Pre-Diabetes, but not Type 2 Diabetes, Is Related to Brain Amyloid in Late Middle-Age

Article type: Research Article

Authors: Luchsinger, José A.^{a; b; *} | Palta, Priya^{a; b} | Rippon, Brady^a | Sherwood, Greysi^a | Soto, Luisa^a | Ceballos, Fernando^a | Laing, Krystal^c | Igwe, Kay^c | He, Hengda^c | Razlighi, Qolamreza^{c; d; e; f} | Teresi, Jeanne^g | Moreno, Herman^h | Brickman, Adam M.^{c; d; e}

Affiliations: [a] Department of Medicine, College of Physicians and Surgeons, Columbia University Irving Medical Center (CUIMC), New York, NY, USA | [b] Department of Epidemiology, Joseph P. Mailman School of Public Health, CUIMC, New York, NY, USA | [c] Department of Neurology, College of Physicians and Surgeons, CUIMC, New York, NY, USA | [d] Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, CUIMC, New York, NY, USA | [e] Gertrude H. Sergievsky Center, CUIMC, New York, NY, USA | [f] Department of Biomedical Engineering, Columbia University, New York, NY, USA | [g] Research Division, Hebrew Home in Riverdale, Bronx, NY, USA | [h] Department of Neurology, SUNY Downstate Medical Center, Brooklyn, NY, USA

Correspondence: [*] Correspondence to: José A. Luchsinger, MD, MPH, Columbia University Irving Medical Center, 622 West 168th Street, PH9 Center room 210, New York, NY 10032, USA. Tel.: +1 212 305 4730; Fax: +1 212 305 9349; E-mail: [email protected].

Abstract: Background:Type 2 diabetes is a dementia risk factor, but its relation to Alzheimer’s disease (AD), the most common cause of dementia, is unclear. Objective:Our primary objective was to examine the association of pre-diabetes and type 2 diabetes with brain amyloid-β (Aβ), the putative main culprit of AD. Our secondary objective was to examine the association of pre-diabetes and type 2 diabetes with neurodegeneration, cerebrovascular disease (CVD), and memory performance. Methods:We conducted a cross-sectional study of 350 late middle-aged Hispanics without dementia in New York City. We classified diabetes status as normal glucose tolerance (NGT), pre-diabetes, and type 2 diabetes following American Diabetes Association criteria. Brain Aβ was ascertained as global Aβ standardized value uptake ratio using PET with 18F-Florbetaben. Neurodegeneration was operationalized as cortical thickness in regions affected by AD using MRI. CVD was operationalized as white matter hyperintensity volume (WMH) on MRI, and memory as performance with the selective reminding test (SRT). Results:Mean age was 64.15±3.34 years, 72.00% were women, and 35.43% were APOE ɛ4 carriers. Pre-diabetes, but not type 2 diabetes, was associated with higher Aβ compared with NGT. Type 2 diabetes treatment was related to lower Aβ. Type 2 diabetes was related to lower cortical thickness, higher WMH, and lower SRT score. Conclusion:Pre-diabetes, but not type 2 diabetes, is associated with higher brain Aβ in late middle age, and this observation could be explained by the relation of diabetes treatment with lower brain Aβ. Whether type 2 diabetes treatment lowers brain Aβ requires further study.

Keywords: Amyloid, middle age, Hispanic, type 2 diabetes

DOI: 10.3233/JAD-200232

Journal: Journal of Alzheimer's Disease, vol. 75, no. 4, pp. 1241-1252, 2020