Regional Hypoperfusion Predicts Decline in Everyday Functioning at Three-Year Follow-Up in Older Adults without Dementia

Article type: Research Article

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

Affiliations: [a] Department of Psychology, San Diego State University, San Diego, CA, USA | [b] Research Service, VA San Diego Healthcare System, San Diego, CA, USA | [c] Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA | [d] 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: kbangen@health.ucsd.edu.

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:Increasing evidence indicates that cerebrovascular dysfunction may precede cognitive decline in aging and Alzheimer’s disease (AD). Reduced cerebral blood flow (CBF) is associated with cognitive impairment in older adults. However, less is known regarding the association between CBF and functional decline, and whether CBF predicts functional decline beyond cerebrovascular and metabolic risk factors. Objective:To examine the association between regional CBF and functional decline in nondemented older adults. Method:One hundred sixty-six (N = 166) participants without dementia from the Alzheimer’s Disease Neuroimaging Initiative underwent neuropsychological testing and neuroimaging. Pulsed arterial spin labeling magnetic resonance imaging was acquired to quantify resting CBF. Everyday functioning was measured using the Functional Assessment Questionnaire at baseline and annual follow-up visit across three years. Results:Adjusting for age, education, sex, cognitive status, depression, white matter hyperintensity volume, cerebral metabolism, and reference (precentral) CBF, linear mixed effects models showed that lower resting CBF at baseline in the medial temporal, inferior temporal, and inferior parietal lobe was significantly associated with accelerated decline in everyday functioning. Results were similar after adjusting for conventional AD biomarkers, including cerebrospinal fluid (CSF) amyloid-β (Aβ) and hyperphosphorylated tau (p-tau) and apolipoprotein E (APOE) ɛ4 positivity. Individuals who later converted to dementia had lower resting CBF in the inferior temporal and parietal regions compared to those who did not. Conclusion:Lower resting CBF in AD vulnerable regions including medial temporal, inferior temporal, and inferior parietal lobes predicted faster rates of decline in everyday functioning. CBF has utility as a biomarker in predicting functional declines in everyday life and conversion to dementia.

Keywords: Activities of daily living, aging, Alzheimer’s disease, biomarkers, cerebrovascular circulation, dementia, magnetic resonance imaging, neuropsychology, perfusion, regional blood flow

DOI: 10.3233/JAD-200490

Journal: Journal of Alzheimer's Disease, vol. 77, no. 3, pp. 1291-1304, 2020