Cognitively defined subtypes of Alzheimer's disease

Abstract

AbstractBackgroundWe have developed a framework for using cognitive test results at Alzheimer’s disease (AD) diagnosis to categorize people into AD subgroups. We have shown that risk factors and genetic variant associations vary across subgroups. We also showed differences in gray matter volume (GMV) using voxel‐based p‐values. Here we present new findings with beta coefficient maps and a movie showing regional atrophy associated with greater global atrophy.MethodWe use data from the first ADNI study visit with AD for 624 amyloid positive patients, and the first visit for 119 amyloid negative cognitively normal controls (CN). We generated voxel‐wise gray matter (GM) W‐scores as (actual GM‐expected GM)/SD. Expected GM is based on voxel‐wise regressions in CN in SPM12 with age, sex, ICV, and field strength. SD is the voxel‐specific SD of residuals from the regression analyses. We obtained global W‐scores as the number of voxels with W<‐1.65. We generated beta‐coefficient maps from SPM, controlling for global W‐score, age, sex, ICV, and field strength. We obtained regional W‐scores using the Desikan‐Killiany cortical parcellation atlas and performed regression analyses predicting regional W‐scores as a function of total W‐score as a continuous predictor, and present the results as a movie for each region.ResultThere were 267 people with no prominent differences across domains (AD‐No Domain), 189 with AD‐Memory, 14 AD‐Executive, 46 AD‐Language, 85 AD‐Visuospatial, and 23 AD‐multiple domains. Groups did not differ with respect to sex, years of education, handedness, or proportion who were non‐Hispanic white. Mean age at diagnosis ranged from 73 (AD‐Visuospatial and controls) to 77 (AD‐Language; omnibus p = 0.015) Compared to other groups, the AD‐Memory group consistently had greater GMV loss in medial temporal lobes (Figure 1). Each of the other groups had substantial areas of cortex with greater GMV loss than the AD‐Memory group (Figure 2). Regions associated with more global atrophy varied substantially across groups (Figure 3: this is a still of coordinated movies for each subgroup).ConclusionCognitively defined AD subgroups differ in patterns of GMV in regions that make sense with the cognitive phenotype.