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. 2021;81(4):1711-1725.
doi: 10.3233/JAD-201474.

Entorhinal Perfusion Predicts Future Memory Decline, Neurodegeneration, and White Matter Hyperintensity Progression in Older Adults

Katherine J Bangen  1   2 , Kelsey R Thomas  1   2 , Danielle L Sanchez  3 , Emily C Edmonds  1   2 , Alexandra J Weigand  4 , Lisa Delano-Wood  2   5 , Mark W Bondi  2   5 ; Alzheimer’s Disease Neuroimaging Initiative
Affiliations

Entorhinal Perfusion Predicts Future Memory Decline, Neurodegeneration, and White Matter Hyperintensity Progression in Older Adults

Katherine J Bangen et al. J Alzheimers Dis. 2021.

Abstract

Background: Altered cerebral blood flow (CBF) has been linked to increased risk for Alzheimer's disease (AD). However, whether altered CBF contributes to AD risk by accelerating cognitive decline remains unclear. It also remains unclear whether reductions in CBF accelerate neurodegeneration and development of small vessel cerebrovascular disease.

Objective: To examine associations between CBF and trajectories of memory performance, regional brain atrophy, and global white matter hyperintensity (WMH) volume.

Method: 147 Alzheimer's Disease Neuroimaging Initiative participants free of dementia underwent arterial spin labeling (ASL) magnetic resonance imaging (MRI) to measure CBF and serial neuropsychological and structural MRI examinations. Linear mixed effects models examined 5-year rate of change in memory and 4-year rate of change in regional brain atrophy and global WMH volumes as a function of baseline regional CBF. Entorhinal and hippocampal CBF were examined in separate models.

Results: Adjusting for demographic characteristics, pulse pressure, apolipoprotein E ɛ4 positivity, cerebrospinal fluid p-tau/Aβ ratio, and neuronal metabolism (i.e., fluorodeoxyglucose standardized uptake value ratio), lower baseline entorhinal CBF predicted faster rates of decline in memory as well as faster entorhinal thinning and WMH progression. Hippocampal CBF did not predict cognitive or brain structure trajectories.

Conclusion: Findings highlight the importance of early cerebrovascular dysfunction in AD risk and suggest that entorhinal CBF as measured by noninvasive ASL MRI is a useful biomarker predictive of future cognitive decline and of risk of both.

Keywords: Aging; Alzheimer’s disease; cognition; entorhinal cortex regional blood flow; magnetic resonance imaging; neuropsychology; perfusion; white matter hyperintensities.

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Conflict of interest statement

CONFLICT OF INTEREST/DISCLOSURE STATEMENT

Dr. Bondi receives royalties from Oxford University Press and serves as a consultant for Eisai, Novartis, and Roche Pharmaceutical. Other authors report no competing interests.

Figures

Figure 1
Figure 1
Trajectories of memory performance by baseline entorhinal CBF Model-predicted values of performance in memory, adjusted for age, education, sex, APOE ε4 genotype, p-tau/Aβ positivity, and FDG-PET. For visual comparison, the graphs display results for low entorhinal cerebral blood flow (CBF) and high entorhinal CBF which were determined by a median split of the values in the analytic sample. Shaded area represents 95% confidence intervals.
Figure 2
Figure 2
Trajectories of entorhinal cortical thinning and WMH progression by baseline entorhinal CBF Model-predicted values of entorhinal cortical thickness and white matter hyperintensity volume, adjusted for age, sex, APOE ε4 genotype, p-tau/Aβ positivity, and FDG-PET. For visual comparison, the graphs display results for low entorhinal cerebral blood flow (CBF) and high entorhinal CBF which were determined by a median split of the values in the analytic sample. Shaded area represents 95% confidence intervals. mm = millimeters
See this image and copyright information in PMC

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