Abstract
INTRODUCTION
Diabetes mellitus (DM) is a major risk factor for dementia, yet it remains unclear whether DM accelerates cognitive decline through amyloid beta (Aβ) or tau accumulation in Alzheimer’s disease (AD).
METHODS
In this study, we included 2784 participants from three independent observational cohorts: the Chinese Preclinical Alzheimer’s Disease Study (CPAS), the Alzheimer’s Disease Neuroimaging Initiative (ADNI), and Health and Aging Brain Study–Health Disparities (HABS-HD). We examined the associations of DM with Aβ positron emission tomography (PET), tau PET, plasma phosphorylated tau (p-tau)217, and longitudinal cognitive change. We also tested whether DM modified the associations of Aβ and plasma p-tau217 with subsequent tau accumulation and explored the association of metformin use with tau accumulation.
RESULTS
We found that DM was associated with lower global Aβ burden and lower tau accumulation in CPAS and ADNI, in which cognitive impairment was more common than in HABS-HD. The associations of Aβ and plasma p-tau217 with tau accumulation were weaker among individuals with DM. In addition, DM was associated with reduced propagation of tau from early to later stage Braak regions. Longitudinal analyses in ADNI indicated that individuals with DM exhibited slower tau-related cognitive decline. In exploratory analyses, metformin use among individuals with DM was associated with lower tau accumulation compared to individuals without DM.
DISCUSSION
These findings suggest that DM is associated with an attenuation of amyloid- and tau-related processes, particularly in participants with cognitive impairment, and further suggest that diabetes-related mechanisms and its management may modulate the progression of AD pathology.
If you do not see content above, kindly GO TO SOURCE.
Not all publishers encode content in a way that enables republishing at Neuro.vip.
This post is Copyright: | November 11, 2026
Neuro-Dementia