Depressive symptomatology has long been shown to be associated with the onset of dementia, though the exact form and directionality of this association remains unclear. While much research has gone into confirming this link, there has been little investigation into the effects of depression on dementia progression after diagnosis. The aim of this study is to investigate the relationship between depressive symptomatology and cognitive and behavioural decline over the following year.

In a Rural and Remote Memory Clinic, 375 patients consecutively diagnosed with mild cognitive impairment (MCI), Alzheimer’s Disease (AD), or non-AD dementia completed the Center for Epidemiological Studies Depression Scale (CES-D) at first visit and one-year follow-up to assess depressive symptomatology. The same cohort were evaluated for cognitive and behavioural decline through the completion of five clinical tests performed at the first visit and at one-year follow-up. Cognitive decline was assessed using the Mini Mental Status Exam (MMSE) and the Clinical Dementia Rating Scale (CDR). Neuropsychiatric symptoms were assessed using two subsets of data from the Neuropsychiatric Inventory (NPI severity and distress), both of which are completed by the patients’ caregivers. Functional decline was assessed using the Functional Activities Questionnaire (FAQ). In both cognitive and functional decline, data were analyzed with linear regression analysis in the population subgroups of All Type Dementia (ATD, which includes MCI for this study) (N=375), Alzheimer’s type dementia (N=187), and Mild Cognitive Impairment (N=74).

In this study, we observed no correlation between CES-D scores at baseline and cognitive or functional decline over one year. However, we observed a significant positive correlation between changes in CES-D scores and NPI-severity scores over one year in patients with ATD (likely the most reliable observation from this study due to larger statistical power) and in the MCI subgroup, but not in the AD subgroup. This relationship may be attributable to a relationship between depression and neuropsychiatric symptoms in general, or to the fact that a person with dementia who exhibits more depressive symptomatology appears more impaired and causes greater distress in their caregivers, despite stability in the objective measures of their cognitive and functional status. This finding may indicate that intervention for depression is needed to alleviated caregiver burden when managing dementia patients.

Increasingly severe depressive symptomatology may exacerbate neuropsychiatric symptomatology but did not correlate with cognitive and functional decline in patients with dementia. More studies are needed to help delineate the relationship between depression and dementia progression.

In the absence of treatments to halt or reverse symptoms of Alzheimer's disease, early detection may extend the window for meaningful treatment, advanced planning, and coping. Positron emission tomography (PET) scans for amyloid and tau are validated biomarkers of AD, yet results are rarely disclosed to participants due to concerns about negative impacts. While prior studies suggest limited anxiety, depression, or suicidality following biomarker disclosure, no study to date has examined broader psychological impacts of PET amyloid/tau disclosure to symptomatic individuals. Therefore, we explored post-disclosure changes in future time perspective (perceptions of limited time or possibilities left in the future), self-efficacy for managing symptoms, and perceived stigma as a function of result received.

Forty-three older adults (age = 72.0±6.2 years; education = 16.5±2.6; 88.4% White Non-Hispanic; 48.8% female) participated in the study, of whom 62.8% were diagnosed with mild cognitive impairment (MCI) and the remainder with Dementia of the Alzheimer's type. All participants underwent pre-disclosure biomarker education and decisional capacity assessment, followed by baseline measures. Participants demonstration decisional capacity completed an interactive disclosure session during which they received dichotomous results of their research positron emission tomography (PET) scans for amyloid and tau (elevated versus not elevated for each biomarker). Findings were discussed in relation to presence/absence of Alzheimer's disease, the etiology of their cognitive difficulties, and risk for conversion or further decline. At baseline, immediately following disclosure, and at 1-week follow-up, participants completed several questionnaires: the Future Time Perspective (FTP) scale, a measure of how much the participant sees time as limited, the Self Efficacy for Managing Chronic Disease scale (SECD), and the Stigma Scale for Chronic Illness (SSCI-8), all of which were modified to apply to Alzheimer's disease and associated experiences.

The main effects of time (F=1.10, p=.334, A?p2=.026), biomarker status (F(1)=3.10, p=.086, Ajp2=.070), and the time by biomarker status interaction (F=0.39, p=.661, Ajp2=.009) on FTP score was not significant. Though neither time (F=0.07, p=.933, A?p2=.002) nor the time by biomarker status interaction (F=2.16, p=.122, Ajp2=.050) effect on SECD was significant, being biomarker positive (A+T-/A+T+) was associated with lower self-efficacy (F(1)=5.641, p=.022, Ajp2=.121). Neither main effect for time (F=0.15, p=.853, Ajp2=.004) or biomarker status (F(1)=0.35, p=.558, A?p2=.009) on SSCI-8 was significant. The time by biomarker status interaction was significant (f=4.27, p=.018, =.096), such that biomarker negative participants experience a transient increase in perceived stigma directly after disclosure that resolves one week later, and biomarker negative participants experience the opposite pattern.

Findings suggest that individuals who receive biomarker positive results may feel less competent to manage their symptoms compared to those who are biomarker negative, emphasizing the need for post-disclosure interventions targeting self-efficacy. The effect of disclosure on perceptions of time being limited and on perceived stigma were minimal, even when those results indicate evidence of Alzheimer's disease and risk for clinical progression. These results further support the safety of biomarker disclosure procedures. Future studies should provide longer-term assessment of psychological, behavioral, and clinical outcomes following Alzheimer's disease biomarker disclosure.

Mild decline in independent functioning is a core diagnostic criterion for Mild Cognitive Impairment. Performance-based assessments have been considered the gold standard to identify subtle deficits in functioning. Existing assessments were largely designed using demographically homogenous samples (white, highly educated, middle class) and often assume tasks are performed similarly across populations. The current study aimed to validate the utility of the Performance Assessment of Self-Care Skills (PASS) in determining cognitive status in a sample of predominantly African American, low-income older adults.

Cognition and functional capacity were measured in n=245 older participants (aged 50+ years) who were recruited from a larger community study located in Pittsburgh, PA. Cognitive status was defined by a mean split on the Modified Mini Mental Status Examination (3MS) score (84/100). Participants above the cutoff were classified as unlikely cognitive impairment (UCI) and those below classified as potential cognitive impairment (PCI). Functional capacity was assessed using the number of cues provided on three PASS subtasks: shopping, medication management, and critical information retrieval (higher score = worse functioning). Self-reported cognitive and functional decline was assessed via the Everyday Cognition (ECog) questionnaire (higher score = greater decline). Generalized linear models compared performance scores between groups adjusting for literacy (WRAT3), age, and education. Receiver operating characteristic curve (ROC) analyses were run for select functional performance scores to assess their predictive ability in discriminating between PCI and UCI.

