Is diabetes associated with increased pathological burden in Alzheimer's disease?

Alzheimers Dement (Amst). 2021 Nov 10;13(1):e12248. doi: 10.1002/dad2.12248. eCollection 2021.

Abstract

Introduction: We examined the association between Alzheimer's disease (AD) and type 2 diabetes mellitus (DM) and hypothesized that diabetes is associated with an increased pathological burden in clinically and pathologically diagnosed AD.

Methods: All data were obtained from the Uniform Data Set (UDS) v3, the Neuropathology Data Set, and the Researcher's Data Dictionary-Genetic Data from the National Alzheimer's Coordinating Center. The dataset (37 cases with diabetes and 1158 cases without) relies on autopsy-confirmed data in clinically diagnosed AD patients who were assessed for diabetes type in form A5 or D2 during at least one visit. Differences in scores were explored using a general linear model. Effect sizes were calculated using sample means and standard deviations (Cohen's d).

Results: The presence of diabetes was associated with a lower Thal phase of amyloid plaques (A score; 4.6 ± 0.79 vs. 4.3 ± 0.85, P < .05) and lower Braak stage for neurofibrillary degeneration (B score; 5.58 ± 0.72 vs. 5.16 ± 0.96, P < 0.05) but not for density of neocortical neuritic plaques (CERAD score-C score). The National Institute on Aging-Alzheimer's Association Alzheimer's disease neuropathologic change (ABC score) was not different between AD+DM and AD-DM.

Discussion: This pilot study found a significantly lower Thal phase of amyloid plaques and Braak stage for neurofibrillary degeneration in AD-confirmed individuals with diabetes compared to those without. Thus type 2 DM is not associated with increased AD pathology in clinically and pathologically confirmed cases of AD.

Keywords: Alzheimer's disease; Alzheimer's disease neuropathologic change (ABC score); Braak neurofibrillary stage (B score); Thal phase (A score); neuritic plaque score (C score); type 2 diabetes mellitus.

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