The accurate assessment of instrumental activities of daily living (iADL) is essential for those with known or suspected Alzheimer's disease or related disorders (ADRD). This information guides diagnosis, staging, and treatment planning, and serves as a critical patient-centered outcome. Despite its importance, many iADL measures used in ADRD research and practice have not been sufficiently updated in the last 40-50 years to reflect how technology has changed daily life. For example, digital technologies are routinely used by many older adults and those with ADRD to perform iADLs (e.g., online financial management, using smartphone reminders for medications.) The purpose of the current study was to a) asses the applicability of technology-related iADL items in a clinical sample; b) evaluate whether technology-based iADLs are more difficult for those living with ADRD than their traditional counterparts; and c) test if adding technology-based iADL items changes the sensitivity and specificity of iADL measures to ADRD.

135 clinically referred older adults (mean age 75.5 years) undergoing neuropsychological evaluation at a comprehensive multidisciplinary memory clinic were included in this study [37% with mild cognitive impairment (MCI) and 51.5% with dementia]. Collateral informants completed the Functional Activities Questionnaire (FAQ; Pfeffer, 1982) as well as 11 items created to parallel the FAQ wording that assessed technology-related iADLs such as digital financial management (i.e. online bill pay), everyday technology skills (i.e. using a smartphone; remembering a password), and other technology mediated activities (i.e. visiting internet sites; online shopping).

Care partners rated tech iADLs items as applicable for the majority of items. For example, technology skill items were applicable to 90.4% of the sample and online financial management questions were applicable for 76.4% of participants. Applicability ratings were similar across patients in their 60's and 70's, and lower in those over age 80. Care partners indicated less overall impairment on technology-related iADLs (M =1.22, SD =.88) than traditional FAQ iADLs (M =1.36, SD = .86), t(129) = 3.529, p =.001). A composite of original FAQ paperwork and bill pay items (M = 1.62, SD = 1.1) was rated as more impaired than digital financial management tasks (M = 1.30, SD = 1.09), t(122) = 4.77, p <.001). In terms of diagnostic accuracy, tech iADL items (AUC= .815, 95% CI [.731, -.890]) appeared to perform comparably to slightly better than the traditional FAQ (AUC =.788, 95% CI [.705, .874]) at separating MCI and dementia, though the difference between the two was not statistically significant in this small pilot sample.

Technology is rapidly changing how older adults and those with ADRD perform a host of iADLs. This pilot study suggests broad applicability of tech iADL to the lives of those with ADRD and highlights how measurement of these skills may help identify trends in iADL habits that may help to mitigate the impact of ADRD on daily functions. Further, this data suggests the need to refine and improve upon existing iADL measures to validly capture the evolving technological landscape of those living with ADRD.

Traumatic brain injuries (TBIs) are a common occurrence among Veterans and may increase risk for neurodegenerative diseases, such as Alzheimer's disease (AD). Neuropathological correlates of AD, including buildup of ß-amyloid (Aß) plaques, formation of neurofibrillary tangles, and cortical atrophy, begin years before the onset of noticeable clinical and cognitive symptoms, emphasizing the importance of identifying early risk factors that could be targeted to prevent the development of AD. Of note, Aß ratios (e.g., Aß 42/40) have been shown to efficiently capture brain amyloid accumulation in prodromal AD, and thus may serve as a useful biological marker of preclinical AD. The present study investigates the mechanism by which TBI is associated with AD by examining the synergistic effects of TBI and genetic risk for AD on Aß among aging Veterans without dementia.

Participants included 88 White, Non-Hispanic/Latino male Vietnam War Veterans (Mage = 68.3 years) from the Alzheimer's Disease Neuroimaging Initiative Department of Defense (ADNI DoD) cohort, 49 of whom reported a history of at least one mild, moderate, or severe TBI. Genetic risk for AD was assessed via genome-wide polygenic risk scores. Aß levels were extracted from cerebrospinal fluid and Aß 42/40 ratios were calculated as an index of Aß deposition in the brain. Linear regression models were run to determine if TBI history and polygenic risk influence Aß 42/40 levels. An ANCOVA was implemented to examine the interaction between TBI severity and polygenic risk. Covariates in all models included age, education, and posttraumatic stress disorder symptoms.

Results demonstrated a significant interaction between TBI and genetic risk on Aß 42/40 (B = -0.45, Puncorrected = 0.029, Pcorrected = 0.0495). Specifically, higher polygenic risk was associated with lower Aß 42/40 ratio, suggesting greater Aß burden in the brain, among those with a history of TBI (pr = -0.33, P = 0.024) compared to individuals without a history of TBI (pr = 0.17, P = 0.308). This relationship trended towards being stronger as a function of increasing TBI severity (F(2, 77) = 3.01, P = 0.055).

These results show that, in the context of TBI, higher genetic risk for AD is associated with greater AD-related pathology, particularly with more severe injuries. TBI and polygenic risk may implicate similar biological pathways, notably amyloid precursor protein processing, to increase Aß burden in the brain and likelihood of progression to AD in future years. These findings could inform early intervention techniques to delay or preclude conversion to AD.

Those at genetic risk for Alzheimer's Disease (AD) because of the ApoE ε4 allele show differences in activation during olfactory information processing and memory in areas such as MTL structures, entorhinal cortex, posterior cingulate, precuneus, and inferior parietal lobule, suggesting preclinical AD neuropathology and olfactory impairment as a biomarker for predicting later AD onset (Murphy, 2019). The effects of smoking on AD have varied, with early studies suggesting either no effect or protective effects, and recent studies suggesting smoking as a risk factor for AD but with the need for further investigation in preclinical stages. Therefore, this study focused on olfaction and smoking as risk factors for preclinical AD neuropathology by studying differences in fMRI BOLD signal changes in smokers and nonsmokers during olfactory tasks.

Archival data from 25 non-demented older adults recruited from the UCSD Alzheimer's Disease Research Center who completed an Assessment Scale-Cognitive Subscale (ADAS-Cog) and functional MRI scans at 3T, acquired during performance of an odor identification task. Odor Identification (OI) measured correct (hits) or incorrect (misses) identification of odors presented by an olfactometer to deliver the odor stimuli in short, controlled durations during fMRI scanning.

fMRI data were preprocessed using fMRIprep, smoothed at 4mm, scaled, and first level analyses were conducted using 3dDeconvolve in AFNI with time points corresponding to hits and misses as regressors. Differences between smokers and nonsmokers revealed smokers show a larger difference in BOLD signal change from hits minus misses at five significant clusters (p = 0.01 with the minimum cluster size [voxels] at 42). Peak areas of significant clusters included the right precuneus, right calcarine gyrus, left inferior parietal lobule, left superior parietal lobule, and left middle occipital gyrus. Analyses suggested a greater difference in activity between hits and misses in smokers compared to nonsmokers, with more activity during hits.

