Given the lack of comprehensive neuropsychological tools and neuropsychological services in Sub-Saharan Africa (SSA), cognitive screeners for dementia can be useful tools to screen for suspected dementia at the population level. However, most available screeners have not been developed or validated in SSA populations. The Community Screening Instrument for Dementia (CSID) was developed for cross-cultural use, and it has a cognitive testing component and informant interview. We have previously demonstrated that lower years of education and female sex are associated with lower scores on the CSID. Here, we examine the utility of demographically adjusted CSID scores in a community sample of Congolese older adults.

354 participants (mean age=73.6±6.7, mean education (years) =7.3±4.7; 50% female) were randomly recruited in Kinshasa, Democratic Republic of the Congo, and completed the CSID and the Alzheimer's Questionnaire (AQ) to examine functional abilities. Raw scores were demographically adjusted for education and sex by adding 1 point for <12 years of education and 1 point for female. Cognitive impairment was classified as a total score below 25.5. Rates of impairment were compared between raw scores and demographically-adjusted scores. Demographic profiles were examined between both classifications

Average raw CSID scores were 25.23 (SD=4.19) and average demographically-adjusted scores were 26.59 (SD= 4.09). Approximately 43.1% of the sample was impaired based on the raw CSID scores compared to 30.4% with the demographically-adjusted scores (x2= 12.334, p<.001). There was a higher proportion of females (n=95; 26.8%) classified as impaired with the raw SCID scores compared to the demographically-adjusted scores (n=62; 17.5%; x2= 8.87, p=0.003). Approximately 27.4% (n=97) of the participants classified as impaired with the raw SCID scores had primary education or less (i.e., 1-6 years) compared to 18.9% with the demographically-adjusted scores (n=67; (x2= 107.77, p<.001). Forty-five participants were re-classified as not impaired with the demographically-adjusted scores with the majority of these participants being female (73.3%), having primary education (66.7%), and being functionally unimpaired on the AQ (91.1% unimpaired).

We demonstrate that raw scores on the CSID can lead to misclassification of impairment in females and in individuals with lower years of education. Demographically-adjusted scores on the CSID can help properly capture those with suspected dementia while reducing false positives. Given the effects of education and sex on performance, future studies should examine if demographically adjusted scores improve the sensitivity and specificity of the CSID in Congolese populations and compare its performance to other screening tools to determine the most appropriate screener for this population.

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 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.

Improving the timeline for intervention in Alzheimer's disease (AD) has considerable potential to delay and mitigate disability and suffering. Neuropsychological assessment is useful for distinguishing AD from normal aging and other dementias but is less useful in preclinical detection due to its limited sensitivity. The N400 (N4), a language-based EEG event-related potential (ERP) related to semantic functioning, is a promising candidate marker of AD with potential to improve early detection and monitoring of AD. For example, studies have shown that individuals with AD show a reduced N4 "effect"—a smaller difference in the size of the N4 to semantically congruent vs. incongruent word-pairs. The goal of this study is to assess the presence of the N4 effect in healthy seniors, and those with amnestic mild cognitive impairment (MCI) or mild AD, and to evaluate associations between performance on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the N4 across these samples.

Fifty older adults (intact=27, combined MCI/mild AD group=23; "impaired") completed neuropsychological testing, including the RBANS, as part of a larger study. Participants were re-contacted and returned for EEG assessment between several weeks to one year later. During EEG recording, participants completed a word-pair judgement paradigm, which involved distinguishing between semantically congruent and incongruent word-pairs. Data was collected and analyzed according to customized N4 analysis scripts provided as part of ERPCORE, an online resource for acquiring and analyzing common ERP components (Kappenman et al., 2021; https://osf.io/thsqg/). The change in N4 amplitude between congruent and incongruent trials (the N4 effect) was used as an index of participants' semantic functioning. Participants' N4 effect was quantified using the mean amplitude from 300-550 milliseconds poststimulus at electrode Cz.

