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Background: Alzheimer disease (AD) is more prevalent in African American (AA) and Hispanic White (HIW) compared to Non‐Hispanic White (NHW) individuals. Similarly, neuropsychiatric symptoms (NPS) vary by population in AD. This is likely the result of both sociocultural and genetic ancestral differences. However, the impact of these NPS on AD in different groups is not well understood. Methods: Self‐declared AA, HIW, and NHW individuals were ascertained as part of ongoing AD genetics studies. Participants who scored higher than 0.5 on the Clinical Dementia Rating (CDR) Scale (CDR) were included. Group similarities and differences on Neuropsychiatric Inventory Questionnaire (NPI‐Q) outcomes (NPI‐Q total score, NPI‐Q items) were evaluated using univariate ANOVAs and post hoc comparisons after controlling for sex and CDR stage. Results: Our sample consisted of 498 participants (26% AA; 30% HIW; 44% NHW). Overall, NPI‐Q total scores differed significantly between our groups, with HIW having the highest NPI‐Q total scores, and by AD stage as measured by CDR. We found no significant difference in NPI‐Q total score by sex. There were six NPI‐Q items with comparable prevalence in all groups and six items that significantly differed between the groups (Anxiety, Apathy, Depression, Disinhibition, Elation, and Irritability). Further, within the HIW group, differences were found between Puerto Rican and Cuban American Hispanics across several NPI‐Q items. Finally, Six NPI‐Q items were more prevalent in the later stages of AD including Agitation, Appetite, Hallucinations, Irritability, Motor Disturbance, and Nighttime Behavior. Conclusions: We identified differences in NPS among HIW, AA, and NHW individuals. Most striking was the high burden of NPS in HIW, particularly for mood and anxiety symptoms. We suggest that NPS differences may represent the impact of sociocultural influences on symptom presentation as well as potential genetic factors rooted in ancestral background. Given the complex relationship between AD and NPS it is crucial to discern the presence of NPS to ensure appropriate interventions. Key points: Our study sought to determine if there are differences in neuropsychiatric symptom prevalence, as measured by the Neuropsychiatric Inventory Questionnaire (NPI‐Q), among self‐declared African American (AA), Hispanic, and Non‐Hispanic White (NHW) individuals with Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI).While the prevalence of several NPI‐Q symptoms was consistent across the three groups our Hispanic participants showed a greater overall burden of neuropsychiatric symptoms—especially anxiety and mood symptoms (i.e., Anxiety, Depression, Apathy, and Irritability items). By contrast, African Americans reported significantly more behavioral problems as reflected on the Disinhibition and Elation items.The variability in the prevalence of neuropsychiatric symptoms among different populations (e.g., mood and anxiety symptoms in HIW) represents both underlying genetic factors rooted in ancestral background as well as sociocultural influences on the measurement and reporting of NPS. [ABSTRACT FROM AUTHOR]

Objective: Memory and cognitive problems are central to the diagnosis of Alzheimer's disease (AD). Psychometric approaches to defining phenotypes can aid in identify genetic variants associated with AD. However, these approaches have mostly been limited to affected individuals. Defining phenotypes of both affected and unaffected individuals may help identify genetic variants associated with both AD and healthy aging. This study compares psychometric methods for developing cognitive phenotypes that are more granular than clinical classifications. Methods: 682 older Old Order Amish individuals were included in the analysis. Adjusted Z‐scores of cognitive tests were used to create four models including (1) global threshold scores or (2) memory threshold scores, and (3) global clusters and (4) memory clusters. An ordinal regression examined the coherence of the models with clinical classifications (cognitively impaired [CI], mildly impaired [MI], cognitively unimpaired), APOE‐e4, sex, and age. An ANOVA examined the best model phenotypes for differences in clinical classification, APOE‐e4, domain Z‐scores (memory, language, executive function, and processing speed), sex, and age. Results: The memory cluster identified four phenotypes and had the best fit (χ2 = 491.66). Individuals in the worse performing phenotypes were more likely to be classified as CI or MI and to have APOE‐e4. Additionally, all four phenotypes performed significantly differently from one another on the domains of memory, language, and executive functioning. Conclusions: Memory cluster stratification identified the cognitive phenotypes that best aligned with clinical classifications, APOE‐e4, and cognitive performance We predict these phenotypes will prove useful in searching for protective genetic variants. Key points: This study compares psychometric methods for developing cognitive phenotypes that are more granular than clinical classifications in individuals from the Old Order Amish.We found that the memory cluster model produced four distinct cognitive phenotypes had the best fit with clinical classification, presence of APOE‐e4, age, and sex in the Old Order Amish.This suggests that stratification of Old Order Amish individuals using cluster analysis based on memory performance performs better than memory threshold stratification, and stratification based on global cognition.Importantly, our memory cluster model stratified individuals into four distinct cognitive phenotypes with significant differences in cognitive performance across memory, executive functioning, and language, but similar prevalence rates of APOE‐e4 in top three performing phenotypes [ABSTRACT FROM AUTHOR]