In the United States, Alzheimer’s disease (AD) is the most common cause of dementia and the seventh leading cause of death. Exercise has demonstrated health benefits in older adults and reduces the risk of developing AD. Exploring underlying biological mechanisms of exercise could aid in identifying therapeutic targets to prevent AD progression, especially for high-risk individuals such as those with Mild Cognitive Impairment (MCI). Many studies of dementia focus on memory; however, executive function and processing speed are also vulnerable to the neuropathology that causes AD. This exploratory study aimed to identify potential mechanisms by which physical activity can facilitate change in cognitive functioning in older adults. This was accomplished by investigating correlations between changes in neurology-related plasma proteins and changes in measures of executive function and processing speed after participation in a water-based exercise intervention.

The sample included 20 older adults with amnestic MCI, ages 55-82 years (mean 68.15 ±7.75). Participants were predominately male (90%), White (70%), and non-Hispanic (85%), with more than high school education (95%). Participants engaged in supervised high-intensity water-based exercise three times per week for six months. Neuropsychological assessments and blood samples were assessed at baseline and after completion of the exercise intervention. Cognitive measures included: the Digit Span subtests from the Wechsler Adult Intelligence Scale, 4th Edition, Trail-Making Test (TMT), Stroop Color Word Test (SCWT), and the Symbol Digit Modalities Test (SDMT). Plasma protein levels were analyzed using the Olink Target 96 Neurology assay (Uppsala, Sweden), selected a priori for the established markers linked to neurobiological processes and diseases. Changes in cognitive measures and protein levels were assessed using paired-sample t-tests, and Pearson’s correlations were calculated for significant findings.

Participants’ cognitive performance significantly improved on the SCWT color trial (t = -2.19, p = 0.042) and SDMT (t = -2.17, p = .043). Significant decreases in plasma proteins levels were found for GDNF family receptor alpha-1 ([GFRA1]: t =2.05, p = 0.055), neuroblastoma suppressor tumorigenicity-1 ([NBL1]: t = 2.13, p= .046), and neuropilin-2 ([NRP2]: t = 2.61 p= 0.017). Correlational analyses showed reductions in NBL1 were significantly associated with changes in both SDMT (r = -.61, p = 0.006) and the color trial of SCWT (r = .48, p = .038), and NRP2 was significantly associated with improvement on the SDMT (r = -.46, p = 0.045). GFRA1 was not significantly associated with change on any cognitive measure.

In a sample of older adults with MCI, participation in high-intensity water-based exercise led to significant improvements in cognitive function as well as changes in neurological plasma proteome. Improved outcomes in processing speed, attention, visuospatial scanning, and working memory were associated with changes in specific plasma protein concentrations. This highlights potential activity-dependent neurobiological mechanisms that may underlie the cognitive benefits derived from physical activity. Future studies should explore these findings in Randomized Control Trials with a comparative condition and larger sample size.

Gait speed is associated with poorer executive functioning performance in older adults such that individuals with slower gait speed have shown declines in cognitive flexibility and set-shifting. Body mass index (BMI) is associated with sedentary lifestyles and slower gait speed, and has demonstrated negative effects on executive set-shifting in this population. However, the interaction between gait speed, BMI, and executive functioning has yet to be examined. The purpose of this study is to investigate the potential mediating effect of BMI on the negative relationship between gait speed and executive functioning in older adults.

The sample included 154 community-dwelling older adults drawn from two clinical trials. Participants were recruited from the VA Palo Alto Health Care System and Stanford/VA Alzheimer’s Disease Research Center. Gait speed was measured using the six-minute walk test, with longer distances representing faster gait speeds. Weight and height were used to calculate BMI. Each participant completed the Trail Making Test Part B (TMTB), which was used to measure executive functioning. A simple mediation analysis was performed using SPSS PROCESS Macro version 3.5. The outcome variable for the analysis was TMTB completion times. The predictor variable was gait speed, and the mediator variable was BMI. Age was entered as a covariate. We hypothesized that gait speed will negatively predict time to completion on the executive functioning task. We also hypothesized that BMI will mediate this relationship.

The analysis found that gait speed negatively predicted executive functioning scores (b = -.12, p = .02). The overall mediation model was statistically significant (F(3,150) =9.17, p < .001). Gait speed and age negatively predicted BMI (p < .001). BMI was a significant predictor of executive functioning (p = .001). The direct effect of gait speed on executive functioning remained significant after including BMI in the model (p < .001), which suggests that BMI partially mediated the relationship between gait speed and executive functioning. The indirect effect of the model when including BMI was tested using the bootstrap estimation approach with 5,000 samples, and was found to be significant (95% CI [.03,.11]), indicating that mediation did occur in the analysis.

BMI partially mediated the relationship between gait speed and executive set-shifting. Thus, the path by which gait speed predicted executive functioning abilities was partially attributable to BMI, one measure of obesity. This finding suggests that older adults with slower gait speeds may have poorer executive function partially due to greater BMI. Given the importance of executive functions on independence and well-being in older adulthood, management of BMI could lead to improved functioning and quality of life. Interventions to decrease weight in older adults is likely to result in several positive health outcomes, and these results suggest that they may also promote important cognitive processes.

Although relationships between Fried frailty criteria (i.e., weakness, slowness, weight loss, exhaustion and low physical activity), cognitive decline, and adverse childhood experiences (ACEs) have been examined (Brigalo et al., 2015, Brown et al., 2022, Fabricio et al., 2020, & Tani et al., 2021), the moderating effect of age on the relationship between ACEs and frailty has yet to be explored. The present study examined whether age moderates the relationship between total number of ACEs and number of frailty criteria in older age.

137 older adults were recruited from University of Miami clinics and surrounding community care centers. Collected data included demographic information, number of frailty criteria met, and number of ACEs endorsed. Participants were primarily Hispanic-White (64.2%) and female (56.9%), with a mean age of 73.62 years (SD=6.252). Data were initially analyzed using descriptive statistics. A hierarchical linear regression was run to test the effect of ACE score on number of frailty criteria met. A simple moderation analysis using the PROCESS macro was then performed with total number of medical conditions included as a covariate to address any potentially confounding effects. To avoid multicollinearity issues, number of ACEs endorsed and age were mean centered and an interaction term between the two was produced.

