Cognitive impairment in Parkinson disease correlates with loss of cholinergic axon projections to cortex in an autopsy study.

INTRODUCTION

People with Parkinson's disease (PD) frequently develop dementia. We investigated the relationship between cognitive impairment and the loss of cholinergic axon projections from the nucleus basalis of Meynert to neocortical regions in PD.

METHODS

Levels of choline acetyltransferase (ChAT), the enzyme required for acetylcholine synthesis, were measured with a sandwich enzyme-linked immunosorbent assay (ELISA) in eight brain regions from 37 PD autopsy cases. Analyses focused on relationships between measures of global cognitive impairment and average ChAT levels in four neocortical regions.

RESULTS

Mean neocortical ChAT levels positively correlated with the Mini-Mental State Examination and a global cognition z-score obtained by averaging performance in multiple cognitive domains. Mean neocortical ChAT levels also showed a trending inverse correlation with the Clinical Dementia Rating sum of boxes.

DISCUSSION: These results indicate a role for the loss of cholinergic projections to neocortical regions in the development of cognitive impairment in PD.