Social determinants of health (SDOH) are social conditions (e.g., employment, access to healthcare, quality schools) which are shown by a growing body of literature to impact many health outcomes, including cognition. The development of community-level measures including the Child Opportunity Index (COI) have allowed for increased understanding of the resources and conditions in neighborhoods and their impact on children’s health. Given the limited existing research on how neighborhood factors impact cognitive development, this study aimed to examine associations between neighborhood context (COI) and cognitive outcomes in children and adolescents who presented for neuropsychological evaluations.

Participants included 4,633 youth (ages 2-22; M = 10.8 years; SD = 4.1 years; 63% Male; 33% with a medical condition involving the central nervous system [CNS]) living in the DC-VA-MD-WV Metro Area who presented to an outpatient clinic for evaluation and completed an intellectual functioning (IQ) measure (88% Weschler, 11% DAS, <1% Leiter, <1% RIAS). COI values were extracted from electronic medical records based on home address. COI values include an overall index and three domain scores in educational (educational access, quality, and outcomes), health/environment (access to healthy food, healthcare, and greenspace) and social/economic (income, employment, poverty); higher scores indicate higher opportunity. Using metro-based norms, children from all opportunity levels were represented (14% Very Low, 13% Low, 18% Moderate, 21% High, 34% Very High). Multiple regression analyses were conducted to examine main effect associations between COI and Full-Scale IQ (FSIQ), Verbal IQ (VIQ), and Non-Verbal IQ (NVIQ) and explore moderation of age, gender, and medical condition on these associations. Additional regression analyses examined these relationships for the three COI domains.

Controlling for age, gender, and medical condition, neighborhood opportunity was positively associated with cognitive function (FSIQ: ß=0.198; VIQ: ß=0.202; NVIQ: ß=0.148, p’s <0.01). Models accounted for approximately 10-14% percent of the variance in cognitive outcomes (FSIQ: F[6,4476]=180.331), Adj.R2=0.138; VIQ: F[6,4556]=161.931), Adj.R2=0.124; NVIQ: F[6,4548]=123.893), Adj.R2=0.098). Age moderated the association between overall COI and cognitive outcomes (FSIQ: ß=0.005, p=0.018; VIQ: ß=0.005, p=0.043; NVIQ: ß=0.005, p<0.01) such that the association between neighborhood opportunity and cognitive outcomes was stronger at older ages, though this was a small effect. When examining subdomains of COI, cognitive outcomes were associated with educational (FSIQ: ß=0.094; VIQ: ß=0.099; NVIQ: ß=0.078, p’s <0.01) and social/economic opportunity (FSIQ: ß=0.115; VIQ: B=0.121; NVIQ: ß=0.084, p’s <0.01) but not health/environmental opportunity (FSIQ: ß=-0.001, p=0.991; VIQ: ß=-0.008, p=0.581; NVIQ: ß=-0.008, p=0.553). Medical diagnosis moderated the association between social/economic opportunity and FSIQ; there was a stronger association between IQ and COI in youth with a medical diagnosis (ß=-0.071, p<0.05).

These findings demonstrate the importance of neighborhood factors, especially education and social/economic opportunities, on cognitive development. Children living in higher opportunity neighborhoods showed higher cognitive functioning. Older age and CNS-involved medical conditions were associated with higher risk in the context of reduced neighborhood opportunities. These findings emphasize the need for advocacy and other efforts to improve community resources (e.g., access to early childhood education) to address inequities in cognitive development.

Compensatory strategies (CS) can assist in supporting everyday memory and functional independence. Digital compensatory strategies (e.g., calendar and notes apps) are being used more by older adults, but their effectiveness compared to paper-based strategies has been questioned due to their novelty and potential suitability. This study examined whether digital and non-digital strategies vary in quality and lead to accuracy differences in carrying out a set of real-world prospective memory (PM) tasks.

Seventy community-dwelling older adults (Mage= 70.80, SD = 7.87) completed two testing sessions remotely from home via Zoom. Participants were presented four real-world PM tasks (packing for overnight trip, creating physical activity summary, paying bill by due date, and calling lab to leave message) and were encouraged to use their typical CS to support task completion. The type and quality of CS, as well as accuracy of PM task completion, were assessed using lab-developed coding schemas. Quality scores were on a 0-3 point scale per task step (maximum total score = 63), and accuracy scores were on a 0-4 point scale (maximum score = 16). Participants were differentiated into two groups: those who used at least one digital CS (40 participants) and those who did not use digital CS (30 participants). T-tests were examined for group differences in number of CS utilized, CS quality, and PM accuracy. Within each group, correlations between CS quality and PM accuracy were conducted. Group comparisons were also conducted for demographics, cognitive test performances, and questionnaires.