Scores on the ACE did substantially effect the total number of frailty criteria met by participants in this study (f=2.37, p=0.028, ΔR2=0.023), independent of number of medical conditions. The overall moderation model was significant (f=2.99, p=0.022, R2=0.103), and the addition of the interaction effect resulted in a statistically significant change to the model (f=4.08, p=0.045, ΔR2=0.035). Taken together, support for a moderating effect was found, specifically within the lower age group (65 - 71years), but not older (greater than 72 years) with ACE score positively predicting the number of frailty criteria met (b =0.230, t=2.62, p=0.010).

Results largely support the positive effect of ACE endorsement on the number of frailty criteria met in later life. Age acted as a moderating effect, for the younger old population, such that as number of ACEs endorsed increased, so too did the number of frailty criteria met. This finding highlights the importance of early intervention among those in younger late life who have experienced trauma. Given the positive relationship between frailty and cognitive decline in late life (Brigalo et al., 2015 & Fabricio et al., 2020), these findings also support the need for a better understanding of how childhood adversity impacts physical well-being over the life course.

Hypertension is a common disorder that has been inconsistently associated with worse cognition in older adults. Antihypertensive medications offer treatment for high blood pressure but previous studies on the association between blood pressure, antihypertensive use, and cognitive performance in older adults have yielded inconsistent findings. Individuals without high blood pressure may also take antihypertensive medications for other medical conditions, including migraines. It is unclear whether antihypertensive medications have any effect on cognitive performance in older adults, and whether the differences, if any, are similar in hypertensives and normotensives.

4,969 participants from the National Alzheimer Coordinating Center (NACC) database were included in this study (Mage=72.4 years, SD=7.3 years). Cognitive assessment included Letter Fluency, Category Fluency (animals and vegetables), Trail Making Test A & B, Digit Ordering (forward and backward), and MoCA total score. Participants were included if they had a clinician diagnosis of hypertension or normotension and recorded history of whether they take any antihypertensive medication. Participants with a history of stroke were excluded. Cognitive differences between medication groups were investigated in hypertensive participants and normotensive participants using Bayesian Mann-Whitney tests.

Bayesian Mann-Whitney tests in hypertensive individuals showed no cognitive differences between those taking antihypertensive medications and those not taking antihypertensives (all BF10s < 3). Bayesian Mann-Whitney tests in normotensive individuals showed individuals taking antihypertensive medications performed worse on Trail Making Test B compared to individuals not taking antihypertensives (123.6 seconds vs 108.8 seconds; BF10 = 35.1), with a small effect size (d=-.156).

These results suggest that antihypertensive use in older adults with normal blood pressure may be associated with worse executive functioning. Antihypertensive use in normotensive older adults may lower blood pressure and reduce cerebral perfusion, resulting in worse cognitive functioning. Future studies should investigate long-term antihypertensive use and associated cognitive changes in both hypertensive and normotensive individuals.

When deciding between now and later, the tendency to devalue later outcomes is known as temporal discounting. The degree of devaluing is known as one’s discounting rate. Steeper temporal discounting rates indicate preferences for immediate gains and delayed losses, reflecting a desire for instant gratification and greater loss aversion, respectfully. Considering that decrements in decision-making abilities may precipitate cognitive dysfunction and decline, a better understanding of decision-making preferences among older adults represents an important endeavor. Thus, the current study aimed to investigate whether differences among temporal discounting rates for gains and losses exist when outcomes are monetary or interpersonal in nature.

One hundred and forty community-dwelling older adults aged 50 to 90 (75% female, Mage=71.6) completed a hypothetical discounting task in which they chose between smaller immediate outcomes and larger delayed outcomes presented at various delay periods of one week, one month, six months, and one year. An iterative algorithm determined the indifference point for each delay period. Indifference points were fit to hyperbolic models using nonlinear regressions to determine discounting rates within each condition. Nonparametric Wilcoxon Signed-Rank tests compared discounting rates.

Older adults more steeply discounted monetary gains as compared to monetary losses (Z=-6.88, p<.001), as well as for social gains compared to social losses (Z=-4.81, p<.001). They also discounted social gains more steeply than monetary gains (Z=-5.44, p<.001), and social losses more steeply than monetary losses (Z=-4.44, p<.001).

Preliminary findings suggest older adults displayed a greater desire for instant gratification of rewards, particularly social rewards, yet also displayed lower loss aversion, particularly for monetary losses. Stronger preferences for instant gratification of gains in certain contexts may inform ways in which healthier lifestyle choices or changes could be framed to appeal to older adults.

COVID-19 misinformation proliferating online has led to adverse health and societal consequences. Older adults are a particularly vulnerable population due to increased risk for both COVID-19 related complications and susceptibility to, as well as sharing of, misinformation on social networking sites. The present study aimed to: 1) investigate differences in COVID-19 headline accuracy discernment and online sharing of COVID-19 misinformation in older and younger adults; and 2) examine individual differences in global cognition, health literacy and verbal IQ in online sharing of COVID-19 misinformation.

Fifty-two younger (age 18 to 35 years) and fifty older adults (age 50 and older) completed a telephone neurocognitive battery, health literacy and numeracy measures and self-report questionnaires. Participants also completed a social media headline-sharing experiment (Pennycook et al.,2020) in which they were presented true and false COVID-19 headlines and asked to indicate: 1) the likelihood that they would share the story on social media; and 2) the factual accuracy of the story.

A repeated measures multivariate analysis of variance controlling for gender and race/ethnicity showed no effects of age (p=.099), but a significant interaction between actual COVID-19 headline accuracy and likelihood of sharing (p<.001), such that accuracy is more strongly related to sharing false headlines (r=-.64) versus true headlines (r=-.43). Moreover, higher likelihood of sharing false COVID-19 headlines was associated with lower verbal IQ and numeracy skills in older adults (rs=-.51--.40; ps<.01) and with lower verbal IQ, numeracy, and global cognition in younger adults (rs=-.66--.60; ps<.01).

