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Vascular risk factors and the effect of white matter lesions on extrapyramidal signs in Alzheimer's disease

Published online by Cambridge University Press:  29 November 2010

Moon Ho Park*
Clinical Research Center for Dementia (CRCD), Seoul, Republic of Korea Departments of Neurology, Korea University Medical College and Korea University Ansan Hospital, Ansan, Republic of Korea
Joo Young Min
Fiona Clinic Hospital, Seoul, Republic of Korea
Do-Young Kwon
Departments of Neurology, Korea University Medical College and Korea University Ansan Hospital, Ansan, Republic of Korea
Seung Hwan Lee
Department of Neurology, Kangwon National University, Chuncheon, Republic of Korea
Hae Ri Na
Clinical Research Center for Dementia (CRCD), Seoul, Republic of Korea Department of Neurology, Bobath Memorial Hospital, Seongnam, Republic of Korea
Sung Tae Cho
Department of Urology, Hallym University, Seoul, Republic of Korea
Duk L. Na
Clinical Research Center for Dementia (CRCD), Seoul, Republic of Korea Department of Neurology, Sungkyunkwan University School of Medicine and Samsung Medical Center, Seoul, Republic of Korea
Correspondence should be addressed to: Moon Ho Park, MD, PhD, Department of Neurology, Korea University College of Medicine, 516, Gojan-1-dong, Danwon-gu, Ansan-si, Gyeonggi-do 425-707, Republic of Korea. Phone: +82-31-412-5150; Fax:+82-31-412-5154. Email:


Background: Extrapyramidal signs (EPSs), which are important characteristics of Parkinson's disease (PD), occur frequently in Alzheimer's disease (AD). Although AD and PD share common clinical features such as EPSs, these diseases vary with respect to vascular risk factors. The presence of vascular risk factors increases the risk of AD; however, these factors have been known to be inversely associated with PD. We aimed to assess the effect of vascular risk factors and white matter lesions (WMLs) on EPSs in AD.

Methods: We recruited 1,187 AD patients and 333 controls with neither cognitive impairment nor EPSs. All participants underwent detailed clinical evaluations which included assessments of vascular risk factors, cognitive function, and EPSs, as well as WMLs on brain MRIs. EPS subtypes were classified into tremor-dominant, postural instability gait difficulty, or indeterminate; WMLs subtypes were classified into periventricular WML (pvWML) or deep WML (dWML).

Results: EPSs were present in 17.9% of subjects with AD and were significantly associated with vascular risk factors such as age, male gender, diabetes mellitus, and WMLs. Additionally, a multivariate logistic regression analysis showed that EPSs in AD were associated with pvWML (odds ratio (OR), 1.61–2.52), not with dWML. With respect to EPS subtypes, the majority (78.4%) of EPSs in AD were postural instability gait difficulty, which was also associated with WMLs (OR 1.84–2.41), pvWML (OR 2.09–3.14), and dWML (OR 1.83–3.42).

Conclusions: EPSs in AD are associated with selected vascular risk factors as well as WMLs.