Differences in activation between smokers and nonsmokers during an olfactory identification task, with greater activity in smokers during hits, suggests greater effort to correctly identify an odor. These findings of hyperactivation in areas (such as the precuneus and inferior parietal lobule) are similar to findings of hyperactivation during odor memory observed in studies of ε4 carriers during preclinical stages. Results provide further insight into smoking as a risk factor for AD. Moreover, results suggest the risk of smoking could potentially be reflected in altered activity in olfactory information processing networks in preclinical stages of AD. The study highlights the need for research to further understand the role smoking plays in the development of AD and the use of olfaction as a biomarker to aid in disease detection, prevention, and stage-associated treatments.

The AD8 is a validated screening instrument for functional changes that may be caused by cognitive decline and dementia. It is frequently used in clinics and research studies because it is short and easy to administer, with a cut off score of 2 out of 8 items recommended to maximize sensitivity and specificity. This cutoff assumes that all 8 items provide equivalent “information” about everyday functioning. In this study, we used item response theory (IRT) to test this assumption. To determine the relevance of this measure of everyday functioning in men and women, and across race, ethnicity, and education, we conducted differential item functioning (DIF) analysis to test for item bias.

Data came from the 2021 follow up of the High School & Beyond cohort (N=8,690; mean age 57.5 ± 1.2; 55% women), a nationally representative, longitudinal study of Americans who were first surveyed in 1980 when they were in the 10th or 12th grade. Participants were asked AD8 questions about their own functioning via phone or internet survey. First, we estimated a one-parameter (i.e., differing difficulty, equal discrimination across items) and two-parameter IRT model (i.e., differing difficulty and differing discrimination across items). We compared model fit using a likelihood-ratio test. Second, we tested for uniform and non-uniform DIF on AD8 items by sex, race and ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic), education level (high school or less, some college, BA degree or more), and survey mode (phone or internet). We examined DIF salience by comparing the difference between original and DIF-adjusted AD8 scores to the standard error of measurement of the original score.

The two-parameter IRT model fit the data significantly better than the one-parameter model, indicating that some items were more strongly related to underlying everyday functional ability than others. For example, the “problems with judgment” item had higher discrimination (more information) than the “less interest in hobbies/activities” item. There were significant differences in item endorsement by race/ethnicity, education, and survey mode. We found significant uniform and non-uniform DIF on several items across each of these groups. For example, for a given level of functional decline (theta) White participants were more likely to endorse “Daily problems with thinking/memory” than Black and Hispanic participants. The DIF was salient (i.e., caused AD8 scores to change by greater than the standard error of measurement for a large portion of respondents) for those with a college degree and phone respondents.

In a population representative sample of Americans ∼age 57, the items on the AD8 contributed differing levels of discrimination along the range of everyday functioning that is impacted by later life cognitive impairment. This suggests that a simple cut-off or summed score may not be appropriate since some items yield more information about the underlying construct than others. Furthermore, we observed significant and salient DIF on several items by education and survey mode, AD8 scores should not be compared across education groups and assessment modes without adjustment for this measurement bias.

Patients and their families often ask clinicians to estimate when full-time care (FTC) will be needed after Alzheimer's Disease (AD) is diagnosed. Although a few algorithms predictive algorithms for duration to FTC have been created, these have not been widely adopted for clinical use due to questions regarding precision from limited sample sizes and lack of an easy, user friendly prediction model. Our objective was to develop a clinically relevant, data-driven predictive model using machine learning to estimate time to FTC in AD based on information gathered from a) clinical interview alone, and b) clinical interview plus neuropsychological data.

The National Alzheimer's Coordinating Center dataset was used to examine 3,809 participants (M age at AD diagnosis = 76.05, SD = 9.76; 47.10% male; 87.20% Caucasian) with AD dementia who were aged >50 years, had no history of stroke, and not dependent on others for basic activities of daily living at time of diagnosis based on qualitative self or informant report. To develop a predictive model for time until FTC, supervised machine learning algorithms (e.g., gradient descent, gradient boosting) were implemented. In Model 1, 29 variables captured at the time of AD diagnosis and often gathered in a clinical interview, including sociodemographic factors, psychiatric conditions, medical history, and MMSE, were included. In Model 2, additional neuropsychological variables assessing episodic memory, language, attention, executive function, and processing speed were added. To train and test the algorithm(s), data were split into a 70:30 ratio. Prediction optimization was examined via cross validation using 1000 bootstrapped samples. Model evaluation included assessment of confusion matrices and calculation of accuracy and precision.

The average time to requiring FTC after AD diagnosis was 3.32 years (Range = 0.53-14.57 years). For the clinical interview only model (Model 1), younger age of onset, use of cholinesterase inhibitor medication, incontinence, and apathy were among the clinical variables that significantly predicted duration to FTC, with the largest effects shown for living alone, a positive family history of dementia, and lower MMSE score. In Model 2, the clinical predictors remained significant, and lower Boston Naming Test and Digit-Symbol Coding scores showed the largest effects in predicting duration to FTC among the neuropsychological measures. Final prediction models were further tested using five randomly selected cases. The average estimated time to FTC using the clinical interview model was within an average of 5.2 months of the recorded event and within an average of 5.8 months for the model with neuropsychological data.

Predicting when individuals diagnosed with AD will need FTC is important as the transition often carries significant financial costs related to caregiving. Duration to FTC was predicted by clinical and neuropsychological variables that are easily obtained during standard dementia evaluations. Implementation of the model for prediction of FTC in cases showed encouraging prognostic accuracy. The two models show promise as a first step towards creation of a user friendly prediction calculator that could help clinicians better counsel patients on when FTC after AD diagnosis may occur, though the development of separate models for use in more diverse populations will be essential.

Onset of Alzheimer’s disease (AD) pathology is estimated to begin 20-30 years prior to clinical symptom onset. Resting state EEG may yield useful early biomarkers of pathology, but its use along the AD clinical continuum is still limited, especially in individuals who are at high risk for AD but have yet to show symptoms. EEG waveform oscillations are classified based by frequency range (alpha, beta, theta, delta). Changes within these frequency bands have been identified in individuals with AD-dementia as compared to those with MCI and normal aging. Typical changes involve increases in low frequency power bands of delta and theta and decreases in beta and alpha frequencies, particularly in more posterior brain regions. However, these methods have yet to be explored in cognitively normal individuals who are at high risk for AD, as work has shown between individuals with MCI and healthy older adults.

