Extrapyramidal symptoms and signs in Alzheimer's disease: prevalence and correlation with the first symptom

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.

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.

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.