Findings indicate that headline accuracy judgements are an important predictor of sharing COVID-19 misinformation in both older and younger adults. Further, individual differences in cognition, IQ, and numeracy may predict the likelihood of misinformation sharing in younger adults, while IQ and numeracy skills may act as important antecedents of misinformation sharing in older adults. Future work might leverage modern, neuropsychologically-based psychoeducation approaches to improving health and science literacy related to COVID-19.

The world population is rapidly aging, and consequently, cognitive decline is becoming a larger public health crisis. There is no cure for dementia, but exercise has been consistently shown to improve cognitive function and slow cognitive decline in older adults. Given the many barriers to starting an exercise routine, walking is a particularly appealing intervention because it is safe, low-impact, and highly accessible (i.e., no upfront costs, no necessary equipment, and can be done almost anywhere and by anyone, given they are ambulatory). This abstract describes a systematic review and meta-analysis on peer-reviewed studies that examined randomized walking interventions for cognitive function in older adults.

The analyses included 1,286 older adults aged 55 and older (mean age = 73.1 years) across 19 studies that met inclusion criteria. All studies were randomized controlled trials (RCTs) of walking interventions with pre-post cognitive outcome data. A total of eight cognitive domains were identified: global cognition, attention, processing speed, working memory, language, visuospatial skills, declarative memory, and executive function. Effect sizes, measured as net treatment gain, were extracted and converted to Hedges’ g. Three-level meta-analysis was used to account for dependency of effect sizes. Meta-regression analyses were used to examine whether the following variables moderated effect sizes: (a) cognitive status, (b) baseline activity level, (c) age, (d) walking intervention duration, and (e) duration of individual walking sessions.

Participation in walking interventions significantly benefitted broad cognitive functioning (Hedges’ g = 0.19). The cognitive domains that specifically benefitted from walking were global cognition (g = 0.60), processing speed (g = 0.15), working memory (g = 0.22), declarative memory (g = 0.18), and executive functioning (g = 0.15). Cognitive status moderated this relationship, so that cognitively impaired older adults showed greater cognitive benefit from walking interventions. Baseline activity level did not moderate the effect; being sedentary at baseline yielded an effect size significantly greater than zero. The remaining moderator analyses were nonsignificant.

This systematic review and meta-analysis shows that walking interventions are associated with broad improvement in cognitive function in older adults. Walking benefits global cognition, processing speed, working memory, declarative memory, and executive function— the same cognitive domains that decline with normal cognitive aging. These findings are particularly important because walking is among the safest and most universally accessible forms of exercise. This will help healthcare providers make better lifestyle recommendations to their older patients. Future research should more rigorously examine potential moderating variables, such as walking intensity.

Compliance with safety precautions plays significant role in containing pandemic. On a personal level, one critical precaution is to disclose sickness status to people who one comes into direct contact with. Yet, factors governing this personal decision remain uncertain. This study examined age-related differences across adulthood in (i) the likelihood to disclose symptoms of sickness (LDSS) during COVID-19 pandemic, (ii) the level of COVID-19-associated anxiety (CAA), and (iii) the relationship between LDSS and CAA.

Data were obtained from a large-scale survey “Measuring Worldwide COVID-19 Attitudes and Beliefs” (Fetzer et al., 2020). Retained data included sociodemographic characteristics, number of chronic conditions and self-rated quality of health for USA sample (n=11,445) which we stratified by age into five groups (18-29 years old n=2065; 30-39 n=3765; 40-49 n=2463; 50-59 n=1760; 60+ n=1392). Disclosure of sickness was measured with statement: “in the past week if I had exhibited symptoms of sickness, I would have immediately informed the people around me”, where participants self-rated it on the scale from 0–“does not apply at all to me” to 100– “applies very much to me”. We computed LDSS score with thresholds: ≤50–unlikely/uncertain, >50–likely, 100–certain to disclose. CAA symptoms were measured with the following statements which participants self-rated on a scale from 1–“does not apply at all” to 5– “strongly applies”: I am nervous when I think about current circumstances; I am calm and relaxed; I am worried about my health; I am worried about the health of my family members; I am stressed about leaving my house. ANOVA w/Bonferroni post-hoc tests compared LDSS and CAA between the age groups. Multivariate regression (accounting for: gender, education, self-rated health, number of chronic conditions) examined LDSS–CAA relationship.

Age groups were comparable in gender (∼40% males), education (∼17 years of education), and relationship status (∼65% married/cohabitating). Most participants rated own health as good and reported one chronic condition. LDSS was increasing with aging, F(df=4)=35.552 (p<0.001), with 72% youngest vs. 85% oldest adults indicating certainty about disclosing sickness status. Anxiety about own health was increasing with age, F(df=4)=7.319 (p<0.001), while anxiety about health of family members was decreasing with age, F(df=4)=25.398 (p<0.001). Middle-aged adults showed the highest anxiety related to thinking about the current circumstances, F(df=4)=10.476 (p<0.001), and feeling stressed about leaving own house, F(df=4)=6.368 (p<0.001). LDSS was positively related to anxiety about health of family members and/or feeling stressed about leaving own house in young and middle-aged adults (B=0.042, p=0.001, CI95%=0.017–0.068), but not related to any CAA symptoms in adults aged 60+.

This study suggests that people can become more likely to disclose sickness status as they age and can be prone to different CAA symptoms across life stages. The results further indicate that distinct CAA symptoms can play a role in LDSS in young and middle adulthood, but may loose significance in older age. Acknowledgement of these diverse mechanisms can inform clinical practice dedicated to individuals with illness anxiety, as well as can help develop age-targeted campaigns that promote compliance with the safety precautions.

