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

TitlePre-Diabetes, but not Type 2 Diabetes, Is Related to Brain Amyloid in Late Middle-Age.
Publication TypeJournal Article
Year of Publication2020
AuthorsLuchsinger JA, Palta P, Rippon B, Sherwood G, Soto L, Ceballos F, Laing K, Igwe K, He H, Razlighi Q, Teresi J, Moreno H, Brickman AM
JournalJ Alzheimers Dis
Volume75
Issue4
Pagination1241-1252
Date Published2020
ISSN1875-8908
KeywordsAged, Amyloid beta-Peptides, Brain, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Female, Glucose Tolerance Test, Hispanic or Latino, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Positron-Emission Tomography, Prediabetic State
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 APOEɛ4 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.

DOI10.3233/JAD-200232
Alternate JournalJ Alzheimers Dis
PubMed ID32390636
PubMed Central IDPMC7659021
Grant ListR01 AG050440 / AG / NIA NIH HHS / United States
K24 AG045334 / AG / NIA NIH HHS / United States
P30 AG059303 / AG / NIA NIH HHS / United States
RF1 AG051556 / AG / NIA NIH HHS / United States
UL1 TR001873 / TR / NCATS NIH HHS / United States
Related Institute: 
Brain Health Imaging Institute (BHII)

Weill Cornell Medicine
Department of Radiology
525 East 68th Street New York, NY 10065