The technology group (M = 13.90, SD = 5.43) utilized significantly more strategies than the non-technology group (M = 9.50, SD = 4.12), t(68) = -3.71, p < .05, d = 0.91, and the technology group’s strategies (M = 42.48, SD = 10.47) were significantly higher quality than the non-technology groups (M = 33.80, SD = 13.02), t(68) = -3.09, p < .05, d = 0.73. However, the technology (M = 12.30, SD = 2.48) and non-technology (m = 11.87, SD = 3.16) groups completed the four PM tasks with equivalent accuracy, p > .05. Correlational analyses revealed that higher quality strategies were associated with better PM performance for both the technology (r = .67, p < .001) and the non-technology group (r = .71, p < .001). Although the technology group reported higher comfort with technology, both groups reported comparable levels of quality of life and functional independence and performed similarly on cognitive tests. The technology group trended towards being younger and having a higher level of global cognitive status (p = .07), but there were no group differences in education level or premorbid verbal ability.

Digital compensatory strategies resulted in higher CS quality scores and more strategies used, but there was no significant difference in PM accuracy scores between digital and non-digital CS. Regardless of technology use, using high quality CS supported real-world PM performance. Interventions that focus on improving the quality of compensatory strategies being utilized by older adults may enhance everyday functioning.

Older adults often spontaneously use compensatory strategies (CS) to support everyday memory and daily task completion. Recent work suggests that evaluating the quality of CS provides utility in predicting real-world prospective memory (PM) task completion. However, there has been little exploration of how CS quality may vary based on PM demands. This study examined differences in CS use and task completion accuracy across time-based (TB) and event-based (EB) PM tasks. Based on differences in self-monitoring demands and ability to engage in cognitive offloading, it was hypothesized that participants would utilize better quality strategies for TB tasks than EB tasks, which would lead to superior accuracy in completing TB tasks.

Seventy community-dwelling older adults (Mage = 70.80, SD = 7.87) completed two testing sessions remotely from home via Zoom. Participants were presented two TB PM tasks (paying bill by due date, calling lab at specified time) and two EB PM tasks (presenting a packed bag to examiner upon a cue, initiating discussion about physical activity log upon cue). Participants were encouraged to use their typical CS to support task completion. Quality of CS (0-3 points per task step) and accuracy of task completion (0-4 points per task) were evaluated through lab-developed coding schemas. For each task, CS Quality scores were assigned based on how well strategies supported retrospective memory (RM) and PM task elements, and RM and PM Quality scores were summed to yield a Total Quality score. Because each task consisted of a different number of steps, CS Quality scores for each task were divided by their respective number of steps to yield measures of average quality. Paired-samples t-tests examined differences in average CS quality (Total, RM, and PM) and PM accuracy across TB and EB tasks.

Participants’ Total CS Quality was equivalent for TB tasks (M = 1.92, SD = 0.64) and EB tasks (M = 1.87, SD = 0.68), t(69) = 0.60, p = .55. Comparisons of subscores revealed that while participants used similar quality RM supports for TB tasks (M = 1.67, SD = 0.66) and EB tasks (M = 1.78, SD = 0.68), t(69) = 1.39, p = .17, participants utilized superior quality PM supports for TB tasks (M = 2.16, SD = 0.70) compared to EB tasks (M = 1.97, SD = 0.73), t(69) = 2.46, p = .02. Additionally, participants completed TB tasks with greater accuracy (M = 3.21, SD = 0.74) than EB tasks (M = 2.84, SD = 0.89), t(69) = 3.62, p < .001.

While participants exhibited similar quality CS for RM components across TB and EB tasks, they displayed superior quality CS for PM components of TB tasks. This difference in quality may have contributed to participants completing real-world TB PM tasks with greater accuracy than EB tasks. Results contrast with trends in lab-based PM tasks, in which participants usually complete EB tasks more accurately. Findings may have implications for interventions, such as an enhanced focus on teaching high-quality CS to support real-world EB tasks.

