Affiliations: [a] The Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University, New York, NY, USA
| [b] Sergievsky Center, College of Physiciansand Surgeons, Columbia University New York, NY, USA
| [c] Department of Neurology, College of Physiciansand Surgeons, Columbia University and the New York, Presbyterian Hospital, New York, NY, USA
| [d] National Alzheimer’s Coordinating Center, University of Washington, WA, USA
| [e] Department of Epidemiology, University of Washington, WA, USA
| [f] Department of Neurology and Psychiatry, University “Sapienza”, Rome, Italy
Correspondence:
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Correspondence to: Richard Mayeux, MD, MSc, 630 W. 168th St., P&S Box 16, New York, NY 10032, USA. Tel.: +1 212 305 2391; Fax: +1 212 305 2518; E-mail: [email protected]
Abstract: Background:Extrapyramidal signs (EPS) are frequent in Alzheimer’s disease (AD) and core manifestation of related diseases, i.e., dementia with Lewy bodies and Parkinson’s disease; furthermore, Lewy bodies and AD-type pathology occur in all three conditions. Objective:To identify clusters of EPS progression over time and their clinical and neuropathological correlates. Methods:3,502 AD patients with longitudinal assessment from the National Alzheimer’s Coordinating Center database were included; 394 provided neuropathological data. k-means algorithm was employed to identify clusters of EPS progression and those were compared in terms of cognitive profile, neuropsychiatric features and neuropathological findings. Results:Three clusters of EPS progression were identified: no/low (n = 1,583), medium (n = 1,259), and high (n = 660) EPS burden. Compared to those with no/low and medium EPS, those with high EPS had greater cognitive and neuropsychiatric impairment, specifically hallucinations. Despite similar AD-pathology across the three clusters, the high EPS cluster had a significantly number of subjects diagnosed with dementia with Lewy bodies. Conclusions:Cluster analysis of EPS progression over time identified different subgroups of AD patients with distinct clinical and neuropathological features.
