and mood. In exploratory stratified analyses, these associations remained significant in the higher stroke risk group only.

Our preliminary findings suggest that SCD severity is associated with cognition and brain markers of preclinical AD in otherwise healthy older adults with overall low CVD burden and that this relationship may be stronger for individuals with higher stroke risk, although larger studies with more diverse samples are needed to confirm these findings. Our results shed light on individual characteristics that may increase the utility of SCD as an early risk marker of cognitive decline.

Educational attainment is a well-documented predictor of later-life cognition, but less is known about upstream contextual factors. This study aimed to identify which early-life contextual factors uniquely predict later-life global cognition and whether educational attainment mediates these relationships.

Participants were drawn from the Michigan Cognitive Aging Project (N = 485; Mage = 63.51; SDage = 3.13; 50% non-Hispanic Black). Early-life exposures included U.S. region of elementary school (Midwest, South, Northeast), average parental education, household composition (number of adults (1, 2, 3+), number of children), school racial demographics (predominantly White, predominantly Black, diverse), self-reported educational quality, and school type (public/private). Later-life global cognition was operationalized with a factor score derived from a comprehensive neuropsychological battery. Sequential mediation models controlling for sociodemographics estimated total, direct, and indirect effects of early-life contextual factors on cognition through educational attainment (years).

Higher educational quality, higher parental education, and attending a private school were each associated with better cognition; attending a predominantly Black or diverse school and reporting three or more adults in the household were associated with lower cognition. After accounting for educational attainment, associations remained for educational quality, school type, and reporting three or more adults in the household. Indirect effects through educational attainment were observed for school region, educational quality, school racial demographics, and parental education.

School factors appear to consistently predict later-life cognition more than household factors, highlighting the potential long-term benefits of school-level interventions for cognitive aging. Future research should consider additional mediators beyond educational attainment such as neighborhood resources and childhood adversity.

Brain reserve, cognitive reserve, and education are thought to protect against late-life cognitive decline, but these variables have not been directly compared to one another in the same model, using future cognitive and functional decline as outcomes. We sought to determine whether the influence of these protective factors on executive function (EF) and daily function decline was dependent upon Alzheimer’s disease (AD) pathology severity, as measured by the total tau to beta-amyloid (T-τ/Aβ1-42) ratio in cerebrospinal fluid (CSF).

Participants were 1201 older adult volunteers in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) study. Brain reserve was defined using a composite index of structural brain volumes (total brain matter, hippocampus, and white matter hyperintensity). Cognitive reserve was defined as the variance in episodic memory performance not explained by brain integrity and demographics.

At higher levels of T-τ/Aβ1-42, brain and cognitive reserve predicted slower decline in EF. Only brain reserve attenuated decline at lower levels of T-τ/Aβ1-42. Education had no independent association with cognitive decline.

These results point to a hierarchy of protection against aging- and disease-associated cognitive decline. When pathology is low, only structural brain integrity predicts rate of future EF decline. The ability of cognitive reserve to predict future EF decline becomes stronger as CSF biomarker evidence of AD increases. Although education is typically thought of as a proxy for cognitive reserve, it did not show any protective effects on cognition after accounting for brain integrity and the residual cognitive reserve index.

This study evaluated: (1) apolipoprotein E (APOE) ϵ4 prevalence among Black, Latino, and White older adults, (2) associations of APOE ϵ4 status with baseline level and change over time of cognitive outcomes across groups, and (3) combined impact of APOE ϵ4 prevalence and magnitude of effect on cognitive decline within each racial/ethnic group.

Participants included 297 White, 138 Latino, and 149 Black individuals from the longitudinal UC Davis Diversity Cohort who had APOE genotyping and ≥2 cognitive assessments. Magnitude of associations of ϵ4 with cognitive baseline and change across racial/ethnic groups was tested with multilevel parallel process longitudinal analyses and multiple group models.

ϵ4 prevalence in Black (46%) and White participants (46%) was almost double that of Latino participants (24%). ϵ4 was associated with poorer baseline episodic memory only in White participants (p = .001), but had a moderately strong association with episodic memory change across all racial/ethnic groups (Blacks= −.061 SD/year, Latinos = −.055,Whites= −.055). ϵ4 association with semantic memory change was strongest in White participants (−.071), intermediate in Latino participants (−.041), and weakest in Black participants (−.022).

Calculated cognitive trajectories across racial/ethnic groups were influenced in an additive manner by ϵ4 prevalence and strength of association with cognitive decline within the group. Group differences in ϵ4 prevalences and associations of ϵ4 with cognition may suggest different pathways from APOE to cognitive decline, and, AD possibly having less salient impact on cognitive decline in non-White participants. Differential effects of APOE on episodic memory and non-memory cognition have important implications for understanding how APOE influences late life cognitive decline.

Most recordings of verbal fluency tasks include substantial amounts of task-irrelevant content that could provide clinically valuable information for the detection of mild cognitive impairment (MCI). We developed a method for the analysis of verbal fluency, focusing not on the task-relevant words but on the silent segments, the hesitations, and the irrelevant utterances found in the voice recordings.

Phonemic (‘k’, ‘t’, ‘a’) and semantic (animals, food items, actions) verbal fluency data were collected from healthy control (HC; n = 25; M age = 67.32) and MCI (n = 25; M age = 71.72) participants. After manual annotation of the voice samples, 10 temporal parameters were computed based on the silent and the task-irrelevant segments. Traditional fluency measures, based on word count (correct words, errors, repetitions) were also employed in order to compare the outcome of the two methods.

Two silence-based parameters (the number of silent pauses and the average length of silent pauses) and the average word transition time differed significantly between the two groups in the case of all three semantic fluency tasks. Subsequent receiver operating characteristic (ROC) analysis showed that these three temporal parameters had classification abilities similar to the traditional measure of counting correct words.

In our approach for verbal fluency analysis, silence-related parameters displayed classification ability similar to the most widely used traditional fluency measure. Based on these results, an automated tool using voiced-unvoiced segmentation may be developed enabling swift and cost-effective verbal fluency-based MCI screening.