Additional research is needed to better understand the relationship between early tau accumulation and cognitive decline in cognitively healthy (CH) older adults. The tau PET tracer 18F-MK-6240 has shown favorable imaging characteristics and is an ideal candidate to identify early tau accumulation in CH older adults. In the present study, we evaluated the associations between in vivo tau levels and retrospective 5-year cognitive change.

Using 18F-MK-6240 PET, we evaluated tau accumulation in 41 CH participants from Cognitive Reserve (CR) and Reference Ability Neural Network (RANN) studies. We investigated the relationships between regional PET signal and retrospective cognitive change, focusing in three cognitive domains well-established to change with aging: episodic memory, speed processing and reasoning. Latent change score analysis was applied to generate latent variables estimating the change in these domains from baseline to follow-up. Regarding tau data, we created meta-ROIs based on 16 AD-vulnerable subregions selected a priori. The tau SUVR of the subregions were averaged to create four meta-ROIs: 1) Total-AD ROI comprising all 16 areas; 2) Medial Temporal Lobe-ROI (MTL-ROI), 3) Lateral Temporal Lobe-ROI (LTL-ROI) and Cingulate/Parietal Lobe (C/P-ROI). The associations between regional tau levels and retrospective cognitive change over 5-years were investigated through regression models adjusted by age, sex, education, and baseline cognitive performance.

The mean age of the sample was 67.5 years (SD=5.8, range 55 to 77 years), 53.8% were male, 63.4% White, 26.1% Black, and 7.3% Latinx. Overall, the sample was highly educated (16.20 ± 2.26) and presented high IQ scores (118.97 ± 7,76) based on American National Adult Reading Test. All participants were CH and showed cognitive decline over 5 years in all cognitive domains analyzed. Most participants were classified as Braak stage 0 (82.9%), some as Braak stage 1 (14.6%) and one participant as Braak stage 2 (2.4%). The regression models showed that higher [18F]MK-6240 SUVR was associated with steeper decline in memory and speed in the Total-AD meta-ROI (memory: p = .03; speed: p = .04), and in the regional ROIs, such as LCL (memory: p = .03; speed: p = .04), C/P (memory: p = .02, speed: p = .05) and MTL (memory: p = .05, speed: p = .02), with large effect sizes (f2) (>.40) for memory and medium effect sizes for speed (.20-.25). There were no associations between [18F]MK-6240 SUVR and reasoning change.

Our finding reinforces the notion that pathological tau in areas of early accumulation influence changes in cognitive domains known to be affected in AD even in cognitively normal individuals. The novel contribution of this work is the relevance of tau accumulation beyond episodic memory, as we observed its association with speed proceeding decline. The fact reasoning decline is commonly observed in normal aging, but here not associated with tau suggest the specificity of the tau-cognition associations. Our results should be considered with caution due to the modest sample size.

Self-reported mild functional difficulties are one of the most salient predictors of future cognitive decline in older adults. However, few measures of objective assessment of mild functional difficulties are available. This study explored the validity and stability of novel, performance-based measures of subtle functional difficulties in older adults without dementia using an objective and standardized test, called the Naturalistic Action Test (NAT), which has been used for people with dementia.

40 older adults (Healthy Controls (HC), Mild Cognitive Impairment (MCI)) completed the NAT at baseline and again after one-month. The NAT requires participants to make a breakfast and a lunch using objects presented on a table. Standard cognitive tests (memory, language, etc.) also were administered at baseline only and were used to compute intraindividual cognitive variability (IIV), a sensitive measure of cognitive ability level. NAT scores reflecting micro-errors and completion time were obtained from video recordings. Micro-errors are inefficient actions that include misreaching toward the wrong object and moving objects around the table without a clear purpose. Validity of the NAT measures was evaluated in correlations with IIV, and the stability of NAT performance was evaluated using within-sample t-tests and correlations between measures at baseline and one-month.

In the full sample (N =40), greater micro errors were significantly correlated with greater IIV at baseline (r=.512, p<.001) and one month followup (r=.327, p=.039). Among HC, paired t tests showed that there were no significant differences in micro-errors over one month; however, completion time was significantly slower at baseline (Md=16.06, SD=24; t(32)=3.76, p<.001). MCI participants showed a significant decrease in micro-errors (M=3.86, SD=4.4; t(6)=2.33, p=.029), but no difference in completion time. Among HC and MCI, micro errors (r=.506, p<.001), and completion time (r=.899, p<.001) were significantly correlated across time points.

Results show promise for novel NAT measures (time, micro-errors) as valid, objective indicators of subtle cognitive difficulties that affect everyday function. Analyses of stability of scores over time showed evidence of practice effects over time, which along with predictive validity, should be explored in future work.

Mayo Test Drive (MTD): Test Development through Rapid Iteration, Validation and Expansion, is a web-based multi-device (smartphone, tablet, personal computer) platform optimized for remote self-administered cognitive assessment that includes a computer-adaptive word list memory test (Stricker Learning Span; SLS; Stricker et al., 2022; Stricker et al., in press) and a measure of processing speed (Symbols Test: Wilks et al., 2021). Study aims were to determine criterion validity of MTD by comparing the ability of the MTD raw composite and in-person administered cognitive measures to differentiate biomarkerdefined groups in cognitively unimpaired (CU) individuals on the Alzheimer’s continuum.

Mayo Clinic Study of Aging CU participants (N=319; mean age=71, SD=11, range=37-94; mean education=16, SD=2, range=6-20; 47% female) completed a brief remote cognitive assessment (∼0.5 months from in-person visit). Brain amyloid and brain tau PET scans were available within 3 years. Overlapping groups were formed for 1) those on the Alzheimer’s disease (AD) continuum (A+, n=110) or not (A-, n=209), and for 2) those with biological AD (A+T+, n=43) or with no evidence of AD pathology (A-T-, n=181). Primary outcome variables were MTD raw composite (SLS sum of trials + an accuracy-weighted Symbols response time measure), Global-z (average of 9 in-person neuropsychological measures) and an in-person screening measure (Kokmen Short Test of Mental Status, STMS; which is like the MMSE). Linear model ANOVAs were used to investigate biomarker subgroup differences and Hedge’s G effect sizes were derived, with and without adjusting for demographic variables (age, education, sex).

