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

Won Jong Chwa, Cyrus A. Raji, Kat Toups, Ann Hathaway, Deborah Gordon, Henrianna Chung, Alan Boyd, Benjamin D. Hill, Sharon Hausman-Cohen, Mouna Attarha, Michael Jarrett, Dale E. Bredesen

Research output: Contribution to journalArticlepeer-review


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. Conclusions: A precision-medicine guided approach to intervention may carry potential in curtailing both WM and GM atrophy, as rates of morphological change aligned more closely with normal aging than AD across all studied regions. Improvements in cognitive scores were statistically significant but may not necessarily represent clinical significance. Further studies should be pursued to further delineate cognitive trends as well as the mechanisms behind subtle regional differences in response to precision medicine-guided intervention.

Original languageEnglish
Pages (from-to)295-302
Number of pages8
JournalAdvances in Alzheimer's Disease
StatePublished - 2024


  • Alzheimer's disease
  • gray matter
  • neuroimaging
  • precision medicine
  • white matter


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