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

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.

Aged↗

Antipsychotics--the future of schizophrenia treatment.

Schizophrenia is a debilitating mental disorder affecting up to five in every thousand people. Although specialist psychiatrists are initially responsible for treating patients suffering from acute schizophrenia, the current structure of mental healthcare in the U.K. puts the onus for the delivery of maintenance therapy of discharged patients on to the general practitioner. It is crucial, therefore, that the general practitioner is aware of all available therapies for the effective, long-term, community-based treatment of patients with schizophrenia. The so-called typical antipsychotics effectively treat the positive but not the negative symptoms of schizophrenia, and up to 40% of patients are nonresponders. These antipsychotics, however, are associated with high levels of extrapyramidal side-effects (EPS), which are the main cause of patient non-compliance and their subsequent relapse and hospital readmission. Clozapine, the first atypical antipsychotic, may cause severe agranulocytosis and patients must undergo regular haematological monitoring, which is both costly and a factor unlikely to foster patient compliance. In contrast, newly developed atypical antipsychotics, such as olanzapine and quetiapine, are not only efficacious in treating the symptoms of schizophrenia, but also give rise to fewer EPS and are generally better tolerated than clozapine. In particular, olanzapine and quetiapine are not associated with severe agranulocytosis. Atypical antipsychotics, therefore, have the potential to enhance patient compliance and thus ease the general practitioner's problems of providing long-term and effective treatment for patients with schizophrenia.

Antipsychotic Agents↗

Extrapyramidal signs, primitive reflexes and frontal lobe function in senile dementia of the Alzheimer type.

Of 146 elderly subjects suffering from Alzheimer-type dementia, 44% were found to have significant extrapyramidal signs. Although extrapyramidal signs were more common in those who had taken neuroleptic drugs in the preceding six months, 22 subjects (15%) who were drug free also had extrapyramidal signs. Scores for cognitive function and for 'frontal lobe' signs (verbal fluency, evidence of perseveration, and primitive reflexes) were found to correlate well with scores for extrapyramidal signs, suggesting that they reflect changes in a common substratum. It is tentatively suggested that this might be an abnormality in the dopamine system.

Aged↗

Motor signs during the course of Alzheimer disease.

BACKGROUND: Motor signs (MOSIs) are common in Alzheimer disease (AD) and may be associated with rates of cognitive decline, mortality, and cost of care. OBJECTIVE: To describe the progression and identify predictors of individual MOSIs in AD. METHODS: A cohort of 474 patients with AD at early stages was followed semiannually for up to 13.1 years (mean 3.6 years) in five centers in Europe and the United States. MOSIs were rated using a standardized portion of the Unified Parkinson's Disease Rating Scale. Overall, 3,030 visits/assessments of MOSIs (average 6.4/patient) were performed. Prevalence and incidence rates were calculated, and cumulative risk graphs were plotted for individual non-drug-induced MOSI domains. Rates of change over time taking into account potential covariates were also estimated. With use of each MOSI domain as outcome in Cox models, predictors of MOSI incidence were identified. RESULTS: At least one MOSI was detected in 13% of patients at first examination and in 36% for the last evaluation. Total MOSI score increased at an annual rate of 3% of total possible score. Rates of annual change for speech/facial expression (4%), rigidity (2.45%), posture/gait (3.9%), and bradykinesia (3.75%) were of similar magnitude, and their occurrence increased from first (3 to 6%) to last (22 to 29%) evaluation. Tremor was less frequent throughout the course of the disease (4% at first and 7% at last evaluation) and worsened less (0.75% increase/year). CONCLUSIONS: Most motor signs occur frequently and progress rapidly in Alzheimer disease. Tremor is an exception in that it occurs less frequently and advances at slower rates.

Aged↗

Visual perception in Parkinson disease dementia and dementia with Lewy bodies.

OBJECTIVE: To quantify visual discrimination, space-motion, and object-form perception in patients with Parkinson disease dementia (PDD), dementia with Lewy bodies (DLB), and Alzheimer disease (AD). METHODS: The authors used a cross-sectional study to compare three demented groups matched for overall dementia severity (PDD: n = 24; DLB: n = 20; AD: n = 23) and two age-, sex-, and education-matched control groups (PD: n = 24, normal controls [NC]: n = 25). RESULTS: Visual perception was globally more impaired in PDD than in nondemented controls (NC, PD), but was not different from DLB. Compared to AD, PDD patients tended to perform worse in all perceptual scores. Visual perception of patients with PDD/DLB and visual hallucinations was significantly worse than in patients without hallucinations. CONCLUSIONS: Parkinson disease dementia (PDD) is associated with profound visuoperceptual impairments similar to dementia with Lewy bodies (DLB) but different from Alzheimer disease. These findings are consistent with previous neuroimaging studies reporting hypoactivity in cortical areas involved in visual processing in PDD and DLB.

Activities of Daily Living↗

Autosomal dominant system degeneration in Portuguese families of the Azores Islands. A new genetic disorder involving cerebellar, pyramidal, extrapyramidal and spinal cord motor functions.

We studied 40 patients in 15 families from the Portuguese Azores Islands. Each family was affected by an autosomal dominant genetic disorder. Symptoms began between ages 20 and 50. Ataxia, ophthalmoplegia, pyramidal signs, dystonia, rigidity, and distal atrophy were the major clinical findings. Evidence suggested that this was a single genetic disease, with variable phenotypic expression. Machado disease, nigrospinodentatal degeneration with nuclear ophthalmoplegia, and autosomal dominant striatonigral degeneration may be variations of this same genetic disease.

Adult↗