Compared to the UCI group (N = 179), the PCI group (N = 66) was older (68 vs. 65 years, p = 0.05), less educated (11 years vs. 12 years, p < 0.01), had lower WRAT3 z-scores (0.19 vs. -0.55, p < .01), and required more cues on the shopping (4.33 vs. 8.54, p < 0.01) and medication management PASS subtasks (2.74 vs. 6.56, p < .01). Both groups reported elevated levels of subjective cognitive complaints on the ECog (1.46 vs. 1.56, p = .09) and performed similarly on the critical information retrieval PASS subtask (0.25 vs 0.54, p = .06). When discerning between UCI and PCI groups, the PASS Shopping subtask had an optimal cut-off score of 4, sensitivity of 0.86, specificity of 0.47, positive predictive value (PPV) of 0.37, and area under the curve (AUC) of 0.71. PASS Medication Management had an optimal cut-off score of 3, sensitivity of 0.77, specificity of 0.56, PPV of 0.39, and AUC of 0.74.

Subjective functional decline and performance on the critical information retrieval subtask were not associated with cognitive groups. PASS shopping and medication management had moderately high AUCs, suggesting they can reliably distinguish between groups. However, both tasks also exhibited low PPVs, low levels of specificity, and high levels of sensitivity, making them strong “rule-out” tests but poor “rule-in” tests in this sample. Because accurate assessment of functioning is useful for MCI and critical to dementia diagnosis, it is imperative we understand how these tasks function across different populations. Future work should 1) validate measures of functional ability across different populations and 2) develop population-appropriate assessments for use in clinical and research settings.

To determine if the degree of split between phonemic verbal fluency and semantic verbal fluency at initial visit is predictive of decline in memory performance between initial evaluation and follow-up.

Data from a retrospective multidisciplinary memory clinic database at Spectrum Health was utilized. We examined data from 90 participants who had both an initial and follow-up evaluation completed (initial age = 77.1±4.7 years, follow-up age = 78.4±4.7 years, education = 13.9±3.1 years, race = 91% White, 7% Black, & 2% Hispanic, sex = 61% female, time between evaluations = 15.2±9.9 months). Patients who returned for follow-up did not meet criteria for dementia at time one. Split between phonemic and semantic fluency, termed the semantic-phonological delta (SPD) was measured at the initial evaluation by subtracting the Controlled Oral Word Association Test (COWAT; FAS) T-score from the Animal Naming Test (ANT) T-score. Change in memory score was defined in two ways: 1) subtracting the follow-up evaluation Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) List Recognition Score (RBANS percentiles were converted to a scaled score) from the initial evaluation List Recognition Score (List Recognition Delta), and 2) computing the difference in the RBANS Delayed Memory Index Standard Score between the initial evaluation and the follow-up evaluation (RBANS Memory Delta).

Average semantic fluency T scores were (M = 40.3, SD = 12.3) and phonemic fluency T scores were (M = 42.7, SD = 10.3) at initial evaluation. Bivariate correlations were used to determine the relationship between the clinical variables. SPD was significantly correlated with List Recognition Delta, r(88) = .23, p = .026, with greater discrepancies in verbal fluency scores associated with higher level of decline in List Recognition at follow-up. By comparison, Semantic Fluency performance itself at initial evaluation was not significantly correlated with List Recognition Delta, r(88) = .17, p = .097. The correlation between SPD and the RBANS Memory Delta was also not significant, r(88) = .14, p = .166. At follow-up evaluation, 39% of the sample received a diagnosis of Alzheimer’s disease. Of those diagnosed with Alzheimer’s disease, 66% had a negative SPD split at time one, performing worse on semantic fluency compared to phonemic fluency.

SPD is a better predictor of decline in RBANS List Recognition performance between evaluations than semantic fluency alone, with a larger negative SPD score (worse semantic fluency performance compared to phonemic fluency) at initial evaluation predicting decline in List Recognition performance at follow-up evaluation. SPD at initial evaluation was not significantly correlated with change in RBANS Delayed Memory Index score between evaluations. This may be because there are some patients who are similarly impaired in both semantic and phonemic verbal fluency at initial evaluation who later demonstrate progressive decline in memory retrieval due to hippocampal-sparing etiologies (e.g., vascular dementia). Overall, these findings are consistent with previous work suggesting that declines in the semantic memory system precede declines in episodic memory retention in conditions such as Alzheimer’s disease.

Dementia prevalence and its costs to the health system continue to rise, highlighting the need for comprehensive care programs. This study evaluates the Care Ecosystem Program (CE) for dementia (memory.ucsf.edu/Care-Ecosystem) in New Orleans, LA and surrounding areas.

The sample consisted of persons with dementia (PWD) and caregiver (CG) dyads enrolled in the CE from February-2019 to June-2022. Participants had a dementia diagnosis, lived in the community, and had at least one emergency department (ED) visit or hospitalization in the year prior. Healthcare utilization data was collected through self-report and electronic medical records. Dementia rating scales (QDRS, NPIQ) and caregiver wellbeing questionnaires (ZBI-12; PHQ-9; Self-Efficacy) were collected at baseline, 6-months, and 12-months. Dyads received monthly calls providing individualized care-management. One-way repeated measures Anovas were performed to identify change in utilization and caregiver wellbeing at 6-months and 12-months compared to baseline. Partial n2 effect sizes and post-hoc Bonferroni were calculated. Healthcare utilization extreme outliers were winsorized to the 95th percentile and a p-value of .05 was set.

A total of 150 dyads completed the program. PWD's age averaged 81 years (SD=8); they were mostly female (65%), White (63%), and had at least a High School education or higher (88%). CG's age averaged 65 years (SD=11.5); they were predominantly female (77%), White (63%), and had more than 12-years of education (70%). Half of the CGs were adult children (50%), followed by spouse/partners (41%). The QDRS indicated mild-moderate dementia severity, PWD had on average five neuropsychiatric symptoms, and Alzheimer's Disease was the most frequent diagnosis (35%).