One of the greatest challenges of the Alzheimer’s disease (AD) epidemic is identifying the disease prior to substantial neurological compromise. The established biomarkers of AD, such as measures of cognitive impairment, hippocampal atrophy, and CSF measures of beta amyloid and tau, used in research and drug trials are less indicative of AD pathology in preclinical, non-demented, populations. Olfactory dysfunction, a well-established sensory impairment of AD found to correlate strongly with tau burden and hippocampal volume measures, has shown to be a promising preclinical biomarker for AD progression. Several studies have found either impaired odor identification or odor memory at baseline to predict 5-year follow-up cognitive decline and conversion from MCI to AD, but less is known about how olfactory performance reflects the integrity of associated brain regions such as the hippocampus. The present analysis aims to explore the value of psychophysical olfactory assessment as biomarker measure in preclinical AD studies and drug trials by investigating its relationships with structural measures of the hippocampus.

A sample consisted of non-demented older adults (age >75), recruited from the UCSD Alzheimer’s Disease Research Center as part of a ongoing olfactory biomarker study. Participants completed the AD Assessment Scale-Cognitive Subscale-13 (ADAS-Cog-13), San Diego Odor Identification Test (SDOIT), tests of odor recognition memory (ORMem) and odor associative memory (OAM), and MRI derived hippocampal volumes and average hippocampal occupancy (Avg HOC). Left and right hippocampal volumes were adjusted for each participant’s estimated intracranial volume. Bivariate correlations were calculated for ADAS-Cog-13 and SDOIT total scores, performance scores for odor recognition and odor associative memory tests, and the three hippocampal measures (bilateral volumes and average occupancy).

ADAS-Cog-13 score did not show significant correlations with either hippocampal measure at the .05 level. SDOIT scores were significantly correlated with the measure of Avg HOC (p<.05). ORMem false positive responses were significantly correlated with Avg HOC (p<.01) and right hippocampal volume (p<.05). ORMem miss responses and OAM errors were both correlated with left (p<.05) and right (p<.01) hippocampal volumes.

These results demonstrate that psychophysical assessments of odor identification and odor memory can better reflect the integrity of the hippocampus in nondemented older adults, compared to the neuropsychological ADAS-Cog-13. This is congruent with olfactory dysfunction preceding cognitive-memory decline in AD cases and provides support for the utility of psychophysical olfactory assessment along with other established AD biomarkers in research and drug trials in preclinical populations.

Supported by NIH grant # R01AG062006-04 from the National Institute on Aging to CM. Special thank you to the staff and participants of the UCSD ADRC, especially Christina Gigliotti, and Aaron Jacobson at the UCSD Center for fMRI.

Neurofilament light chain (NfL), a plasma-based biomarker for neurodegeneration, is a promising marker for early Alzheimer disease (AD) detection in individuals at increased risk. We previously reported that Presenilin1 (PSEN1) E280A carriers have increased levels of plasma NfL relative to non-carrier family members twenty years before the onset of clinical symptoms. Abstract reasoning is one of the first cognitive abilities to deteriorate in AD. Here, we examined whether levels of plasma NfL were associated with non-verbal abstract reasoning performance in non-demented PSEN1-E280A carriers and non-carriers.

A total of 798 members of the Colombian kindred with the PSEN1 E280A mutation (462 cognitively-unimpaired and 336 non-carriers; mean age= 34.02 (10.53), mean education= 8.23(4.60), 57% females and 43% males) were included in the study. Participants completed the Raven’s Progressive Matrices (RPM), Mini Mental State Examination (MMSE), and underwent blood sampling. Plasma NfL concentrations were measured with a single molecule array (Simoa) method. Mann-Whitney U test and education-adjusted Spearman partial correlation were used to examine group differences and associations between abstract reasoning performance and NfL levels.

Non-carriers were older (p<.001) and had higher levels of education than carriers (p=.025). Compared to non-carriers, carriers had higher levels of NfL (p=.014), lower performance on the MMSE (p<.001) and on the RPM (p=.001). In the whole sample, performance on the RPM was significantly associated with age (r= -.144, p<.001), and MMSE score (r=.198, p<.001). In carriers only, performance on the RPM was negatively associated with NfL levels (r=-.121, p=.009). This association was not significant in non-carriers.

Our findings support the hypothesis that plasma NfL levels may be indicators of disease progression and early cognitive dysfunction in autosomal dominant AD. Future work with NfL, abstract reasoning and memory with larger samples across the preclinical/prodromal spectrum will allow a more comprehensive examination of these associations.

Intraindividual variability (IIV) is defined as fluctuations in an individual’s cognitive performance over time1. IIV has been identified as a marker of neurobiological disturbance making it a useful method for detecting changes in cognition among cognitively healthy individuals as well as those with prodromal syndromes2. IIV on laboratory-based computerized tasks has been linked with cognitive decline and conversion to mild cognitive impairment (MCI) and/or dementia (Haynes et al., 2017). Associations between IIV and AD risk factors including apolipoprotein (APOE) ε4 carrier status, neurodegeneration seen on brain imaging, and amyloid (Aß) Positron emission tomography (PET) scan status have also been observed1. Recent studies have demonstrated that evaluating IIV on smartphone-based digital cognitive assessments is feasible, has the capacity to differentiate between cognitively normal (CN) and MCI individuals, and may reduce barriers to cognitive assessment3. This study sought to evaluate whether such differences could be detected in CN participants with and without elevated AD risk.

