Document Type
Article
Publication Date
11-1-2025
Original Citation
Chong Chie J,
Persohn S,
Pandey R,
Carter GW,
Simcox O,
Salama P,
Territo P,
.
Neurometabolic and vascular dysfunction as an early diagnostic for Alzheimer's disease and related dementias. Alzheimers Dement. 2025;21(11):e70790.
Keywords
JGM, Humans, Alzheimer Disease, Male, Female, Aged, Retrospective Studies, Early Diagnosis, Disease Progression, Brain, Biomarkers, Aged, 80 and over, Neuroimaging
JAX Source
Alzheimers Dement. 2025;21(11):e70790.
ISSN
1552-5279
PMID
41201009
DOI
https://doi.org/10.1002/alz.70790
Grant
Initiative ADNI; National Institutes of Health, Grant/Award Numbers: U01 AG024904, W81XWH-12-2-0012; National Institute on Aging, Grant/Award Number: T32AG071444
Abstract
INTRODUCTION: Recent studies suggest that the brain undergoes anatomical and functional restructuring, resulting in neurometabolic and vascular dysregulation (MVD) prior to amyloid beta accumulation, which begins at an early age and leads to the onset of Alzheimer's disease (AD).
METHODS: Using a retrospective clinical population (n = 403) from the Alzheimer's Disease Neuroimaging Initiative, cerebral perfusion and metabolism changes across 59 brain regions were evaluated from clinical studies. Results were verified by transcriptomic signatures and clinical cognitive assessments.
RESULTS: Our findings suggest that disease progression follows a stage-dependent MVD pattern that can identify at-risk regions. Although each region progresses at a different pace, regions related to memory, cognition, and motor function showed significant early dysregulation. Importantly, these changes aligned with transcriptomic and cognitive signatures.
DISCUSSION: This study underscores that MVD in brain regions varies by sex and disease stage, making it a sensitive tool for early AD diagnosis. This approach could improve patient monitoring, stratification, and therapeutic testing.
HIGHLIGHTS: The potential of metabolic and vascular dysfunction as an early biomarker was assessed. An analytical method to assess dysregulation via imaging was developed. An analytical and graphical method to visualize the changes across disease spectrum was developed. Brain regions progress at different rates across Alzheimer's disease progression. Results were aligned with transcriptomics and cognitive signatures.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.