A statistically significant decrease occurred in ED visits [F(1, 115)=14.970, p<.001, n2=.115] from baseline to 6-months (MD=1.043, p<.001) and 12-months (MD=.621, p<.001), while an increase was noted when comparing 12-month to 6-month data (MD=.422, p<.001). A similar pattern was observed for hospitalizations [F(1,115)=19.021, p<.001, n2=.142] were admissions were reduced significantly compared to baseline (6-month MD=.483, p<.001; 12-month MD=3.88, p<.001) and an increase was seen after the 6-month mark (MD=.095, p<.001). Caregiver self-efficacy significantly improved [F(1,115)=15.478, p<.001, n2=.119] from baseline to 6-months into the CE (MD=-1.457, p<.001) and was maintained a year after enrollment (MD=-1.474, p<.001). There were no differences in self-efficacy when comparing 6-month and 12-month data. Robust effect sizes were noted for all results previously reported. No other caregiver wellbeing measures showed significant changes over the three time points.

CE successfully reduces healthcare utilization and improves caregiver self-efficacy for PWD-CG dyads 6-months and 12-months after enrollment. The utilization increase noted from the 6-month to the 12-month mark does not surpass baseline rates. This pattern is also consistent with literature reporting that healthcare utilization rises with the progression of dementia. More research is needed to identify potential moderating factors in the relationship between dementia progression and utilization. Future research will also benefit from including control groups to further understand the impact of comprehensive care programs for dementia.

Prior studies have determined the Apolipoprotein-E (ApoE) ε4 allele presents a greater risk for developing Alzheimer's disease and for earlier onset of cognitive decline compared to individuals without the gene. Research has also recognized that traumatic brain injuries (TBIs) with loss of consciousness increase the risk for earlier development of the disease. This study sought to determine the moderating factor of TBI history on ApoE-ε4 risk associated with earlier Alzheimer's disease onset.

Participants included 9,585 individuals with autopsy confirmed Alzheimer's disease pathology, that had available ApoE genotype data, TBI data, and clinician determined age of cognitive decline, representing disease onset. A 2x3 factorial ANOVA was conducted to compare the main effects of ApoE-ε4 status and TBI history and the interaction effect between the two on disease onset. The analyses used three ApoE-ε4 groups and two TBI groups. The groups included: (1) no ApoE-ε4 allele; (2) one ApoE-ε4 allele; (3) two ApoE-ε4 alleles; (4) no TBI history, (5) positive TBI history.

Results indicated a significant interaction effect between ApoE-ε4 status and TBI history. Secondary analyses determined the driving force behind the interaction was the effect of ApoE-ε4, which had a significant impact on the age of onset in both TBI groups, while TBI history only significantly impacted onset in individuals without an ApoE-ε4 allele.

Contrary to prior research, these findings did not indicate TBI was significant in determining earlier onset. However, it is important to consider the large variability within the TBI group from the lack of differentiation between mild, moderate, and severe TBIs. Overall, these findings underline the greater risk and stronger impact that ApoE-ε4 poses for Alzheimer's disease onset compared to TBI. The results of this study emphasize the importance of evaluating ApoE-ε4 status for determining risk of earlier onset AD. Clinicians can better determine risk by considering patients' ApoE-ε4 status alongside TBI history.

Previous research established that white matter hyperintensities (WMH), a biomarker of small vessel cerebrovascular disease, are strong predictors of cognitive function in older adults and associated with clinical presentation of Alzheimer’s disease (AD), particularly when distributed in posterior brain regions. Secondary prevention clinical trials, such as the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) study, target amyloid accumulation in asymptomatic amyloid positive individuals, but it is unclear the extent to which small vessel cerebrovascular disease accounts for performance on the primary cognitive outcomes in these trials. The purpose of this study was to examine the relationship between regional WMH volume and performance on the Preclinical Alzheimer Cognitive Composite (PACC) among participants screened for participation in the A4 trial. We also determined whether the association between WMH and cognition is moderated by amyloid positivity status.

We assessed demographic, amyloid PET status, cognitive screening, and raw MRI data for participants in the A4 trial and quantitated regional (by cerebral lobe) WMH volumes from T2-weighted FLAIR in amyloid positive and amyloid negative participants at screening. Cognition was assessed using PACC scores, a z-score sum of four cognitive tests: The Mini-Mental State Examination (MMSE), the Free and Cued Selective Reminding Test, Logical Memory Test, and Digit Symbol Substitution Test. We included 1329 amyloid positive and 329 amyloid negative individuals (981 women; mean age=71.79 years; mean education=16.58 years) at the time of the analysis. The sample included Latinx (n=50; 3%), non-Latinx (n=1590; 95.9%), or unspecified ethnicity (n=18; 1.1%) individuals who identified as American Indian/Alaskan Native (n=7; 0.4%), Asian (n=38; 2.3%), Black/African American (n=41; 2.5%), White (n=1551 ; 93.5%), or unspecified (n=21; 1.3%) race. We first examined the associations of total and regional WMH volume and amyloid positivity on PACC scores (the primary cognitive outcome measure for A4) using separate general linear models and then determined whether amyloid positivity status and regional WMH statistically interacted for those WMH regions that showed significant main effects.

Both increased WMH, in the frontal and parietal lobes particularly, and amyloid positivity were independently associated with poorer performance on the PACC, with similar magnitude. In subsequent models, WMH volume did not interact with amyloid positivity status on PACC scores.

Regionally distributed WMH are independently associated with cognitive functioning in typical participants enrolled in a secondary prevention clinical trial for AD. These effects are of similar magnitude to the effects of amyloid positivity on cognition, highlighting the extent to which small vessel cerebrovascular disease potentially drives AD-related cognitive profiles. Measures of small vessel cerebrovascular disease should be considered explicitly when evaluating outcomes in trials, both as potential effect modifiers and as possible targets for intervention or prevention. The findings from this study cannot be generalized widely, as the participants are not representative of the overall population.

Novel blood-based biomarkers for Alzheimer's disease (AD) could transform AD diagnosis in the community; however, their interpretation in individuals with medical comorbidities is not well understood. Specifically, kidney function has been shown to influence plasma levels of various brain proteins. This study sought to evaluate the effect of one common marker of kidney function (estimated glomerular filtration rate (eGFR)) on the association between various blood-based biomarkers of AD/neurodegeneration (glial fibrillary acidic protein (GFAP), neurofilament light (NfL), amyloid-b42 (Ab42), total tau) and established CSF biomarkers of AD (Ab42/40 ratio, tau, phosphorylated-tau (p-tau)), neuroimaging markers of AD (AD-signature region cortical thickness), and episodic memory performance.