Repeated measures ANOVAs indicated a significant effect of trial type on the N400 amplitude in the intact individuals (F(1, 26)=77.66, p<.001), which remained significant in the sample as a whole (F(1, 48)=65.18, p<.001). Although intact participants numerically showed a larger N4 effect (intact: M=-4.02, SD=2.37; impaired: M=-2.60, SD=3.40), the expected group-by-trial interaction was not significant (F(1, 48)=3.01, p=.089). Correlational analyses revealed no significant associations between the N4 effect and the RBANS Total Scale scores (r=-.14, p=.32), nor for the Immediate Memory (r=-.002, p=.99), Visuospatial/Constructional (r=-.069, p=.63), Language (r=-.15, p=.30) Attention (r=-.21, p=.14), or Delayed Memory (r=-.18 p=.58) indexes.

Results confirmed the presence of the N4 effect in intact participants and in the sample as a whole. Although the N4 effect was numerically smaller in the impaired group as expected, this difference was not significant in the present sample. Likewise, we observed no evidence for associations between the size of N4 effect and performance on RBANS indexes. Overall, the present study provides mixed evidence for the utility of the N4 as a biomarker in mild AD. Factors that may have contributed to the lack of associations between the N4 effect and the RBANS include the limited sample size and variable lengths of time between participants' initial cognitive assessments and EEG testing.

Abnormalities in social and emotional behavior are the major diagnostic criteria for behavioral variant frontotemporal dementia (bvFTD). Investigators have attributed their behavioral disturbances to disease in mesial prefrontal and related networks, such as the salience network. This study examined the main neural correlates of informant-reported socioemotional dysfunction among patients with bvFTD compared to those with early-onset (before age 65) Alzheimer's Disease (EOAD).

Participants included 13 patients with bvFTD and their caregivers and 18 patients with EOAD and their caregivers. The caregivers consisted of a spouse, family member, or other informant who resided with the patient. They completed the informant-based Socioemotional Dysfunction Scale (SDS), a 40-item scale which rates common disturbances in social and emotional behavior on a five-point Likert scale (1-5). The patients underwent magnetic resonance imaging (MRI) with tensor-based morphometry (TBM) analysis of the 3D T1-weighted MRI scans. Computations of mean Jacobian values within select regions of interest (ROIs) in frontal and temporal lobes generated numerical summaries of regional volumes, and voxel-wise regressions created 3D statistical maps of the association between tissue volume and SDS total scores. Statistical analyses included independent samples t-tests group differences in ROIs and SDS scores, Pearson correlations between SDS scores and brain volumes, and multiple regression of ROIs with SDS scores and group as predictor variables.

Compared to the EOAD group, the bvFTD group had significantly higher SDS scores (p < .001; d = 2.24), smaller frontal lobe volumes (specifically dorsolateral-prefrontal cortex, p = .003; d = 1.24), and larger temporal lobe volumes (specifically hippocampus, p = .014; d = 0.979). Within the bvFTD group, higher SDS scores were associated with a smaller right anterior temporal lobe (ATL; p = .005; r = -.729), especially the lateral ATLs (p = .002; r = -.776), and a smaller bilateral orbitofrontal cortex (OFC; p = .016; r = -.650). In contrast, within the EOAD group, higher SDS scores were associated with a smaller right parietal cortex (p = .030; r = .542). In the entire sample (both bvFTD and EOAD), higher SDS scores was associated with a smaller lateral ATL volumes (p = .019; r = -.431). Regression analyses confirmed that SDS score predicted lateral ATL volume (p = .041; b = -.262) after controlling for diagnosis (p < .001; b = -.692).

These findings are consistent with greater socioemotional dysfunction, smaller frontal, and larger mesial temporal regions in bvFTD, when compared to EOAD. The findings, however, suggest that positively disturbed socioemotional behavior in bvFTD, as reported by caregivers, results from involvement of the right temporal lobe and the lateral temporal region, with further contribution from disease in OFC. The association of SDS scores and ATL volume across diagnostic groups suggests that this region is instrumental in socioemotional functioning and that the SDS may have diagnostic value in distinguishing the "right-temporal variant" of bvFTD.