We compared differences in resting state EEG between older adults (age 60+) at high risk for AD (positive family history, genetic risk defined as carrying 1 + ApoE ε4 alleles) and individuals at low risk (negative family history, no ε4 allele). We collected 1) neuropsychological test performance; 2) self-report measures of subjective cognitive complaints and cognitive reserve; and 3) five minutes of eyes-open resting state EEG using 64-channel active electrodes. Clusters of three electrodes were average for regions and absolute power within 5 frequency bands was calculated. Theta/beta ratio was calculated by dividing absolute power of bands at its respective site. Correlations between absolute power for specific regions, self-report measures, and neuropsychological test scores.

Analysis of 20 individuals collected to date (14 high risk, 6 low risk) found associations (p<0.05) between risk group and beta and gamma power across multiple electrode clusters, with high-risk individuals having higher power. Significant correlations were also found between calculated measures of cognitive reserve and posterior theta/beta ratio, subjective cognitive complaints and beta power, and neuropsychological test composites of learning performance with delta and executive functioning with frontal theta power.

This work provides preliminary evidence for differences in resting state EEG activity in those at risk for AD, prior to onset of clinical symptoms. Future work will examine patients with mild cognitive impairment as a comparison group to characterize resting state EEG across the early AD continuum.

Agitation is a common neuropsychiatric symptom within the dementia spectrum, experienced by 70 percent of individuals with cognitive decline. Prior literature demonstrates a strong association between care recipient agitation and burden in caregivers of individuals with dementia, as these symptoms are often difficult to manage and predict. Understanding how agitation symptoms in the person with dementia may influence caregiver burden is imperative given these strong associations; however, both agitation and burden are complex, multidimensional constructs. Agitation in dementia involves a range of behaviors including increased motor activity, emotional distress, and aggressive behaviors. Caregiver burden is also multi-faceted and often incorporates dimensions of social/relationship, emotional, and physical health strain. The current study sought to determine whether specific presentations of agitation differentially relate to distinct patterns of caregiver burden.

Medical record data from an outpatient memory clinic were extracted for 609 persons with dementia and their caregivers. Caregivers completed the Zarit Burden Interview (ZBI) to assess caregiver burden and the Cohen-Mansfield Agitation Inventory (CMAI) to assess care recipient agitation behaviors. At their initial outpatient appointment, care recipients were also administered a measure of global cognitive functioning (either the Montreal Cognitive Assessment or the Mini-Mental State Examination). Demographic information was extracted from medical records. Exploratory factor analysis was used to determine ZBI and CMAI factor structures. Hierarchical multiple regression analyses then examined whether factors of the CMAI differentially predicted ZBI factors, controlling for dementia severity and demographic variables.

Exploratory factor analysis yielded three domains of agitation on the CMAI ("Physically Aggressive," "Physically NonAggressive," "Verbally Agitated") and four domains of burden on the ZBI ("Impact on Life," "Guilt/Uncertainty," "Embarrassed/Frustrated," and "Overwhelm"). Regression analyses demonstrated all domains of agitation positively predicted overall burden. Regarding specific aspects of burden, Physically Aggressive behaviors predicted only Embarrassment/Frustration (B=.41, SE=.10, ß=.16, p<.001). Non-Aggressive behaviors predicted Impact on Life (B=.14, SE=.05, ß=.13, p<.01) and Guilt/Uncertainty (B=.05, SE=.02, ß=.10, p<.05). Verbally Agitated behaviors predicted all burden dimensions: Impact on Life (B=.35, SE=.06, ß=.32, p<.001), Guilt/Uncertainty (B=.12, SE=.03, ß=.22, p<.001), Embarrassment/Frustration (B=.17, SE=.02, ß=.38, p<.001), and Overwhelm (B=.16, SE=.02, ß=.40, p<.001).

Findings enhance understanding of the relationships between specific agitation symptoms and distinctive aspects of caregiver burden, suggesting that targeted interventions for aspects of caregiver burden based on agitation symptoms may be useful in alleviating burden. Interventions focused on caregivers' feelings of guilt, personal health decline, lack of time for themselves, and fear and uncertainty about the future may be effective when care recipients present with physically nonaggressive behaviors (e.g., pacing, restlessness, inappropriate dress or disrobing). When a care recipient presents with physically aggressive behaviors, helping the caregiver cope with embarrassment or anger may be of benefit. When a care recipient presents with verbally agitated behaviors, interventions targeting burden globally may be most useful. Future work should seek to replicate the current findings and explore such interventions.

Alzheimer’s disease (AD), a leading cause of dementia worldwide, affected an estimated 47 million people in 2015, placing a burden of over $1 trillion on health systems. Subclinical markers of AD pathology are seen many years before the clinical onset of dementia, suggesting that steps could be taken to prevent progression to disease in healthy individuals. Sleep optimizes cognition by creating a window of opportunity to consolidate memories, prune synaptic networks, and clear waste products. Studies that characterize the relationship between sleep and cognitive function prior to the onset of clinical AD could guide research into effective methods of delaying AD onset or preventing it altogether. The objective of our study is to describe how sleep quality and quantity correlate with performance on cognitive assessments within a healthy, aging population.

Seventeen participants, between 62-82 years of age enrolled in an ongoing clinical trial assessing the effects of melatonin (5mg daily) versus placebo, were included in our study. Participants were observed over a 2-month period, during which no experimental interventions were administered. At study entry, participants underwent a comprehensive neuropsychological evaluation evaluating cognitive domains of attention, memory, speed of information processing, language, executive functioning, and mood. Afterwards, all participants wore a watch that measured actigraphy and light data (Philips Actiwatch Spectrum Pro actigraphy monitor) for 8 weeks to evaluate their sleep habits. Pearson and Spearman partial correlations were used to evaluate relationships between objective sleep parameters and baseline cognitive function test scores.

Aberrations of sleep length, sleep fragmentation, and daytime activity measures significantly correlated with cognitive performance on memory, language, visuospatial skills, and speed of processing tests (p = <0.05). Greater variability of awakenings at nighttime associated with better scores on memory tests but worse scores on language tests. Longer sleep times associated with worse language scores, while greater variability in daily activity correlated with poorer scores on visuospatial skills tests and speed of processing tests.

This study establishes a framework for obtaining longitudinal sleep data in conjunction with serial cognitive function testing, encouraging further exploration into how sleep metrics affect specific domains of cognitive function. Findings suggest that having a less consistent sleep routine correlates with poorer cognitive function across multiple domains. The authors recommend broader analysis of actigraphy and cognitive function testing as objective measures of sleep and cognition in research and clinical practice.

