The association of diabetes with Alzheimer's disease biomarkers and vascular burden across European aging and memory clinic cohorts

Oct 30, 2025Alzheimer's & dementia : the journal of the Alzheimer's Association

Diabetes linked to Alzheimer's markers and blood vessel problems in older Europeans and memory clinic patients

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Abstract

Of the 5550 participants, 8.7% had (DM), which was associated with lower odds of abnormal biomarkers.

DM was linked to reduced odds of abnormal amyloid beta (Aβ) in individuals with mild cognitive impairment (odds ratio [OR] = 0.70) and dementia (OR = 0.44).
In dementia patients, DM was also associated with lower odds of abnormal phosphorylated tau (p-tau181) (OR = 0.64).
Secondary analyses showed that DM was associated with increased odds of total tau (OR = 1.57) and medial temporal atrophy (MTA) (OR = 1.96) in individuals with normal Aβ.
These findings suggest that DM may relate to neurodegenerative processes distinct from Alzheimer's disease.

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INTRODUCTION: It remains unclear whether (DM) is associated with (AD) pathology and associated vascular burden.

METHODS: We included (CN), mild cognitive impairment (MCI), and dementia individuals. We assessed associations between DM and AD biomarkers (amyloid beta [Aβ], phosphorylated tau-181 [p-tau181], total tau [t-tau], and medial temporal atrophy [MTA]) and vascular burden (white matter hyperintensities, microbleeds) by logistic regression. Secondary analyses assessed associations between DM and profiles of Aβ combined with p-tau181/t-tau/MTA/white matter hyperintensity/microbleeds.

RESULTS: We included 5550 participants (65.8+-8.7 years, 8.7% DM). DM was associated with lower odds of abnormal AD biomarkers: Aβ in MCI (odds ratio [OR] = 0.70, 95% confidence interval [CI]: 0.51-0.95, p = 0.02) and dementia (OR = 0.44, 0.26-0.78, p = 0.003), and p-tau181 in dementia (OR = 0.64, 0.41-1.00, p = 0.045). Secondary analyses indicated associations of DM with abnormal t-tau (OR = 1.57, 1.00-2.46, p = 0.048) and MTA (OR = 1.96, 1.05-3.68, p = 0.04) only in CN individuals with normal Aβ.

DISCUSSION: In cognitively impaired individuals, DM was associated with lower odds of Aβ pathology, whereas DM was associated with neurodegeneration markers in CN individuals without Aβ pathology.

HIGHLIGHTS: Diabetes mellitus (DM) was associated with lower odds of amyloid beta (Aβ) and phosphorylated tau (p-tau) pathology across clinical populations. DM was associated with total tau and medial temporal atrophy in cognitively normal individuals without Aβ pathology. DM may be associated with dementia through neurodegenerative pathways other than Alzheimer's disease.

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0.44

Decrease in Odds of Abnormal Aβ in Dementia

Odds ratio for abnormal Aβ in dementia patients with

0.70

Decrease in Odds of Abnormal Aβ in

Odds ratio for abnormal Aβ in patients with

1.57

Increase in Odds of Abnormal in

Odds ratio for abnormal in individuals with

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The association of diabetes with Alzheimer's disease biomarkers and vascular burden across European aging and memory clinic cohorts

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