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

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

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

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

We examined the use of pupillometry as an early risk marker of Alzheimer's disease (AD). Pupil dilation during a cognitive task has been shown to be an index of cognitive effort and may provide a marker of early change in cognition even before performance begins to decline. Individuals who require more effort to successfully perform a task may be closer to decline. We previously found greater compensatory effort to perform the digit span task in individuals with amnestic mild cognitive impairment (aMCI) who may be at greater risk for AD than individuals with non-amnestic MCI (naMCI). Task evoked pupil dilation is linked to increased norepinephrine output from the locus coeruleus (LC), a structure affected early in the AD pathological process. In this study, we measured pupil dilation during verbal fluency tasks in participants with aMCI or naMCI, and cognitively normal (CN) individuals. Based on our findings using the digit span task, we hypothesized that participants with aMCI would show greater compensatory cognitive effort than the other two groups.

This study included 101 older adults without dementia recruited from the UC San Diego Shiley-Marcos Alzheimer's Disease Research Center and San Diego community (mean [SD] age = 74.7 [5.8]; education = 16.6 [2.5]; N=58 female; N=92 White); 62 CN, 20 aMCI and 19 naMCI participants. Pupillary responses (change relative to baseline at the start of each trial) were recorded at 30 Hz using a Tobii X2-30 (Tobii, Stockholm, Sweden) during semantic (animals, fruits, vegetables) and phonemic (letters F, A, S) fluency tasks. Participants generated as many words as possible in a category (semantic) or starting with a given letter (phonemic) in 60 seconds.

Repeated measures ANOVA (3 groups X 2 fluency conditions) with age, education and sex as covariates showed a significant main effect of group (F(2,95)=3.64, p=.03), but no group X condition interaction (F<1). Pairwise comparisons showed significantly greater fluency task-evoked dilation for aMCI relative to CN (p=.015) and naMCI (p=.019) participants. When controlling for performance (total letter or category words produced), pupil dilation (cognitive effort) remained significantly greater in aMCI relative to the other two groups in both fluency conditions, suggesting pupil dilation informs risk beyond information provided by task performance.

In a previous sample of community-dwelling men who were an average of 13 years younger than the present sample, we found significantly greater pupil dilation during a digit span task in aMCI relative to naMCI and CN groups. In the present study, we replicated those findings in an older sample using a different cognitive task. Significantly greater pupil dilation was found in individuals with aMCI on verbal fluency tasks, indicating greater compensatory cognitive effort to maintain performance. Pupillometry provides a promising biomarker that might be used as an inexpensive and noninvasive additional screening tool for risk of AD.

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

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

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

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

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

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

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

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

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

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

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

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

Late-life depression is a complex condition impacted by both mental and physical health outcomes and psychosocial factors. Psychosocial predictors of depression are reliant on cultural factors including socioeconomic variables, stigmas, and cultural values. Most research on late-life depression and its effect on cognitive functioning has been completed in so-called Western, Educated, Industrialized, Rich, and Democratic (WEIRD) populations and findings may not generalize to older adults living in other areas of the world. The current study explored predictors of depressive symptoms as well as the association between depressive symptoms and neuropsychological functioning in Congolese older adults.

A total of 319 participants (mean age=72.7±6.15, mean education in years=7.6±4.56; 47% female) were randomly recruited. Depressive symptoms were assessed with the Geriatric Depression Scale. Given the exploratory nature of the current study, forward stepwise linear regression models were run to assess predictors of depressive symptoms. The independent variables assessed as potential predictors included age, years of education, gender, participant income, parental income, living arrangement (i.e., alone or with others), functional abilities (FAQ), fragility, and self-rated overall health. Analyses were run in the overall sample as well as stratified by gender. The association between depressive symptoms and performance on the Community Screening Instrument for Dementia (SCID) was also explored.