The presence of an e4 allele of the apolipoprotein E gene (APOE ε4) is considered the strongest genetic risk factor for Alzheimer’s disease (AD) in the US. Evidence suggests that APOE ε4 carriers have worse memory performances compared to APOE ε4 non-carriers in cognitively normal older adults and that female APOE ε4 carriers are at greater risk of AD compared to male carriers. Recent advancements in estimating biological age using DNA methylation markers may enhance understanding of the associations between sex and APOE ε4 on cognitive aging. Thus, the current study aimed to investigate whether associations between APOE ε4 status and memory vary according to rates of biological aging, using a DNA methylation age biomarker, in older men and women without dementia.

Cross-sectional data were obtained from 1771 older adults enrolled in the 2016 wave of the Health and Retirement Study (Mean age = 75, SD = 7; 57% female; 76% non-Hispanic white). The standardized residual from regressing chronological age on the epigenetic clock “DNAGrimAge” was used as a measure of the aging rate. A series of ANCOVAs with Bonferroni corrected post hoc pairwise tests, adjusting for education, white blood cell count, chronological age, and depressive symptoms were used to test the main and interaction effects of APOE ε4 status (non-carriers = 0; carriers = 1) and aging rates, defined as 1 standard deviation below (i.e., slow rate), or above (i.e., fast rate) sex-specific mean rate (i.e., average) of aging, on a standardized composite measure of verbal memory. Alpha was set at .05 and all raw scores were converted to z-score metric prior to analyses.

APOE ε4 female carriers with slow rates of aging (n = 34) had significantly better memory performances compared to APOE ε4 female carriers with fast rates of aging (n = 41), mean difference = .61, p = .006, and average rates of aging (n = 170), mean difference = .44, p = .017. There was no effect of aging rate on memory in the female non-carriers and there were no significant differences in memory performances based on rates of aging in either male APOE ε4 carriers or non-carriers.

Although the presence of the APOE ε4 has previously been shown to represent a stronger risk of AD for women compared to men, results from the current study suggest that slower rates of aging in this high-risk group may confer protection against clinical symptoms (i.e., memory impairment). Conversely, faster than average aging in female APOE ε4 carriers may represent a group at greater risk of memory impairment due to AD. However, longitudinal studies with larger sample sizes are needed to evaluate the risk of dementia/memory impairment based on rates of aging in female APOE ε4 carriers.

Higher cardiovascular burden and peripheral inflammation are associated with small vessel vascular disease, a predominantly dysexecutive cognitive profile, and a higher likelihood of conversion to vascular dementia. The digital clock drawing test, a digitized version of a standard neuropsychological tool, is useful in identifying cognitive dysfunction related to vascular etiology. However, little is known about the specific cognitive implications of vascular risk, peripheral inflammation, and varying levels of overall brain integrity. The current study aimed to examine the role of cardiovascular burden, peripheral inflammation, and brain integrity on digitally acquired clock drawing latency and graphomotor metrics in non-demented older adults.

The final prospectively recruited IRB-consented participant sample included 184 non-demented older adults (age: 69±6 years, education: 16±3 years, 46% female, 94% white) who completed digital clock drawing, vascular assessment, blood draw, and brain MRI. Digital clock drawing variables of interest included: total completion time (TCT), pre-first hand latency (PFHL), digit misplacement, hour hand distance from center, and clock face area (CFA). Cardiovascular burden was calculated using the revised version of the Framingham Stroke Risk Profile (FSRP-10). Peripheral inflammation was operationalized using interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor alpha (TNF-a), and high sensitivity C-reactive protein (hsCRP). The brain integrity composite was comprised of bilateral entorhinal cortex volume, bilateral ventricular volume, and whole brain leukoaraiosis.

Over and above age and cognitive reserve, hierarchical regressions showed FSRP-10, inflammatory markers, and brain integrity explained an additional 13.3% of the variance in command TCT (p< 0.001), with FSRP-10 (p=0.001), IL-10 (p= 0.019), and hsCRP (p= 0.019) as the main predictors in the model. FSRP-10, inflammatory markers, and brain integrity explained an additional 11.7% of the variance in command digit misplacement (p= 0.009), with findings largely driven by FSRP-10 (p< 0.001).

Overall, in non-demented older adults, subtle behavioral nuances seen in digital clock drawing metrics (i.e., total completion time and digit misplacement) are partly explained by cardiovascular burden, peripheral inflammation, and brain integrity over and above age and cognitive reserve. These nuanced behaviors on digitally acquired clock drawing may associate with an emergent disease process or overall vulnerability.

Funding sources: Barber Fellowship; K07AG066813; R01 AG055337; R01 NR014810; American Psychological Foundation Dissertation Award; APA Dissertation Research Award

Subjective cognitive decline (SCD), the self-reported experience of worsening cognitive abilities (Jessen et al., 2014), is associated with increased risk of developing Alzheimer’s disease and Mild Cognitive Impairment. Modifiable factors such as purpose in life (PiL), the experience of living a meaningful life where one’s life goals are attainable or being achieved (Boyle et al., 2009), and loneliness, an individual’s perceived social isolation (Luhmann & Hawkley, 2016), are known to be associated with SCD. These relationships are understudied among ethnically diverse groups. Using an online survey, we examined associations between PiL, loneliness and SCD in older ethnically diverse individuals living in the US.

870 older adults (126 Latino, 74 Black, 33 Asian, and 637 White; average age=67.0 [7.6]) completed an online survey including the Life Purpose Questionnaire, the Gierveld Loneliness Scale, and the Everyday Cognition scale (ECog), which measures subjective cognitive concerns in memory, language, executive function, and divided attention. Chi-square tests and analyses of variance were conducted to assess group differences in SCD and demographic/lifestyle predictors. Multiple regressions and correlations were conducted to assess the relationships between ethnicity and PiL with SCD, and the moderating effect of race/ethnicity. Multiple regressions and correlations were conducted to identify sociodemographic and lifestyle predictors of SCD in each study group.