There is a pressing need for sensitive, non-invasive indicators of cognitive impairment in those at risk for Alzheimer’s disease (AD). One group at an increased risk for AD is APOEε4 carriers. One study found that cognitively normal APOEε4 carriers are less likely to produce low frequency (i.e., less common) words on semantic fluency tasks relative to non-carriers, but this finding has not yet been replicated. This study aims to replicate these findings within the Wake Forest ADRC clinical core population, and examine whether these findings extend to additional semantic fluency tasks.

This sample includes 221 APOEε4 non-carriers (165 females, 56 males; 190 White, 28 Black/African American, 3 Asian; Mage = 69.55) and 79 APOEε4 carriers (59 females, 20 males; 58 White, 20 Black/African American, 1 Asian; Mage = 65.52) who had been adjudicated as cognitively normal at baseline. Semantic fluency data for both the animal task and vegetable task was scored for total number of items as well as mean lexical frequency (attained via the SUBTLEXus database). Demographic variables and additional cognitive variables (MMSE, MoCA, AMNART scores) were also included from the participants’ baseline visit.

APOEε4 carriers and non-carriers did not differ on years of education, AMNART scores, or gender (ps > 0.05). APOEε4 carriers were slightly younger and included more Black/African American participants (ps < 0.05). Stepwise linear regression was used to determine the variance in total fluency score and mean lexical frequency accounted for by APOEε4 status after including relevant demographic variables (age, sex, race, years of education, and AMNART score). As expected, demographic variables accounted for significant variance in total fluency score (p < 0.0001). Age accounted for significant variance in total fluency score for both the animal task (ß = -0.32, p <0.0001) and the vegetable task (ß = -0.29, p < 0.0001), but interestingly, not the lexical frequency of words produced. After accounting for demographic variables, APOEε4 status did not account for additional variance in lexical frequency for either fluency task (ps > 0.05). Interestingly, APOEε4 status was a significant predictor of total words for the vegetable semantic fluency task only (ß = 0.13, p = 0.01), resulting in a model that accounted for more variance (R2 = 0.25, F(6, 292) = 16.11, p < 0.0001) in total words than demographic variables alone (R2 = 0.23, F(5, 293) = 17.75, p < 0.0001).

Unsurprisingly, we found that age, AMNART, and education were significant predictors of total word fluency. One unexpected finding was that age did not predict the lexical frequency - that is - regardless of age, participants tended to retrieve words of the same lexical frequency, which stands in contrast to the notion that retrieval efficiency of infrequent words declines with age. With regard to APOEε4, we did not replicate existing work demonstrating differences in lexical frequency and semantic fluency tasks for ε4 carriers and non-carriers; possibly due to differences in the demographic characteristics of the sample.

Contextual memory, which refers to the ability to remember spatial or temporal circumstances related to an event, is affected early in Alzheimer’s Disease (AD). Computerized cognitive tasks have been suggested to be an ecological way to assess memory, but there are few studies that utilize these tools. Studying contextual memory via a computerized task in a Colombian kindred with autosomal dominant AD due to the Presenilin-1 (PSEN1) E280A mutation and a well-characterized disease progression may help us understand contextual memory changes in the preclinical AD stage. In this study we investigated whether a novel computerized task examining contextual memory can help identify those at increased risk for dementia.

A group of 31 non-carriers (mean age=38.97±6.11; mean education=11.45±4.34) and 15 cognitively unimpaired PSEN1E280A mutation carriers from the Colombia-Boston (COLBOS) Biomarker Study (mean age=35.67±5.50), mean education=10.60±3.83) performed the “MAPP Room Memory Task” on a computer. As part of this task, participants are asked to remember ten rooms and the specific location of a few objects for later recall. During the immediate recall phase, participants are asked to recognize the objects presented in each room (Immediate Object Recognition) and their location (Immediate Object Placement). During the subsequent delay phase of the task, participants are asked to select the correct room in which an object was first presented (Delayed Room Recognition) and place the objects previously seen in each room (Delayed Object Placement). We conducted Mann Whitney U tests to analyze differences between groups and Spearman Rho correlations to examine associations among the Room Memory Task performance, age, education, and Mini Mental State Examination (MMSE).

There were no differences in age or education between carriers and non-carriers (p>0.05, for both). Carriers had worse Delayed Room Recognition than non-carriers (Carriers mean score=0.893±0.18, non-carriers mean score=0.987±0.05; U=168.0, p=0.02), while there were no differences in the other task conditions (all p>0.05). In carriers, education was positively associated with Immediate Object Placement (rs=0.61, p=0.02), Delayed Object Placement (rs=0.76, p=0.001), and Delayed Room Recognition (rs=0.68, p=0.006). There were no significant associations between Room Memory Task conditions and age or MMSE scores in carriers. Further, no significant associations were observed between Room Memory Task performance, and age, education or MMSE scores in non-carriers.

Our preliminary findings show that the MAPP Room Memory Task, in particular the Delayed Room Recognition condition, may be helpful to discriminate those at increased risk of dementia. Future studies with larger samples using the Room Memory Task and AD-related biomarkers are needed to examine whether this task can be sensitive to early preclinical changes associated with AD and can potentially help track disease progression in those at risk.

Studies on vulnerability to interference have shown promise in distinguishing between normal and pathological aging, such as the early stage of Alzheimer’s disease (AD) or amnestic Mild Cognitive Impairment (aMCI). However, these studies did not include a non-semantic condition essential in distinguishing between what is attributable specifically to semantic memory impairments and more generalized vulnerability to interference. The present study aimed to determine whether the increased vulnerability to semantic interference previously observed in individuals at increased risk of AD (aMCI) is specifically associated with the semantic nature of the material, or if it also affects other types of material, suggesting more generalized executive and inhibitory impairment.

Seventy-two participants (N = 72) divided into two groups (33 aMCI and 39 NC) matched for age and education were included in the study. They underwent a comprehensive neuropsychological examination, and took the adapted French version of the LASSI-L (semantic interference test), as well as a homologous experimental phonemic test, the TIP-A. Independent sample t-tests, mixed ANOVA and ANCOVA on memory and vulnerability to interference scores with the Group (NC, aMCI) as between-group factor and the Type of material (semantic, phonemic) as within-subject factor were conducted to compare memory and interference in both contexts for both groups.

For all memory scores, results revealed a significant main effect of group (NC > aMCI), a significant main effect of the type of material (semantic > phonemic) and a significant Group x Type interaction (disproportionately poorer performance in a semantic context for aMCI compared to NC). Word recognition was equivalent in both contexts for aMCI, whereas NC were better in a semantic context. aMCI also committed more phonemic false recognition errors, were disproportionately more vulnerable to retroactive semantic interference and showed a disproportionately higher percentage of intrusion errors associated with proactive semantic interference than NC.

