Objective: To test whether the cholinergic dysfunction in Alzheimer’s disease (AD) is a primary event, or a retrograde event secondary to neuronal loss at the cholinergic targets.
Methods: In vivo neuroimaging markers of neural activity using 18F-fluorodeoxyglucose (FDG) were obtained from 13 patients with mild cognitive impairment (MCI), 20 with early AD, and 14 healthy subjects, using high-resolution research tomography and a novel method of spatial normalization based on a subcortical volume-of-interest. The FDG uptake was compared among the groups and correlated with the Mini Mental Status Examination (MMSE) score.
Results: MCI patients showed significantly higher FDG uptake at the basal forebrain than healthy subjects and AD patients, and the uptake showed an inverted-U relationship with MMSE score only in those with high education. Furthermore, cross-voxel analysis over the whole brain revealed a significant correlation between the basal forebrain and the fronto-temporal cortices in MCI patients.
Conclusions: Neuronal activity at the basal forebrain was increased in MCI and decreased only with further cognitive decline. The increase is consistent with a secondary compensation against neurodegeneration at target areas, and may provide cognitive reserve against functional impairments at early stages of the disease.
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