Research Article
Copyright © International Psychogeriatric Association 2010

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Baloh, R. W., Ying, S. H. and Jacobson, K. M. (2003). A longitudinal study of gait and balance dysfunction in normal older people. Archives of Neurology, 60, 835839.CrossRefGoogle ScholarPubMed
Burn, D. J. et al. (2003). Extrapyramidal features in Parkinson's disease with and without dementia and dementia with Lewy bodies: a cross-sectional comparative study. Movement Disorders, 18, 884889.CrossRefGoogle ScholarPubMed
Burns, J. M., Galvin, J. E., Roe, C. M., Morris, J. C. and McKeel, D. W. (2005). The pathology of the substantia nigra in Alzheimer disease with extrapyramidal signs. Neurology, 64, 13971403.CrossRefGoogle ScholarPubMed
de la Torre, J. C. (2004). Is Alzheimer's disease a neurodegenerative or a vascular disorder? Data, dogma, and dialectics. Lancet Neurology, 3, 184190.CrossRefGoogle ScholarPubMed
Emre, M. et al. (2007). Clinical diagnostic criteria for dementia associated with Parkinson's disease. Movement Disorders, 22, 16891707; quiz 1837.CrossRefGoogle ScholarPubMed
Fahn, S. and Elton, R. L. (1987). Unified Parkinson's disease rating scale. In Fahn, S., Marsden, C. D., Goldstein, M. and Calne, D. B. (eds.), Recent Developments in Parkinson's Disease (pp. 153163) Florham Park, NJ: Macmillan Healthcare Information.Google Scholar
Gibb, W. R. and Lees, A. J. (1988). The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease. Journal of Neurology, Neurosurgery, and Psychiatry, 51, 745752.CrossRefGoogle Scholar
Hennerici, M. G., Oster, M., Cohen, S., Schwartz, A., Motsch, L. and Daffertshofer, M. (1994). Are gait disturbances and white matter degeneration early indicators of vascular dementia? Dementia, 5, 197202.Google ScholarPubMed
Honig, L. S., Kukull, W. and Mayeux, R. (2005). Atherosclerosis and AD: analysis of data from the US National Alzheimer's Coordinating Center. Neurology, 64, 494500.CrossRefGoogle Scholar
Jacobsson, S. O. and Fowler, C. J. (1999). Dopamine and glutamate neurotoxicity in cultured chick telencephali cells: effects of NMDA antagonists, antioxidants and MAO inhibitors. Neurochemistry International, 34, 4962.CrossRefGoogle ScholarPubMed
Jankovic, J. et al. (1990). Variable expression of Parkinson's disease: a base-line analysis of the DATATOP cohort: the Parkinson Study Group. Neurology, 40, 15291534.CrossRefGoogle ScholarPubMed
Kim, K. W., MacFall, J. R. and Payne, M. E. (2008). Classification of white matter lesions on magnetic resonance imaging in elderly persons. Biological Psychiatry, 64, 273280.CrossRefGoogle ScholarPubMed
Lee, J. M. et al. (2007). Carotid intima-media thickness in Parkinson's disease. Movement Disorders, 22, 24462449.CrossRefGoogle ScholarPubMed
Maggio, R. et al. (1998). Nicotine prevents experimental parkinsonism in rodents and induces striatal increase of neurotrophic factors. Journal of Neurochemistry, 71, 24392446.CrossRefGoogle ScholarPubMed
Mayeux, R., Stern, Y. and Spanton, S. (1985). Heterogeneity in dementia of the Alzheimer type: evidence of subgroups. Neurology, 35, 453461.CrossRefGoogle ScholarPubMed
McKeith, I. G. et al. (1996). Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop. Neurology, 47, 11131124.CrossRefGoogle Scholar
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D. and Stadlan, E. M. (1984). Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology, 34, 939944.CrossRefGoogle ScholarPubMed
Merello, M. et al. (1994). Extrapyramidalism in Alzheimer's disease: prevalence, psychiatric, and neuropsychological correlates. Journal of Neurology, Neurosurgery, and Psychiatry, 57, 15031509.CrossRefGoogle ScholarPubMed
Morris, J. C. (1993). The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology, 43, 24122414.CrossRefGoogle ScholarPubMed
Petersen, R. C. et al. (2001). Current concepts in mild cognitive impairment. Archives of Neurology, 58, 19851992.CrossRefGoogle ScholarPubMed
Piccini, P. et al. (1995). White matter hyperintensities in Parkinson's disease: clinical correlations. Archives of Neurology, 52, 191194.CrossRefGoogle ScholarPubMed
Portet, F., Scarmeas, N., Cosentino, S., Helzner, E. P. and Stern, Y. (2009). Extrapyramidal signs before and after diagnosis of incident Alzheimer disease in a prospective population study. Archives of Neurology, 66, 11201126.CrossRefGoogle Scholar
Scarmeas, N. et al. (2004). Motor signs during the course of Alzheimer disease. Neurology, 63, 975982.CrossRefGoogle ScholarPubMed
Seo, W. K., Lee, J. M., Park, M. H., Park, K. W. and Lee, D. H. (2008). Cerebral microbleeds are independently associated with arterial stiffness in stroke patients. Cerebrovascular Diseases, 26, 618623.CrossRefGoogle ScholarPubMed
Snijders, A. H., van de Warrenburg, B. P., Giladi, N. and Bloem, B. R. (2007). Neurological gait disorders in elderly people: clinical approach and classification. Lancet Neurology, 6, 6374.CrossRefGoogle ScholarPubMed
Stern, Y. et al. (1997). The absence of an apolipoprotein ε4 allele is associated with a more aggressive form of Alzheimer's disease. Annals of Neurology, 41, 615620.CrossRefGoogle ScholarPubMed
Verghese, J., Lipton, R. B., Hall, C. B., Kuslansky, G., Katz, M. J. and Buschke, H. (2002). Abnormality of gait as a predictor of non-Alzheimer's dementia. New England Journal of Medicine, 347, 17611768.CrossRefGoogle ScholarPubMed
Watts, R. L. and Mandir, A. S. (1992). The role of motor cortex in the pathophysiology of voluntary movement deficits associated with parkinsonism. Neurologic Clinics, 10, 451469.CrossRefGoogle ScholarPubMed
Williams-Gray, C. H., Foltynie, T., Brayne, C. E., Robbins, T. W. and Barker, R. A. (2007). Evolution of cognitive dysfunction in an incident Parkinson's disease cohort. Brain, 130, 17871798.CrossRefGoogle Scholar