White participants were older (p<.001), and White and Asian groups had higher levels of education (p=.009) compared to Latinos. The White group had a higher proportion of female (p=.016) and middle-income (p=.019) respondents. Black participants had higher PiL (p=.035) and lower loneliness (p=.047) compared to White participants; there were no group differences in ECog ratings (p=.143). Regression results indicated that higher PiL associated with lower SCD in the whole sample (β=-.435, p<.001). The interaction between PiL and ethnic group was significant (β=.078, p=.025), suggesting the relationship between PiL and SCD was strongest in White participants, followed by Asian, then Latino, and finally Black participants. In Latinos, female sex (β=-.281, p=.004) and higher PiL (β=-.240, p=.034) predicted lower SCD ratings. In White participants, higher PiL (β = -.394, p < .001), and lower loneliness (β = .128, p = .003) predicted lower SCD ratings. Correlation analyses revealed no significant associations with SCD in the Black group, although the correlation between loneliness and SCD was trending (r=.222, p=.063). In the Asian group, greater PiL was associated with lower SCD ratings (r=-.439, p=.011).

Our findings suggest that PiL may be protective against SCD, particularly in Latino, Asian, and White adults. Differential predictive factors of SCD were also identified for our study groups, suggesting certain groups may benefit from specific targeted interventions. Overall, findings suggest that interventions geared toward increasing PiL and/or mitigating loneliness may help reduce SCD and the risk of cognitive decline in older adults in the US. As the current study was cross-sectional and faced sample size limitations in Asian and Black groups, future studies should include longitudinal assessment of these associations with larger and more representative samples to confirm our findings.

Depression is a common problem among older adults and is further exacerbated by poor treatment response. The vascular depression hypothesis suggests that white matter hyperintensities (WMH) and executive dysfunction are main contributors to treatment non-response in older adults. While a previous meta-analysis has demonstrated the effects of executive dysfunction on treatment response, similar techniques have not been used to address the relationship between WMH and treatment response. Multiple commonly-cited studies demonstrate a relationship between WMH and treatment response, however, the literature on the predictive nature of the relationship is quite inconsistent. Additionally, many studies supporting this relationship are not randomized controlled studies. Critically examining data of well-controlled treatment response outcome studies using meta-analytic methods will allow for an aggregate evaluation of the relationship between WMH burden and treatment response.

A MEDLINE search was conducted to identify regimented antidepressant treatment trials contrasting white matter hyperintensity burden between remitters and non-remitters. Only regimented treatment trials for depressed outpatients aged 50 and older that had a pre-treatment measure of WMH burden and remitter/non-remitter comparison were included. Hedge’s g was calculated for each trial’s treatment effect. A Bayesian meta-analysis was used to estimate an aggregate effect size.

Eight studies met inclusion criteria. The log odds ratios average was significantly less than zero (.25, SE=.12, p=.019), suggesting that there is a significant effect of WMH hyperintensity burden on antidepressant remission status.

The purpose of this meta-analysis was to rigorously evaluate randomized controlled trials to determine the relationship between WMH burden and antidepressant treatment response. Findings revealed that WMH burden predicted antidepressant remission, that is, individuals with high WMH burden are less likely to meet remission criteria compared to individuals with low WMH burden. Results suggest that it may be important to consider vascular depression as a distinct treatment target of alternate interventions.

Although the relationship between visual attention, impulsivity, and cognitively restrained eating patterns has been established in previous research, less is known about the relationship of cognitive processes and disinhibited eating patterns in older adults. Research postulates that disinhibited eating behaviors may be associated with stress, limited emotional capacity, anxiety, and impulsivity. The current study investigated impulsivity as a potential mediator of the relationship between visual attention and disinhibited eating in older veterans.

This study included 101 Veterans who were screened as part of a larger study assessing the impact of multi-modal activity-based interventions on brain health in older adulthood. The sample included largely White (76%), male (94%) Veterans aged 54 to 88 (M = 70.1, SD 8.9). The Three-Factor Eating Questionnaire was used to assess daily disinhibited eating patterns, and attentional impulsivity was assessed with the Barratt Impulsiveness Scale. Visual attention was evaluated using the Stroop Color Word Test (Color Trial). Mediation analyses were conducted using the SPSS PROCESS Macro. The outcome variable for analysis was disinhibited eating. The predictor variable was visual attention. The mediator variable was impulsivity. Body mass index (BMI) was included as a covariate as it was significantly associated with the predictor and outcome variables.

The indirect effect of visual attention on disinhibited eating was found to be statistically significant (effect = 0.06, 95%: 0.02, 0.12)

Attentional impulsivity appears to mediate the relationship between visual attention and disinhibited eating behaviors. This finding extends the current literature about the relationship between visual attention, impulsivity, and other eating patterns (e.g., cognitively restrained eating) in older adults. Exploring this relationship helps us better understand the impact of eating habits through the aging process. Caregivers and older adults should be informed about the impact of increased impulsivity on disinhibited eating behaviors, especially in those with limited visual attention processes. Further understanding of the neurobiological impact of eating behaviors on cognition in older adulthood may assist in developing awareness about the importance of healthy eating patterns when considering brain health in the aging process.

Cannabis use in older adults is becoming increasingly common as cannabis becomes both more socially acceptable and legally permissible, whether for medical or recreational purposes. While previous research has found harmful effects of cannabis use on cognition in adolescents and younger adults, few studies have explored cognition and cannabis use in older adults. This study aimed to examine the relationship between lifetime cannabis use patterns and subjective cognitive performance in older adults.

The sample (N=51) consisted of adults ages 60 and older residing in the United States who endorsed cannabis use within the previous year. Participants completed online questionnaires on demographics, mental health [Geriatric Anxiety Scale (GAS) short form and Geriatric Depression Scale (GDS) short form], and measures of subjective cognitive function [Cognitive Failures Questionnaire (CFQ), the Cognitive Problems and Strategies Assessment (CPSA), and part IV of the Cognitive Self Efficacy Questionnaire (CSEQ)]. The Daily Sessions, Frequency, Age of Onset, and Quantity of Cannabis Use Inventory (DFAQCU) and the Cannabis Use Disorder Identification Test (CUDIT) were used to assess cannabis use, and the Alcohol Use Disorders Identification Test Consumption items (AUD-C) were used to assess alcohol use. Partial Pearson’s correlations were used to examine relationships between scores of subjective cognitive functioning and cannabis use patterns while controlling for alcohol consumption.