Vanderbilt Memory and Aging Project participants (n=329, 73±7 years, 40% mild cognitive impairment, 41% female) completed fasting venous blood draw, fasting lumbar puncture, 3T brain MRI, and neuropsychological assessment at study entry and at 18-month, 3-year, and 5-year follow-up visits. Plasma GFAP, Ab42, total tau, and NfL were quantified on the Quanterix single molecule array platform. CSF biomarkers for Ab were quantified using Meso Scale Discovery immunoassays and tau and p-tau were quantified using INNOTEST immunoassays. AD-signature region atrophy was calculated by summing bilateral cortical thickness measurements captured on T1-weighted brain MRI from regions shown to distinguish individuals with AD from normal cognition. Episodic memory functioning was measured using a previously developed composite score. Linear mixed-effects regression models related predictors to each outcome adjusting for age, sex, education, race/ethnicity, apolipoprotein E-e4 status, and cognitive status. Models were repeated with a blood-based biomarker x eGFR x time interaction term with follow-up models stratified by chronic kidney disease (CKD) staging (stage 1/no CKD: eGFR>90 mL/min/1.73m2, stage 2: eGFR=60-89 mL/min/1.73m2; stage 3: eGFR=44-59mL/min/1.73m2 (no participants with higher than stage 3)).

Cross-sectionally, GFAP was associated with all outcomes (p-values<0.005) and NfL was associated with memory and AD-signature region cortical thickness (p-values<0.05). In predictor x eGFR interaction models, GFAP and NfL interacted with eGFR on AD-signature cortical thickness, (p-values<0.004) and Ab42 interacted with eGFR on tau, p-tau, and memory (p-values<0.03). Tau did not interact with eGFR. Stratified models across predictors showed that associations were stronger in individuals with better renal functioning and no significant associations were found in individuals with stage 3 CKD. Longitudinally, higher GFAP and NfL were associated with memory decline (p-values<0.001). In predictor x eGFR x time interaction models, GFAP and NfL interacted with eGFR on p-tau (p-values<0.04). Other models were nonsignificant. Stratified models showed that associations were significant only in individuals with no CKD/stage 1 CKD and were not significant in participants with stage 2 or 3 CKD.

In this community-based sample of older adults free of dementia, plasma biomarkers of AD/neurodegeneration were associated with AD-related clinical outcomes both cross-sectionally and longitudinally; however, these associations were modified by renal functioning with no associations in individuals with stage 3 CKD. These results highlight the value of blood-based biomarkers in individuals with healthy renal functioning and suggest caution in interpreting these biomarkers in individuals with mild to moderate CKD.

Spontaneous speech undergoes subtle but significant changes years before the onset of Alzheimer's dementia (AD). In monolinguals, these changes, or linguistic markers of AD, include the use of syntactically simpler structures, reduced lexical diversity, reduced semantic detail/specificity, and increased disfluencies (Ostrand & Gunstad, 2020; Slegers et al., 2018; Venneri et al., 2018). No studies have examined if bilinguals exhibit similar changes in their language output prior to diagnosis of AD though this question has important clinical relevance and can also shed light on which cognitive abilities decline first with AD pathology. Of particular interest, changes in semantic representations might affect both languages (because semantics are shared between the two), but changes in executive control might be more prominent in the nondominant language (because of interference from the dominant language).

Seventeen older Spanish-English bilinguals completed an interview in which they described a picture in each language and answered a series of questions beginning with "warm-up" questions and progressing to questions that elicited higher level language (e.g., defending an opinion). All participants were considered cognitively healthy at the time of testing, but 8 participants later developed Alzheimer's Disease (i.e., converters) on average after 4.1 (SD=2.5) years, while 9 matched controls remained cognitively healthy on average for 5.7 (SD=3.6) years (for as long as they were followed). Converters and controls were matched for age, education, language proficiency, and cognitive status at the time of testing. Language samples were transcribed word for word and analyzed using the Systematic Analysis of Language (Miller & Iglesias, 2012).

Converters and controls were compared on measures of syntactic complexity, lexical diversity, abandoned utterances, errors, and disfluencies. In the dominant language, the number of different words (using a moving window average; a measure of lexical diversity), showed promise for classifying who would eventually convert (Area Under the Curve = 77), though the difference between converters and controls was significant only in a 1-tailed test (t(15)=-1.96, p=.034). In the nondominant language, converters showed a higher percent of Maze words compared to controls (2-tailed t (15) = 2.27, p = 0.039). Mazes combine repetitions, filled pauses, and revisions. Further exploration of Maze subcomponents revealed that filled pauses and revisions produced no differences between groups in either language (all ps3.18), but converters produced more repetitions (e.g., "the the boy" or "the cou-counter") than controls, (2-tailed t-tests in both languages were significant; ps <.03). However, variability in repetitions was high, making it less sensitive in the ROC analysis.

Changes in bilinguals' spoken language output occur years before diagnosis, in agreement with literature on monolinguals. However, in bilinguals, the two languages may be differentially affected by cognitive changes. The dominant language may be more sensitive for discriminating groups possibly reflecting semantic decline and decreased ability to quickly access a variety of words. But changes in the nondominant language reveal a broader nature of cognitive deficits in prodromal AD, including decreased circumlocution abilities to avoid disfluencies when faced with word-finding difficulties.

Older age is associated with an increase in altruistic behaviors such as charitable giving. However, few studies have investigated the cognitive correlates of financial altruism in older adults. This study investigated the cognitive correlates of financial altruism measured using an altruistic choice paradigm in a community-based sample of older adults.

In the present study, a sample of older adults (N = 67; M age = 69.21, SD = 11.23; M education years = 15.97, SD = 2.51; 58.2% female; 71.6% Non-Hispanic White) completed a comprehensive neuropsychological assessment and an altruistic choice paradigm in which they made decisions about allocating money between themselves and an anonymous person.

In multiple linear regression analyses that controlled for age, education, and sex, financial altruism was negatively associated with performance on cognitive measures typically sensitive to early Alzheimer’s Disease. These included CVLT-II Short Delay Free Recall (Beta=-0.26, p=0.03); CVLT-II Long Delay Cued Recall (Beta=-0.32, p=0.04), Craft Story 21 Delayed Recall (Beta=-0.32, p=0.01), and Animal Fluency (Beta=-0.27, p=0.02). Findings held when responses were grouped according to how much was given (Gave Equally, Gave More, Gave Less) for word list memory and story memory measures.

