Hemodynamic effects of cholinesterase inhibition in mild Alzheimer's disease

To evaluate the spatiotemporal progression of perfusion changes in early stages of Alzheimer's disease (AD), we imaged the perfusion response to pharmacological treatment in a group of mild AD patients and contrasted it to the perfusion of age-, sex-, and education-matched healthy volunteers over the same time interval.

We used pseudo continuous arterial spin labeling (PCASL) MRI for quantitative three-dimensional mapping of perfusion immediately before and 6 months after cholinesterase inhibitor treatment.

Before treatment, patients were found hypoperfused relative to their healthy counterparts in the gray matter of lateral temporal lobe, posterior cingulate, and anterior cingulate as well as in the white matter of the posterior cingulate. Most of the cortical regions investigated and the white matter of posterior cingulate and prefrontal regions showed treatment-elicited increases in perfusion, which were not secondary to changes in regional tissue volume nor were they associated with improvement in either MMSE or ADAS-Cog scores, although lack of deterioration suggested a cognitive benefit.

This study provides a hemodynamic profile of mild AD and sheds light on the perfusion changes related to prolonged cholinesterase inhibition in this early disease stage.