Remotely administered MTD raw composite showed comparable to slightly larger effect sizes compared to Global-z. Unadjusted effect sizes for MTD raw composite for differentiating A+ vs. A- and A+T+ vs. A-T- groups, respectively, were -0.57 and -0.84 and effect sizes for Global-z were -0.54 and -0.73 (all p’s<.05). Because biomarker positive groups were significantly older than biomarker negative groups, group differences were attenuated after adjusting for demographic variables, but MTD raw composite remained significant for A+T+ vs A-T- (adjusted effect size -0.35, p=.007); Global-z did not reach significance for A+T+ vs A-T- (adjusted effect size -0.19, p=.08). Neither composite reached significance for adjusted analyses for the A+ vs A- comparison (MTD raw composite adjusted effect size= -.22, p=.06; Global-z adjusted effect size= -.08, p=.47). Results were the same for an alternative MTD composite using traditional z-score averaging methods, but the raw score method is preferred for comparability to other screening measures. The STMS screening measure did not differentiate biomarker groups in any analyses (unadjusted and adjusted p’s>.05; d’s -0.23 to 0.05).

Remotely administered MTD raw composite shows at least similar ability to separate biomarker-defined groups in CU individuals as a Global-z for person-administered measures within a neuropsychological battery, providing evidence of criterion validity. Both the MTD raw composite and Global-z showed greater ability to separate biomarker positive from negative CU groups compared to a typical screening measure (STMS) that was unable to differentiate these groups. MTD may be useful as a screening measure to aid early detection of Alzheimer’s pathological changes.

One common concern amongst the aging population is that of worsening memory. Speed of processing and executive functions are also areas of age-related decline that affect daily living. Lifestyle modifications such as diet, exercise, and sleep have garnered intense interest as potential methods to prevent or delay cognitive decline. Among dietary factors, omega-3 fatty acids (FAs) have been documented as containing a myriad of health benefits, including neuroprotective effects. The aim of this study is to examine the associations between omega-3 FAs, cognitive function, and neuroanatomical regions of interest in a healthy aging population.

Adults aged 65 and older (n=40, 48.9% Female) were recruited for the Loma Linda University Adventist Health Study-2 Cognitive and Neuroimaging Substudy. Participants had a mean age of 76.25 years (SD=8.29), 16.78 years of education (SD=2.53), and were predominantly White (85.0%). Participants received a two-hour neurocognitive battery, including measures of immediate and delayed memory (Rey Auditory Verbal Learning Test, RAVLT; WMS-IV Logical Memory, LM), processing speed (Stroop), and executive functions (Stroop Color/Word). Participants underwent brain imaging on a 3T Siemens MRI, including a 3D T1-weighted MPRAGE sequence. Cortical reconstruction and volumetric segmentation were performed using FreeSurfer software. Blood samples were collected for fatty acid analysis. Individual FAs were expressed as a percent of total FAs. An omega-3 index was constructed as the sum of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) FAs. Correlational analyses, controlling for age, sex, and education, investigated relationships between omega-3 levels (individual and index) and (a) cognitive function (immediate and delayed memory, processing speed, executive functions), and (b) brain volumes in specific regions of interest (hippocampus, entorhinal cortex, frontal pole, white matter).

EPA was significantly positively correlated with Stroop Color (r=.34, p=.048). Although not statistically significant, trends were observed between the omega-3 index and Stroop Color (r=.30, p=.08), and between both DHA and the omega-3 index with RAVLT – delayed recall (r=.29, p=.095; r=.30, p=.08, respectively). With regards to regional brain volumes, EPA and the omega-3 index were both significantly positively correlated with the entorhinal cortex (r=.34, p=.041; r=.41, p=.01, respectively) and white matter volume (r=.36, p=.028; r=.34, p=.038, respectively). DHA was significantly positively correlated with white matter volume (r=.34, p=.044).

Blood levels of EPA were positively correlated with a measure of processing speed, and trends were observed between DHA, the omega-3 index and[GN1] verbal memory, and between the omega-3 index and processing speed. We also found that omega-3 FA values were associated with greater brain volume in the entorhinal cortex and white matter in our sample of healthy older adults. Atrophy of the entorhinal cortex has been associated with pathological processes. Additionally, white matter is known to effect processing speed. These findings may offer support for the idea that omega-3 FAs exert their neuroprotective effects by fortifying areas of the brain, specifically the entorhinal cortex and white matter, that promote maintenance of cognitive function in late life.

Cognitive reserve has been linked to functional ability, and depression has been shown to be associated with more functional impairment in older adults. While cognitive reserve and depression are associated and have each been shown to impact functional impairment, the independent impact of cognitive reserve on functional ability after accounting for depressive symptoms has not been explored. For the purpose of this study, years of education served as a proxy for cognitive reserve, which is consistent with the literature. It was predicted that higher levels of education would be associated with better functional ability regardless of age and severity of depressive symptoms.

Participants (ages 55 to 90) were drawn from the Alzheimer’s Disease Neuroimaging Initiative (N=3407); participants with major depression were not included. Subsyndromal depressive symptoms were measured using the Geriatric Depression Scale (GDS < 6) and functional impairment was assessed using the Functional Activities questionnaire. A three-stage hierarchical regression was conducted with functional ability as the dependent variable.

Age, entered at stage one of the regression model, was a significant predictor (F(1,1427) =49.75, p<.001) and accounted for 3.4% of the variance in functional ability. Adding depressive symptoms to the regression model led to a significant increase in variance explained (F(1,1426) = 64.57, p<.001), accounting for an additional 4.2% of the variance in functional ability. Adding years of education to the regression model explained an additional 1.4% of variance in functional ability and this increase in variance explained was significant (F(1,1425) = 22.53, p<.001).

Cognitive reserve (operationalized as higher levels of education) was associated with higher functional ability even after accounting for age and depressive symptoms.

