Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 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.

PubMed Disclaimer

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

References

    1. Zlokovic BV (2011) Neurovascular pathways to neurodegeneration in Alzheimer’s disease and other disorders. Nat Rev Neurosci 12, 723–738. - PMC - PubMed
    1. Lee S, Viqar F, Zimmerman ME, Narkhede A, Tosto G, Benzinger TL, Marcus DS, Fagan AM, Goate A, Fox NC, Cairns NJ, Holtzman DM, Buckles V, Ghetti B, McDade E, Martins RN, Saykin AJ, Masters CL, Ringman JM, Ryan NS, Forster S, Laske C, Schofield PR, Sperling RA, Salloway S, Correia S, Jack C Jr., Weiner M, Bateman RJ, Morris JC, Mayeux R, Brickman AM (2016) White matter hyperintensities are a core feature of Alzheimer’s disease: Evidence from the dominantly inherited Alzheimer network. Ann Neurol 79, 929–939. - PMC - PubMed
    1. Liu TT, Brown GG (2007) Measurement of cerebral perfusion with arterial spin labeling: Part 1. Methods. J Int Neuropsychol Soc 13, 517–525. - PubMed
    1. Kisler K, Nelson AR, Montagne A, Zlokovic BV (2017) Cerebral blood flow regulation and neurovascular dysfunction in Alzheimer disease. Nat Rev Neurosci 18, 419–434. - PMC - PubMed
    1. Iturria-Medina Y, Sotero RC, Toussaint PJ, Mateos-Pérez JM, Evans AC (2016) Early role of vascular dysregulation on late-onset Alzheimer’s disease based on multifactorial data-driven analysis. Nat Commun 7, 11934. - PMC - PubMed

Publication types