Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Mar;21(3):e70039.
doi: 10.1002/alz.70039.

Motor symptoms in autopsy-confirmed Alzheimer's disease increase the risk of progression to severe cognitive impairment

Jacob S Shaw  1 , Philip C Huang  1 , Paul B Rosenberg  1 , Matthew E Peters  1
Affiliations

Motor symptoms in autopsy-confirmed Alzheimer's disease increase the risk of progression to severe cognitive impairment

Jacob S Shaw et al. Alzheimers Dement. 2025 Mar.

Abstract

Introduction: Motor symptoms may present throughout the Alzheimer's disease (AD) course. We evaluated the impact of motor symptoms on the risk of progression to severe cognitive impairment, severe neuropsychiatric symptoms (NPSs), and mortality in patients with autopsy-confirmed AD. We also examined the rates of non-AD pathology and identified the predictors of disease progression among these patients.

Methods: Data from the National Alzheimer's Coordinating Center (NACC) were used for this analysis. Participants (N = 1167) were required to have autopsy-confirmed AD.

Results: Motor symptoms were predictive of progression to severe cognitive impairment but not progression to severe NPSs or death. Presenting with gait disturbance and slowness but not falls or tremor was predictive of progression to severe cognitive impairment. Patients with motor symptoms had higher rates of Lewy body disease pathology on autopsy.

Discussion: Our findings suggest that the presence of motor symptoms in autopsy-confirmed AD, particularly gait disturbance and slowness, are predictive of more rapid cognitive decline.

Highlights: Clinician-defined motor symptoms in patients with Alzheimer's disease (AD) predicted more rapid progression to severe cognitive impairment but not to severe neuropsychiatric symptoms (NPSs) or death. Among AD patients with motor symptoms, presenting with gait disturbance and slowness was predictive of progression to severe cognitive impairment, whereas presenting with falls and tremor was not predictive of progression to severe cognitive impairment. Patients with motor symptoms, particularly gait disturbance and slowness, had higher rates of comorbid Lewy body disease pathology.

Keywords: Alzheimer's disease; Lewy body disease; motor symptoms; neuropathology; neuropsychiatric symptoms; parkinsonism.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest. Author disclosures are available in the supporting information.

Figures

FIGURE 1
FIGURE 1
Eligibility criteria for NACC participants included in this analysis (N = 1167). Participants were included if they (1) had moderate or severe Alzheimer's neuropathological change found on autopsy (ABC score >1) and (2) scored ≤1 on the CDR‐Global at the first visit at which they had available motor symptom data. CDR, Clinical Dementia Rating; NACC, National Alzheimer's Coordinating Center.
FIGURE 2
FIGURE 2
Unadjusted Kaplan–Meier plots for progression to severe cognitive impairment, severe NPSs, and death by presenting with any motor symptom. CDR, Clinical Dementia Rating; NPSs, neuropsychiatric symptoms.
FIGURE 3
FIGURE 3
Unadjusted Kaplan–Meier plots for progression to severe cognitive impairment and death by first‐presenting motor symptom and progression to death by CDR‐Global score at first presenting motor symptom visit. CDR, Clinical Dementia Rating.
See this image and copyright information in PMC

References

    1. Feigin VL, Nichols E, GBD 2016 Neurology Collaborators . Global, regional, and national burden of neurological disorders, 1990‐2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019;18(5):459‐480. - PMC - PubMed
    1. Albers MW, Gilmore GC, Kaye J, et al. At the interface of sensory and motor dysfunctions and Alzheimer's disease. Alzheimers Dement. 2015;11(1):70‐98. - PMC - PubMed
    1. Koppelmans V, Silvester B, Duff K. Neural mechanisms of motor dysfunction in mild cognitive impairment and Alzheimer's disease: a systematic review. J Alzheimers Dis Rep. 2022;6(1):307‐344. - PMC - PubMed
    1. Scarmeas N, Hadjigeorgiou GM, Papadimitriou A, et al. Motor signs during the course of Alzheimer disease. Neurology. 2004;63(6):975‐982. - PMC - PubMed
    1. Buchman AS, Bennett DA. Loss of motor function in preclinical Alzheimer's disease. Expert Rev Neurother. 2011;11(5):665‐676. - PMC - PubMed

Grants and funding