Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring

ImportancePsychological traits reflecting neuroticism, depressive symptoms, loneliness, and purpose in life are risk factors of AD dementia; however, the underlying biologic mechanisms of these associations remain largely unknown. ObjectiveTo examine whether one or more multi-omic brain molecular subtypes of AD is associated with neuroticism, depressive symptoms, loneliness, and/or purpose in life. DesignTwo cohort-based studies; Religious Orders Study (ROS) and Rush Memory and Aging Project (MAP), both ongoing longitudinal clinical pathological studies that began enrollment in 1994 and 1997. SettingOlder priests, nuns, and brothers from across the U.S. (ROS) and older adults from across the greater Chicago metropolitan area (MAP). Participants822 decedents with multi-omic data from the dorsolateral prefrontal cortex. Exposure(s)Pseudotime, representing molecular distance from no cognitive impairment (NCI) to AD dementia, and three multi-omic brain molecular subtypes of AD dementia representing 3 omic pathways from no cognitive impairment (NCI) to AD dementia that differ by their omic constituents. Main outcome(s) and measure(s)We first ran four separate linear regressions with neuroticism, depressive symptoms, loneliness, purpose in life as the outcomes, and pseudotime as the predictor, adjusting for age, sex and education. We then ran four separate analyses of covariance (ANCOVAs) with Bonferroni-corrected post-hoc tests to test whether the three multi-omic AD subtypes are differentially associated with the four traits, adjusting for the same covariates. ResultPseudotime was positively associated (p<0.05) with neuroticism and loneliness. AD subtypes were differentially associated with the traits: AD subtypes 1 and 3 were associated with neuroticism; AD subtype 2 with depressive symptoms; AD subtype 3 with loneliness, and AD subtype 2 with purpose in life. Conclusions and RelevanceThree multi-omic brain molecular subtypes of AD dementia differentially share omic features with four psychological risk factors of AD dementia. Our data provide novel insights into the biology underlying well-established associations between psychological traits and AD dementia. Key pointsO_ST_ABSQuestionC_ST_ABSAre three distinct multi-omic brain molecular subtypes of Alzheimers disease (AD) dementia associated with four well-established psychological AD risk factors (neuroticism, depressive symptoms, loneliness and purpose in life)? FindingsWe found differential associations: AD subtypes 1 and 3 were associated with neuroticism, AD subtype 2 was associated with depressive symptoms, AD subtype 3 was associated with loneliness; and AD subtype 2 was associated with purpose in life. MeaningPsychological risk factors might be associated with AD dementia via shared multi-omic molecular pathways.

ObjectiveCognitive impairment is associated with language changes that may be elicited from verbal responses during neuropsychological assessments that are not captured in traditional scoring. The current study investigated the utility of a linguistic analysis of paragraph recall responses for differentiating participants with and without cognitive impairment. MethodsDigital voice recordings of Logical Memory (LM) were available from 598 participants from the Long Life Family Study with normal cognition and 112 with cognitive impairment. Linguistic polyfeature scores for immediate (PFS-IR) and delayed recall (PFS-DR) were created from a weighted sum of features associated with cognitive impairment. Logistic regression models assessed the predictive value of each PFS and demographics for classifying cognitive impairment. Repeated measures models with Generalized Estimating Equations assessed whether PFSs predict decline on a cognitive screener. ResultsBoth immediate and delayed PFSs were significantly associated with cognitive status (PFS-IR {beta} = 0.05, p<.001; PFS-DR {beta} = 0.07, p<.001). A classifier with PFS-DR and demographics closely approximated the accuracy of the traditional LM score and demographics (AUC-PR = 0.81 vs 0.84, respectively). A higher PFS-DR was also associated with greater cognitive decline over an average of 5 years of follow-up ({beta} = -0.08, p<.001). ConclusionQuantification of linguistic features from paragraph recall using a linguistic PFS provides sufficient information for detecting cognitive impairment and predicting incident cognitive decline. The linguistic PFS has the potential to be integrated into automated testing, recording, and scoring pipelines allowing for the implementation of sensitive neuropsychological assessments in broader clinical and research settings.

