Pattern of extrapyramidal signs in Alzheimer's disease.
Patients with Alzheimer's disease (AD) often develop extrapyramidal signs (EPS), which increase in frequency as the disease progresses. We aimed to investigate the patterns of presentation of EPS in AD and their correlation with clinical and neuropathological features. 4284 subjects diagnosed with AD from the National Alzheimer's Coordinating Center (NACC) database with at least one abnormal Unified Parkinson's Disease Rating Scale (UPDRS) assessment were included. Individuals were assigned to a discovery sample and a sensitivity analysis sample (moderate and mild dementia, respectively) and a subset of subjects provided neuropathological data (n = 284). Individuals from the Washington Heights and Inwood Columbia Aging Project (WHICAP) served as validation sample. Patterns of presentation of EPS were identified employing categorical principal component analysis (CATPCA). Six principal components were identified in both mild and moderate AD samples: (I) hand movements, alternating movements, finger tapping, leg agility ("limbs bradykinesia"); (II) posture, postural instability, arising from chair, gait and body bradykinesia/hypokinesia ("axial"); (III) limb rigidity ("rigidity"); (IV) postural tremor; (V) resting tremor; (VI) speech and facial expression. Similar results were obtained in the WHICAP cohort. Individuals with hallucinations, apathy, aberrant night behaviors and more severe dementia showed higher axial and limb bradykinesia scores. "Limb bradykinesia" component was associated with a neuropathological diagnosis of Lewy body disease and "axial" component with reduced AD-type pathology. Patterns of EPS in AD show distinct clinical and neuropathological correlates; they share a pattern of presentation similar to that seen in Parkinson's disease, suggesting common pathogenic mechanisms across neurodegenerative diseases.
The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA.|Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Giuseppe
G
Tosto
National Alzheimer's Coordinating Center, University of Washington, Seattle, USA.
Sarah E
SE
Monsell
National Alzheimer's Coordinating Center, University of Washington, Seattle, USA.|Department of Epidemiology, University of Washington, Seattle, USA.
Stephen E
SE
Hawes
The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA. rpm2@cumc.columbia.edu.|Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA. rpm2@cumc.columbia.edu.|Department of Neurology, College of Physicians and Surgeons, Columbia University and the New York Presbyterian Hospital, New York, NY, USA. rpm2@cumc.columbia.edu.|, 630 W. 168th St., P&S Box 16, New York, NY, 10032, USA. rpm2@cumc.columbia.edu.
Richard
R
Mayeux
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000503:physiopathology*; D001480:Basal Ganglia Diseases / Q000209:etiology / Q000503:physiopathology*; D005149:Facial Expression; D005260:Female; D020233:Gait Disorders, Neurologic / Q000209:etiology; D006801:Humans; D018476:Hypokinesia / Q000209:etiology; D020961:Lewy Body Disease / Q000150:complications / Q000503:physiopathology*; D008297:Male; D009127:Muscle Rigidity / Q000209:etiology; D004856:Postural Balance / Q000502:physiology; D012720:Severity of Illness Index; D013064:Speech Disorders / Q000209:etiology; D014202:Tremor / Q000209:etiology
Alzheimer’s disease; CATPCA; Extrapyramidal signs; Lewy bodies