DOI: 10.1002/alz.083024 ISSN: 1552-5260

Characterization of data‐driven cognitive and amyloid‐beta phenotypes in older Veterans

Kelsey R. Thomas, Alexandra L Clark, Alexandra J. Weigand, Alin Alshaheri Durazo, Rachel Membreno, Britney Luu, Peter Rantins, Monica T. Ly, Lindsay J Rotblatt, Katherine J. Bangen
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Geriatrics and Gerontology
  • Neurology (clinical)
  • Developmental Neuroscience
  • Health Policy
  • Epidemiology



Within older Veterans, multiple factors may contribute to cognitive difficulties. Beyond Alzheimer’s disease (AD), military‐related exposures leading to vascular disease (e.g., agent orange), posttraumatic stress disorder (PTSD), and traumatic brain injury (TBI) may also impact cognition. This study aimed to derive groups based on objective cognition, subjective cognition, and amyloid burden, and then compare groups on demographic, clinical, and biomarker characteristics.


A hierarchical cluster analysis was conducted on 233 Vietnam‐Era Veterans without dementia from the Department of Defense‐Alzheimer’s Disease Neuroimaging Initiative. Variables entered in the cluster analysis included: immediate and delayed memory, language, and attention/executive functioning domain scores; subjective cognitive decline (SCD) severity; and cortical amyloid PET SUVR. A discriminate function analysis (DFA) tested the extent to which the individual variables predicted cluster‐group membership. ANOVAs and chi‐squared tests examined demographic, clinical, and biomarker characteristics by group.


Cluster analysis identified 4 groups: Group 1 with high cognition, low SCD, and average amyloid (n = 41); Group 2 with average cognition, average SCD, and low amyloid (n = 121); Group 3 with low attention/executive functioning, average SCD, and high amyloid (n = 28); and Group 4 with low memory/language, high SCD, and average amyloid (n = 43; Figure 1). The DFA correctly classified 88.8% of participants. Group 3 had the greatest proportion of APOE ε4 carriers and individuals with TBI, highest tau burden, and lowest hippocampal volume. Group 4 had the fewest years of education, highest proportion of Hispanic/Latino participants, PTSD, and worst sleep quality. Groups did not differ on age, depressive symptoms, hypertension, or substance use (Table 1).


Within Vietnam‐Era Veterans, there were high and average cognition groups (Groups 1 and 2), both with low amyloid burden. Group 3 was most consistent with biological AD, yet attention/executive function was the lowest score. The complexity of older Veterans’ co‐morbid conditions may interact with AD pathology to show attention/executive dysfunction (rather than memory) as a prominent early symptom. Group 4 had the worst cognitive scores and highest SCD despite low amyloid; education, PTSD symptoms, sleep quality, and perhaps sociocultural factors may be contributing to this profile. Future work will investigate longitudinal cognitive and functional declines by group.

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