Abstract
Objectives: To determine the prevalence and clinical correlates of extrapyramidal signs (EPS) in outpatients with probable Alzheimer's disease (AD); to examine the appearance of EPS in association with the first symptom that led the patient or family to ask for medical help; to examine the association of the prevalence of EPS with gender, age at onset of the disease, duration of the disease, severity of dementia, functional disability, and potential use of neuroleptics; and to address the issue of the possible role of EPS as a predictive factor for the clinical course of the disease.
Patients and methods: We examined 126 patients meeting NINCDS-ADRDA* criteria for probable AD and 29 healthy, nondementia controls of comparable age and gender. Thirteen of the patients taking neuroleptics at the time of the examination were excluded from the main study group and formed a separate subgroup of AD/neuroleptics-positive. Twenty-eight of the AD/neuroleptics-free patients were re-examined during an 18-month period in order to determine the possible role of EPS as a predictive factor of the clinical course of the disease.
Results: Only 8 percent of the AD/neuroleptics-free patients were free of EPS, while the corresponding percentage in the control group was 61.5 percent. The most common types of EPS presented in the patient group were hypomimia ([facial mask] 60 percent), difficulty in talking (53.66 percent), bradykinesia (51.4 percent), postural instability (47.33 percent), abnormal gait (34.66), and rigidity (26 percent), respectively. No significant differences were found when examining for the presence of resting tremor, other tremors, dystonias, and dyskinesias. With regard to the presence of EPS and the first symptom, no significant difference was found among patients whose first complaint was memory disorder (probable AD) and patients with other symptoms. When examining the association between the prevalence of EPS and gender or age at onset of the disease, no special correlation was detected. However, such a correlation was found between the prevalence of EPS and duration of the disease, as indicated by the fact that EPS appear in 78.9 percent of the patients with a duration of illness less than two years, but in 97 percent of the patients with a corresponding duration of two years or more. The mean duration of the disease in patients appearing with EPS is found to be 2.68 ± 1.98 years. The presence of EPS increases proportionally with the progression of the disease and cognitive and functional decline. Patients with poor results in the MMSE (score of less than 11) appear to present EPS at a greater percentage than those with better performance on the examination (MMSE scores greater than 11). With regard to the association between EPS and functional ability in AD, it seems that the presence of EPS imposes difficulties in daily activities, as seen by the fact that patients with EPS have lower FRSSD scores (mean ± SD: 14.87 ± 10.53) than patients without EPS (5 ± 2.58). After controlling for duration of the disease, the use of neuroleptics is found to influence the appearance of EPS in patients with AD. Almost all of the patients AD/neuroleptics-positive patients presented EPS (100 percent), while 92 percent of the AD/neuroleptics-free patients manifested such symptoms.
Finally, we re-evaluated 28 patients, who were part of the initial AD/neuroleptics-free group, in order to determine whether the appearance of EPS could have prognostic value for the clinical course of the disease. Patients who presented EPS at initial examination appeared to deteriorate faster, mainly cognitively, but also functionally. The mean decrease in MMSE scores in patients with EPS was found to be 2.65 ± 3.46; while in patients without EPS at initial visit, MMSE scores were 0.63 ± 3.88. The functional decline seems to be less influenced by the presence of EPS. The corresponding mean decrease in FRSSD scores of the two groups was 2.1 ± 5.55 and 1.8 ± 2.1, respectively.
Keywords: Alzheimer's disease (AD), extrapyramidal signs (EPS), neuroleptics
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National Institute of Neurological and Communicative Disorders and Stroke—Alzheimer Disease and Related Disorders Association.