Cognitive performance, particularly in the domains of memory and executive functioning (EF), have been shown in previous research to predict decline in everyday functioning in older adults. The goal-control model posits that episodic memory difficulties cause weak or decaying task goals that lead to the omission of every day task steps (low accomplishment). EF difficulties preclude control over the execution of task goals that lead to inefficient and error-prone performance (high errors). Intraindividual variability (IIV) in neuropsychological test performance has been proposed as a noninvasive early marker of dementia and has utility in cognitively healthy older adults. In this study we examined cross-sectional relations between within-domain IIV in memory and attention/EF with performance of everyday tasks in the lab. We expected greater memory IIV to be associated with task accomplishment (goal decay), and greater attention/EF IIV to be associated with errors (poor control over goals).

40 cognitively normal (CN) older adult (65+) participants (M age=71.44, SD=10.62; 73.8% women; 85.7% White; M education=18.55, SD=8.38) completed the Naturalistic Action Test (NAT), requiring completion of standardized, everyday tasks (i.e., breakfast, lunch) and scored for accomplishment of steps and various errors (micro-errors - misreach to distractor object, extra actions; overt -sequence, perseverative behaviors, etc.; motor errors). Within-domain IIV measures were calculated for 6 memory measures (HVLT-R, BVMT-R) and 6 attention/EF measures (Digit Span, Trail Making Test, Salthouse Letter/Pattern Comparison). First, raw scores for each test were z-transformed, then the intraindividual standard deviation of all z-scores was calculated. Bivariate Spearman’s rank-order correlations were used to examine associations between NAT performance and within-domain IIV, as well as mean performance. Linear regressions were used to examine the associations of IIV score with NAT scores, adjusting for age, sex, and mean cognitive performance.

Among CN participants, higher memory IIV was significantly associated with lower NAT accomplishment (r=-.329, p=.038), and better mean memory performance was significantly associated with fewer errors (micro-errors r=-.509, p=.003; overt r=-.438, p=.012; motor errors r=-.463, p=.008). Regression models revealed that memory IIV, after controlling for mean memory performance, age, and sex, did not significantly predict NAT performance. High attention/EF IIV was significant associated with more errors (overt r=.377, p=.016), whereas mean attention/EF performance was not significantly correlated with any NAT measures. Attention/executive function IIV significantly predicted errors (micro-errors B=4.15, p=.03; Overall model: R2=0.285, F(4, 24)=2.393, p=.079; overt B=.562, p=.032; Overall model: R2=0.371, F(4, 24)=3.543, p=.021) after adjusting for mean attention/executive function performance, age, and sex.

Consistent with the goal-control model framework, greater variability in memory was associated with lower task accomplishment, whereas greater variability in attention/EF was associated with more errors. However, only attention/EF IIV predicted NAT performance, specifically errors (micro-errors, overt errors), after adjusting for age, sex, and mean attention/EF performance. Within-domain IIV can be used to predict mild functional difficulties in cognitively healthy older adults. Future research should examine within-domain IIV in a larger sample with more diversity to maximize generalizability, and in a longitudinal design to evaluate within-domain IIV predictive validity for cognitive/functional impairment.

1) Evaluate the association of self- and study-partner report of subjective cognitive decline (SCD) to objective cognitive performance across ethnoracial groups. 2) Evaluate the concordance of self- and study partner report of SCD across ethnoracial groups.

Participants were 5241 non-Hispanic White (NHW), 267 non-Hispanic Black (NHB), 225 Hispanic, and 228 Asian participants screened for the A4 study (N=5961). Participants completed the Preclinical Alzheimer Cognitive Composite (PACC), and self- and study partner-report of SCD using the Cognitive Function Index (CFI). Analysis of variance was used to assess difference in key variables by ethnoracial group. Regression analyses were conducted to evaluate the association of SCD and objective performance by ethnoracial group, and the association between self-and study partner report of SCD by ethnoracial group.

Asian participants reported the highest mean CFI relative to all other groups, while NHW reported the lowest (F(3,5957)=41.93, p <.001). Asian and NHW participants had higher PACC scores relative to NHB and Hispanic participants (F(3,5957)=41.93, p <.001). Regression analyses revealed higher CFI was associated with lower PACC score across groups, and this association was strongest in the Asian sample relative to other groups (F(10, 5897)=40.49, p<.001,R2=.06). Evaluation of study partner characteristics suggested NBH participants had the highest proportion on non-spousal study partners relative to other groups. Regression analyses revealed no differences in the association of self- and study partner report of SCD across ethnoracial groups (F(10, 5859)=132.9, p<.001, R2=0.18).

Results suggest that that SCD is associated with objective cognitive performance across racial groups, although the strength of this association appears to vary in this sample. There is also consistent concordance between self- and study partner report of SCD across groups, despite differences in study partner relationships. SCD may be considered a valid predictor of subtle cognitive change across groups in the A4 sample. Limitations include small group sizes relative to the large NHW sample. Future work with larger, more representative samples are needed to further validate these findings.

Cardiovascular disease (CVD) is a well-known risk factor for cognitive impairment and dementia, particularly among minoritized groups that have experienced a history of low childhood socioeconomic status (SES). Although previous literature has linked all levels of SES to varying degrees of stress exposure, children raised in higher SES households have more access to resources and services that encourage optimal growth and development than children who grow up in lower SES households. Given the disproportionate burden of dementia and cognitive deficits within minoritized groups, the present study examined whether childhood SES is associated with later life cognition among Black and White older adults and if this association persists after accounting for hypertension, a possible mediator of the relationship between childhood SES.

1,184 participants were from the first wave of the STAR (n = 397 Black [Mage= 75.0 ±6.8 years]) and KHANDLE (386 Black [Mage= 76.2 ±7.2 years] and 401 White [Mage= 78.4 ±7.5 years]) cohorts. We used general linear models to examine the relationship between childhood SES and later-life executive function, semantic memory, and verbal memory scores, and midlife hypertension. Childhood SES was measured by self-reported perceived financial status (with participants given the following options: ‘pretty well off financially’, ‘about average’, ‘poor’, or ‘it varied’). These models were assessed in the full sample and also stratified by race.