Participants aged 60+ (M=68.06, SD=5.80, 49% women) had 15.39 (SD=2.21, range 12-18) years of education on average. Participants’ race/ethnicity was reported as 90.2% White (n=47), 5.9% Latinx or Hispanic (n=3), 2% Black or African American (n=1), and 1% Other (n=1). Most participants (59%) reported first using cannabis as a child or adolescent (range of ages 7-17 years), while 31% reported first using cannabis as an adult (ages 18-58 years), and only 8% endorsed initial use in older adulthood (62-84 years). On average, this sample reported using cannabis for 19.75 days (SD=11.14) in the last month with n=35 (69%) and having used cannabis for 20 or more years (range 1-60 years). The total CUDIT score was positively correlated with CFQ (rp=.47, p<.001), CPSA problems (rp=.46, p<.001), GAS (rp=.43, p=.002), and GDS (rp=.35, p=.014), and negatively correlated with the CSEQ (rp=-.33, p=.02), all while controlling for alcohol consumption. Days of use in the past month and total years of use were not significantly associated with subjective cognitive function.

Among older adult cannabis users, symptoms of Cannabis Use Disorder (CUD) were significantly associated with greater self-reported cognitive failures/problems and worse self-efficacy for cognitive ability, as well as symptoms of anxiety and depression, when controlling for alcohol use. Notably, there was no relationship between subjective cognition and frequency of recent use or lifetime use. For patients who use cannabis, neuropsychologists may find it helpful to focus their clinical interview on CUD symptoms when discussing cognitive complaints rather than other measures of cannabis use. Additional research is needed to examine objective measures of cognitive functioning in older adult cannabis users.

The current study investigated whether older adults’ cognitive test scores at the time of long-term care nursing home admission are associated with psychological well-being over the first six months. We analyzed the link between Mattis Dementia Rating Scale (DRS-2) subscale scores and anxiety, depression, quality of life, and positive/negative affect.

Participants were recently admitted long-term care residents from 13 nursing homes in the Louisville, KY area. Sixty-two older adults were administered the DRS-2 shortly after nursing home admission. Using a cutoff of less than 6 scaled score on the DRS-2, 52% of participants scored as cognitively impaired. Self-report measures of anxiety (RAID), depression (PHQ9), quality of life (QoL-AD), and positive/negative affect (Philadelphia Geriatric Center Affect Rating Scale) were collected at time of admission, and 3 and 6 months later.

The DRS-2 attention subscale significantly correlated with baseline depression symptoms. No other DRS-2 subscale or the DRS-2 total score correlated with anxiety, depression, quality of life, or affect ratings at admission. Baseline DRS-2 attention, initiation/perseveration, and memory had significant correlations with self-report measures at 3 and 6 months; these DRS-2 scores were selected for further analysis. Mixed ANOVAs found a significant main effect of group (impaired vs. not-impaired) for the initiation/perseveration subscale, memory subscale, and DRS-2 total score on negative affect; impairment in any of these domains was associated with lower reported negative affect at all three time points. There was no significant effect of cognitive scores on any other self-report measure. There was a significant, positive linear trend in quality of life over time. There was a significant quadratic trend in depression symptoms, with decreased depression reported at 3 months and increase at 6 months.

Impaired performance on the DRS-2 was associated with lower negative affect over time. Cognitive impairment was not associated with anxiety, depression, quality of life, or positive affect. There appear to be reliable trends in some psychological factors regardless of cognitive scores, with an increase in quality of life over time and a temporary decrease in reported depression captured at 3 months. The relationship between cognitive impairment and negative affect should be interpreted with caution, as only 22 residents completed the affect self-report at all three time points. Overall, we found limited evidence of an association between cognitive scores at time of admission and self-reported psychological factors at 3 and 6 months.

Social support may protect against Alzheimer’s disease and related dementias (ADRD), potentially through emotional or instrumental support elements. Black and Hispanic/Latinx older adults bear a disproportionate burden of ADRD. However, independent effects of emotional and instrumental support on cognition, a primary indicator of ADRD risk, are largely understudied in these groups. Guided by the differential vulnerability hypothesis – the theoretical framework which posits that systemic racism disadvantages Black and Hispanic/Latinx individuals’ health – we hypothesize that emotional and instrumental support may be particularly important to protect against worse cognition for Black and Hispanic/Latinx older adults, who often have fewer resources due to these inequalities (e.g., wealth, educational opportunities) to otherwise maintain health. Using the NIH Toolbox Emotion Module measures of emotional (e.g., the extent to which individuals can rely on others in challenging times) and instrumental support (e.g., the extent to which individuals can rely on others for assistance in daily activities), we aimed to identify positive social support factors (i.e., emotional and instrumental support) that may protect against ADRD risk (i.e., longitudinal executive function and memory performance) among Black and Hispanic/Latinx older adults.

Participants were 362 Black and 265 Hispanic/Latinx adults aged 65-89 (63% female, average age=75) from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) Study who completed baseline and up to two additional waves of assessments (every 1.5 years), including questionnaires, neuropsychological evaluations, and the NIH toolbox. Predictors included baseline covariates (i.e., age, language of test administration, gender, education, income, self-rated health) and NIH toolbox emotional and instrumental support variables. Outcomes were baseline and longitudinal memory (visual and verbal episodic memory) and executive functioning (verbal fluency and working memory) composites from the Spanish and English Neuropsychological Assessment Scales (SENAS). Latent growth curve models were conducted separately in Black and Hispanic/Latinx participants to estimate effects of emotional and instrumental support on baseline cognition and subsequent change in each domain.