Findings of this study point to a negative relationship between financial altruism and cognitive functioning in older adults on measures known to be sensitive to Alzheimer’s Disease (AD). Findings also point to a potential link between financial exploitation risk and AD in older age.

Higher educational attainment is associated with reduced risk for Alzheimer's disease (AD) dementia, and its protective effect may act through alterations in cerebral blood flow (CBF) that allow for better coping with accumulating neuropathology. Additionally, there are sex differences in both the risk of developing AD as well as the potential protective effects of education. We therefore sought to investigate whether education moderates the association of hippocampal CBF and memory in cognitively unimpaired older adults, and to examine if these interactions were moderated by sex.

Cognitively unimpaired older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI; 51 men, 50 women) underwent neuropsychological evaluation and arterial spin labeling MRI, which was used to quantify bilateral hippocampal CBF. Sex was defined as sex at birth. Multiple linear regressions assessed (1) the independent associations among education, CBF, and memory performance separately in men and women and (2) the three-way interactions among CBF, sex, and education, followed by sex-stratified analyses. Three outcome measures were examined: Logical Memory Story A immediate and delayed recall, and Rey Auditory Verbal Learning Test (RAVLT) intrusions. All models adjusted for age and APOE epsilon-4 allele frequency, and all models with CBF additionally adjusted for cerebral metabolism (baseline FDG-PET composite) and pulse pressure.

CBF was not associated with education or memory in either women or men. There was a positive association between education and delayed memory in women (ß=0.14, t=2.64, p=0.008) as well as trending, positive associations between education and immediate memory in women (ß=0.09, t=1.79, p=0.074) and education and delayed memory in men (ß=0.09, t=1.94, p=0.054). Three-way interactions among sex, CBF, and education were significant on immediate recall (ß=2.55, t=2.53, p=0.013), delayed recall (ß=2.56, t=2.44, p=0.017), and RAVLT intrusions (ß=-2.28, t=-2.27, p=0.026). In women, there were interactions between education and hippocampal CBF on both immediate (ß=2.49, t=2.90, p=0.006) and delayed recall (ß=2.30, t=2.78, p=0.009), such that as education increased, the strength of the association between CBF and immediate memory increased. There was also an interaction between education and hippocampal CBF on RAVLT intrusions in women (ß=-2.42, t=-3.05, p=0.004), such that as education increased, the strength of the association between CBF and number of intrusions decreased; there was a main effect where in women with lower education, as CBF increased, the number of intrusions increased (ß=0.76, t=2.59, p=0.032); in women with higher education, there was no association between CBF and intrusions. In men, none of these two-way interactions were significant.

These results suggest that, in cognitively unimpaired older women, the relationship between hippocampal CBF and memory is moderated by education level, even when adjusting for several other factors. Specifically, higher education may serve as a protective factor in the hippocampal CBF-memory relationship, and this relationship was sex-dependent, occurring in women only. Further research is needed to examine these relationships longitudinally across the clinical continuum of AD. Additionally, this work needs to be conducted in more diverse samples to allow for analyses investigating the impact of education on the intersection of race/ethnicity and sex/gender.

Due to the pathology of Alzheimer's disease (AD), it is not uncommon for patients to struggle with cognitive tasks involving figure copying. However, figure copying requires involvement from multiple other domains, including visuospatial and frontal-executive abilities. Less clear is whether figure copying performance, as measured by the Rey-Osterrieth Complex Figure (ROCF), is more affected by visuospatial or frontal-executive compromise in patients with AD. This study aims to discover whether performance on the ROCF varies more with executive or visuospatial abilities in patients with AD.

A total of 156 patients (79 women, M age = 77.82, M education = 14.21) diagnosed with Alzheimer's disease (AD) participated in comprehensive neuropsychological assessment as part of outpatient neurology evaluations. In addition to the ROCF Copy trial, participants completed measures of visuospatial function (WAIS-IV Block Design & Picture Completion) and frontalexecutive functioning (Trails B, DKEFS Inhibition, WAIS-IV Similarities).

Canonical correlations revealed that ROCF Copy was significantly and positively related to the set of tests measuring visuospatial functioning, p < .001, and frontal-executive functioning, p < .001. Post-hoc bivariate correlations showed significant positive correlations between ROCF Copy and each visuospatial, ps < .01, and each frontalexecutive, ps < .04, measure. The relationship between ROCF Copy and each visuospatial measure was significantly stronger than the relationship between ROCF Copy and every frontal-executive measure except WAIS-IV Similarities, ps < .01. Those with visuospatial impairment (>1.5 SD) performed significantly worse on the ROCF Copy than those without impairment, p <.01. This difference persisted even when the effects of frontal-executive measures were controlled, p < .01. In contrast, those with frontal-executive impairment did not perform significantly worse on the ROCF Copy than those without frontal-executive impairment, p < .01. This did not change when controlling for the effects of visuospatial measures. Finally, the significant difference in ROCF Copy between those with mild cognitive impairment (MCI) and those with dementia (p < .01) disappeared when visuospatial measures were controlled, but it remained when frontal-executive measures were covariates, p < .03.

These findings suggest the figure copying of those with AD is significantly related to both their visuospatial and frontal-executive functioning, but the relationship with visuospatial functioning is stronger. Impairment in visuospatial, but not frontal-executive, functions, seems to have a negative impact on the figure copying of those with AD, and performance on visuospatial compared to frontal-executive measures better accounts for the weaker ROCF Copy scores among those with dementia relative to MCI. Therefore, the pathological effects of AD on figure copying appear to occur predominantly through visuospatial rather than frontalexecutive channels, and interventions for offsetting decline in figure copying may be most effective when targeting visuospatial abilities, such as visual perception and visual construction.

Alzheimer's disease (AD) is associated with the accumulation of neuropathological beta-amyloid (Ab) plaques, which is thought to be caused by an imbalance between Ab overproduction and dysfunctional Ab clearance. Both animal and human studies have shown that increased cerebrospinal fluid (CSF) levels of Ab peptides, especially Ab-38 and Ab-40 due to their high solubility, may be indicators of overall Ab dysregulation in preclinical AD, years before pathological Ab plaques begin to aggregate. This overabundance of Ab and later sequestration onto plaques eventually triggers a cascade of subsequent brain changes that may lead to cognitive decline. Indeed, alterations in gray matter integrity may play a role, as imaging studies have shown specific atrophy patterns in preclinical AD, particularly in language regions of the bilateral temporal lobes, which relate to cognitive performance. Here, we aimed to explore whether temporal lobe cortical volume is implicated in the relationship between increased CSF Ab levels and cognitive decline, as measured by confrontation naming performance -- an age-independent language task often impaired in preclinical AD -- in AD-vulnerable populations.