BackgroundThe ability to predict Alzheimers disease (AD) before diagnosis is a topic of intense research. Early diagnosis would aid in improving treatment and intervention options, however, there are no current methods that can accurately predict AD years in advance. This study examines a novel machine learning approach that integrates the combined effects of vascular (white matter hyperintensities, WMHs), and structural brain changes (gray matter, GM) with clinical factors (cognitive status) to predict post-mortem neuropathological outcomes. MethodsHealthy older adults, participants with mild cognitive impairment, and AD from the Alzheimers Disease Neuroimaging Initiative dataset with both post-mortem neuropathology data and antemortem MRI and clinical data were included. Longitudinal data were analyzed across three intervals before death (post-mortem data): 0-4 years, 4-8 years, and 8-14 years. Additionally, cross-sectional data at the last visit or interval (within four years, 0-4 years) before death were also examined. Machine learning models including gradient boosting, bagging, support vector regression, and linear regression were implemented. These models were applied towards feature selection of the top seven MRI, clinical, and demographic data to identify the best performing set of variables that could predict postmortem neuropathology outcomes (i.e., neurofibrillary tangles, neuritic plaques, diffuse plaques, senile/amyloid plaques, and amyloid angiopathy). ResultsA total of 94 participants (55-90 years of age) were included in the study. At last visit, the best-performing model included total and temporal lobe WMHs and achieved r=0.87(RMSE=0.62) during cross-validation for neuritic plaques. For longitudinal assessments across different intervals, the best-performing model included regional GM (i.e., hippocampus, amygdala, caudate) and frontal lobe WMH and achieved r=0.93(RMSE=0.59) during cross-validation for neurofibrillary tangles. For MRI and clinical predictors and clinical-only predictors, t-tests demonstrated significant differences at all intervals before death (t[-13.60-7.90], p-values<0.001). Overall, post-mortem neuropathology outcome were predicted up to 14 years before death with high accuracies ([~]90%). ConclusionsPrediction accuracy was higher for post-mortem neuropathology outcomes that included MRI (WMHs, GM) and clinical features compared to clinical-only features. These findings highlight that MRI features are critical to successfully predict AD-related pathology years in advance which will improve participant selection for clinical trials, treatments, and intervention options.

BackgroundOlfactory impairment often precedes cognitive decline in Alzheimers disease (AD). Recent studies suggest odor specificity in olfactory deficits during early AD stages, making olfactory tests a promising tool for early diagnosis. However, the mechanisms underlying olfactory impairment remain unclear, complicating the identification of optimal odorants for diagnostic purposes. ObjectiveIn this study, we assessed olfactory sensitivity in a knock-in mouse model of Alzheimers disease (AppNL-G-F mice) that recapitulates key features of human AD pathology. MethodsTo evaluate odor detection thresholds, we employed an olfactory assay that leverages innate behavior without requiring associative learning. Six odorants representing distinct functional groups were tested in wild-type (WT) and AppNL-G-F mice at 2 and 4 months of age. ResultsAppNL-G-F mice exhibited odorant-specific hyposmia at 4 months of age, coinciding with amyloid deposition in cortical and subcortical regions but preceding measurable cognitive deficits. Unexpectedly, at an earlier stage (2 months), these mice showed odorant-specific hyperosmia to ester odorants, which transitioned to hyposmia by 4 months, indicating dynamic, age-dependent alterations in olfactory sensitivity as AD pathology progresses. ConclusionsOur findings demonstrate that odorant-specific olfactory testing could serve as a promising diagnostic tool for early-stage AD, providing insights into the mechanisms underlying olfactory dysfunction in neurodegenerative diseases.

INTRODUCTIONAlzheimers disease (AD) is a public health priority. AD biomarkers may vary based on race, but recruitment of diverse participants has been challenging. METHODSThree groups of Black and White participants with and without prior research advocacy or participation were interviewed individually or in focus groups to better understand perspectives related to AD biomarker research participation. Thematic analytic approach was used to analyze the data. RESULTSIdentified barriers to AD biomarker research participation included hesitancy due to fear, distrust of research and researchers, lack of relevant knowledge, and lack of research test results disclosure. Drivers for engagement in biomarker research procedures included knowledge about research, AD, and related clinical procedures, perceived benefits of participation, and outreach from trusted sources. DISCUSSIONParticipants comments related to the need for diversity in research and desire for results disclosure suggest opportunities to engage Black individuals.