Black participants reported greater emotional support. There were no group differences in levels of instrumental support. Greater instrumental support was associated with better initial memory (standardized β= .194, 95%CI: [.063, .325]) among Black participants but not among Hispanic/Latinx participants. In Hispanic/Latinx participants, greater emotional support was associated with better initial executive functioning (standardized β= .215, 95%CI: [.079, .350]. Emotional support was not associated with either cognitive domain in Black participants. There were no associations between emotional or instrumental support on cognitive change in either group.

Results point to differences between Black and Hispanic/Latinx older adults in the impact of specific aspects of social support on different cognitive domains. Positive associations between instrumental support and baseline memory in Black participants and between emotional support and executive functioning in Hispanic/Latinx participants suggest unique cognitive consequences of social support across groups. Differences in the role of specific types of social supports may be useful in identifying intervention targets specifically for Black and Hispanic/Latinx older adults, who are disproportionately affected by ADRD. Future research will examine these constructs using multiple group models to test these associations more rigorously.

The brain is reliant on mitochondria to carry out a host of vital cellular functions (e.g., energy metabolism, respiration, apoptosis) to maintain neuronal integrity. Clinically relevant, dysfunctional mitochondria have been implicated as central to the pathogenesis of Alzheimer’s disease (AD). Phosphorous magnetic resonance spectroscopy (31p MRS) is a non-invasive and powerful method for examining in vivo mitochondrial function via high energy phosphates and phospholipid metabolism ratios. At least one prior 31p MRS study found temporal-frontal differences for high energy phosphates in persons with mild AD. The goal of the current study was to examine regional (i.e., frontal, temporal) 31p MRS ratios of mitochondrial function in a sample of older adults at-risk for AD. Given the high energy consumption in temporal lobes (i.e., hippocampus) and preferential age-related changes in frontal structure-function, we predicted 31p MRS ratios of mitochondrial function would be greater in temporal as compared to frontal regions.

The current study leveraged baseline neuroimaging data from an ongoing multisite study at the University of Florida and University of Arizona. Participants were older adults with memory complaints and a first-degree family history of AD [N = 70; mean [M] age [years] = 70.9, standard deviation [SD] =5.1; M education [years] = 16.2, SD = 2.2; M MoCA = 26.5, SD = 2.4; 61.4% female; 91.5% non-latinx white]. To achieve optimal sensitivity, we used a single voxel method to examine 31p MRS ratios (bilateral prefrontal and left temporal). Mitochondrial function was estimated by computing 5 ratios for each voxel: summed adenosine triphosphate to total pooled phosphorous (ATP/TP; momentary energy), ATP to inorganic phosphate (ATP/Pi; energy consumption), phosphocreatine to ATP (PCr/ATP; energy reserve), phosphocreatine to inorganic phosphate (PCr/Pi; oxidative phosphorylation), and phosphomonoesters to phosphodiesters (PME/PDE; cellular membrane turnover rate). All ratios were corrected for voxel size and cerebrospinal fluid fraction. Separate repeated measures analyses of variance controlling for scanner site differences (RM ANCOVAs) were performed.

31p MRS ratios were unrelated to demographic characteristics and were not included as additional covariates in analyses. Results of separate RM ANCOVAs revealed all 31p MRS ratios of mitochondrial function were greater in left temporal relative to bilateral prefrontal voxel: ATP/TP (p < .001), ATP/Pi (p = .001), PCr/ATP (p = .004), PCr/Pi (p = .004), and PME/PDE (p = .017). Effect sizes (partial eta squared) ranged from 0.6-.20.

Consistent and extending one prior study, all 31p MRS ratios of mitochondrial function were greater in temporal as compared to frontal regions in older adults at-risk for AD. This may in part be related to the intrinsically high metabolic rate of the temporal region and preferential age-related changes in frontal structure-function. Alternatively, findings may reflect the influence of unaccounted factors (e.g., hemodynamics, auditory stimulation). Longitudinal study designs may inform whether patterns of mitochondrial function across different brain regions are present early in development, occur across the lifespan, or some combination. In turn, this may inform future studies examining differences in mitochondrial function (as measured using 31p MRS) in AD.

Aging is associated with changes in cortical excitability which may affect motor learning and cognitive function via selective modulation of gamma aminobutyric acid (GABA). Previous studies using magnetic resonance spectroscopy (MRS) to measure GABA in older adults found that increased baseline GABA levels in the sensorimotor cortex (M1S1) were associated with better motor performance. GABA levels in M1S1 have tended to decrease during the execution of a repeated motor sequence. The dynamic change in GABA density in M1S1 in older adults is currently unknown and represents a critical gap in our understanding of how it could impact motor learning and cognitive performance. As such, the purpose of the current study is to quantify changes in cortical GABA during motor learning in the aging brain and examine those changes in relation to motor and cognitive performance. We hypothesize that older adults with greater dynamic range in M1S1 GABA levels will display more efficient motor learning and increased cognitive scores.

We report on a total of 18 healthy older adults aged 64 to 80 years (M = 70.44, SD = 4.99, 12 females). Using MRS at 3T, we measured changes in GABA concentration in M1S1 at rest, during an eight or 12 finger-movement motor entrainment task, and during a recall task. Gannett was used for GABA quantification relative to water. Change in GABA was calculated by subtracting Rest1 GABA from Recall1 GABA. In a separate session, participants completed a battery of cognitive assessments. We computed linear regressions to examine the relationship between dynamic GABA change, recall accuracy of the motor task and cognitive performance.

In relation to motor performance, we found that both greater baseline (Rest1) GABA levels and greater dynamic change in GABA significantly predicted better recall accuracy on the motor task. For cognitive performance, we found that greater dynamic change in GABA significantly predicted better performance on Word Reading in the Stroop Color and Word Test and Delayed Recall in the Hopkins Verbal Learning Test (HVLT). No additional significant relationships were found for the remaining cognitive assessments.

