Abstract • Cumulative risks of developing extrapyramidal signs, psychosis, and myoclonus in the course of Alzheimer's disease (AD) were estimated in 72 patients with probable AD by the Kaplan-Meier survival method. The cumulative risk functions were found to increase at different rates for different signs as AD progressed. Comparisons of the cumulative risk functions revealed that in the early stages of AD, extrapyramidal signs and psychosis were more likely to develop than myoclonus. As AD progressed, the risk of developing myoclonus became as great as that of developing the other two signs. This study suggests that extrapyramidal signs, psychosis, and myoclonus represent developmental features that mark the progression of AD, rather than indicators of disease subtypes. The estimated cumulative risk functions set a reasonable expectation for the timing and likelihood of the emergence of the clinical signs. This, in turn, might aid in disease prognosis because the biological bases of these signs have been established and they have been shown to be predictive of other markers of disease course. References 1. Mayeux R, Stern Y, Spanton S. Heterogeneity in dementia of the Alzheimer's type: evidence of subgroups . Neurology . 1985;35:453-461.Crossref 2. Kaye JA, May C, Daly E, et al. Cerebral fluid monoamine markers are decreased in dementia of the Alzheimer's type with extrapyramidal features . Neurology . 1988;38:554-557.Crossref 3. Chui HC, Teng EL, Henderson VW, Moy AC. Clinical subtypes of dementia of the Alzheimer type . Neurology . 1985;35:1544-1550.Crossref 4. Drevets WC, Rubin EH. Psychotic symptoms and the longitudinal course of senile dementia of the Alzheimer's type . Biol Psychiatry . 1989;25:38-48.Crossref 5. Wragg RE, Jeste DV. Overview of depression and psychosis in Alzheimer's disease . Am J Psychiatry . 1989;146:577-587. 6. Duffy P, Mayeux R, Kupsky W. Familial Alzheimer's disease with myoclonus and spongy change . Arch Neurol . 1988;45:1097-1103.Crossref 7. Kaye JA, May C, Atack JR, et al. Cerebrospinal fluid neurochemistry in the myoclonic subtype of Alzheimer's disease . Ann Neurol . 1988;24:647-650.Crossref 8. Stern Y, Mayeux R, Sano M, Hauser WA, Bush T. Predictors of disease course in patients with probable Alzheimer's disease . Neurology . 1987;37:1649-1653.Crossref 9. Stern Y, Mayeux R, Hesdorffer D, Sano M. Measurement and prediction of functional capacity in Alzheimer's disease . Neurology . 1990;40:8-14.Crossref 10. Stern Y, Mayeux R, Chen JY, Sano M. Predictors of mortality in Alzheimer's disease . Ann Neurol . 1989;26:132. 11. Kaplan EL, Meier P. Nonparametricestimation from incomplete observations . J Am Stat Assoc . 1958;53:457-481.Crossref 12. Diagnostic and Statistical Manual of Mental Disorders-III-Revised . Washington, DC: American Psychiatric Association; 1986. 13. McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA work group under the auspices of the Department of Health and Human Services Task Force on Alzheimer's disease . Neurology . 1984;34:939-944.Crossref 14. Fahn S, Marsden C, Calne D, et al. Recent Developments in Parkinson's Disease . Florham Park, NJ: Macmillan Healthcare Information; 1987;2:153-163. 15. Sano M, Stern Y, Mayeux R, Hartman S, Devanand DP. A standardized technique for establishing the onset symptoms of probable Alzheimer's disease J Exp Clin Neuropsychol . 1987;9:65. Abstract. 16. Lee E. Statistical Methods for Survival Data Analysis . Belmont, Calif: Lifetime Learning Publications; 1980. 17. SAS User's Guide. Statistics. 5 ed. Cary, NC: SAS Institute Inc; 529-557. 18. Rothman KJ. Modern Epidemiology . Boston, Mass: Little Brown & Co Inc; 1986. 19. Ditter SM, Mirra SS. Neuropathologic and clinical features of Parkinson's disease in Alzheimer's disease patients . Neurology . 1987;37:754-760.Crossref 20. Molsa PK, Marttila RJ, Rinne UK. Extrapyramidal signs in Alzheimer's disease . Neurology . 1984;34:1114-1116.Crossref 21. Pearce J. The extrapyramidal disorder of Alzheimer's disease . Eur Neurol . 1974;12:94-103.Crossref 22. National Institutes of Health Conference. Alzheimer's disease: clinical and biological heterogeneity . Ann Intern Med . 1988;109:298-311.Crossref 23. Breitner JCS, Murphy EA, Silverman JM, Mohs RC, David KL. Age-dependent expression of familial risk in Alzheimer's disease . Am J Epidemiol . 1988;128:536-548. 24. Farrer LA, Myers RH, Cupples LA, et al. Transmission and age-at-onset patterns in familial Alzheimer's disease: evidence for heterogeneity . Neurology . 1990;40:395-403.Crossref
Archives of Neurology – American Medical Association
Published: Nov 1, 1991
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