In the full sample, childhood financial status was not associated with semantic memory, verbal episodic memory, or executive function. Financial status was associated with semantic memory in Black adults (β = -.124, t(771) = -2.52, p = .01) and this association persisted after accounting for hypertension (β = -.124, t(770) = -2.53, p = .01). There was no association between childhood financial status and later life semantic memory among White adults. There was no association between childhood financial status and later life verbal episodic memory or executive function in either Black or White adults in models with or without adjustment for hypertension.

Our findings showed no relationship between childhood SES and cognition, except for semantic memory in Black participants; this relationship persisted after accounting for midlife CVD. Future analyses will assess both direct and indirect effects of more predictive measures of childhood SES on late-life cognition with midlife CVD as a mediator.

Dementia worry (DW) is anxious rumination about personal risk for dementia. Personal experience with dementia may affect DW, such that individuals with personal experience with dementia may have higher worry about developing dementia themselves. Further, dementia knowledge (DK), including what may increase one’s dementia risk as well as treatment options for dementias, may be influenced by one’s dementia experience. Prior studies have suggested that personal experience alters the relationship of age to DW; no prior studies have examined this for DK. In the present study, we examined whether DW and/or DK were differentially related to age in older adults.

Adults (≥ 50 years old; N=252) in Ohio and Louisiana completed an online survey. 94 participants reported no personal dementia experiences, and 158 participants endorsed having a biological relative with dementia. The sample ranged in age from 23 to 92 (M=65, SD=9.3), with 96% identifying as White and 76% holding advanced degrees. DW was measured with the Dementia Worry Scale. Dementia knowledge was measured with true or false questions about causes and treatments for dementia.

Groups did not differ in age (p=.73), education (p=.50), or perceived SES (p=.28), but did differ in gender (p=.06). The experience group had higher dementia knowledge (p=.02). In those with biological dementia experience, lower age was related to higher dementia worry (r=-.24, p=.003) and greater dementia knowledge (r=-.18, p=.03). However, in those with no experience, age was not related to either dementia worry (r=.04) or to dementia knowledge (r=.16). Dementia worry did not relate to dementia knowledge in either group (no experience r=.03, experience r=.13).

Findings suggest that younger individuals who have personal experience with dementia are highly worried about personal risk for dementia, despite having higher knowledge of dementia. Further, these results demonstrate that dementia knowledge is not related to dementia worry in older individuals with or without biological dementia experience. Findings may be important for informing dementia prevention education efforts.

Research examining dietary fat in relation to physical and cognitive health is mixed. Generally, it has been hypothesized that polyunsaturated fatty acids (PUFAs) have vascular, anti-inflammatory, and neuroprotective effects1,2,3. Monounsaturated fatty acids (MUFAs) commonly occur with saturated fatty acids (SFA) in certain foods, and some research suggests that consumption is associated with increased vascular risk4; however, there is limited research examining combined MUFAs and SFAs consumption from traditional Western diet foods (e.g., pizza, desserts) compared to animal (e.g., butter, cow milk, salmon) and plant products (e.g., coconut oil, cocoa butter). Furthermore, much of the research examining dietary components/supplementation and cognition is in older adult or at-risk samples, with limited research examining the relationships among middle-aged and cognitively unimpaired adults. We present preliminary data from an ongoing pilot study.

39 middle-aged (40-65 years, inclusive) cognitively unimpaired individuals were recruited from the community. The Food Frequency Questionnaire (Short-Form; SF-FFQ) was used to calculate diet components and servings during a “typical week.” Attention and working memory were measured using trial one of the California Verbal Learning Test - Third Edition (CVLT-III), Oral Trail Making Test Part B, Number Span (forward and backward), Stroop Color and Color-Word trials. Genetic and other plasma-based data for 25 participants have also been obtained, and analysis is in progress; we plan to analyze these additional components in greater detail once we have achieved our target sample size.

Nonparametric correlation analyses revealed no significant relationships between total dietary fat (as measured by the SF-FFQ) and cognitive performance, which included CVLT Trial 1 (r = .28, p = .09), Oral Trail Making Test Part B (r = .02, p = .89), Number Span Forward (r = .18, p = .27) and Number Span Backward (r = -.04, p = .83), Stroop Color trial (r = -.10, p = .56), and Stroop Color-Word trial (r = -.09, p = .58). Notably, however, data is continuing to be collected and these relationships will be examined further with additional data.

While total fat consumption was expected to be associated with attention and working memory measures, correlations revealed nonsignificant relationships. Notably, there are important limitations to consider, as other expected relationships based on previous research findings/theoretical relationships (e.g., positive correlation between waist-to-hip ratio and fat consumption) were lacking. A primary limitations of this study included a small sample size of cognitive and physically healthy middle-aged adults. Regardless, these relationships should be explored further with a greater and more diverse sample size.

Females outperform males on verbal memory tests across the lifespan. Females also exhibit greater Alzheimer’s disease (AD) pathology at preclinical stages and faster atrophy and memory decline during disease progression. Synaptic factors influence the accumulation of AD proteins and may underpin cognitive resilience against AD, though their role in sex-related cognitive and brain aging is unknown. We tested interactive effects of sex and genetic variation in SNAP-25, which encodes a presynaptic protein that is dysregulated in AD, on cognition and AD-related biomarkers in cognitively unimpaired older adults.

Participants included a discovery cohort of 311 cognitively unimpaired older adults (age mean [range]=70 [44-100]; 56% female; education mean=17.3 years; 24% APOE-e4+), and an independent, demographically-comparable replication cohort of 82 cognitively unimpaired older adults. All participants completed neurological examination, informant interview (CDR=0), neuropsychological testing, and blood draw. Participants were genotyped for the SNAP-25 rs105132 (T→C) single-nucleotide polymorphism via Sequenom (discovery cohort) or Omni 2.5M (replication cohort). In vitro models show the C-allele is associated with increased SNAP-25 expression compared to T/T genotype. A subset of the discovery cohort completed structural MRI (n=237) and florbetapir Aβ-PET (n=97). Regression analyses across cohorts examined the interaction of sex and SNAP-25 genotype (T/T homozygotes [53% prevalence] vs. C-carriers [47% prevalence]) on cognitive z-scores (verbal memory, visual memory, executive function, language), adjusting for age, education, APOE-e4, and APOE-e4 x sex. Discovery cohort models also examined sex-dependent effects of SNAP-25 on temporal lobe volumes and Aβ-PET positivity.