We selected 87 non-demented Veterans (Sex: 99% male; Age: M=68.2, SD=3.7; Education: M=15.5, SD=2.2) from the Alzheimer's Disease Neuroimaging Initiative-Department of Defense (ADNI-DOD) database based on available Boston Naming Test (BNT) scores, CSF measures of Ab-38 and Ab-40, and structural neuroimaging data. The 30-item BNT assessed confrontation naming performance. CSF Ab concentrations were measured using a 2D-UPLC-tandem mass spectrometry method outlined by ADNI-DOD. T1-weighted images were acquired on a 3T scanner and processed by ADNI to calculate cortical volumes (CVs) for regions of interest (ROIs); the present study focused on three bilateral ROIs in the temporal lobe (fusiform gyrus [FFG], inferior temporal gyrus [ITG], and middle temporal gyrus [MTG]). All CVs were adjusted (CV_adj) for intracranial volume (ICV) using the covariance formula (CV_adj = CV - b [ICV - mean(ICV)]). Linear regression models explored the relationship between CSF Ab peptides and BNT with temporal lobe ROIs as moderators using the PROCESS macro.

CV of the bilateral FFG significantly moderated the relationship between BNT performance and both CSF Ab-38 (p=.025, R2=.05, b=.0008) and Ab-40 (p=.016, R2=.06, b=.0002) levels. We then explored effects of the left and right FFG separately and found that the relationship between CSF Ab-38 and BNT was significantly moderated by the left FFG (p=.032, R2=.05, b=.0006) and nominally by the right FFG (p=.072, R2=.03, b=.0006). The relationship between CSF Ab-40 and BNT was significantly moderated by both the left (p=.032, R2=.05, b=.0001) and right (p=.038, R2=.04, b=.0001) FFG. CV of the bilateral ITG and MTG had no effect on any model (all p >.10).

Increased Ab may trigger alterations in neural gray matter integrity, specifically in the FFG of the temporal lobe, and these changes may in turn be implicated in AD-related cognitive decline, particularly in the language domain. These findings suggest that biomarker models incorporating CSF Ab and CV may aid early identification of disease and risk for cognitive decline in preclinical AD stages, which could help inform early interventions.

Growing evidence demonstrates that subtle changes in spontaneous speech can be used to distinguish older adults with and without cognitive impairment, including those with Alzheimer's disease (AD). Recent work suggests that quantification of the meaningful connectedness of speech - termed semantic coherence - may be sensitive to cognitive dysfunction. The current study compared global coherence (GC; the degree to which individual utterances relate to the overall topic being discussed) and local coherence (LC; the degree to which adjoining utterances relate meaningfully to each other) in persons with AD and healthy controls.

Speech transcripts from 81 individuals with probable AD (Mage = 72.7 years, SD = 8.8, 70.3% female) and 61 healthy controls (HC) (Mage = 63.9 years, SD = 8.5, 62.2% female) from Dementia Bank were analyzed. All participants completed the Cookie Theft and MMSE as part of that larger project. Machine learning analyses of GC and LC were conducted and models evaluated classification accuracy (i.e., AD vs HC) as well as ROC-AUC. Relationships between coherence indices and MMSE performance were also quantified.

Though no significant group differences emerged in LC (Estimate = 0.012, p = 0.32), persons with AD differed from healthy controls in GC (Estimate = 0.03, p = 0.006) and produced less semantically coherent speech. GC indices predicted AD diagnoses with 65% accuracy. Interestingly, coherence indices showed only modest correlation with MMSE scores (r = .19).

GC metrics of spontaneous speech differentiated between persons with AD and controls, but did not strongly correlate with MMSE performance. Such findings support the notion that many aspects of language are impacted in persons with AD. In addition to replication, future work should evaluate whether GC is also disrupted in persons with pre-clinical AD and its potential to assist with early detection.

Semantic memory deficits have been reported in both Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI). However, the nature of this decline is still a matter of debate. The aim of this study was to explore the patterns of semantic memory impairment in aMCI by examining performance on naming tasks, and on tests assessing both general and specific semantic knowledge.

Participants were divided in two groups matched for age and education, one comprising 33 aMCI individuals and the other 39 healthy controls. Three experimental tests assessing naming and semantic knowledge of unique items of famous persons (FACE) and places (PLACE), logos recognition (LOGO: brands and pictograms), and non-unique entities (Boston Naming Test: BNT) were administered, and the performance of the two groups was compared.

Lower scores were observed on all naming tests (PLACE, FACE, LOGO and BNT) in the aMCI group compared to controls. On the PLACE test, the general knowledge mean score (M=84.5, SD=12.9) was significantly higher than the specific knowledge mean score (M=54.2, SD=18.5) in aMCI participants (t(31)=11.9, p<.001), but not in controls (general: M=92.2, SD=11.1; specific: M=73.7, SD=15.8), and there was a significant Group X Type of knowledge interaction (F(1,1)=15.13, p <.001, n2 = 18). On the FACE test, in addition to significant group and condition (naming, semantic questions) main effects, a significant interaction was found (F(1,1)=7.19, p = .009, n2 = .09). On the LOGO task, controls were significantly better on brand items (M= 94.4, SD=10.5) than on pictograms (M=83.3, SD=12.2), while no significant difference was noted in aMCI (brands: M=81.5, SD=22.6; pictograms: M=77.5, SD=14.1). Lastly, on the BNT, aMCI participants benefited more from phonemic cues than controls (F(1,1)=16.56, p<.001, n2=19), suggesting a lexical access deficit, in addition to their semantic memory impairment.

This study adds to the growing evidence confirming the presence of semantic memory deficits in aMCI. Specific semantic knowledge seems to be more affected than general semantic knowledge, a finding reported in previous studies. Lexical access deficits, in addition to semantic decline, were also observed in the aMCI group. These results allow for a better understanding of the pattern of semantic memory deficits in the prodromal stage of AD and could potentially facilitate diagnosis of aMCI.

Semantic processing dysfunction has been shown to be an early indicator of cognitive decline in Alzheimer's disease (AD) and has been linked to early accumulation of AD-pathology. We examined semantic processing and its relation to AD pathology in non-demented individuals from a Colombian kindred with autosomal dominant AD due to the Presenilin1 E280A mutation (PSEN1).