References
- Pearce J : The extrapyramidal disorder of Alzheimer's disease. Eur Neurol. 1974; 12: 94-103. [DOI] [PubMed] [Google Scholar]
- Molsa PK , Martilla RJ, Rinne UK: Extrapyramidal signs in Alzheimer's disease. Neurology. 1984; 34: 1114-1116. [DOI] [PubMed] [Google Scholar]
- McKhann G , Drachman D, Folstein M, et al.: 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. 1984; 34: 939-944. [DOI] [PubMed] [Google Scholar]
- Chui HC , Teng EL, Henderson VW, Moy AC: Clinical subtypes of dementia of the Alzheimer type. Neurology. 1985; 35: 1544-1550. [DOI] [PubMed] [Google Scholar]
- Mayeux R , Stern Y, Spanton S: Heterogeneity in dementia of the Alzheimer type: Evidence of subgroups. Neurology. 1985; 35: 453-461. [DOI] [PubMed] [Google Scholar]
- Stern Y , Mayeux R, Sano M, et al.: Predictors of disease course in patients with probable Alzheimer's disease. Neurology. 1987; 37: 1649-1653. [DOI] [PubMed] [Google Scholar]
- Stern Y , Mayeux R, Chen JY: Predictors of mortality in Alzheimer's disease. Ann Neurol. 1989; 26: 132-132. [Google Scholar]
- Hansen L , Salmon D, Galasko D, et al.: The Lewy body variant of Alzheimer's disease: A clinical and pathologic entity. Neurology. 1990; 40: 1-8. [DOI] [PubMed] [Google Scholar]
- Drachman DA , O'Donnell BF, Lew RA, Swearer JM: The prognosis in Alzheimer's disease: “How far” rather than “how fast” best predicts the course. Arch Neur. 1990; 47: 851-856. [DOI] [PubMed] [Google Scholar]
- Morris JC , Drazner M, Fulling K, et al.: Clinical and pathologic aspects of Parkinsonism in Alzheimer's disease: A role for extranigral factors? Arch Neurol. 1989; 46: 651-657. [DOI] [PubMed] [Google Scholar]
- Girling MD , Berrios GE: Extrapyramidal signs, primitive reflexes and frontal lobe function in senile dementia of Alzheimer's type. Brit J Psychiatry. 1990; 157: 888-893. [DOI] [PubMed] [Google Scholar]
- Huff FJ , Belle SH, Shim YK, et al.: Prevalence and prognostic value of neurologic abnormalities in Alzheimer's disease. Dementia. 1990; 1: 32-40. [Google Scholar]
- Richards M , Marde PK, Bell K, et al.: Interrater reliability of extrapyramidal signs in a group assessed for dementia. Arch Neurol. 1991; 48: 1147-1149. [DOI] [PubMed] [Google Scholar]
- Miller TP , Tinklenberg J, Brooks JE, Yesavage JA: Cognitive decline in patients with Alzheimer disease: Differences in patients with and without extrapyramidal signs. Alzheimer Dis Assoc Disord. 1991; 5: 251-256. [DOI] [PubMed] [Google Scholar]
- Mortimer J , Ebbitt B, Jun S, Finch MD: Predictors of cognitive and functional progression in patients with probable Alzheimer's disease. Neurology. 1992; 42:1690-1696. [DOI] [PubMed] [Google Scholar]
- Soininen H , Lauluman V, Helkala EL, et al.: Extrapyramidal signs in Alzheimer's disease: A 3-year follow-up study. J Neyral Transm(P-D sect). 1992; 4:107-119. [DOI] [PubMed] [Google Scholar]
- McKeith G , Perry RH, Fairbairn A, et al.: Operational criteria for senile dementia of Lewy body type. Psycol Med J. 1992; 22: 911-922. [DOI] [PubMed] [Google Scholar]
- Stern Y , Folstein M, Albert M, et al.: Multicenter study of predictors of disease course in Alzheimer disease (“the predictors study”): I. Study design, cohort description, and intersite comparison. Alzheimer Dis Assoc Disord. 1993; 7: 3-21. [DOI] [PubMed] [Google Scholar]
- Richards M , Folstein M, Albert M, et al.: Multicenter study of predictors of disease course in Alzheimer disease (“the predictors study”): II. Neurological, psychiatric and demographic influences on baseline measures of disease severity. Alzheimer Dis Assoc Disord. 1993; 7: 22-32. [DOI] [PubMed] [Google Scholar]
- Forstl H , Burns A, Luthert P, et al.: The Lewy body variant of Alzheimer's disease: Clinical and pathologic findings. Brit J Psychiatry. 1993; 162: 385-392. [DOI] [PubMed] [Google Scholar]