To our knowledge, this is the first study to meticulously compare aMCI and elderly control vulnerability to inter-list interference and its impact on memory processes in two very similarly designed conditions using different types of material (semantic vs. phonemic). Indeed, many studies on interference focused solely on intra-list buildup of interference or on semantic material. Taken together, our results suggest that aMCI patients present generalized difficulties in source memory and inhibition, but that their inability to benefit normally from the depth of processing of semantic material results in even more semantic intrusion errors during proactive interference. This superficial semantic processing also significantly impacts the ability of aMCI to show good recall after being exposed to an interference list and the passage of time, resulting in a greater vulnerability to semantic retroactive interference than controls. In summary, our results suggest that impairment of semantic memory, and, more precisely, the loss of benefit from the depth of semantic processing, represents the cornerstone of their memory and vulnerability to interference patterns. The classical level of processing theory therefore constitutes an ideal, simple framework to predict aMCI patients’ performance when facing interference, a parallel too rarely addressed in the literature.

Research has indicated that racial and ethnic minoritized groups in the United States are disproportionately affected by dementia (e.g., Alzheimer’s disease), and seek help (HS) later in the disease course, if at all. It has also been posited that individuals from different ethno-racial groups have divergent perceptions of the aging process, which may influence HS. These disparities warrant tailored preventive efforts to encourage identification of factors which contribute to HS to enable earlier psychoeducation and enhanced access to resources. The factors which influence HS may differ across ethnoracial groups. Here we examine the relative influence of subjective cognitive decline (SCD), a risk factor for AD, and aging perceptions to HS in these groups.

The current sample consisted of 161 healthy older adults (51 Male, 110 Female), aged 51 to 92 (M=73.43, SD=6.85) with a mean education of 16 years (SD=2.3 years) who performed > -1.5 SD on clinical neuropsychological testing. 26.7% of the sample self-reported as race/ethnic minorities (e.g., Hispanic or Non-Hispanic African American, Asian, Other.) Participants completed a 20-item SCD questionnaire assessing perceived cognitive difficulties in comparison to same aged peers, in addition to measures assessing HS behavior, (e.g., Have you gone to the doctor specifically for memory concerns?), and aging perceptions (e.g., older adulthood group identification, explicit stereotypes, essentialism). Point biserial correlations examined relationships between SCD, HS and aging perceptions, and multinomial logistic regressions examined the contribution of SCD and aging perceptions to HS across majority (White) and minoritized groups (Non-White participants).

In bivariate analyses of the White participant group, HS was associated with SCD (r=0.43, p<0.001) and age group identification (r=0.27, p<0.01), and the latter were also associated (r=-0.19, p<0.05). The logistic regression model correctly classified 86% of participants (same as null), explaining a relatively small proportion of variance in HS, Snell R2 = 0.09, Nagelkerke’s R2 = 0.16. Age group identification was not associated with HS (b=-0.02, SE=0.26, p=0.94, 95% CI [0.59, 1.63] but SCD was (p=0.04). In the non-White group (n=42), bivariate analyses showed that HS was associated with essentialism (r=-0.41, p<0.01; belief aging as a fixed and inevitable process)) and explicit stereotypes (r=-0.42, p<0.01) but not with SCD (r=0.21, p=0.19). SCD was also associated with essentialism (p=-0.32, p<0.05), stereotypes (p=0.32, p<0.05), and age group identification (r=0.38, p<0.01). The regression model correctly classified 88.9% of participants (same as null); neither SCD (p=0.39), explicit stereotypes (p=0.43), essentialism (p=0.72), nor age group identification (p=0.62) contributed to HS when all were considered.

When both SCD and age perceptions are examined together as predictors of HS, SCD alone predicts HS in the majority group. Neither construct predicts HS in the minoritized group—despite significant bivariate associations between HS, aging perceptions and SCD that varied across ethno-racial groups. Findings illustrate that SCD and aging perceptions may contribute differently to HS across ethno-racial groups in the US, and as such may indicate different priorities when implementing HS tools (e.g., screeners for detection of cognitive impairment). Ongoing work is addressing illness perceptions, another key barrier in HS in these groups to further inform on tailoring of services.

There are many potential benefits of early identification of those with Alzheimer’s disease (AD), including more opportunity for early intervention to slow AD progression (e.g., treatment, lifestyle changes, etc.) and to plan for the future. Positron emission tomography (PET) scans for abnormal amyloid and tau are commonly conducted in research settings. Despite strong interest in learning AD biomarker results, participants rarely receive their research data, in part due to concern about the possibility of undue distress based on results. We aimed to explore both positive and negative emotional reactions following PET biomarker disclosure as a function of result received.

Forty-three older adults (age = 72.0±6.21 years, education = 16.5±2.62 years, 49% Female, 88% White Non-Hispanic) completed PET amyloid and tau testing and disclosure. Sixty-three percent were diagnosed with mild cognitive impairment (MCI) while the remainder of participants were diagnosed with Dementia Alzheimer’s type (DAT). Participants completed pre-disclosure biomarker education and a decisional capacity assessment followed by baseline measures. Participants then completed a disclosure session where they received personal PET amyloid and tau results on an elevated vs. not elevated scale for each ligand. Results were discussed in relation to presence/absence of Alzheimer’s disease, how the result relates to their cognitive difficulties, and risk of developing Dementia-Alzheimer’s Type. At baseline (pre-disclosure), immediately post-disclosure, and 1-week post-disclosure, participants completed the Beck Anxiety Inventory (BAI), The Geriatric Depression Scale - 15 Item (GDS-15), Impact of Neuroimaging in AD (INI-AD) Scale, and the Positive and Negative Affective Scale - Short Form (PANAS-SF). All questionnaires were modified to apply to Alzheimer’s disease and related experiences.

Of the 43 participants who participated in disclosure, 74% received biomarker positive results (either A+T- or A+T+); all others were biomarker negative. We conducted a series of mixed analysis of variance (ANOVA) tests to determine the effect of disclosure and biomarker status for each of the outcomes of interest. Neither the effect of time nor the time by biomarker status interaction was significant for any of the outcomes (all p>.05). The main effect of biomarker status was significant for BAI (F(1)=5.12, p=.031, n,p2=.146) and INI-AD Distress (F(1)=12.70, p=.001, np2=.241) and Positive (F(1)=34.57, p<.001, np2=.464) subscale scores with A+T-/A+T+ participants reporting higher negative affect than those who were A-/T-; however, even among biomarker positive individuals, scores did not exceed clinical thresholds. GDS-15, PANAS-Negative and Positive Subscale scores did not differ significantly by biomarker status (all p>.05) and no significant adverse events occurred following disclosure. Additionally, no participants cited regret about receiving their results.