A total of 13 cognitively unimpaired PSEN1 mutation carriers (mean age: 36.92± 4.94), 7 carriers with mild cognitive impairment (MCI; mean age: 45±2.65), and 17 family non-carriers (mean age: 36±6.38) from the Colombia-Boston (COLBOS) longitudinal biomarker study were included. We used the Bateria IV Woodcock-Munoz verbal analogies and text comprehension subtests to examine semantic processing, the Mini-Mental State Examination (MMSE) to assess global cognition and the CERAD word list delayed recall task to measure verbal memory. Participants also underwent PiB and flortaucipir-PET to measure mean cortical amyloid and regional tau burden (entorhinal cortex and precuneus), respectively. Mann-Whitney U tests and Spearman's Rho correlations compared group differences in semantic processing, and its associations with age and pathological markers. Post-hoc analyses excluded carriers with MCI and controlled for education.

Carriers (including cognitively unimpaired and symptomatic individuals) performed significantly worse on the MMSE (carriers: 14.55, non-carriers: 24.24; U=81.00, p=.006), CERAD word list delayed recall (carriers: 13.63, non-carriers: 25.32; U=48.00, p=.001), and text comprehension (carriers: 16.36, non-carriers: 23.81; l/=107.00, p=.042,) than non-carriers, and showed a trend towards worse performance on verbal analogies (carriers: 17.16, non-carriers: 23.68; U=124.50, p=.077). There were no differences in text comprehension or verbal analogies performance between cognitively-unimpaired carriers and non-carriers.Across the whole sample, age was negatively associated with performance on verbal analogies (r=-.341, p=.039), but not text comprehension (r=-.136, p=.428). Among carriers only, better MMSE and CERAD delayed recall performance was associated with higher verbal analogies (r=.561, p=<.001; r=.662, p=<.001, respectively) and text comprehension scores (r=.468, p=.004; r=.480, p=.003, respectively). Greater amyloid burden was associated with worse verbal analogies performance (r=-.432, p=.007) and text comprehension (r=-.430, p=.008). Greater entorhinal cortex (r=-.384, p=.016) and precuneus tau burden (r=-.318, p=.049) was associated with worse performance on verbal analogies, but not text comprehension. These associations did not survive when excluding carriers with MCI or controlling for education.

Preliminary results show that non-demented mutation carriers had worse performance in semantic processing than non-carriers and performance was associated with markers of AD pathology. These findings suggest that changes in semantic processing may be early indicators of disease progression in individuals at increased risk for Alzheimer's disease dementia. Future studies with larger samples need to examine the role of education and the longitudinal trajectory of semantic processing dysfunction in AD.

Higher baseline dispersion (intra-individual variability) across neuropsychological test scores at a single time-point has been associated with more rapid cognitive decline, onset of Mild Cognitive Impairment (MCI) and Alzheimer’s disease (AD), faster rates of hippocampal and entorhinal atrophy, and increased AD neuropathology. Comparison between predictions made from test score dispersion within a cognitive domain versus global, cross-domain dispersion is understudied. Global dispersion may be influenced by ability-and test-specific characteristics. This study examined the performance of global versus domain-specific dispersion metrics to identify which is most predictive of cognitive decline over time.

Data for baseline and five follow-up visits of 308 participants with normal cognition (Mage=73.90, SD=8.12) were selected from the National Alzheimer’s Coordinating Center (NACC) Dataset. Participants were required to have no focal neurological deficits, or history of depression, stroke, or heart attack. Diagnoses and progression to MCI and/or dementia were determined at each visit through consensus conferences. Raw neuropsychological scores were standardized using NACC norms. Global baseline dispersion was defined as the intraindividual standard deviation (ISD) across the 10 scores in the NACC battery. Domain-specific dispersions were calculated by constructing composites and ISD was computed across tests sampling their respective domains (executive functioning/attention/processing speed [EFAS], language, and memory; see Table 1 for details on these tests). Higher values on each of these metrics reflect greater dispersion. Multinomial logistic regression model fit statistics and parameter estimates were compared across four different models (global, EFAS, Language, and Memory dispersion) covarying for age, years of education, sex, race, ethnicity, and ApoE4 status. Models were compared using the Likelihood Ratio Test (LRT) and the Akaike Information Criteria (AIC) of Models statistics.

Of the 308 participants, 70 (22.7%) progressed to MCI, and 82 (26.6%) progressed to dementia. Tables 1 and 2 show the results of the logistic regressions for the four models. All models fit the data well, with statistically significant predictions of conversion. Model 1 (global dispersion) showed a better fit than domain-specific models of dispersion per LRT and AIC values. Consistent with the results from mean differences between groups, parameter estimates showed that only global dispersion and EFAS dispersion significantly predicted conversion to dementia (when included with other covariates in models), with higher dispersion reflecting a greater risk of conversion.

In this sample, baseline global and EFAS dispersion measures significantly predicted conversion to dementia. Although global dispersion was a stronger predictor of dementia progression, findings suggest that executive functioning performance may be driving this relationship. A single index of global variability, from the calculation of standard deviation across test scores, may be supplementary for clinicians when distinguishing individuals at risk for dementia progression. None of the models were predictive of conversion to MCI. Further research is required to examine cognitive variability differences among patients who progress to MCI and patient-specific factors that may relate to test score dispersion and its utility in predicting the progression of symptoms.

Research has shown significant deficits in cognitive domains and a decline in activities of daily living (ADL) in patients with Alzheimer disease (AD). Patients with Mild Cognitive Impairment (MCI) also experience struggles with ADL; moreover, research documents that many MCI patients' symptoms gradually worsen such that their diagnosis eventually converts to AD. Different cognitive domains (i.e., memory, executive function, attention etc.) impact ADL performance. Commonly used instruments for assessing ADL are subjective measures filled by primary caregivers. Subjective measures are not able to assess actual ADL performance. Thus, performance-based tests, such as the Direct Assessment of Functional Status (DAFS), tests of ADLs are more informative. The purpose of this study is to analyze classification accuracy rates for AD and MCI patients with use of five ADL subscales and overall performance a performance-based ADL test.