INTRODUCTIONSouth Asian (SA) and East Asian (EA) older adults represent the fastest growing group of Americans at risk for dementia, but their participation in aging and dementia research has been limited. While recruiting healthy SA older adults into a brain health study, we encountered unexpected hesitancy towards structural brain MRI analysis along with some stigmatizing attitudes related to internal locus of control (LoC) for future dementia risks. We hypothesized that support for MRI-related research was influenced by these attitudes as well as ones own MRI experience, perceived MRI safety, and concerns for ones own risks for future dementia/stroke. METHODSWe developed a brief cross-sectional survey to assess older adults MRI experiences and perceptions, desire to learn of six incidental findings of increasing health implications, and attitudes related to dementia as well as research participation. We recruited a convenience sample of 256 respondents (74% reporting as 50+) from the New Jersey/New York City area to complete the survey, and modeled the proportional odds (P.O.) for pro-research attitudes. RESULTS77 SA and 84 EA respondents were analyzed with 95 non-Asian adults. White (P.O.=2.54, p=0.013) and EA (P.O.=2.14, p=0.019) respondents were both more likely than SA respondents to endorse healthy volunteers participation in research, and the difference between White and SA respondents was mediated by the latters greater internal LoC for dementia risks. EA respondents had more worries for future dementia/stroke than SA respondents (p=0.006), but still shared SA respondents low desire to learn of incidental MRI findings. DISCUSSIONSA and EA older adults had different attitudes towards future dementia/stroke risks, but shared a low desire to learn of incidental MRI findings. A culturally-appropriate protocol to disclose incidental MRI findings may improve SA and EA participation in brain health research. Color printingPlease have figure one and two be in color; figure three is in black and white

BackgroundRemote, smartphone-based cognitive testing may improve access to cognitive assessments for Alzheimers disease and related dementias. We evaluated the feasibility, reliability, and validity of unsupervised smartphone-based cognitive tests in a registry-based cohort. MethodsAdults without a record of cognitive impairment (N=1,815; ages 18-92) were recruited from the UCSF Brain Health Registry to complete unsupervised ALLFTD-mApp cognitive tasks three times over two weeks. Reliability was assessed with correlations between sessions. Linear regression models tested associations of ALLFTD-mApp tasks with demographics, self- and informant-rated cognitive concerns (Everyday Cognition Surveys; ECog), and web-based cognitive testing (CogState Brief Battery; CBB). ResultsAdherence was high (82.2%) and usability favorable. Test-retest reliability was moderate to strong ({rho}s = 0.61-0.85, all ps < .001). Lower ALLFTD-mApp scores were associated with older age, lower education, cognitive concerns, and worse CBB performance. ConclusionFindings support the feasibility, reliability, and validity of the ALLFTD-mApp in adults without a record of cognitive impairment.

BackgroundThe global rise of cognitive impairment and dementia poses significant public health challenges. Existing clinical practice and many social services focused on diagnosis and management after onset. The Hong Kong-Vigilance and Memory Test (HK-VMT) platform combines dementia risk assessment and cognitive test in one accessible tool to enable early detection of dementia in community setting. ObjectiveThis study aimed to evaluate the effectiveness of the HK-VMT platform in assessing dementia risk and a broad spectrum of cognitive impairment in community-dwelling adults. It also assesses the impact of the platform on improving public awareness and encouraging lifestyle changes. MethodsThis cross-sectional study assessed 517 adults aged 50 and above recruited through outreach activities between July 2024 and March 2025. Participants underwent a two-stage screening process consisting of dementia risk assessment and cognitive test. The platform collected data on socio-demographic, psychological, medical, and physiological factors for assessing dementia risk using Cognitive Ageing Risk Score (CARS). Cognitive performance was measured by the HK-VMT. User feedback on platform accessibility, adoption, user engagement, public awareness, and attitudes toward healthy lifestyles was obtained through interview. Results19.7% of participants were at high risk of dementia. Cognitive impairments were detected in 34.3% of participants through the HK-VMT platform. For user experience, 78% of participants with cognitive impairments were unaware of their condition before screening. Over 95% of participants reported improved understanding of their cognitive health status and over 80% expressed intentions to adopt healthy lifestyle. ConclusionsThe HK-VMT platform shows to enhance early detection of cognitive impairments, improve accessibility, increase public awareness and engage the public in brain health management. It represents a scalable solution to support healthy ageing and reduces disparities in early dementia preventive care by bridging community cognitive health services.

