Amyloid-PET Levels in the Precuneus and Posterior Cingulate Cortices Are Associated with Executive Function Scores in Preclinical Alzheimer’s Disease Prior to Overt Global Amyloid Positivity

Article type: Research Article

Authors: Ali, Doaa G.^{a; b} | Bahrani, Ahmed A.^a | Barber, Justin M.^a | El Khouli, Riham H.^c | Gold, Brian T.^{a; d} | Harp, Jordan P.^{a; e} | Jiang, Yang^{a; b} | Wilcock, Donna M.^{a; f} | Jicha, Gregory A.^{a; b; e; *}

Affiliations: [a] Sanders-Brown Center on Aging, College of Medicine, University of Kentucky, Lexington, KY, USA | [b] Department of Behavioral Science, College of Medicine, University of Kentucky, Lexington, KY, USA | [c] Department of Radiology, College of Medicine, University of Kentucky, Lexington, KY, USA | [d] Department of Neuroscience, College of Medicine, University of Kentucky, Lexington, KY, USA | [e] Department of Neurology, College of Medicine, University of Kentucky, Lexington, KY, USA | [f] Department of Physiology, College of Medicine, University of Kentucky, Lexington, KY, USA

Correspondence: [*] Correspondence to: Gregory A. Jicha, MD, PhD, Sanders-Brown Center on Aging, College of Medicine, University of Kentucky, Lexington, KY 40504, USA. Tel.: +1 859 323 5550; E-mail: gregory.jicha@uky.edu.

Abstract: Background:Global amyloid-β (Aβ) deposition in the brain can be quantified by Aβ-PET scans to support or refute a diagnosis of preclinical Alzheimer’s disease (pAD). Yet, Aβ-PET scans enable quantitative evaluation of regional Aβ elevations in pAD, potentially allowing even earlier detection of pAD, long before global positivity is achieved. It remains unclear as to whether such regional changes are clinically meaningful. Objective:Test the hypothesis that early focal regional amyloid deposition in the brain is associated with cognitive performance in specific cognitive domain scores in pAD. Methods:Global and regional standardized uptake value ratios (SUVr) from 18F-florbetapir PET/CT scanning were determined using the Siemens Syngo.via® Neurology software package across a sample of 99 clinically normal participants with Montreal Cognitive Assessment (MoCA) scores≥23. Relationships between regional SUVr and cognitive test scores were analyzed using linear regression models adjusted for age, sex, and education. Participants were divided into two groups based on SUVr in the posterior cingulate and precuneus gyri (SUVR≥1.17). Between group differences in cognitive test scores were analyzed using ANCOVA models. Results:Executive function performance was associated with increased regional SUVr in the precuneus and posterior cingulate regions only (p < 0.05). There were no significant associations between memory and Aβ-PET SUVr in any regions of the brain. Conclusion:These data demonstrate that increased Aβ deposition in the precuneus and posterior cingulate (the earliest brain regions affected with Aβ pathology) is associated with changes in executive function that may precede memory decline in pAD.

Keywords: Amyloid-β positron emission tomography, cognition, preclinical Alzheimer’s disease, regional standardized uptake value ratio

DOI: 10.3233/JAD-220294

Journal: Journal of Alzheimer's Disease, vol. 88, no. 3, pp. 1127-1135, 2022