SNAP-25 T/T vs. C-carriers did not differ on demographics or APOE-e4 status across cohorts or within sexes. Sex interacted with SNAP-25 to predict verbal memory (p=.024) and language (p=.008) in the discovery cohort, with similar verbal memory differences observed in the replication cohort. In sex-stratified analyses, C-carriers exhibited better verbal memory than T/T carriers among females (d range: 0.41 to 0.64, p range: .008 to .046), but not males (d range: 0.03 to 0.12, p range: .499 to .924). In SNAP-25-stratified analyses, female verbal memory advantages were larger among C-carriers (d range: 0.74 to 0.89, p range: <.001 to .034) than T/T (d range: 0.13 to 0.36, p range: .022 to .682). Sex also interacted with SNAP-25 to predict Aβ-PET positivity (p=.046) such that female C-carriers exhibited the lowest prevalence of Aβ-PET positivity (13%) compared to other groups (23% to 35%). C-carriers exhibited larger temporal lobe volumes across sex, yet this effect only reached statistical significance among females (females: d=0.41, p=.018; males: d=0.26, p=.179). In post-hoc analyses, larger temporal lobe volumes were selectively associated with better verbal memory in female C-carriers (β=0.36, p=.026; other groups: |βs|<0.10, ps>.538).

Among clinically normal older adults, we demonstrate female-specific advantages of carrying the SNAP-25 rs105132 C-allele across cognitive, neural, and molecular markers of AD. The rs105132 C-allele putatively reflects higher endogenous levels of SNAP-25. Our findings suggest a female-specific pathway of cognitive and neural resistance, whereby higher genetically-driven expression of SNAP-25 may reduce likelihood of amyloid plaque formation and support verbal memory, possibly through fortification of temporal lobe structure.

Behavioral interventions are a non-pharmacological treatment that shows improvement in the everyday functioning of people with Mild Cognitive Impairment (MCI). Multiple studies have focused on examining factors that can reduce or enhance adherence to behavioral interventions. However, few studies use adherence as a predictor of functional changes. The goal of this study was to analyze the association between adherence, age, and education in factor score changes of participant impairment, participant adjustment, and partner adjustment in a sample of participants with amnestic MCI (aMCI) and their study partners.

We included fifty-two dyads of a person with aMCI and their study partner with intervention data at baseline and 24-week follow-up from the Physical Exercise and Cognitive Engagement Outcomes for Mild Neurocognitive Disorder (PEACEOFMND) study. At baseline, participants were randomized to one of three behavioral interventions: computerized cognitive training (BrainHQ; n=19), yoga (n=15), or wellness education (n=18). Factors were established from a larger clinical sample that used the same measures as PEACEOFMND. The three-factor latent structure was constructed as the following: 1) participant adjustment combined scores of the Center for Epidemiologic Studies Depression Scale (CES-D), Quality of Life in Alzheimer’s Disease (QoL-AD), and Self-Efficacy for managing MCI scales; 2) partner adjustment included study partner’s scores in CES-D, QoLAD and Caregiving Competence and Mastery Components (CCMC) of the Pearlin scales; 3) participant impairment included participant’s scores in E-Cog memory domain, and study partner’s scores in the Functional Activity Questionnaire (FAQ) and Zarit Burden Interview. We calculated factor changes by obtaining the difference between factor scores at follow-up and baseline. Bayesian correlation analysis was performed to investigate the association between age, education, adherence to the combined behavioral interventions, participant adjustment, participant impairment, and partner adjustment.

The Bayesian correlation results showed moderate evidence (BF10=6.8, Pearson’s r=0.38) supporting a positive correlation between adherence and change in participant adjustment. Additionally, there was moderate evidence (BF10=2.18, Pearson’s r=0.32) supporting a positive correlation between change in participant impairment and participant level of education as well as participant age and change in partner adjustment (BF10=2.8, Pearson’s r=0.33).

Bayesian correlations replicated results from previous analysis using a traditional method, showing that increased adherence to combined behavioral interventions is associated with an increase in participant’s quality of life, self-efficacy, and better mood. Thus, commitment to behavioral intervention completion in aMCI participants is related to overall participant adjustment.

Cognitive impairment can affect an individual’s ability to perform routine tasks. In this study, we investigate how cognitive abilities relate to the accuracy and efficiency of performance on a naturalistic cooking task completed in older adults’ home environments. We hypothesized a positive association between task accuracy and global cognitive status, and task efficiency and executive functioning. We further hypothesized a negative association between omission errors and immediate and delayed memory recall.

Fourteen community-dwelling older adults (Age, M = 73.92 years; Female = 9; Education, M = 16.38 years) along the continuum from normal aging to mild dementia completed a “Cooking Task” in their home environment. Specifically, participants were instructed to fry or scramble an egg, prepare slice of toast with jelly, serve side of sliced apple, pour glass of water, bring prepared items to table, and clean dishes used. Participants received ingredients necessary for task completion and a task list to reference. The task efficiency score (range 0-6) was based on multi-tasking and organizational skills (e.g., beginning the egg task early in session, plating items as prepared). Overall accuracy was computed by identifying error types (e.g., inefficiencies, substitutions, omissions, and subtasks attempted) and scaling accuracy (range 1-5) for each subtask, then summing all six subtask accuracy scores to get overall accuracy (range 6-30). Participants also completed a range of neuropsychological assessments, which included the Telephone Interview for Cognitive Status, Letter and Category Fluency from the Delis-Kaplan Executive Function System, and immediate and delayed recall measures from the Repeatable Battery for the Assessment of Neuropsychological Status. Due to the small sample size, findings are preliminary, and scatterplots were evaluated for outliers that might influence findings.