We assessed long-term recall and perceived impact of amyloid PET results among 92 cognitively normal adults who received structured result disclosure 6-9 years earlier. Two-thirds correctly recalled their result; only three misremembered the result as the opposite of what was communicated. Participants reported limited behavior change, though those with elevated scans more often endorsed lifestyle modifications. Perceived AD risk aligned with scan status but did not appear to cause lasting psychological distress. Most participants, regardless of result, viewed the experience positively and would undergo testing again. These findings support the long-term acceptability of disclosing amyloid PET results.

ObjectivesGrowing evidence suggests that place of birth (PoB) and related circumstances may have long-lasting and multiplicative contributions to various later-life outcomes. However, the specific contributions to different domains of cognitive function in late life remain less understood. This study aimed to investigate the extent to which PoB contribute to a wide range of later-life cognitive outcomes. MethodsA nationally representative sample of Americans aged 65 and older (N=3,216) from the Health and Retirement Study (HRS) Harmonized Cognitive Assessment Protocol (HCAP) was utilized. Cognitive outcomes were assessed in HCAP and linked to HRS state-level PoB data to explore the contribution of birthplace to later-life cognitive disparities. Regression-based Shapley decompositions were employed to quantify this contribution. ResultsPoB significantly contributed to all assessed cognitive outcomes including memory, executive function, language and fluency, visuospatial function, orientation, global cognitive performance, cognitive impairment and dementia. Geographic disparities in cognitive outcomes were evident, with individuals born in US southern states and foreign-born individuals performing worse than those born in other states. PoB overall accounted for 2.4-13.9% of the total variance in cognition after adjusting for age and sex. This contribution reduced by half when adjusting for a rich set of sociodemographic and health factors over the life course, but PoB still independently explained 2.0-7.1% of the total variance in cognition. DiscussionPoB has lasting contributions to later-life cognitive health, with significant geographic disparities observed. Addressing these disparities requires promoting more equalized place-based policies, resources, and early-life environments to improve health equities over the life course.