As part of a larger study, 61 patients diagnosed with AD and 54 age- and education matched patients diagnosed with MCI were administered the DAFS. All patients were administered the Direct Assessment of Functional Status test. This test assesses orientation to time, communication skills, knowledge of transportation rules, financial abilities, and ability to shop for groceries, as well as basic daily skills such as grooming and eating skills. For the purpose of this study, grooming and eating abilities were not used in the analysis.

Discriminant functional analysis was performed to assess the classification accuracy rates for AD and MCI patients using their ability to perform various types of ADL tasks on the DAFS. The analysis revealed total DAFS scores and all five subscales significantly classified AD and MCI patients performance (all p values < .01). While performance across the DAFS subscale scores accurately classified MCI at rates ranging from 67% - 90%, the rates of accurate classification was much lower for AD patients (29.5% - 62.3%). Of the subscales, the DAFS Shopping task best discriminated and classified the performance of AD at 62% and MCI at 67%.

These results indicates that a performance-based ADL test can aid in classification of AD and MCI. The fact that the DAFS shopping subscale which requires learning and memory abilities had the best accuracy rates, is consistent with profound memory deficits found in AD patients. This study further highlights the importance of using observational-based measures to assess ADL in MCI and AD patients.

Early identification of individuals at risk for dementia provides an opportunity for risk reduction strategies. Many older adults (30-60%) report specific subjective cognitive complaints, which has also been shown to increase risk for dementia. The purpose of this study is to identify whether there are particular types of complaints that are associated with future: 1) progression from a clinical diagnosis of normal to impairment (either Mild Cognitive impairment or dementia) and 2) longitudinal cognitive decline.

415 cognitively normal older adults were monitored annually for an average of 5 years. Subjective cognitive complaints were measured using the Everyday Cognition Scales (ECog) across multiple cognitive domains (memory, language, visuospatial abilities, planning, organization and divided attention). Cox proportional hazards models were used to assess associations between self-reported ECog items at baseline and progression to impairment. A total of 114 individuals progressed to impairment over an average of 4.9 years (SD=3.4 years, range=0.8-13.8). A subset of individuals (n=352) underwent repeat cognitive assessments for an average of 5.3 years. Mixed effects models with random intercepts and slopes were used to assess associations between baseline ECog items and change in episodic memory or executive function on the Spanish and English Neuropsychological Assessment Scales. Time in years since baseline, the ECog items, and the interaction were key terms of interest in the models. Separate models for both the progression analyses and mixed effects models were fit for each ECog item that included age at the baseline visit, gender, and years of education as covariates.

More complaints on five of the eight memory items, three of the nine language items, one of the seven visuospatial items, two of the five planning items, and one of the six organization items were associated with progression to impairment (HR=1.25 to 1.59, ps=0.003 to 0.03). No items from the divided attention domain were significantly associated with progression to impairment. In individuals reporting no difficulty on ECog items at the baseline visit there was no significant change over time in episodic memory(p>0.4). More complaints on seven of the eight memory items, two of the nine language items, and three of the seven visuospatial items were associated with more decline in episodic memory (ps=0.003 to 0.04). No items from the planning, organization, or divided attention domains were significantly associated with episodic memory decline. Among those reporting no difficulty on ECog items at the baseline visit there was slight decline in executive function (ps=<0.001 to 0.06). More complaints on three of the eight memory items and three of the nine language items were associated with decline in executive function (ps=0.002 to 0.047). No items from the visuospatial, planning, organization, or divided attention domains were significantly associated with decline in executive function.

These findings suggest that, among cognitively normal older adults at baseline, specific complaints across several cognitive domains are associated with progression to impairment. Complaints in the domains of memory and language are associated with decline in both episodic memory and executive function.

High levels of stress may increase risk for Alzheimer’s disease (AD) dementia. Religious coping practices to deal with stress (i.e., prayer, having faith, attending religious services) may reduce risk of dementia. Studying religious stress coping in cognitively unimpaired individuals with autosomal-dominant AD (ADAD), who will develop dementia later in life, may inform us about the role of religious coping in modifying the clinical trajectory from preclinical to clinical stages of the disease. We examined religious stress coping in cognitively unimpaired mutation carriers from the world’s largest ADAD kindred and its relation to markers of brain pathology and memory.

16 cognitively unimpaired Presenilin-1 E280A mutation carriers and 19 age and education-matched noncarrier family members from the Colombia-Boston (COLBOS) Biomarker Study were included. A subsample (n=26; 13 cognitively unimpaired carriers) underwent amyloid and tau PET imaging. Participants completed the Coping Strategies Questionnaire (CAE) that includes a subscale used to assess religious stress coping, where a higher score indicates more coping, and underwent memory testing using the Free and Cued Selective Reminding Test (FCSRT). The Geriatric Depression Scale (GDS) was used to assess depression. Mann-Whitney U tests were used to examine group differences in religious stress coping, brain pathology (i.e., cortical amyloid-beta, entorhinal and precuneus tau), memory, and depression. Nonparametric correlations were used to examine associations among religious stress coping, age, education, depression, memory, and pathology.

Carriers had poorer FCSRT immediate free recall than noncarriers (U=84.5, p=.024). There was no difference between groups in CAE religious stress coping, other FCSRT memory scores, nor GDS score (all p>.05). Compared to non-carriers, carriers had more cortical amyloid (U=152.0, p<.001) and more precuneus tau (U=123.0, p=.05). In carriers, religious stress coping was positively associated with education (r=.57, p=.022), FCSRT immediate free recall (a=.75, p<.001), FCSRT cued recall (a=.50, p=.047), and FCSRT delayed recall (r=.52, p=.038). After controlling for education, religious stress coping remained positively associated with FCSRT immediate free recall (r=.65, p=.009), but not other FCSRT memory scores (all p>.05). Religious stress coping was not associated with age or GDS score regardless of controlling for education (all p>.05). In carriers, religious stress coping was negatively associated with entorhinal tau (r=-.73, p=.005) and precuneus tau burden (r=-.58, p=.037). The association between religious stress coping and entorhinal tau remained significant after controlling for education (r=-.67, p=.016), but not precuneus tau (p>.05). Religious stress coping was not associated with cortical amyloid regardless of controlling for education in carriers (all p>.05). None of the associations with brain pathology or memory were significant in the non-carrier group.

Religious stress coping was associated with better memory performance and a low AD pathology burden in individuals at genetic risk for developing AD dementia. Future studies with independent and larger samples should further examine religious stress coping strategies and their associations with other AD-related biomarkers, as well as with other risk and protective factors to better understand their role at the preclinical and prodromal stages of Alzheimer’s disease.