Consistent with hypotheses, as overall accuracy on the Cooking Task increased so did performance on the global cognitive measure (TICS: r = 0.61, p = 0.02). Lower rates of omission errors were also associated with better performance on both immediate (r = -0.75, p < 0.01) and delayed (r = -0.55, p = 0.04) recall indices. However, these findings were not specific, as overall accuracy also significantly correlated with the memory indices and verbal fluency measures (ps < 0.05). Additionally, lower rates of omission errors significantly correlated with performance on the TICS and the D-KEFS Letter Fluency (ps < 0.05). Contrary to our hypothesis, no significant associations were found between cooking task efficiency and executive functioning (D-KEFS subtests). There were also no significant correlations between cooking task efficiency and global cognitive status or memory.

The present study supported our hypotheses that better overall task accuracy is associated with higher cognitive status and lower rates of omission errors correlate with better immediate and delayed recall abilities. However, the findings were not specific to these domains of functioning but rather suggest that clinical assessments measuring a range of cognitive abilities are related to the accuracy of daily task performance and omission errors on routine daily tasks. Future research will explore the validity of the efficiency measure.

To examine the relationships between baseline gray matter volumes, diagnostic status, and executive function performance at 24-month follow-up, and the relative importance of predictors of executive function in a cohort of non-demented older adults.

The study sample included 147 participants from the Alzheimer’s Disease Neuroimaging Initiative (mean age = 70.6, SD = 6.4; mean education = 17 years, SD = 2.4). At baseline, 49 participants were diagnosed as cognitively normal (CN), 60 as early mild cognitive impairment (EMCI), and 38 as late mild cognitive impairment (LMCI). Magnetic resonance imaging (MRI) data were collected at baseline. A composite score of executive function and FreeSurfer-derived gray matter regions-of-interest (ROI; whole brain, superior frontal gyrus, middle frontal gyrus, inferior frontal gyrus, orbitofrontal cortex, anterior cingulate cortex, superior parietal lobule, inferior parietal lobule, hippocampus) were examined. Hierarchical linear regression models were employed to assess whether brain volume predicted executive function at 24-month follow-up and interaction effects between baseline ROI volume and diagnostic status. Age, gender, education, Mini-Mental State Examination scores, and APOE-e4 allele status were included as control variables in each model. Relative importance metrics, which quantifies an individual regressor’s contribution to a multiple regression model, were computed using the Lindemen, Merenda, and Gold (lmg) method to assess the relative contribution of each variable in predicting executive function performance.

Across all participants, baseline gray matter ROI volume accounted for a significant amount of variance in executive function at 24-months after accounting for control variables. Specifically, anterior cingulate cortex and superior parietal lobule accounted for an additional 7% and 6% of variance in executive function at 24-months. Significant brain region X diagnostic status interaction effects were observed in executive function performance at 24-months. Relative importance metrics within each group indicated that age is the most important predictor of executive function at 24-months for CN, anterior cingulate cortex is most important for EMCI, and Mini-Mental Examination score is most important for LMCI.

Our findings implicate frontoparietal gray matter regions as significant predictors of executive function performance at 24-months, and that this relationship is moderated by diagnostic status. Our results indicate that the value of specific variables to predict executive function performance varies based on diagnostic status. Specifically, anterior cingulate cortex was a significant predictor of executive function performance across all participants and was the most important variable in predicting performance in the earliest stage of mild cognitive impairment. These results support previous studies examining gray matter correlates of executive function and extend the literature by exploring predictors of executive function in early and late stages of mild cognitive impairment.

In research, and particularly clinical trials, it is important to identify persons at high risk for developing Alzheimer’s Disease (AD), such as those with Mild Cognitive Impairment (MCI). However, not all persons with this diagnosis have a high risk of AD as MCI can be broken down further into amnestic MCI (aMCI), who have a high risk specifically for AD, and non-amnestic MCI (naMCI), who are predominantly at risk for other dementias. People with aMCI largely differ from healthy controls and naMCI on memory tasks as it is the hallmark criteria for an amnestic diagnosis. Given the growing use of the NIH Toolbox Cognition battery in research trials, this project investigated which Toolbox Cognition measures best differentiated aMCI from naMCI and in comparison to persons with normal cognition.

A retrospective data analysis was conducted investigating performance on NIH Toolbox Cognition tasks among 199 participants enrolled in the Michigan Alzheimer’s Disease Research Center. All participants were over age 50 (51-89 years, M=70.64) and had a diagnosis of aMCI (N=74), naMCI (N=24), or Normal Cognition (N=101). Potential demographic differences were investigated using chi-square and ANOVAs. Repeated measure general linear model was used to look at potential group differences in Toolbox Cognition performance, covarying for age which was statistically different in aMCI versus Normal participants. Linear regression was used to determine which cognitive abilities, as measured by the Uniform Data Set-3 (UDS3), might contribute to Toolbox differences noted in naMCI versus aMCI groups.

As expected, aMCI had lower Toolbox memory scores compared to naMCI (p=0.007) and Normals (p<0.001). Interestingly, naMCI had lower Oral Reading scores than both aMCI (p=0.008) and Normals (p<0.001). There were no other Toolbox performance differences between the MCI groups. 19.4% of the variance in Oral Reading scores was explained by performance on the following UDS3 measures: Benson delayed recall (inverse relationship) and backward digit span and phonemic fluency (positive relationship).

In this study, Toolbox Picture Sequence Memory and Oral Reading scores differentiated aMCI and naMCI groups. While the difference in memory was expected, it was surprising that the naMCI group performed worse than the aMCI and normal groups on the Toolbox Oral Reading task, a task presumed to reflect Crystalized abilities resistive to cognitive decline. Results suggest that Oral Reading is primarily positively associated with working memory and executive tasks from the UDS3, but negatively associated with visual memory. It is possible that the Oral Reading subtest is sensitive to domains of deficit aside from memory that can best distinguish aMCI from naMCI. A better understanding of the underlying features in the Oral Reading task will assist in better characterizing deficit patterns seen in naMCI, making selection of aMCI participants more effective in clinical trials.

