Plasma Oligomeric Amyloid‐β partially mediates the effects of Diabetes Mellitus on Cognition in Mild Cognitive Impairment

Abstract

AbstractBackgroundOligomeric amyloid‐beta (OAβ) is postulated to be the major neurotoxic species that is implicated in the pathophysiology of Alzheimer’s disease (AD). Emerging evidence suggest that plasma OAβ levels are higher in AD compared to cognitively unimpaired individuals and correlate well with AD biomarkers. Diabetes Mellitus (DM) is consistently linked to cognitive dysfunction and epidemiological studies show that patients with DM have an increased risk of AD. While cerebral amyloid deposition is hypothesized to be the link between AD and DM, the association of OAβ and DM on cognition among mild cognitive impairment (MCI) remains unknown. Here, we aim to evaluate the effects of plasma OAβ levels and DM on cognition among MCI patients from a memory clinic in Singapore.MethodIn this retrospective cross‐sectional study, 54 MCI patients (mean age 68.31, 44.4% males) stratified by DM diagnosis, underwent cognitive assessment and plasma OAβ measurements using the Multimer Detection System‐Oligomeric Aβ (MDS‐OAβ) in National Neuroscience Institute Singapore between 2019 to 2021. Multiple linear regression models evaluated the main effects of OAβ and DM on cognition while mediation analysis evaluated the effect of DM on cognition mediated via OAβ. All analyses were controlled for age, sex, education.Result13 (24.1%) of the total MCI cohort had DM and OAβ levels were higher in DM patients (0.68 vs 0.53 ng/ml, p=0.023).OAβ levels were associated with lower MMSE scores (β= ‐4.08, p=0.004) while DM was associated with lower MMSE (β = ‐1.26, p=0.046) and MoCA (β = ‐1.83, p=0.025) scores. Plasma OAβ partially mediates the effect of DM on MoCA scores (Figure 1).ConclusionThe effect of DM on poorer global cognition is partially mediated by higher plasma OAβ levels. While these results need to be replicated in a larger cohort, our findings suggest that optimizing DM control among MCI may reduce the burden of OAβ and improve cognition.