Older adults who were able to accurately perform the task had a greater dynamic change in GABA and increased baseline GABA levels. These adults with greater dynamic change also had better cognitive performance on HVLT Delay and Stroop Word Reading. This modulation of GABA associated with better performance could be related to changes in neuroplasticity. Although these results are in the preliminary stages, they point to a greater understanding of aging related changes in motor and cognitive performance. We’ll continue to explore the relationship between sensory motor performance and changes in GABA concentration as a potential predictor for cognitive performance and future rehabilitation.

Pain is a mechanism for attention disruption due, in part, to a shared reliance on the prefrontal cortex (PFC). Amongst older adults, the experience of pain is both prevalent and functionally impactful. Dual-task walking (DTW) paradigms are a useful means of assessing the impact of pain on attentional control and known to be sensitive to changes in the cortical hemodynamic response within the PFC. To date, however, few studies have utilized such paradigms to examine the impact of self-reported pain on attentional control via assessment of cognitive, gait and neuroimaging outcomes. Examining these associations would facilitate a better understanding of the ways in which pain may negatively impact neural efficiency, thereby increasing risk of adverse functional outcomes, in healthy aging.

Study participants (N= 408; mean age = 76 ± 6.5ys; % female =55.4) were grouped into pain (n= 266) and no pain (n= 142) groups based upon their responses on the MOS-PSS and MOS-PES. These questionnaires were also used to assess self-reported levels of pain severity and interference amongst individuals with reported pain. Functional near-infrared spectroscopy was used to measure intraindividual variability (IIV) of the cortical hemodynamic response within the PFC during a DTW paradigm which consisted of Single-Task-Walk (STW), Cognitive Interference (Alpha), and Dual-Task-Walk (DTW) conditions. Participants walked along an electronic walkway and quantitative gait data were extracted in order to assess IIV in stride length during STW and DTW conditions. The rate of correct letter generation was used as a measure of cognitive accuracy during Alpha and DTW conditions. Linear mixed effects models (LMEMs) were used to examine the effects of perceived pain on neural and behavioral responses as well as on the change in these outcomes form single- to dual-task conditions. Stratified LMEMs were used to examine whether these associations differed by gender.

LMEMs revealed that perceived pain presence was associated with reduced IIV in PFC oxygenation (estimate = -0.032, p = 0.037) and reduced IIV in stride length in the DTW condition (estimate = -1.180, p = 0.006). High pain severity was associated with a greater increase in stride length IIV from STW to DTW (estimate = -1.301, p = 0.039). Stratified LMEMs revealed that the association between pain and neural IIV was significant in only males (estimate = -0.049, p = 0.037), while the association between pain and gait IIV was significant in only females (estimate = -1.712, p = .008).

Study results suggest that self-reported pain over one month is associated with differential patterns of neural and behavioral responding amongst healthy, community-dwelling older adults. Furthermore, it appears that males are more susceptible to the neural effects of pain, while females are more susceptible to the behavioral effects under attention-demanding conditions. In this population, these patterns may reflect a tendency towards inefficient neural and behavioral modifications in response to perceived pain. These findings highlight the need for clinical use of routine pain assessments and, when appropriate, the implementation of timely and effective pain treatments in aging.

Women are at greater risk of developing Alzheimer’s disease (AD) than men. The menopausal transition, which involves a neuroendocrine shift, is a potential contributor to this sex difference. Multiple estrogen-regulated systems (i.e., circadian rhythms) are disrupted during this transition which affects cognitive functioning (Barha & Liu-Ambrose, 2020), most notably verbal learning and memory. Little is known about how lifestyle factors (i.e., sleep, physical activity (PA), stress) may promote neurocognitive functioning across this transition (Maki & Weber, 2021). Utilizing data from the Human Connectome Aging project (HCP-A), the current study will examine whether distinct lifestyle profiles including sleep, PA, and stress relate to multiple domains of cognitive performance among a sample of perimenopausal/menopausal women.

Perimenopausal/menopausal women (ages 45 to 65) from the HCP-A were included (n =150, M age = 54.6, SD = 5.5). Demographic information, menopausal status, sleep problems (Pittsburgh Sleep Quality Index), PA (International Physical Activity Questionnaire), stress (Distress subscale of the Perceived Stress Scale) were assessed with surveys, and participants completed several lab-based tasks including: dimensional change card sort (DCCS), flanker, pattern recognition processing speed (PS), working memory (WM), picture sequencing, oral reading, Trails Making Test A and B (TMT), and Rey Auditory Verbal Learning (RAVLT) tasks. Using latent profile analysis (LPA), lifestyle profiles were identified via sleep problems, PA, and stress levels. A MANOVA compared cognitive performance between these lifestyle profiles, above and beyond age and education status.

Fit indices indicated that a three-class solution fit the sample best: high PA, low stress and sleep problems (Class 1, n=38), high PA, stress, and sleep problems (Class 2, n= 17), and low PA, high stress and sleep problems (Class 3, n= 95) which were not significantly different based on age or menopausal status (p>0.05). A significant multivariate effect of age and education on cognitive performance (p<.001) emerged. There was a significant multivariate effect of lifestyle profile on cognitive performance, F (18, 260) = 1.73, p=.034, eta squared = .11, after controlling for age and education. Univariate analyses determined that certain lifestyle profiles were associated with better performance on all cognitive tasks except verbal memory. Contrary to expectation, Class 3 performed better on TMT A & B, DCCS, flanker, WM, and PS tasks as compared to Class 1. Class 3 performed better on reading and picture sequencing tasks than Class 2. There was no difference in performance between Class 1 and 2.

Results suggest three distinct lifestyle profiles exist in this analytic sample. After controlling for age and education, cognitive performance on all tasks except for verbal memory significantly differed between lifestyle profiles. The profile characterized by low PA and high stress and sleep problems demonstrated superior performance as compared to other classes. These findings provide preliminary evidence that women who have high levels of stress and sleep problems with low PA are performing better on cognitive tasks, but replication of these findings utilizing longitudinal designs are needed.