Approximately 6.5 million Americans ages 65 and older have Alzheimer’s disease and related dementias, a prevalence projected to triple by 2060. While subtle impairment in cognition and instrumental activities of daily living (IADLs) arises in the mild cognitive impairment (MCI) phase, early detection of these insidious changes is difficult to capture given limitations. Traditional IADL assessments administered infrequently are less sensitive to early MCI and not conducive to tracking subtle changes that precede significant declines. Continuous passive monitoring of IADLs using sensors and software in home environments is a promising alternative. The purpose of this study was to determine which remotely monitored IADLs best distinguish between MCI and normal cognition.

Participants were 65 years or older, independently community-dwelling, and had at least one daily medication and home internet access. Clinical assessments were performed at baseline. Electronic pillboxes (MedTracker) and computer software (Worktime) measured daily medication and computer habits using the Oregon Center for Aging and Technology (ORCATECH) platform. The Survey for Memory, Attention, and Reaction Time (SMART; Trail A, Trail B, and Stroop Tests) is a self-administered digital cognitive assessment that was deployed monthly. IADL data was aggregated for each participant at baseline (first 90 days) in each domain and various features developed for each. The receiver operating characteristic area under the curve (ROC-AUC) was calculated for each feature.

Traditional IADL Questionnaires.

At baseline, 103 participants (normal n = 59, Mage = 73.6±5.5; MCI n = 44, Mage = 76.0±6.1) completed three functional questionnaires (Functional Activities Questionnaire; Measurement of Everyday Cognition (ECog), both self-report and informant). The Informant ECog demonstrated the highest AUC (72% AUC, p = <.001).

Remotely monitored in-home IADLs and self-administered brief online cognitive test performance.

Eighty-four had medication data (normal n = 48, Mage = 73.2±5.4; MCI n = 36, Mage = 75.6±6.9). Four features related to pillbox-use frequency (73% AUC) and four features related to pillbox-use time (62% AUC) were developed. The discrepancy between self-reported frequency of use versus actual use was the most discriminating (67% AUC, p = .03).

Sixty-six had computer data (normal n = 38, Mage = 73.6±6.1; MCI n = 28, Mage = 76.6±6.8). Average usage time showed 64% AUC (p = .048) and usage variability showed 60% AUC (p = .18).

One hundred and two completed the SMART (normal n = 59, Mage = 73.6±5.5; MCI n = 43, Mage = 75.9±6.2). Eleven features related to survey completion time demonstrated 80% AUC in discriminating cognition. Eleven features related to the number of clicks during the survey demonstrated 70% AUC. Lastly, seven mouse movement features demonstrated 71% AUC.

Pillbox use frequency combined features and self-administered brief online cognitive test combined features (e.g., completion times, mouse cursor movements) have acceptable to excellent ability to discriminate between normal cognition and MCI and are relatively comparable to informant rated IADL questionnaires. General computer usage habits demonstrated lower discriminatory ability. Our approach has applied implications for detecting and tracking older adults’ declining cognition and function in real world contexts.

Alzheimer’s disease (AD) is expected to affect over 7 million older Americans by 2025. Development of fast and inexpensive screening measures for routine screening is critical for identifying those suffering from the earliest stages of AD including Mild Cognitive Impairment (MCI) and Subjective Cognitive Decline (SCD). Here we assess the validity and utility of a brief, 5-item SCD screener and its associations with neuropsychological performance as compared to an existing objective cognitive screener, the Mini Mental Status Exam (MMSE).

Development: A brief, 5-item SCD questionnaire was developed based on a more extensive 20-item version previously validated (Chapman et al. 2021). Participants: 27 cognitively diverse (MCI and cognitively normal) community dwelling older adults were recruited for this study. Mean age: 71.9 ± 7. Inclusion criteria include memory concerns. Exclusion criteria include no previous diagnoses of neurodegenerative diseases and/or major stroke. Administration: Participants completed a brief, 5-item SCD screener along with cognitive testing including the MMSE and a clinically validated list-learning test, the Selective Reminding Test (SRT). Statistical Methods: Spearman 2-tailed correlations were conducted to assess the relationship between the two screening measures, and their relationships to the SRT. Outcome measures on the SRT included total recall (max: 72) and delayed recall (max: 12). All cognitive measures were demographically adjusted with normative data.

The mean total for the SCD screener was 2.1 ±1.1, and the mean MMSE score was 29.2 ± 1.2. The SCD screener was associated with MMSE scores (r= -.39, p= .043), SRT Total Recall (r= -.43, p= .024) and Delayed Recall (r=-.42, p=.031) measures. MMSE scores did not associate with either SRT outcome (p>.05).

Results support the utility and validity of a brief subjective cognitive decline screener for identifying those who may be experiencing memory dysfunction. The brief SCD screener outperformed the MMSE, an existing and widely used objective screening measure. Associations between the SCD screener and SRT outcomes support the validity and utility of the brief screener and recapitulate previous findings with the more extensive version of the SCD questionnaire (Chapman et al. 2021). Ongoing research is focusing on the utility of the screener in frontline clinical settings and translation of the screener into Spanish.

We assess the association between self-reported history of periodontal disease diagnosis with self-reported cognitive and functional decline at age ∼60. We also investigate (1) the roles of social background, demographic characteristics, education, and adolescent test scores in confounding that association and (2) the role of cardiovascular disease in mediating that association.

We use data from a nationally representative sample of 13,525 people who participated in the 2021 wave of the High School & Beyond (HSB) cohort study. HSB began in 1980 with a nationally-representative sample of American 10th and 12th grade students; these students have been followed up on six occasions since 1980, yielding extraordinary and prospectively-collected life course data on all key measures for a large, multicultural sample.

In 2021, HSB sample members were evaluated with neuropsychological tests that evaluated list learning and memory, semantic and letter fluency, and working memory. They were also asked to self-report memory and functional decline using the AD8, using a cutoff of 2 or more items for significant concerns. Mild Cognitive Impairment will be identified using an algorithm validated in a similar sample of middle aged participants.

Sample members were also asked in 2021 whether a medical professional had ever diagnosed them with periodontal disease; those responding affirmatively were then asked the years in which they started and stopped having periodontal disease.

Measures of social and economic background; demographic characteristics; and educational contexts, opportunities, and attainments were measured prospectively—and in great detail—in the surveys administered in the 1980s. Critically, almost all sample members completed a series of cognitive tasks during adolescence, allowing us to address a key set of confounders in the relationship between periodontal disease and MCI. Markers of cardiovascular disease were measured in both 2013 and 2021.

