Cognition and Amyloid-β in Older Veterans: Characterization and Longitudinal Outcomes of Data-Derived Phenotypes

Article type: Research Article

Authors: Thomas, Kelsey R.^{a; b; *} | Clark, Alexandra L.^c | Weigand, Alexandra J.^d | Edwards, Lauren^d | Durazo, Alin Alshaheri^{a; e} | Membreno, Rachel^{a; e} | Luu, Britney^{a; e} | Rantins, Peter^{a; e} | Ly, Monica T.^{a; b} | Rotblatt, Lindsay J.^{a; b} | Bangen, Katherine J.^{a; b} | Jak, Amy J.^{a; b} | for the Department of Defense Alzheimer’s Disease Neuroimaging Initiative^*

Affiliations: [a] VA San Diego Healthcare System, San Diego, CA, USA | [b] Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA | [c] Department of Psychology, University of Texas at Austin, Austin, TX, USA | [d] San Diego State University/University of California, San Diego Joint Doctoral Program in Clinical Psychology, San Diego, CA, USA | [e] San Diego State University, San Diego, CA, USA

Correspondence: [*] Correspondence to: KelseyKelsey R. Thomas, PhD, VA San Diego Healthcare System, 3350 La Jolla Village Drive (151), San Diego, CA 92161, USA. E-mail: [email protected].

Note: [*] Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.

Abstract: Background: Within older Veterans, multiple factors may contribute to cognitive difficulties. Beyond Alzheimer’s disease (AD), psychiatric (e.g., PTSD) and health comorbidities (e.g., TBI) may also impact cognition. Objective: This study aimed to derive subgroups based on objective cognition, subjective cognitive decline (SCD), and amyloid burden, and then compare subgroups on clinical characteristics, biomarkers, and longitudinal change in functioning and global cognition. Methods: Cluster analysis of neuropsychological measures, SCD, and amyloid PET was conducted on 228 predominately male Vietnam-Era Veterans from the Department of Defense-Alzheimer’s Disease Neuroimaging Initiative. Cluster-derived subgroups were compared on baseline characteristics as well as 1-year changes in everyday functioning and global cognition. Results: The cluster analysis identified 3 groups. Group 1 (n = 128) had average-to-above average cognition with low amyloid burden. Group 2 (n = 72) had the lowest memory and language, highest SCD, and average amyloid burden; they also had the most severe PTSD, pain, and worst sleep quality. Group 3 (n = 28) had the lowest attention/executive functioning, slightly low memory and language, elevated amyloid and the worst AD biomarkers, and the fastest rate of everyday functioning and cognitive decline. CONCLUSIONS:Psychiatric and health factors likely contributed to Group 2’s low memory and language performance. 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. These results could have important implications for the implementation of AD-modifying drugs in older Veterans.

Keywords: Alzheimer’s disease, amyloid, cognition, phenotypes, PTSD, Veterans

DOI: 10.3233/JAD-240077

Journal: Journal of Alzheimer's Disease, vol. 99, no. 1, pp. 417-427, 2024