While disclosure of biomarker positivity may result in mild increases in acute anxiety or distress, or fewer positive emotions, it does not result in clinically significant emotional reactions and was not associated with regret. Overall, findings are consistent with literature indicating safety of biomarker disclosure procedures for symptomatic individuals. Future research should follow participants over longer periods to evaluate the impacts of biomarker disclosure.

Among people with HIV (PWH), the apolipoprotein e4 (APOE-e4) allele, a genetic marker associated with Alzheimer’s disease (AD), and self-reported family history of dementia (FHD), considered a proxy for higher AD genetic risk, are independently associated with worse neurocognition. However, research has not addressed the potential additive effect of FHD and APOE-e4 on global and domain-specific neurocognition among PWH. Thus, the aim of the current investigation is to examine the associations between FHD, APOE-e4, and neurocognition among PWH.

283 PWH (Mage=50.9; SDage=5.6) from the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study completed comprehensive neuropsychological and neuromedical evaluations and underwent APOE genotyping. APOE status was dichotomized into APOE-e4+ and APOE-e4-. APOE-e4+ status included heterozygous and homozygous carriers. Participants completed a free-response question capturing FHD of a first- or second-degree relative (i.e., biologic parent, sibling, children, grandparent, grandchild, uncle, aunt, nephew, niece, half-sibling). A dichotomized (yes/no), FHD variable was used in analyses. Neurocognition was measured using global and domain-specific demographically corrected (i.e., age, education, sex, race/ethnicity) T-scores. t-tests were used to compare global and domain-specific demographically-corrected T-scores by FHD status and APOE-e4 status. A 2x2 factorial analysis of variance (ANOVA) was used to model the interactive effects of FHD and APOE-e4 status. Tukey’s HSD test was used to follow-up on significant ANOVAs.

Results revealed significant differences by FHD status in executive functioning (t(281)=-2.3, p=0.03) and motor skills (t(278)=-2.0, p=0.03) such that FHD+ performed worse compared to FHD-. Differences in global neurocognition by FHD status approached significance (t(281)=-1.8, p=.069). Global and domain-specific neurocognitive performance were comparable among APOE-e4 carriers and noncarriers (ps>0.05). Results evaluating the interactive effects of FHD and APOE-e4 showed significant differences in motor skills (F(3)=2.7, p=0.04) between the FHD-/APOE-e4+ and FHD+/APOE-e4- groups such that the FHD+/APOE-e4- performed worse than the FHD-/APOE-e4+ group (p=0.02).

PWH with FHD exhibited worse neurocognitive performance within the domains of executive functioning and motor skills, however, there were no significant differences in neurocognition between APOE-e4 carriers and noncarriers. Furthermore, global neurocognitive performance was comparable across FHD/APOE-e4 groups. Differences between the FHD-/APOE-e4+ and FHD+/APOE-e4- groups in motor skills were likely driven by FHD status, considering there were no independent effects of APOE-e4 status. This suggests that FHD may be a predispositional risk factor for poor neurocognitive performance among PWH. Considering FHD is easily captured through self-report, compared to blood based APOE-e4 status, PWH with FHD should be more closely monitored. Future research is warranted to address the potential additive effect of FHD and APOE-e4 on rates of global and domain-specific neurocognitive decline and impairment over time among in an older cohort of PWH, where APOE-e4 status may have stronger effects.

Olfactory function declines during normal aging; however, accelerated olfactory decline is observed in neurodegenerative diseases, such as Alzheimer’s disease (AD). Moreover, olfactory deficits in pre-clinical AD are associated with future cognitive decline. Odor identification and memory deficits have been consistently reported in early stage AD indicating its potential sensitivity to AD pathophysiology in olfactory and limbic structures, yet few studies of olfaction have incorporated structural measures in a well-characterized cohort of older adults. In the current study we examined the association between odor identification impairment, cognition, and medial temporal lobe (MTL) sub-regions in cognitively unimpaired and impaired older adults.

We enrolled 140 participants (age=72.25±6.54, 56% female, years of education=16.30±2.63, 82% Caucasian, 15% Black/AA, 3% Multiracial) from the Penn Alzheimer’s Disease Research Center Clinical Cohort. Participants completed the Sniffin’ Sticks Odor Identification Test (SS-OIT), cognitive testing (NACC UDS2 or UDS3 and additional cognitive tests), and MRI scans (3T Siemens MAGNETOM Prisma MRI scanner). For the SS-OIT, participants were presented with 16 odorants using felt-tipped pen dispensers and asked to identify each odor from four multiple-choice options. Scores range from 0 to 16. Additionally, cognitive domains were created by averaging z-scores from tests within each domain: attention, memory, language, executive function, and visuospatial. This cohort was divided into participants with unimpaired cognition (n=96) and impaired cognition (MCI, dementia; n=44) using established normative data and consensus diagnosis. Linear regressions were performed to examine the association between SS-OIT score, each cognitive domain, and MTL measurements for unimpaired and impaired groups. For all analyses, we controlled for age, race, sex, education, smoking status, and hypertension and additionally for MOCA score and intracranial volume with MTL measurements.

In the unimpaired group, SS-OIT significantly associated with language (p<.05). In the impaired group, SS-OIT significantly associated with language and memory (p<.05). In the unimpaired group, SS-OIT significantly associated with right anterior hippocampal volume (p<.05). In the impaired group, significant associations were found between SS-OIT and right anterior hippocampal volume (p<.05) and left hippocampal mean thickness (p<.05). Additionally, SS-OIT significantly associated with left and right entorhinal cortex volume (p<.05) and mean thickness (p<.05).

This study reveals that lower odor identification performance is related to lower performance on measures of cognition and atrophy in MTL sub-regions in unimpaired and impaired older adults. Our findings support prior results demonstrating relationships between olfactory function, cognition, and MTL sub-regions. Specifically, olfactory function and episodic memory have been shown to follow similar patterns of decline in the course of AD, potentially reflecting AD pathology in shared regions of the MTL subserving episodic memory and olfactory function. Our findings demonstrate that reductions in both cortical thickness and grey matter volume of MTL regions are linked to olfactory deficits in individuals at risk for Alzheimer’s dementia. Future steps will include the analysis of longitudinal cognitive and imaging indices and the incorporation of fluid biomarker data.