ImportanceStudies on racial disparities in cognition have primarily focused on mid-life to late-life risk factors. Given the critical role of neurocognitive development in early life, understanding contributions of early-life circumstances has important implications for preventive strategies. ObjectiveTo assess the extent to which racial differences in early-life circumstances, particularly educational quality and experience, can individually and collectively contribute to racial disparities in late-life cognition. Design, Setting, and Participants9,015 participants (7,381 non-Hispanic White (White) and 1,634 non-Hispanic Black (Black) with comprehensive life-history data were assembled from the Health and Retirement Study (HRS) (1995-2018), a nationally representative longitudinal survey of Americans 50 years or older. Main Outcomes and MeasuresBlinder-Oaxaca Decomposition (BOD) was used to quantify disparities in cognitive outcomes between White and Black participants attributable to racial differences in early-life circumstances. Cognitive score and cognitive impairment were assessed using the Telephone Interview for Cognitive Status (TICS). Early-life educational quality and experience were included as key explanatory variables, and traditional early-life factors including cohort, regional, financial, health, trauma, relationship factors, and educational attainment were included as additional explanatory variables. Demographic and genetic factors were included as covariates. ResultsAmong White and Black participants, the mean (SD) ages were 73.2 (10.1) and 69.2 (9.2) years, respectively, and 4,410 (59.7%) and 1,094 (67.0%) were female. Cognitive scores (range: 0-27 points) were significantly lower in Black (13.5, 95% CI, 13.3-13.7) than White participants (15.8, 95% CI, 15.7-15.9), while the prevalence of cognitive impairment was significantly higher in Black (33.6, 95% CI, 31.3-35.9) than White participants (16.4, 95% CI, 15.6-17.2). Substantial racial differences were observed in early-life circumstances. Overall, racial differences in early-life circumstances accounted for 65.9% and 85.1% of the gaps in cognitive score and impairment, respectively. Educational quality and experience played a prominent role, independently explaining 34.1% of the gap in cognitive score and 51.3% in cognitive impairment. Notably, school racial segregation (attending all minority schools before college) explained 26.7%-40.6% of the gaps in cognition. These findings remained consistent after adjusting for genetic risks. Conclusions and RelevanceLess favorable early-life circumstances contribute to clinically meaningful and statistically significant racial gaps in late-life cognition. Policies that improve educational equity may have long-lasting impacts on reducing racial disparities in cognition into older ages. Key PointsO_ST_ABSQuestionsC_ST_ABSHow much do differences in early-life circumstances, including educational quality and experience, individually and collectively explain late-life disparities in cognitive outcomes between non-Hispanic Black (Black) and non-Hispanic White (White) older adults? FindingsEarly-life circumstances contribute substantially to racial disparities in cognitive outcomes over age 50. Educational quality and experience are the most important early-life contributors, independent of a rich set of sociodemographic and genetic factors. MeaningExposure to less favorable early-life circumstances for Black than White adults is associated with large racial gaps in cognitive outcomes.

Cost-effective, noninvasive screening methods for preclinical Alzheimers disease (AD) and other neurocognitive disorders remain an unmet need. The olfactory neural circuits develop AD pathological changes prior to symptom onset. To probe these vulnerable circuits, we developed the digital remote AROMHA Brain Health Test (ABHT), an at-home odor identification, discrimination, memory, and intensity assessment. The ABHT was self-administered among cognitively normal (CN) English and Spanish speakers (n=127), participants with subjective cognitive complaints (SCC; n=34), and mild cognitive impairment (MCI; n=19). Self-administered tests took place remotely at home under unobserved (among interested CN participants) and observed modalities (CN, SCC, and MCI), as well as in-person with a research assistant present (CN, SCC, and MCI). Olfactory performance was similar across observed and unobserved remote self-administration and between English and Spanish speakers. Odor memory, identification, and discrimination scores decreased with age, and olfactory identification and discrimination were lower in the MCI group compared to CN and SCC groups, independent of age, sex, and education. The ABHT revealed age-related olfactory decline, and discriminated CN older adults from those with cognitive impairment. Replication of our results in other populations would support the use of the ABHT to identify and monitor individuals at risk for developing dementia.

