Differential Cholinergic Pathway Involvement in Alzheimer’s Disease and Subcortical Ischemic Vascular Dementia

Abstract

BACKGROUND: This study aimed to evaluate the relationship between loss of white matter cholinergic pathways, atrophy of the nucleus basalis of Meynert (NBM), and cognitive function in patients with subcortical ischemic vascular dementia (SIVD) or Alzheimer's disease (AD). METHODS: The participants included 26 SIVD, 17 probable AD with or without white-matter changes, and 20 age-matched healthy controls. Thin-section coronal T2-weighted images were acquired using 3.0 T MR. The extent of white matter hyperintensities within cholinergic pathways were assessed using the cholinergic pathways hyperintensities scale (CHIPS). NBM atrophy was assessed from the thickness of the substantia innominata (SI) at the level of the crossing of the anterior commissure. Cognitive impairment was measured using the Mini-Mental State Examination (MMSE) and Clinical Dementia Rating (CDR). Correlations between CHIPSs, SI thickness, and cognitive impairment were evaluated using the Spearman ranked correlation test. RESULTS: In AD, MMSE scores and CDR were correlated with SI thickness (ρ = 0.450, p = 0.006 and ρ = ?0.520, p = 0.030, respectively) but not with CHIPS scores (ρ = ?0.160, p = 0.530 and ρ = 0.270, p = 0.292, respectively). By contrast, aggravated MMSE score and CDR in SIVD had a tendency to correlate with elevated CHIPS scores (ρ = ?0.344, p = 0.127 and ρ = 0.521, p = 0.021, respectively) but not with SI thickness (ρ = ?0.210, p = 0.480 and ρ = 0.080, p = 0.736, respectively). CONCLUSIONS: Loss of cholinergic pathways correlates with cognitive dysfunction in both AD and SIVD. The mechanisms appear to differ: NBM atrophy is likely to be the predominant contributor to cognitive impairments in AD, whereas, the cognitive dysfunction of SIVD was associated with compromised subcortical cholinergic fibers not with nucleus itself.