Categorizing people with late-onset Alzheimer’s disease into biologically coherent subgroups is important for personalized medicine. We evaluated data from five studies (total n = 4050, of whom 2431 had genome-wide single-nucleotide polymorphism (SNP) data). We assigned people to cognitively defined subgroups on the basis of relative performance in memory, executive functioning, visuospatial functioning, and language at the time of Alzheimer’s disease diagnosis. We compared genotype frequencies for each subgroup to those from cognitively normal elderly controls. We focused on APOE and on SNPs with p < 10−5 and odds ratios more extreme than those previously reported for Alzheimer’s disease (<0.77 or >1.30). There was substantial variation across studies in the proportions of people in each subgroup. In each study, higher proportions of people with isolated substantial relative memory impairment had ≥1 APOE ε4 allele than any other subgroup (overall p = 1.5 × 10−27). Across subgroups, there were 33 novel suggestive loci across the genome with p < 10−5 and an extreme OR compared to controls, of which none had statistical evidence of heterogeneity and 30 had ORs in the same direction across all datasets. These data support the biological coherence of cognitively defined subgroups and nominate novel genetic loci.

Objective: Studies use different instruments to measure cognitirating cognitive tests permit direct comparisons of individuals across studies and pooling data for joint analyses. Method: We began our legacy item bank with data from the Adult Changes in Thought study (n = 5,546), the Alzheimer's Disease Neuroimaging Initiative (n = 3,016), the Rush Memory and Aging Project (n = 2,163), and the Religious on such as the Mini-Mental State Examination, the Alzheimer's Disease Assessment Scale-Cognitive Subscale, the Wechsler Memory Scale, and the Boston Naming Test. CocalibOrders Study (n = 1,456). Our workflow begins with categorizing items administered in each study as indicators of memory, executive functioning, language, visuospatial functioning, or none of these domains. We use confirmatory factor analysis models with data from the most recent visit on the pooled sample across these four studies for cocalibration and derive item parameters for all items. Using these item parameters, we then estimate factor scores along with corresponding standard errors for each domain for each study. We added additional studies to our pipeline as available and focused on thorough consideration of candidate anchor items with identical content and administration methods across studies. Results: Prestatistical harmonization steps such qualitative and quantitative assessment of granular cognitive items and evaluating factor structure are important steps when trying to cocalibrate cognitive scores across studies. We have cocalibrated cognitive data and derived scores for four domains for 76,723 individuals across 10 studies. Conclusions: We have implemented a large-scale effort to harmonize and cocalibrate cognitive domain scores across multiple studies of cognitive aging. Scores on the same metric This document is copyrighted by the American Psychological Association or one of its allied publishers.This article is intended solely for the personal use of the individual user and is not to be disseminated broadly.

Introduction: Composite scores may be useful to summarize overall language or visuospatial functioning in studies of older adults. Methods:We used item response theory to derive composite measures for language (ADNI-Lan) and visuospatial functioning (ADNI-VS) from the cognitive battery administered in the Alzheimer's Disease Neuroimaging Initiative (ADNI). We evaluated the scores among groups of people with normal cognition, mild cognitive impairment (MCI), and Alzheimer's disease (AD) in terms of responsiveness to change, association with imaging findings, and ability to differentiate between MCI participants who progressed to AD dementia and those who did not progress.Results: ADNI-Lan and ADNI-VS were able to detect change over time and predict conversion from MCI to AD. They were associated with most of the pre-specified magneticThis is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Objectives To characterize the extent to which brief cognitive assessments administered in the population-representative US Health and Retirement Study (HRS) and its International Partner Studies can be considered to be measuring a single, unidimensional latent cognitive function construct. Method Cognitive function assessments were administered in face-to-face interviews in 12 studies in 26 countries (N=155,690), including the US HRS and selected International Partner Studies. We used the time point of first cognitive assessment for each study to minimize differential practice effects across studies, and documented cognitive test item coverage across studies. Using confirmatory factor analysis models, we estimated single factor general cognitive function models, and bifactor models representing memory-specific and non-memory-specific cognitive domains for each study. We evaluated model fits and factor loadings across studies. Results Despite relatively sparse and inconsistent cognitive item coverage across studies, all studies had some cognitive test items in common with other studies. In all studies, the bifactor models with a memory-specific domain fit better than single factor general cognitive function models. The data fit the models at reasonable thresholds for single factor models in six of the 12 studies, and for the bifactor models in all 12 of the 12 studies. Discussion The cognitive assessments in the US HRS and its International Partner Studies reflect comparable underlying cognitive constructs. We discuss the assumptions underlying our methods, present alternatives, and future directions for cross-national harmonization of cognitive aging data.