Associations Between Depression, Traumatic Brain Injury, and Cognitively-Defined Late-Onset Alzheimer's Disease Subgroups

Background: There is considerable heterogeneity in clinical presentation among people with late-onset Alzheimer's disease (LOAD). We have categorized people with LOAD into subgroups based on relative impairments across cognitive domains. These 6 groups are people with no relatively impaired domains (AD-No Domains), 4 groups with one relatively impaired domain (AD-Memory, AD-Executive, AD-Language, and AD-Visuospatial), and a group with multiple relatively impaired domains (AD-Multiple Domains). Our previous analysis demonstrated that genetic factors vary across cognitively-defined LOAD groups. Objective: To determine whether risks associated with depression and traumatic brain injury with loss of consciousness (TBI) for cognitively defined LOAD subgroups are similar. Methods: We used cognitive data at LOAD diagnosis from three prospective cohort studies to determine cognitively-defined subgroups. We compared subgroups in endorsement of items from the Centers for Epidemiological Studies Depression (CES-D) scale and history of TBI. Results: Among 1,505 people with LOAD from the three studies, there were substantial differences across subgroups in total CES-D score, with lower scores (less depression) for people with AD with relative impairments in memory (AD-Memory) compared to those in other groups. Differences were noteworthy for the sleep-related item of the CES-D, as people with AD-Memory were less likely to report restless sleep than people in other groups. There were no differences in TBI history across groups. Conclusions: Differences in risk factor associations across subgroups such as differences in endorsement of depression symptoms and restless sleep provide support for the hypothesis that there are biologically coherent subgroups of AD.