Subclinical but high level of glycemia and platelet activity are associated with decreased structural and functional integrity in Alzheimer’s disease‐sensitive brain regions

Abstract

AbstractBackgroundThere is an increasing research focus on type 2 diabetes (T2D) as a risk factor for Alzheimer’s disease (AD) (Lee, 2018). T2D is a disease characterized notably by hyperglycemia and platelet hyper‐reactivity (Schneider, 2009). However, relatively little is known about subclinical but high levels of glycemia and platelet reactivity in the context of ageing and AD. The aim of this study was to investigate the association between glycemia and platelet level, size and activity (platelet count and mean platelet volume (MPV)) and neuroimaging markers of ageing and AD.Method107 cognitively unimpaired adults (18‐84 years old) from the IMAP+ study (Caen) were included, comprising 23 amyloid‐negative older adults (Aβ‐ controls) and 48 amyloid‐positive patients with mild cognitive impairment or dementia (Aβ+ patients). Participants underwent blood tests to dose glycemic and platelet indices, structural MRI, FDG‐PET and amyloid‐PET assessments. Multiple regressions were performed between blood indices and neuroimaging data and inter‐group comparisons of blood indices were assessed between Aβ+ patients and Aβ‐ controls.ResultCompared to Aβ‐ controls, Aβ+ patients showed no difference in glycemia levels but had lower platelet count and higher MPV. Increased MPV was associated with entorhinal and perirhinal cortex atrophy in Aβ+ patients (fig.B) while platelet count was not associated with any neuroimaging data. High glycemia levels were associated with both atrophy of the right hippocampus and posterior cingulate cortex (PCC) and hypometabolism in the precuneus, cuneus, PCC, angular cortex and medial temporal gyrus in cognitively unimpaired adults (fig.A). None of the blood indices were associated with amyloid‐PET.ConclusionBoth high glycemia and MPV levels were associated with atrophy and/or hypometabolism in AD‐sensitive brain regions, notably the entorhinal cortex, hippocampus and posterior cingulate cortex. These results suggest that subclinical but high levels of glycemia and MPV could be associated with more vulnerability in brain regions sensitive to AD but not at the same stage, while amyloid deposition does not appear to be involved at these stages. Our findings highlight the importance of monitoring these blood indices as risk factors early in the context of AD prevention.