Basal forebrain atrophy and cortical amyloid deposition in nondemented elderly subjects

Abstract

Background: Both neurodegeneration of the cholinergic basal forebrain (BF) and deposition of β-amyloid are early events in the course of Alzheimer's disease (AD). Associations between increased amyloid pathology and cholinergic atrophy have been described in autopsy studies.

Methods: We used structural MRI and AV45-PET amyloid imaging data of 225 cognitively normal or mildly impaired elderly subjects from the Alzheimer's Disease Neuroimaging Initiative to assess in vivo associations between BF atrophy and cortical amyloid deposition. Associations were examined using region-of-interest (ROI) and voxel-based approaches with reference to cytoarchitectonic mappings of the cholinergic BF nuclei.

Results: ROI- and voxel-based approaches yielded complementary evidence for an association between BF volume and cortical amyloid deposition in presymptomatic and predementia stages of AD, irrespective of age, gender, and APOE genotype.

Conclusions: The observed correlations between BF atrophy and cortical amyloid load likely reflect associations between cholinergic degeneration and amyloid pathology as reported in neuropathologic examination studies.

Keywords: AV45-PET; Alzheimer's disease; Amyloid; Cholinergic basal forebrain; Cytoarchitectonic; MRI; Mild cognitive impairment; Nucleus basalis Meynert; Preclinical; Predementia; Substantia innominata; Voxel-based.