Diabetes accelerates Alzheimer's disease progression in the first year post mild cognitive impairment diagnosis

Abstract

Background: Mild cognitive impairment (MCI) heightens Alzheimer's disease (AD) risk, with diabetes mellitus (DM) potentially exacerbating this vulnerability. This study identifies the optimal intervention period and neurobiological targets in MCI to AD progression using the Alzheimer's Disease Neuroimaging Initiative dataset.

Methods: Analysis of 980 MCI patients, categorized by DM status, used propensity score matching and inverse probability treatment weighting to assess rate of conversion from MCI to AD, neuroimaging, and cognitive changes.

Results: DM significantly correlates with cognitive decline and an increased risk of progressing to AD, especially within the first year of MCI follow-up. It adversely affects specific brain structures, notably accelerating nucleus accumbens atrophy, decreasing gray matter volume and sulcal depth.

Discussion: Findings suggest the first year after MCI diagnosis as the critical window for intervention. DM accelerates MCI-to-AD progression, targeting specific brain areas, underscoring the need for early therapeutic intervention.

Highlights: Diabetes mellitus (DM) accelerates mild cognitive impairment (MCI)-to-Alzheimer's disease (AD) progression within the first year after MCI diagnosis. DM leads to sharper cognitive decline within 12 months of follow-up. There is notable nucleus accumbens atrophy observed in MCI patients with DM. DM causes significant reductions in gray matter volume and sulcal depth. There are stronger correlations between cognitive decline and brain changes due to DM.

Keywords: Alzheimer's disease; diabetes mellitus; mild cognitive impairment; nucleus accumbens.

FIGURE 1

Flow chart of the study. AD, Alzheimer's disease; DM, diabetes mellitus; MCI, mild cognitive impairment.

FIGURE 2

Kaplan–Meier curves depicting MCI to AD conversion and comparison of AD proportions at 12‐month follow‐up between patients with and without DM. AD, Alzheimer's disease; DM, diabetes mellitus; MCI, mild cognitive impairment.

FIGURE 3

Morphological analysis of subcortical nuclei in patients with and without diabetes mellitus: left nucleus accumbens at baseline (A) and 12‐month follow‐up (B), and right nucleus accumbens at 12‐month follow‐up (C).

FIGURE 4

Voxel‐based morphometry analysis of gray matter volume from group (A) and time effects (B). DM, diabetes mellitus; FDR, false discovery rate.

FIGURE 5

Patients with DM showed a significant decrease in sulcal depth compared to those without DM during the 12‐month follow‐up (FDR corrected, P < 0.05; A). Meanwhile, there were significant differences regarding the sulcal depth (A), gyrification index (B), and cortical thickness (C) in time effect during the 12‐month follow‐up (FDR corrected, all P < 0.05).

FIGURE 6

Correlation between brain structures and cognitive function changes in patients with DM (A) and without DM (B). (* represents P < 0.05). ADASQ4, score from task 4 of the Alzheimer's Disease Assessment Scale; DM, diabetes mellitus; EcogPtPlan, Participant‐reported Everyday Cognition Scale Plan; EcogSPOrgan, Study Partner‐reported Everyday Cognition Scale Organ; FAQ, Functional Assessment Questionnaire; MOCA, Montreal Cognitive Assessment; RAVLT‐immediate, Rey's Auditory Verbal Learning Test immediate recall.