Higher depressive symptoms were found in women (ß=.228, p=0.036), those with lower parental income (ß=-.156, p=.005), higher fragility (ß=-.237, p<.001), and worse overall health (ß=-.311, p=.020). Among women, lower parental income, (ß=-.230, p=.002), higher fragility (ß=-.312, p<.001), and lower overall health (ß=-.235, p=.004) predicted higher depressive symptoms, while in men only higher fragility (ß=-.164, p=.041) and living alone (ß=-.184, p=.022) predicted higher depressive symptoms. There was also a significant association between depressive symptoms and lower scores on the CSID (ß=-.189, p=.001)

Similar to results in WEIRD populations, general health and fragility predicted depressive symptoms in Congolese older adults. However, parental income (more so than participant income) also predicted depressive symptoms in Congolese older adults, particularly in women, while living alone was a predictor in Congolese older men. It is possible that the difference in depressive symptoms between men and women is driven by underreporting of depressive symptoms among men. Our results also showed that there was an association between depressive symptoms and global cognitive functioning similar to prior findings in WEIRD populations. Our results are important for clinicians assessing depressive symptoms in patients in or from Congo or sub-Saharan Africa.

There is a need to identify scalable cognitive paradigms that are sensitive enough to relate to Alzheimer's disease biomarkers (amyloid and tau) in the preclinical stage. Here, we determine whether initial performance and practice effects on the memory-focused Computerized Cognitive Composite (C3) relate to demographic variables, amyloid status [abnormal (A+), normal (A-)], and regional tau in clinically unimpaired (CU) older adults.

We examined pre-randomization data from CU older adults screened for the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study. We focused on participants who completed the C3 (n=3287), most of whom completed an alternate version of the C3 again approximately 51 days later (n=4141), as well as a subset of preclinical AD participants (i.e., A+ CU) who completed the C3 and tau PET imaging with [18]F-flortaucipir (initial C3: n=354; repeat C3: n=343). C3 initial performance and practice effects were examined in relation to amyloid status (A+, A-) and continuous regional tau burden.

Initial C3 performance was associated with amyloid status [B(SE) = -0.075 (0.021), p < 0.001] across all participants, as well as tau burden in the medial temporal lobe (MTL) [B (SE) = -0.728 (0.220), p = 0.001], inferior temporal (IT) cortex [B (SE) = -0.782 (0.264), p = 0.003], and inferior parietal (IP) cortex [B (SE) = -0.721 (0.281), p = 0.011] amongst preclinical AD individuals. Short-term practice effects were also associated with reduced tau burden in MTL [B (SE) = -0.471 (0.202), p = 0.020], IT [B (SE) = -0.640 (0.240), p = 0.008], and IP [B( SE) = - 0.584 (0.255), p = 0.023] amongst preclinical AD participants, but were not associated with amyloid status [B (SE) = -0.018 (0.020), p = 0.348]. Critically, these effects with tau were only detected when baseline performance was accounted for presumably due to opposing influence from both practice effects and regression to the mean effects.

This is the first study to show that performance on a brief cognitive battery administered in a multisite context is associated with both amyloid and tau among CU older adults. These findings suggest that computerized assessments may be a cost-effective and scalable approach for early detection efforts. Further, diminished practice effects on memory-based measures are associated with elevated tau burden in preclinical AD, suggesting that high-frequency cognitive testing collected over a short follow-up period may provide additional insights regarding early disease processes than single assessments.

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.

Individuals with Down syndrome (DS) experience intellectual disability, such that measures of cognitive and adaptive functioning are near the normative floor upon evaluation. Individuals with DS are also at increased risk for Alzheimer's disease (AD) beginning around age 40; and test performances and adaptive ratings at the normative floor make it difficult to detect change in cognition and functioning. This study first assessed the range of raw intelligence scores and raw adaptive functioning of individuals with DS at the normative floor. Next, we assessed whether those raw intelligence scores were predictive of raw adaptive functioning scores, and by association, whether they may be meaningful when assessing change in individuals with a lower baseline of cognitive functioning.

Participants were selected from a cohort of 117 adults with DS in a longitudinal study examining AD risk. Participants (n=96; M=40.9 years-old, SD=10.67; 57.3% female) were selected if they had both a completed measure of IQ (Kaufmann Brief Intelligence Test; KBIT2) and informant ratings of adaptive functioning (Vineland Adaptive Behavior Scales; VABS-II). Multiple regression was conducted predicting VABS-II total raw score using K-BIT2 total raw score, while controlling for age.