We estimate logistic regression models predicting significant cognitive and functional concerns as a function of periodontal disease history; we also estimate models that account for confounders, including social background, demographic characteristics, education, and cognitive skills during adolescence; finally, we estimate models that account for the mediating role of cardiovascular disease. All models account for the clustered sampling design of HSB and employ sampling weights to account for HSB’s complex sampling design and selective attrition from the panel.

About 15% of the cohort has been diagnosed with periodontal disease, and nearly one in five had significant cognitive and functional concerns.

People with a history of periodontal disease were more likely to report significant cognitive and functional concerns. This association remains substantive and statistically significant after adjusting for confounders. All else equal, the odds of people with a history of periodontal disease having an AD8 score of 2 or higher were about 60% greater than the odds of those not reporting periodontal disease. Very little of this association can be attributed to cardiovascular disease as a mediating pathway.

People with a history of periodontal disease are at greatly elevated risk of self-reported cognitive and functional concerns at age ∼60. This supports evidence— never before collected at this scale in a long-term, representative cohort study—that oral pathogens may contribute to cognitive well-being over the life course.

We ask about the degree to which the association between (1) the quantity and quality of people’s education and (2) midlife self-reported concerns about cognition and daily function is mediated by occupational complexity. The overarching hypothesis is that amount and quality of education provides people with access to better jobs, including jobs that are more cognitively complex. Occupational complexity, in turn, may be protective against cognitive impairment. If true, this means that part of the poorly-understood connection between education and cognitive impairment can be attributed to occupational complexity.

We use data from a nationally representative sample of 13,525 people who participated in the 2021 wave of the High School & Beyond (HSB) cohort study. HSB began in 1980 with a nationally-representative sample of American 10th and 12th grade students; these students have been followed up on six occasions since 1980, yielding extraordinary and prospectively-collected life course data on all key measures for a large, multicultural sample.

In 2021, HSB sample members were evaluated with neuropsychological tests that evaluated list learning and memory, semantic and letter fluency, and working memory. They were also asked to self-report memory and functional decline using the AD8, using a cutoff of 2 or more items for significant concerns. Mild Cognitive Impairment will be identified using an algorithm validated in a similar sample of middle aged participants.

HSB surveys gathered information about sample members’ labor force activities in every survey between 1980 and 2021, including information sufficient to code verbatim reports of occupations to the standards of the 2010 Standard Occupational Classification. We have linked these codes for sample members’ 2013 and 2021 occupations to the O*Net database, which includes extensive information about the cognitive complexity (and other attributes) of every occupation.

Measures of key confounders—including social and economic background; demographic characteristics; educational contexts, opportunities, and attainments that are associated with labor force outcomes; adolescent achievement test scores; and aspects of midlife occupations besides complexity (e.g., how well they pay)—were measured prospectively and in great detail in the surveys administered between the 1980s and 2021.

We estimate logistic regression models predicting significant cognitive and functional concerns as a function of educational contexts, opportunities, and outcomes; we also estimate models that account for the confounders listed above. Our main focus is on coefficients for education in models that do and do not include occupational complexity as a mediator. All models account for the clustered sampling design of HSB and use sampling weights to account for HSB’s complex sampling design and selective attrition from the panel.

Nearly one in five cohort members had significant cognitive and functional concerns; rates are lower for non-Latinx Whites and for better educated people. Associations between educational contexts, opportunities, and outcomes (including attainment) are robust, even after adjusting for confounders.

Between one quarter and one third of the conditional association between education and self-reported cognitive and functional concerns can be attributed to occupational complexity.

Occupational complexity is an important pathway through which more and better education protects people from concerns about cognitive and functional decline at about age 60.

The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is a well validated and reliable clinical assessment tool that can be used for characterizing cognitive function in older adults. The RBANS has been shown to reliably discriminate between Alzheimer’s disease (AD), mild cognitive impairment (MCI), and cognitively healthy (CH) individuals. While the RBANS has traditionally been administered in a face to face setting, administration is also feasible via telehealth. Due to the COVID-19 pandemic, cognitive assessments were unexpectedly moved to telehealth formats. Given this, the current study assessed whether differences emerged between face to face and telehealth RBANS scores in both individuals who were CH and had MCI.

A total of 61 individuals (NCH = 27, NMCI = 34) completed baseline and 1-year follow-up visits in the current study. The sample was predominantly female (N = 43, 70.5%), identified as white (N = 57, 93.4%), and were well educated (MYears = 15.93). Participants completed the RBANS form B at an in-person baseline visit and form C at a one year follow-up visit. Higher RBANS scores indicate overall better cognitive performance. As expected, CH individuals performed better than those with MCI on immediate memory, language, attention, delayed memory, and total score. There were no significant differences found for the visuospatial index. Repeated measures ANOVAs were conducted to assess whether differences in RBANS performance existed based on test administration method.

Group differences between testing formats were observed in CH individuals on immediate memory [F(1,37) =9.10, p < .01)], language [F(1, 37)=9.41=p < .01)], and total score [F(1,37)=6.56, p < .05], with higher performance in those who completed the followup session in-person.There were no differences in baseline performance on any RBANS index between those who received an in person versus telehealth format (p’s > .05). No differences were observed in the MCI group. There were no significant differences observed between the CH and MCI group on demographic factors.

Results from the current study suggest that CH counterparts experienced a greater degree of difference in scores between testing formats, whereas individuals with MCI did not. The lack of difference in MCI individuals may be due to less room for variability over time for this group given already low scores. These results suggest that while telehealth has been shown to be a viable option for RBANS administration in some samples, further work needs to be conducted regarding the equivalence of in-person vs. telehealth formats. This study is not without limitations. The small MCI group was segmented into in-person and telehealth groups, further reducing power to detect statistically significant results. The sample was also homogenous with highly educated, Caucasian women. Future research should aim to assess a larger, more diverse sample to identify whether RBANS is a reliable measure alone for assessing cognitive change over time via telehealth for MCI.