Relationship between amyloid burden, cholinergic integrity, and cognitive function

BackgroundAmyloid accumulation and degeneration of the cholinergic white matter pathways are key factors in early Alzheimer's disease pathogenesis and progression. However, the relationship between them remains unclear.ObjectiveTo investigate the association between amyloid accumulation, the integrity of cholinergic white matter pathways, and cognitive performance.MethodsThis cross-sectional study recruited 109 individuals, including 37 controls with normal cognition and 72 patients with early Alzheimer's disease. All participants underwent neuropsychological testing: the Mini-Mental Status Examination (MMSE), Clinical Dementia Rating scale with sum of box (CDR-SB), and verbal fluency tests. Cholinergic white matter integrity and amyloid burden were assessed through diffusion tensor imaging study (DTI) and amyloid positron emission tomography (PET). Stepwise linear regression analyses were performed. Partial correlations between amyloid burden and cholinergic integrity were also evaluated according to apolipoprotein E4 (APOE4) carrier status.ResultsAcross all participants, amyloid burden and cholinergic integrity were independently associated with all cognitive performances. In subgroup analysis, amyloid burden was associated with MMSE only in the early Alzheimer's disease group (p = 0.012). Cholinergic integrity was significantly associated with all cognitive performances in the early Alzheimer's disease group (p < 0.05) but not in the control group. Amyloid burden remained significantly correlated with cholinergic integrity only in APOE4 noncarriers (p < 0.05) but not in APOE4 carriers.ConclusionsCholinergic white matter integrity, the severity of which is associated with amyloid burden, may be a specific imaging marker in early-stage Alzheimer's disease. In this study, this phenomenon was more pronounced in APOE4 noncarriers.