Research suggests greater perceived social support is associated with better general cognitive function in community-dwelling older adults. While these findings expand our understanding of the role of social support in healthy aging, further work is needed to investigate the role of social support in mild cognitive impairment (MCI). Of particular interest is the relationship between executive function (EF), communicative effectiveness, and social support, as these are common areas of decline and are likely to impact one’s ability to meaningfully interact with others. The present study aimed to evaluate the association between perceived social support, EF, and communicative effectiveness. We hypothesize better EF performance and communicative effectiveness would be associated with higher levels of perceived social support in older adults with MCI.

One hundred and twenty-one older adults with MCI were included in the current study. All participants were enrolled in Charles and Harriett Schaffer Cognitive Empowerment Program (CEP) at Emory University, a comprehensive lifestyle program for individuals diagnosed with MCI and their care partners. Upon CEP enrollment, participants completed self-report questionnaires, including the Multidimensional Scale of Perceived Social Support (MSPSS), the Communicative Effectiveness Index (CETI), and EF assessments including Letter Fluency (phonemic fluency), Digit Span Backward (working memory), and the Test of Practical Judgment (decision making). Additionally, a subset of participants completed the written Trail Making Test - Part B (set-shifting; n = 63). Pearson bivariate correlations were utilized to explore the relationship between MSPSS, CETI, and EF performance.

Higher levels of perceived social support were significantly associated with communicative effectiveness (r = .210, p = .021), such that participants who endorsed having more social support also reported greater confidence in their communicative effectiveness. Perceived social support was associated with better working memory performance (r = .342, p < .001), phonemic fluency output (r = .261, p = .041), and shorter time to complete TMT-B (r = -.244, p = .052), indicating individuals with higher perceived social support demonstrated better EF abilities. Finally, greater confidence in communicative effectiveness was associated with better performances in working memory (r = .274; p = .008), phonemic fluency output (r = .213; p = .020) and decision making (r =.192; p = .044), suggesting stronger working memory, phonemic fluency, and practical decision-making abilities support better communicative effectiveness. There was no association between social support and practical decision-making abilities (r = .146, p = .129).

The current findings demonstrate a link between higher levels of social support, communicative effectiveness, and EF abilities, particularly in the subdomains of working memory, phonemic fluency, and set-shifting. This link suggests individuals with stronger EF abilities may have greater communicative effectiveness and, in turn, may be better able to maintain social relationships and garner social support. Future research is needed to evaluate the causality in this relationship, as it remains possible those with stronger social support networks maintain communicative effectiveness and EF for longer. Thus, further evaluation of the mechanism(s) underlying the relationships between social support, EF, and communicative effectiveness is needed.

Neuropsychiatric symptoms concerning mood are common in Alzheimer's disease (AD), but it is unclear if they are etiologically related to AD pathophysiology or due to factors considered to be non-pathogenic, such as small vessel cerebrovascular disease. New generation clinical trials for AD often enroll participants with evidence of AD pathophysiology, indexed by amyloid PET scanning, but who are cognitively asymptomatic. We used screening data from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) study to examine the extent to which depressive symptoms are associated with amyloid pathophysiology and small vessel cerebrovascular disease, in the form of white matter hyperintensities (WMH).

The A4 study randomizes cognitively healthy older adults with evidence of amyloid pathophysiology on PET scanning. We used screening data, which included amyloid status (positive, negative) by visual read, amyloid PET standard uptake value ratio (SUVR) in cortical regions, and MRI data acquired in a subset (n=1,197, mean age 71.6 +/- 4.8 years, 57% women) to quantitate total WMH volume. Depressive symptoms were evaluated with the 15-item Geriatric Depression Scale, which we used both as a continuous variable and to define 'depressed' and 'non-depressed' groups, based on a cut score of > 5. We examined whether 1) depressive symptoms and proportion of depressed individuals differed between amyloid positive and negative groups, 2) there is a relationship between amyloid SUVR and depressive symptoms that differs as a function of amyloid positivity status, and 3) there is a relationship between WMH volume and depressive symptoms that differs as a function of amyloid positivity status.

Although depressive symptom severity did not differ between groups (t=0.14, p=0.88), a greater proportion of individuals were classified as depressed in the amyloid negative group than the amyloid positive group (3.5% vs. 1.9%, X2=4.60, p=0.032). Increased amyloid SUVR was associated with increased GDS scores among amyloid positive individuals (r=0.117, p=0.002) but not among amyloid negative individuals (r=0.006, p=0.68, Positivity Status x SUVR interaction on GDS: ß=0.817, p=0.029). Increased WMH was associated with higher GDS scores (ß=0.105, p=0.017) but not differentially in amyloid positive and negative participants (Positivity Status x WMH interaction on GDS: ß=-0.010, p=0.243).

These analyses have several implications. First, individuals who are screened to participate in a clinical trial but do not have evidence of amyloidosis may be misattributing concerns about underlying AD pathophysiology to depressive symptoms. Second, the severity of AD pathophysiology, indexed by amyloid PET SUVR, may drive a small increase in depressive symptomatology among individuals over visual diagnostic thresholds. Third, small vessel cerebrovascular changes are additionally associated with depressive symptoms but in a manner that is independent of AD pathophysiology. Overall, depressive symptoms and depression are likely multiply determined among prospective clinical trial participants for preclinical AD.

The objectives of this study were to investigate family members’ perception of the impact of the neuropsychological evaluation and subsequent feedback session on (1) caregiver understanding of the patient’s diagnosis and symptoms and (2) treatment planning, patient well-being, caregiver stress, and support utilization.

Participants included family members of patients undergoing a neuropsychological dementia evaluation and subsequent oral feedback session at a midwestern university medical center by one of five neuropsychology providers. The average age of patients undergoing dementia evaluation was 73.4 (range = 52 - 92). Patients in the sample were categorized as having dementia (67%), mild cognitive impairment (24%), or no cognitive disorder (9%), with 46% of the sample suspected to have Alzheimer’s disease or mixed Alzheimer’s and vascular disease. Immediately following the feedback session, family members were provided a brief survey, $10 prepaid gift card to keep regardless of survey completion, and a stamped, pre-addressed envelope to return the survey anonymously by mail. A total of 200 surveys were disseminated and 127 (64%) were completed and returned. Family members completing the survey were most often the spouse (60.6%) or the child (29.1%) of the patient. Eighty-two percent of respondents identified as being the patient’s primary caregiver.