ImportanceExisting studies concentrate on exploring mid-life to late-life risk factors on racial disparities in cognition. Given the critical role of neurocognitive development in early life, understanding contributions of early-life circumstances has important implications for early-stage interventions. ObjectiveTo evaluate the association between early-life circumstances and racial disparities in cognition, and to determine their overall and respective contributions. Design, Setting, and ParticipantsWe assembled three analytic samples from the Health and Retirement Study (HRS) (1995-2018), a nationally representative longitudinal survey of Americans 50 years or older. 17,092 participants, with 13,907 identifying as non-Hispanic White (White) and 3,185 as non-Hispanic Black (Black), were included in the Core sample. The Trauma and PGS samples respectively included 6,533 participants (5,696 White, 837 Black) and 5,532 participants (4,893 White, 639 Black). Main Outcomes and MeasuresThe main outcomes were cognitive score and cognitive impairment, as assessed by the Telephone Interview for Cognitive Status (TICS). We used the Blinder-Oaxaca Decomposition (BOD) to evaluate disparities in cognitive outcomes between White and Black participants attributable to differences in early-life circumstances. ResultsAmong all White and Black participants at initial survey, their respective average age were 58.1 (95% CI, 58.0-58.3) years and 55.8 (95% CI, 55.5-56.0) years; their respective average cognitive score were 17.3 (95% CI, 17.2-17.3) points and 14.6 (95% CI, 14.4-14.7) points; and their respective proportion with cognitive impairment were 7.2 (95% CI, 6.8-7.6) percentage points (pp) and 22.9 (95% CI, 21.5-24.4) pp. Across three analytic samples, overall differences in early-life circumstances respectively explained 23.5%-40.4% and 33.8%-65.3% of the racial gaps in cognitive score and proportion of cognitive impairment between White and Black participants. Difference in educational attainment contributed the most. In the Trauma sample, for example, years of education explained 3.1 (95% CI, 1.9-4.3) pp or 18.6% of the racial gap in proportion of cognitive impairment using the baseline assessment, and 3.3 (95% CI, 2.0-4.5) pp or 26.9% using the latest assessment. Additional early-life contributors included educational environments (e.g., ownership of books, parental education, time spent with mothers) and socioeconomic status (e.g., financial difficulty). However, childhood trauma and selected genetic factors were not significant contributors. Conclusions and RelevanceLess favorable early-life circumstances are associated with clinically meaningful and statistically significant racial gaps in cognition. Key PointsO_ST_ABSQuestionsC_ST_ABSHow much do differences in early-life circumstances explain late-life disparities in cognitive outcomes between non-Hispanic Black (Black) and non-Hispanic White (White) older adults? What are the key early-life contributors to these racial disparities? FindingsEarly-life circumstances contribute substantially to racial disparities in cognitive outcomes over age 50. Educational attainment and early-life educational environment are the most important contributors, even after accounting for a rich set of other early-life socioeconomic, demographic, health, traumatic, and genetic factors. MeaningExposure to less favorable early-life circumstances for Black than White adults was associated with large racial gaps in cognitive outcomes.

BackgroundLoneliness is an emerging public health concern linked to adverse mental and physical outcomes. It may play a key role in cognitive aging, yet its population-level association with subjective cognitive decline (SCD) across demographic groups is not well characterized. We evaluated how the frequency of loneliness relates to SCD in U.S. adults and whether associations differ by sex, age and race/ethnicity. MethodsWe performed a cross-sectional analysis of adults aged [&ge;]16 years using nationally representative 2016-2023 Behavioral Risk Factor Surveillance System data (BFRSS). Loneliness was categorized as never, rarely, sometimes, usually or always. The primary outcome was self-reported SCD in the past year. Survey-weighted logistic regression models adjusted for sociodemographic factors, health insurance, metropolitan status and survey year were used to estimate adjusted marginal probabilities of SCD across loneliness categories. Interaction terms and stratified margins evaluated effect modification by sex, age group (16-44, 45-64 and [&ge;]65 years) and race/ethnicity (non-Hispanic White, non-Hispanic Black and Hispanic). ResultsAmong 85,969 adults who reported loneliness, 13,879 (16.2%) experienced subjective cognitive decline (SCD), with a mean age of 65.7 {+/-} 10.6 years. Loneliness showed a strong dose-response relationship with SCD. Predicted probabilities of SCD increased from 9.9 % (95 % CI, 9.3-10.5 %) among respondents who never felt lonely to 15.0 % (14.1-15.9 %) for rarely, 24.9 % (23.6-26.1 %) for sometimes, 38.4 % (34.4-42.5 %) for usually and 45.7 % (41.0-50.4 %) for always lonely adults (p < 0.001). Women who were always lonely had an adjusted probability of SCD that was 10.7 percentage points higher than men; sex differences were negligible at lower loneliness levels. Age differences were minimal across most loneliness categories; however, among adults who were always lonely, those aged >64 years had significantly lower predicted cognitive function compared with adults aged 18-64 years (p < 0.001). Racial and ethnic differences were modest; the only significant contrast was a 1.7 percentage-point lower probability of SCD for non-Hispanic Black adults compared with Whites among those who never felt lonely. Other subgroup differences were not statistically significant. ConclusionsLoneliness is independently and strongly associated with higher likelihood of subjective cognitive decline among U.S. adults, and this relationship is most pronounced for chronic loneliness. While sex and age modified the effect of loneliness, racial/ethnic disparities were minimal. These findings identify loneliness as a modifiable social determinant of cognitive health, supporting the need for broad social connection initiatives and targeted efforts for women and mid-life adults with chronic loneliness.

