Longitudinal White and Gray Matter Response to Precision Medicine-Guided Intervention for Alzheimer’s Disease

Article type: Research Article

Authors: Chwa, Won Jong^{a; b} | Raji, Cyrus A.^b | Toups, Kat^c | Hathaway, Ann^d | Gordon, Deborah^e | Chung, Henrianna^f | Boyd, Alan^g | Hill, Benjamin D.^h | Hausman-Cohen, Sharonⁱ | Attarha, Mouna^j | Jarrett, Michael^f | Bredesen, Dale E.^k

Affiliations: [a] Saint Louis University School of Medicine, Saint Louis, MO, USA | [b] Mallinckrodt Institute of Radiology, Washington University School of Medicine, Saint Louis, MO, USA | [c] Bay Area Wellness, Walnut Creek, CA, USA | [d] Dr. Ann Hathaway, San Rafael, CA, USA | [e] Northwest Memory Center, Ashland, OR, USA | [f] Quesgen Systems, Burlingame, CA, USA | [g] CNS Vital Signs, Morrisville, NC, USA | [h] Department of Psychology, University of South Alabama, Mobile, AL, USA | [i] IntellxxDNA, Austin, TX, USA | [j] Posit Science, San Francisco, CA, USA | [k] Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA

Correspondence: [*] Correspondence to: Cyrus A. Raji, MD, PhD, Washington University School of Medicine, Saint Louis, MO, USA. E-mail: craji@wustl.edu..

Abstract: Background:Alzheimer’s disease (AD) is a debilitating condition that is widely known to adversely affect gray matter (GM) and white matter (WM) tracts within the brain. Recently, precision medicine has shown promise in alleviating the clinical and gross morphological trajectories of patients with AD. However, regional morphological changes have not yet been adequately characterized. Objective:Investigate regional morphological responses to a precision medicine-guided intervention with regards to white and gray matter in AD and mild cognitive impairment (MCI). Methods:Clinical and neuroimaging data were compiled over a 9-month period from 25 individuals who were diagnosed with AD or MCI receiving individualized treatment plans. Structural T1-weighted MRI scans underwent segmentation and volumetric quantifications via Neuroreader. Longitudinal changes were calculated via annualized percent change of WM or GM ratios. Results:Montreal Cognitive Assessment scores (p < 0.001) and various domains of the Computerized Neurocognitive Screening Vital Signs significantly improved from baseline to 9-month follow-up. There was regional variability in WM and GM atrophy or hypertrophy, but none of these observed changes were statistically significant after correction for multiple comparisons.

DOI: 10.3233/JAD-230481

Journal: Journal of Alzheimer's Disease, vol. 96, no. 3, pp. 1051-1058, 2023