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From the Cognitive Neuroscience Division of the Taub Institute for Research in Alzheimer’s Disease and the Aging Brain (Drs. Scarmeas, Wegesin, and Stern), the Gertrude H. Sergievsky Center (Drs. Scarmeas, Marder, Bell, Honig, and Stern) and the Department of Neurology (Drs. Scarmeas, Marder, Bell, Honig, and Stern), Columbia University Medical Center, New York, NY; the Department of Psychiatry and Behavioral Sciences (Drs. Albert and Brandt), Johns Hopkins University, Baltimore, MD; the Department of Psychiatry (Dr. Blacker), Massachusetts General Hospital, Harvard Medical School, Boston; the Department of Neurology (Drs. Hadjigeorgiou and Papadimitriou), University of Thessaly, Larissa, Greece; and the Department of Neurology (Drs. Dubois and Sarazin), Hospital de la Salpetriere, Paris, France.
Address correspondence and reprint requests to Dr. Nikolaos Scarmeas, Columbia University Medical Center, 622 West 168th street, PH 19th floor, New York, NY 10032; e-mail: ns257{at}columbia.edu
Objective: To examine whether the presence of motor signs has predictive value for important outcomes in Alzheimer disease (AD).
Methods: A total of 533 patients with AD at early stages (mean Folstein Mini-Mental State Examination [MMSE] 21/30 at entry) were recruited and followed semiannually for up to 13.1 years (mean 3) in five University-based AD centers in the United States and European Union. Four outcomes, assessed every 6 months, were used in Cox models: cognitive endpoint (Columbia Mini-Mental State Examination 
20/57 [~MMSE 10/30]), functional endpoint (Blessed Dementia Rating Scale 
10), institutionalization equivalent index, and death. Using a standardized portion of the Unified PD Rating Scale (administered every 6 months for a total of 3,149 visit-assessments, average 5.9 per patient), the presence of motor signs, as well as of individual motor sign domains, was examined as time-dependent predictor. The models controlled for cohort, recruitment center, sex, age, education, a comorbidity index, and baseline cognitive and functional performance.
Results: A total of 39% of the patients reached the cognitive, 41% the functional, 54% the institutionalization, and 47% the mortality endpoint. Motor signs were noted for 14% of patients at baseline and for 45% at any evaluation. Their presence was associated with increased risk for cognitive decline (RR, 1.72; 95% CI, 1.24 to 2.38), functional decline (1.80 [1.33 to 2.45]), institutionalization (1.68 [1.26 to 2.25]), and death (1.38 [1.05 to 1.82]). Tremor was associated with increased risk for reaching the cognitive and bradykinesia for reaching the functional endpoints. Postural-gait abnormalities carried increased risk for institutionalization and mortality. Faster rates of motor sign accumulation were associated with increased risk for all outcomes.
Conclusions: Motor signs predict cognitive and functional decline, institutionalization, and mortality in Alzheimer disease. Different motor sign domains predict different outcomes.
Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the May 24 issue to find the title link for this article.
Supported by Federal grants AG07370, RR00645, P50-AG 08702, and the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain.
Received October 19, 2004. Accepted in final form January 31, 2005.
This article has been cited by other articles:
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  E. P. Helzner, N. Scarmeas, S. Cosentino, F. Portet, and Y. Stern Leisure Activity and Cognitive Decline in Incident Alzheimer Disease Arch Neurol, December 1, 2007; 64(12): 1749 - 1754. [Abstract] [Full Text] [PDF]
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N. Scarmeas, J. Brandt, D. Blacker, M. Albert, G. Hadjigeorgiou, B. Dubois, D. Devanand, L. Honig, and Y. Stern Disruptive Behavior as a Predictor in Alzheimer Disease Arch Neurol, December 1, 2007; 64(12): 1755 - 1761. [Abstract] [Full Text] [PDF]
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 N. Scarmeas, J. A. Luchsinger, R. Mayeux, and Y. Stern Mediterranean diet and Alzheimer disease mortality Neurology, September 11, 2007; 69(11): 1084 - 1093. [Abstract] [Full Text] [PDF]
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 A. S. Buchman, P. A. Boyle, R. S. Wilson, Y. Tang, and D. A. Bennett Frailty is Associated With Incident Alzheimer's Disease and Cognitive Decline in the Elderly Psychosom Med, June 1, 2007; 69(5): 483 - 489. [Abstract] [Full Text] [PDF]
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N. Scarmeas, Y. Stern, R. Mayeux, and J. A. Luchsinger Mediterranean Diet, Alzheimer Disease, and Vascular Mediation Arch Neurol, December 1, 2006; 63(12): 1709 - 1717. [Abstract] [Full Text] [PDF]
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K. Stavitsky, A. M. Brickman, N. Scarmeas, R. L. Torgan, M.-X. Tang, M. Albert, J. Brandt, D. Blacker, and Y. Stern The progression of cognition, psychiatric symptoms, and functional abilities in dementia with lewy bodies and Alzheimer disease. Arch Neurol, October 1, 2006; 63(10): 1450 - 1456. [Abstract] [Full Text] [PDF]
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C. W. Zhu, N. Scarmeas, R. Torgan, M. Albert, J. Brandt, D. Blacker, M. Sano, and Y. Stern Longitudinal study of effects of patient characteristics on direct costs in Alzheimer disease Neurology, September 26, 2006; 67(6): 998 - 1005. [Abstract] [Full Text] [PDF]
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C. W. Zhu, N. Scarmeas, R. Torgan, M. Albert, J. Brandt, D. Blacker, M. Sano, and Y. Stern Clinical features associated with costs in early AD: Baseline data from the Predictors Study Neurology, April 11, 2006; 66(7): 1021 - 1028. [Abstract] [Full Text] [PDF]
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