Identifying Subtypes of Alzheimer’s Disease: An analysis of possible cognitive subgroups through the life span

Abstract

AbstractBackgroundTypical Alzheimer’s disease (AD) is linked to memory impairment and medial temporal lobe atrophy. However, different patterns of cognitive decline in individuals with AD have been described in the literature (e.g., Murray et al., 2011; Lam et al., 2013; Scheltens et al., 2015). The variability of AD is also observed throughout the life span, as aging processes develop (Ferreira et al., 2017), which highlights the importance of investigating changes over time and establishing possible stages and therapeutic windows.MethodThe Toronto Cognitive Assessment (TorCA) was used to provide a characterization of cognitive profiles including orientation, immediate recall, delayed recall, delayed recognition, visuospatial function, executive control and language in 609 individuals with possible AD. Normative data for the TorCA (Freedman et al., 2018) suggest different levels of impairment can be identified depending on age groups. The present study investigated 27 neuropsychological subtests within the TorCA. Scores were summed based on cognitive domains and transformed into z‐scores. Further, the dataset was split into 4 age groups (Group 1 = less than 59; Group 2 = 60 to 69; Group 3 = 70 to 79; and Group 4 = over 80 years of age). The scores were analyzed with latent profile analyses (LPA) to identify cluster memberships among subjects.ResultDifferent AD subtypes were identified in each age group characterized by patterns of cognitive impairment as follows:a) Group 1:1. Cluster 1: mild;2. Cluster 2: amnestic;3. Cluster 3: executive;4. Cluster 4: moderate diffuse.b) Group 2:1. Cluster 1: mild diffuse;2. Cluster 2: executive / visuospatial;3. Cluster 3: moderate with preserved orientation and visuospatialc) Group 3:1. Cluster 1: moderate executive;2. Cluster 2: mild diffuse;3. Cluster 3: amnestic;4. Cluster 4: moderate diffuse.d) Group 4:1. Cluster 1: severe diffuse;2. Cluster 2: mild diffuse.ConclusionThese findings suggest that different subtypes of AD can be identified throughout the life span. Further investigation of these differences will aid in the development of clinical tools to diagnose and treat subgroups, in the development of protocols that stratify this population for better research recruitment, and establishing relevant neuropsychological and clinical tools.