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

Article type: Research Article

Authors: Bangen, Katherine J.^{a; b; *} | Thomas, Kelsey R.^{a; b} | Sanchez, Danielle L.^c | Edmonds, Emily C.^{a; b} | Weigand, Alexandra J.^d | Delano-Wood, Lisa^{b; e} | Bondi, Mark W.^{b; e} | for the Alzheimer’s Disease Neuroimaging Initiative¹

Affiliations: [a] Research Service, VA San Diego Healthcare System, San Diego, CA, USA | [b] Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA | [c] Department of Psychology, San Diego State University, San Diego, CA, USA | [d] San Diego Joint Doctoral Program in Clinical Psychology, San Diego State University/University of California, San Diego, CA, USA | [e] Psychology Service, VA San Diego Healthcare System, San Diego, CA, USA

Correspondence: [*] Correspondence to: Katherine J. Bangen, PhD, 3350 La Jolla Village Drive (151B), San Diego, CA 92161, USA. Tel.: +1 858 552 8585 /Ext. 5794; E-mail: [email protected].

Note: [1] Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf

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

DOI: 10.3233/JAD-201474

Journal: Journal of Alzheimer's Disease, vol. 81, no. 4, pp. 1711-1725, 2021