Family members were asked to rate their agreement to perceptions held both prior to and following the neuropsychological evaluation. Ninety-seven percent strongly agreed (81%) or agreed (16%) that the neuropsychological evaluation was helpful, and 95% strongly agreed (62%) or agreed (33%) that the neuropsychological evaluation would help the patient get better or more targeted care. Comparison using Wilcoxon signed-rank tests indicated that family members were significantly more likely to agree (p < .001) with the following beliefs after, as opposed to preceding, the neuropsychological evaluation: (1) the patient’s symptoms had been well addressed (z = -7.95), (2) I was explained the diagnosis (z = -8.12), (3) I am confident in my family member’s diagnosis (z = -7.88), and (4) I am more likely to use dementia-related community resources (z = -5.78). Additionally, family members nearly unanimously agreed or strongly agreed that, following the neuropsychological evaluation, their family member’s symptoms had been well addressed (98%), they were explained the patient’s diagnosis (98%), and they were confident in the diagnosis (97%). In instances where dementia was diagnosed, 91% of family members agreed/strongly agreed that they planned to use dementia-related community resources. Furthermore, a majority of family members reported that the neuropsychological evaluation positively impacted the patient’s psychological wellbeing (82%), caregiver stress (74%), caregiver interactions with the patient (76%), treatment plan (82%), and overall patient care (79%).

Results indicate that family members of patients undergoing neuropsychological evaluation for suspected dementia perceive the neuropsychological evaluation as improving diagnostic understanding and confidence. Additionally, family members nearly unanimously agreed that the neuropsychological evaluation had a positive impact on treatment planning, patient well-being, caregiver stress, and utilization of supports.

Medical providers often express difficulty in detecting dementia (Bradford et al., 2009), feel ill-equipped to address issues related to dementia care, or neglect to communicate dementia diagnoses and treatment recommendations (Alzheimer’s Association, 2015). Despite this, neuropsychologists, who are specifically trained in dementia diagnosis and treatment planning, are not always utilized in the dementia care process. The objective of this study was to investigate family members’ perceptions regarding the incremental benefit of the neuropsychological evaluation, relative to previously rendered services, in addressing patient diagnosis/symptoms and in discussing future care plans.

A survey questionnaire was distributed to family members of patients who had undergone a neuropsychological dementia workup at a university medical center in the Midwest by one of five neuropsychology providers. Immediately following the neuropsychological feedback session, family members were provided a $10 gift card and a stamped, pre-addressed envelope to return the survey anonymously by mail. Respondents were typically spouses (60.6%) or adult children (29.1%), with 82.4% identifying themselves as the primary caregiver. Patient age ranged from 52 to 92 years (M=73.4). Sixty-seven percent of patients were diagnosed with dementia and 24% with mild cognitive impairment; 9% were not diagnosed with a cognitive disorder. The most commonly suspected etiology for cognitive impairment was Alzheimer’s disease or mixed Alzheimer’s and vascular disease (46%). Providers noted as previously having been involved in the care of the patients’ cognitive symptoms included primary care providers (88%), neurologists (60%), psychiatrists (13%), and psychologists (9%).

Two-hundred surveys were disseminated with a response rate of 64% (n=127). Family members were asked to compare the benefit of the neuropsychological evaluation in addressing the patients’ symptoms as compared with services rendered by previous providers using a Likert scale ranging from 1 (not beneficial) to 5 (extremely beneficial). The average benefit rating was 4.6/5.0 (SD=0.7) for the neuropsychological evaluation as compared with 3.0/5.0 (SD=1.1) for previous services, a statistically significant difference (p <.001). Family members were also asked to rate the helpfulness of both the neuropsychologist and previous providers in discussing aspects of the patient’s diagnosis and care plan using a Likert scale ranging from 1 (not helpful) to 5 (extremely helpful). Comparison using Wilcoxon signed-rank tests indicated neuropsychologists were rated as significantly more helpful than previous providers (p < .001) in discussing the cause or diagnosis for their family member’s symptoms (M=4.6/5.0 vs. M=3.0/5.0), strategies for providing care to their family members (M=4.5/5.0 vs. M=2.8/5.0), a comprehensive treatment and care plan (M=4.3/5.0 vs. M=2.6/5.0), symptom impact on activities of daily living (M=4.4/5.0 vs. M=2.9/5.0), and symptom impact on current and future functioning (M=4.4/5.0 vs. M=2.8/5.0).

Overall, family members reported the neuropsychological evaluation and feedback session to be significantly more helpful in addressing patient cognitive diagnoses, symptoms, and care plan as compared to previously rendered services by non-neuropsychologists. The results underscore the unique and incremental benefit of the neuropsychological evaluation, not only in diagnosis, but also in assisting family in understanding symptom nature, functional impact, and resultant care needs.

Early cognitive signs of Alzheimer's disease are often subtle and go unnoticed until they become more prominent and debilitating. Thus, symptoms begin long before an actual Alzheimer's diagnosis is given. However, it is known that cognitively healthy older individuals with lower amyloid/tau ratios (PAT) are more likely to develop Alzheimer's disease than those with higher amyloid/tau ratios (NAT). Therefore, we explored whether this ratio can be used in conjunction with neuropsychological tests to isolate cognitive predictors of Alzheimer's disease amongst cognitively healthy older adults. We were interested in potential group differences on the California Verbal Learning Test, Second Edition (CVLT-II) Long Delay Free Recall scores and Cued Recall scores. We hypothesized that: (a) individuals in the PAT group would have weaker CVLT-II Long Delay Free Recall scores than individuals in the NAT group; and (b) individuals in the PAT group would recall fewer words on the CVLT-II Long Delay Cued Recall trial than individuals in the NAT group.

There were 115 older individuals recruited via Huntington Medical Research Institutes and the University of Southern California who had their cerebral spinal fluid extracted to measure amyloid/tau ratios. They completed the California Verbal Learning Test-II as part of a larger neuropsychological battery and were determined to be cognitively healthy. The mean age of these participants was 74.5 years (SD = 8.3), and there were 36 who met the threshold for the amyloid/tau ratio associated with Alzheimer's disease (PAT) while the other 79 did not (NAT). A hierarchical linear regression tested the hypotheses, with two blocks used for the analyses. Block 1 for both analyses contained variables to control for the potential effects of various factors in performance on the Long Delay tasks. Block 2 consisted of the amyloid groups (NAT vs. PAT).

After controlling for age, sex, education, body mass index, Montreal Cognitive Assessment scores, and depression, we found no significant difference between CVLT-II Long Delay Free Recall scores or Long Delay Cued Recall scores for the two groups.

While no significant difference was found on the long delay trials of the CVLT-II, it is important to note that it is unclear at what stage Alzheimer's related decline begins or can be detected using cognitive testing. Longitudinal studies would help to better understand if this lack of association holds true over time. Other aspects of the CVLT-II, such as intrusions and repetitions, would also help to better understand the different ways that symptoms of Alzheimer's disease can manifest early on.