Objective: We correlated severity of dementia in Alzheimer's disease with the degree of neuropathology in cortical and subcortical brain regions.

Methods: In 13 patients with Alzheimer's disease who underwent neuropsychological testing before death, we assessed neurofibrillary tangles, senile plaques, and neuronal and synaptic density in the midfrontal cortex and the nucleus basalis of Meynert.

Results: In the midfrontal cortex, synapse density was the strongest correlate of dementia severity, followed by neurofibrillary tangles. In the nucleus basalis, by contrast, neurofibrillary tangles were the strongest correlate, followed by synapse density. Stepwise regression analyses showed midfrontal synapse density to be the strongest predictor of tests emphasizing higher cortical functions, but neurofibrillary tangles in the nucleus basalis were the strongest predictor on memory-oriented tests.

Conclusions: The specificity of pathology in cortical vs subcortical locations for predicting a particular quality of neuropsychological deficit probably reflects disruption of corticocortical connections vs derangement of the basal forebrain cholinergic system.

• AG05131/AG/NIA NIH HHS/United States
• AG08201/AG/NIA NIH HHS/United States
• AG08205/AG/NIA NIH HHS/United States