A slight majority (57.3%) of the sample had a standardized IQ score of 40 with the majority (95.7%) having a standardized score at or below 60. Additionally, 85.3% of the sample had a standard VABS-II score at or below 60. Within the normative floor for the KBIT2 (IQ=40), there was a normal distribution and substantial range of both KBIT2 raw scores (M = 31.19, SD = 13.19, range: 2 to 41) and VABS-II raw scores (M = 406.33, SD = 84.91, range: 198 to 569). Using the full sample, age significantly predicted raw VABS-II scores (ß = -.283, p = .008). When KBIT2 raw scores were included in the model, age was no longer an independently significant predictor. KBIT2 raw scores significantly predicted raw VABS-II scores (ß = .689, p < .001). Age alone accounted for 8.0% of variance in VABS-II raw scores and KBIT2 raw scores accounted for 43.8% additional variance in VABS-II raw scores. This relationship was maintained when the sample was reduced to individuals at the normative floor (n = 51) where KBIT2 raw scores accounted for 23.7% of the variance in raw VABS-II scores (ß = .549, p < .001).

The results indicate that meaningful variability exists among raw intelligence test performances that may be masked by scores at the normative floor. Further, the variability in raw intelligence scores is associated with variability in adaptive functioning, such that lower intelligence scores are associated with lower ratings of adaptive functioning. Considering this relationship would be masked by a reduction of range due to norming, these findings indicate that raw test performances and adaptive functioning ratings may have value when monitoring change in adults with DS at risk for AD.

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.

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

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

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

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

Compensatory strategy training has been identified as a useful mechanism to improve everyday cognitive function among older adults with Mild Cognitive Impairment (MCI). Despite this, few studies have looked at cognitive factors that support adherence and engagement in these programs, which are key to maximizing benefit. The present study aimed to evaluate the relationship between cognition, adherence, and engagement during a group-based compensatory strategy training for people with MCI. We hypothesized individuals with better memory and executive function performance would show better adherence and higher engagement scores in cognitive training classes.

Twenty-five participants enrolled in Emory University's Charles and Harriet Schaffer Cognitive Empowerment Program (CEP) completed an 11-week compensatory strategy training group (CEP-CT). CEP-CT is adapted from Ecologically Oriented Neurorehabilitation to be suitable for people with MCI. Participants enrolled were on average 74.3 years old (SD= 5.4), 52% Male, primarily Caucasian (80%; 16% African American), and college educated (M= 16.5 years; SD= 2.7). All participants received clinical diagnoses of MCI prior to enrollment in the program. Participants completed multiple cognitive measures, including Montreal Cognitive Assessment (MoCA), Hopkins Verbal Learning Test (HVLT), Trail Making Test A & B (TMT), Number Span Forward (NSF) and verbal fluency (S-words and Animals). For all group sessions, class attendance (present vs. not present) was recorded for each participant and their care partner, and engagement ratings for participants were recorded by the facilitator on a 1 to 5 scale (higher scores indicate better engagement). Outcomes include adherence to cognitive training (percentage of sessions attended; M= 82% class attendance, SD= 18%) as well as the average engagement ratings across 11 weeks (M= 3.25, SD= .40).

Bivariate Pearson correlations revealed that individuals who attended more classes also demonstrated better engagement in class, r= .44, p= .03. Class attendance was significantly related to performance on measures of memory and executive function (HVLT: r= -.42, p= .04; TMT-B: r= .69, p= .04), such that participants who performed worse on these measures attended more CEP-CT classes. Average engagement ratings were unrelated to cognitive performance.

Results did not support initial hypotheses, and instead indicate individuals with poorer performance on measures of memory and executive function had better adherence to CEP-CT classes, as measured by attendance. These results may indicate individuals experiencing cognitive difficulties are more likely to attend cognitive training classes. Subjective engagement ratings were unrelated to cognition; however, individuals who attended more sessions were more engaged in cognitive training classes. Future areas of research include objective measurement of class engagement as well as the incorporation of nuanced adherence metrics to further elucidate the relationship between these factors and cognition in MCI.