Participants (n=57) were cognitively normal older adults who previously received an Aß PET scan through the Butler Hospital Memory and Aging Program. The sample consisted of primarily non-Hispanic (n=49, 86.0%), White (n=52, 91.2%), college-educated (M=16.65 years), females (n=39, 68.4%). The average age of the sample was 68 years old. Approximately 42% of the sample (n=24) received a positive PET scan result. Participants completed brief cognitive assessments (i.e., 3-4 minutes) three times per day for eight days (i.e., 24 sessions) using the Mobile Monitoring of Cognitive Change (M2C2) application, a mobile app-based cognitive testing platform developed as part of the National Institute of Aging’s Mobile Toolbox initiative (Sliwinski et al., 2018). Participants completed visual working memory, processing speed, and episodic memory tasks on the M2C2 platform. Intraindividual standard deviations (ISDs) across trials were computed for each person at each time point (Hultsch et al., 2000). Higher ISD values indicate more variability in performance. Linear mixed effects models were utilized to examine whether differences in IIV existed based on PET scan status while controlling for age, sex at birth, and years of education.

n interaction between PET status and time was observed on the processing speed task such that Aß- individuals were less variable over the eight assessment days compared to Aß + individuals (B= -5.79, SE=2.67, p=.04). No main or interaction effects were observed on the visual working memory task or episodic memory task.

Our finding that Aß- individuals demonstrate less variability over time on a measure of processing speed is consistent with prior work. No associations were found between IIV in other cognitive domains and PET status. As noted by Allaire and Marsiske (2005), IIV is not a consistent phenomenon across different cognitive domains. Therefore, identifying which tests are the most sensitive to early change is crucial. Additional studies in larger, more diverse samples are needed prior to widespread clinical use for early detection of AD.

Using a humanized APOE3/4 (Alzheimer’s disease genetic risk allele) mouse model we investigated the potential modulating effects of exercise on systemic risk factors and the ability of this mouse model to translate to active or sedentary, midlife, human participants. We present preliminary results of an ongoing, translational pilot study.

26 Midlife individuals, ages 40-65, were recruited from the community and dichotomized into active or sedentary groups following health screening and cognitive assessment. Blood samples were drawn from human participants for lipid assessment and other general health measures as well as peripheral growth factors concentrations (VEGF, BDNF and FGF21). Traditional, transgenic mouse models have helped the scientific community to understand biological mechanisms of Alzheimer’s disease (AD), but they do not develop significant neuronal loss, a hallmark of AD pathology. The MODEL-AD consortium has created a new “humanized” APOE4 model that has the human APOE4 allelic sequence in place of the mouse APOE gene; the model has shown known human phenotypes including deficits in cholesterol trafficking, amyloid clearance and BBB integrity. Of upmost importance, this model does not develop a full AD phenotype indicating that additional genetics and/or environmental factors are required as would be seen in human populations. We used males and females of this model to complete identical sedentary and active measures of each APOE genotype.

Lipid and general health marker assessment between mouse and human were similar and reproduced published literature. In both humans and mice we saw increased total cholesterol and HDL in active females and decreased total cholesterol and HDL in active males. We also saw similar relationships between APOE genotype, sex, and activity with regards to triglycerides. Although total cholesterol, HDL and LDL measures are the primary lipids needed to confirm or deny translation, other lipid measurements were not equivalent between the two models. Growth factor assessment in both species are also similar and reproduce published literature with regards to VEGF and BDNF as we see trending elevated levels in the active group. Less published on is the finding seen between active females and these elevated growth factors levels; our results indicates that although elevated as a result of exercise, this increase may be more prominent in females.

Based on the results found here we conclude that The Jackson Laboratory’s humanized APOE3/4 mouse model is a translatable model of vascular dysfunction, dementia and Alzheimer’s disease. We also conclude that exercise modulates these aspects by growth factor activation and increases resulting in downstream effects that reduce peripheral vascular risk factors and therefore reduce the risk of Alzheimer’s disease as a result of neuroinflammation. Complete, APOE genotype results from human participants are still ongoing. Descriptive analysis is limited by human samples size.

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.