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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.