INTRODUCTIONRepeated cognitive testing can boost scores due to practice effects (PEs). It remains unclear whether PEs persist across multiple follow-ups and long durations. We examined PEs across multiple assessments from midlife to old age in a nonclinical sample. METHODMen (N=1,608) in the Vietnam Era Twin Study of Aging (VETSA) underwent neuropsychological assessment across 4 waves from mean age 56 to 74. We leveraged age-matched attrition-replacement (AR) participants to estimate PEs at each wave. We compared cognitive trajectories and prevalence of mild cognitive impairment (MCI) using unadjusted versus PE-adjusted scores. RESULTSAcross follow-ups, a range of 7-12 out of 30 measures demonstrated significant PEs, especially in episodic memory and visuospatial domains. Adjusting for PEs resulted in steeper cognitive decline with up to 29% higher MCI prevalence. DISCUSSIONPEs persist across multiple assessments and decades. The AR-participant method provides accurate sample-specific PE estimates that enable significantly earlier detection of MCI.

ObjectivesA Script Generation Task (SGT), requiring participants to verbally describe the steps of everyday activities, was investigated as an efficient tool to detect mild functional difficulties and mild cognitive impairment (MCI). Methods83 participants (n=57 HC; n=26 MCI) completed a SGT, performance-based test of everyday function, cognitive tests, and questionnaires. SGT responses were transcribed and scored by human raters and automated text analysis. ResultsParticipants with MCI generated fewer SGT steps in a shorter amount of time and more pronouns relative to nouns, reflecting less specificity. Performance on the SGT was associated with cognitive tests of episodic memory, performance-based tests of everyday function, and questionnaires regarding everyday functioning. Conclusions The SGT holds promise as a highly efficient measure of mild cognitive and functional difficulties in older adults.

BackgroundDetecting cognitive impairment in clinical practice is challenging as most instruments do not perform well in diverse samples of older adults. These same instruments are often used for eligibility into clinical trials making it difficult to recruit minoritized adults into Alzheimers disease (AD) studies. Cognivue Clarity(R) is an FDA-cleared computerized cognitive screening platform using adaptive psychophysics to detect cognitive impairment. ObjectiveTest the ability of Cognivue Clarity to detect cognitive impairment in a diverse community sample compared with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). MethodsThis study enrolled 452 participants across 6 US study sites and completed both Cognivue Clarity device and RBANS. Psychometric properties and exploratory factor analysis of Cognivue Clarity were explored and comparisons against RBANS across different age, sex, education, and ethnoracial groups were conducted. ResultsParticipants had a mean age of 47.9{+/-}16.1 years (range: 18-85), 63.6% were female, 45.9% had <12 years of education, 31.2% were African American and 9.2% were Hispanic. Cognivue Clarity had strong internal consistency, test-retest and minimal practice effects. A 4-factor structure (Memory, Attention, Visuomotor, and Discrimination) had excellent goodness of fit. Normalizing age effects improved performance. Race and education effects were similar to those seen with RBANS. Cognivue Clarity had strong correlation with RBANS. ConclusionsOur study supports the use of Cognivue Clarity as an easy-to-use, brief, and valid cognitive assessment that can be used for identifying individuals with likely cognitive impairment in the clinical setting and those who could be candidates for AD research studies.

