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

IF 12.8 1区医学 Q1 CLINICAL NEUROLOGY

Alzheimer's & Dementia Pub Date : 2026-10-06 DOI:10.1002/alz.71868

Rebecca Miller, Jennifer O'Shea, Laura M. Rosok, Sydney Lim, Erin E. Franklin, Richard J. Perrin, Helen Hwang, Dhruva Dhavale, Joel Perlmutter, Meghan C. Campbell, Paul Kotzbauer

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Abstract

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.

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帕金森病的认知障碍与胆碱能轴突向皮质的投射丧失有关

帕金森氏症（PD）患者经常发展为痴呆。我们研究了PD患者认知障碍与Meynert基底核向新皮质区域胆碱能轴突投射丢失之间的关系。方法采用夹心酶联免疫吸附法（ELISA）测定37例PD尸检患者脑8个区域的胆碱乙酰转移酶（ChAT）水平，ChAT是合成乙酰胆碱所需的酶。分析的重点是全球认知障碍的测量和四个新皮质区域的平均ChAT水平之间的关系。结果平均新皮质ChAT水平与迷你精神状态检查和通过多个认知领域的平均表现获得的整体认知z得分呈正相关。平均新皮质ChAT水平也与临床痴呆评分的方框总和呈趋势负相关。这些结果表明，新皮质区域胆碱能投射的丧失在PD认知障碍的发展中起作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Alzheimer's & Dementia 医学-临床神经学

CiteScore

14.50

自引率

5.00%

发文量

299

审稿时长

3 months

期刊介绍： Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.