- Richards M , Stern Y, Mayeux R: Subtle extrapyramidal signs can predict the development of dementia in elderly individuals. Neurology. 1993; 43: 2184-2188. [DOI] [PubMed] [Google Scholar]
- Corey-Bloom J , Galasko D, Hofstetter CR, et al.: Clinical features distinguishing large cohorts with possible AD, probable AD and mixed dementia. J Am Geriatr Soc. 1993; 41: 31-37. [DOI] [PubMed] [Google Scholar]
- Richards M , Bell K, Dooneiet G, et al.: Patterns of neuropsychological performance in Alzheimer's disease patients with and without extrapyramidal signs. Neurology. 1993; 43: 1708-1710. [DOI] [PubMed] [Google Scholar]
- Funkenstein H , Albert MS, Cook NR, et al.: Extrapyramidal signs and other neurologic findings in clinically diagnosed Alzheimer's disease. Arch Neur. 1993; 50: 51-56. [DOI] [PubMed] [Google Scholar]
- Chui HC , Lyness SA, Sobel E, Shneidei LS: Extrapyramidal signs and psychiatric symptoms predict faster cognitive decline in Alzheimer's disease. Arch Neurol. 1994; 51: 676-681. [DOI] [PubMed] [Google Scholar]
- Merello M , Sabe L, Teson A, et al.: Extrapyramidalism in Alzheimer's disease: Prevalence, psychiatric and neuropsychological correlates. J Neurology, Neurosurgery & Psychiatry. 1994; 57: 1503-1509. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kraemer HC , Tinklenberg J, Yesavage JA: How far vs. how fast in Alzheimer's disease: The question revisited. Arch Neurol. 1994; 51: 275-279. [DOI] [PubMed] [Google Scholar]
- Stern Y , Albert M, Brant J, et al.: Utility of extapyramidal signs and psychosis as predictors of cognitive and functional decline, nursing home admission and death in Alzheimer's disease: Prospective analyses from the predictors study. Neurology. 1994; 44: 2300-2307. [DOI] [PubMed] [Google Scholar]
- Stern Y , Liu X, Albert M, et al.: Modeling the influence of extrapyramidal signs on the progression of Alzheimer's disease. Arch Neurol. 1996; 53: 1121-1125. [DOI] [PubMed] [Google Scholar]
- Ellis RJ , Caligiuri M, Galasko D, Thal LJ: Extrapyramidal motor signs in clinically diagnosed Alzheimer's disease. Alzheimer Dis Assoc Disord. 1996; 10: 103-114. [DOI] [PubMed] [Google Scholar]
- Mega MS , Masterman DL, Benson DF, et al.: Dementia with Lewy bodies: Reliability and validity of clinical and pathologic criteria. Neurology. 1996; 47: 1403-1409. [DOI] [PubMed] [Google Scholar]
- Clarc CU , Ewbank D, Lerner A, et al.(the CERAD collaborators): The relationship between extrapyramidal signs and cognitive performance in patients with Alzheimer's disease enrolled in the CERAD study. Neurology. 1997; 49: 70-75. [DOI] [PubMed] [Google Scholar]
- Ballard C , McKeith I, Burn D, et al.: The UPDRS scale as a means of identifying extrapyramidal signs in patients suffering from dementia with Lewy bodies. Acta Neurol Scand. 1997; 96: 366-371. [DOI] [PubMed] [Google Scholar]
- Lopez OL , Wisnieski SR, Becker JT, et al.: Extrapyramidal signs in patients with probable Alzheimer's disease. Arch Neurol. 1997; 54: 969-975. [DOI] [PubMed] [Google Scholar]
- Nyenhuis DL , Garron DC: Psychometric considerations when measuring cognitive decline in Alzheimer's disease. Neuroepidemiology. 1997; 16: 185-190. [DOI] [PubMed] [Google Scholar]
- Liu Y , Stern Y, Chun MR, et al.: Pathological correlates of extrapyramidal signs in Alzheimer's disease. Ann Neurol. 1997; 41: 368-374. [DOI] [PubMed] [Google Scholar]
- Perl DP , Olanow CW, Calne D: Alzheimer's disease and Parkinson's disease: Distinct entities or extremes of a spectrum of neurodegeneration? Ann Neurol. 1998; 44: 19-31. [DOI] [PubMed] [Google Scholar]
- Chen JY , Stern Y, Sano M, Mayeux R: Cumulative risks of developing extrapyramidal signs, psychosis or myoclonus in the course of Alzheimer's disease. Arch Neurol. 1991; 48: 1141-1143. [DOI] [PubMed] [Google Scholar]