INTRODUCTIONWidespread language complaints in the cognitively unimpaired (CU) may reflect Alzheimers Disease (AD) pathology and future objective impairments. METHODS138 CU, 45 mild cognitive impairment and 28 dementia participants from the TRIAD cohort underwent 18F-MK-6240 tau-PET and 18F-AZD-4694 amyloid-PET. Word-finding complaints, confrontation naming, semantic and phonemic fluency and word-knowledge were evaluated. Covariance, direct and stepwise discriminant, and voxel-wise regression analyses were conducted. RESULTSWord-finding complaints appeared in early tau stages (Braak 1-2), followed by naming difficulties (Braak 3-4), and widespread language impairments in later stages (Braak 5-6). Complaints over forgetting the names of objects, naming, and APOE significantly improved classification of early AD pathology. In CU, complaints over forgetting names of objects were linked to left fusiform and inferior temporal gyri tau accumulation. DISCUSSIONLanguage measures are useful in detecting and tracking AD-related pathophysiologies. Results encourage refinement of clinical tools for early detection and disease monitoring. HighlightsLanguage decline parallels tau buildup across PET-based Braak stages of AD. Subjective anomia marks earliest tau-related language symptom (Braak 1-2). Objective naming deficits emerge in the middle tau spread stages (Braak 3-4). Advanced tau spread reflects significant and widespread language impairments. Word-finding complaints correlate with left fusiform and inferior temporal tau. Research in contextSystematic review: The literature was reviewed using traditional sources. The core biological definition of Alzheimers disease (AD) has recently been linked to its defining cognitive clinical features of episodic memory impairments. Widespread subjective language complaints amongst cognitively unimpaired (CU) older adults and objective language impairments observed across the AD continuum suggests these measures and the further bridging of biological and clinical definitions of AD could play a critical, cost-effective role in disease detection and monitoring. Interpretation: Results extend to tau previous findings describing language changes in AD and related to amyloid status and grey-matter atrophy. They also establish the likely staging of language impairments across the biological AD continuum. Future directions: The manuscript contextualises the use of subjective word-finding complaints, alongside genetic risks to significantly enhance the prediction of underlying AD related pathology in CU. Languages measures used in clinical practice remain limited however and better test should be utilized and developed.

INTRODUCTIONSouth Asian and Chinese individuals are the largest and fastest-growing ethnoracial groups in Canada, yet they remain underrepresented in dementia research. To address this gap, we established the CAnadian Multi-Ethnic Research on Aging (CAMERA) study. METHODSCAMERA is a longitudinal observational study conducted in Toronto, Canada, enrolling 300 adults aged 55-85 who self-identify as South Asian, Chinese, or non-Hispanic White (NHW). Participants complete in-person visits at baseline, Year 3, and Year 5, which include clinical and cognitive assessments, brain MRI, and blood biomarkers. Annual remote questionnaires track health and lifestyle. RESULTSAmong 200 participants, vascular and metabolic profiles differed across groups. South Asian and Chinese participants reported greater cognitive concerns than NHW participants and had lower MoCA scores, driven primarily by language-heavy and culturally dependent items. Eye-tracking measures did not differ across groups. DISCUSSIONCAMERA provides a deep phenotyping framework to investigate dementia risk and resilience in Asian Canadians.

Up to 80% of women breast cancer survivors (BCS), particularly those treated with chemotherapy, report persistent cognitive impairment. Several meta-analyses and empirical studies assessing cancer and chemotherapy-related cognitive impairment (CRCI) in BCS have reported cognitive deficits across many general domains of cognition. Moreover, discrepancies often arise between objectively measured and self-reported impairment, potentially due, in part, to the use of non-specific neuropsychological assessments. Cognitive impairments faced by BCS may only be experienced by a portion of individuals due to the interaction of several contributing factors (e.g., age, fatigue, stress), although this possibility has not been assessed systematically. This study measured cognitive performance using multiple modalities: 1) self-report measures, 2) traditional neuropsychological assessments, and 3) experimental cognitive paradigms. Using machine learning, we generated models to distinguish BCS from healthy aging individuals without breast cancer, and to assess the relative predictive value of these three assessment modalities. We found that self-report measures of fatigue, distractibility, and stress were able to successfully differentiate BCS from healthy control participants. Further, a model combining these self-report measures with measures from experimental cognitive paradigms and neuropsychological assessments increased predictive accuracy; performance on cognitive paradigms ranked more important for prediction than performance on neuropsychological assessments. Although preliminary, results highlight the predictive utility of combining measures from several modalities and indicate that several distinct factors may contribute to CRCI. As the nature of CRCI is complex, this approach may help identify the best combination of assessments and performance metrics to measure subtle cognitive impairments in women BCS.