Extrapyramidal Motor Signs in Clinically Diagnosed Alzheimer Disease

Summary: We reviewed clinical case series published over a 10-year period addressing the cross-sectional frequency, incidence, and diagnostic and prognostic significance of extrapyramidal signs (EPS) in Alzheimer disease (AD). The review was prompted by recent reports of Lewy body (LB) pathology in the brains of many AD patients and the association of LB pathology with clinical parkinsonism in AD. In the clinical case series reviewed, we evaluated several possible determinants of prevalent EPS, including neuroleptic use, EPS assessment technique, and dementia severity. Neuroleptics were a well recognized cause of parkinsonism in these reports, though some failed to document the frequency of neuroleptic use. Assessment methods were also important: Studies using structured clinical research scales to rate EPS reported higher frequencies than studies employing routine neurological examination. The relationship between parkinsonism and dementia severity was complex. Some studies found bradykinesia, facial masking, and parkinsonian postural changes even in mildly demented, neuroleptic-naive AD patients. Rigidity, on the other hand, became increasingly common as dementia progressed. AD patients with EPS showed faster cognitive and functional decline and earlier death than those without EPS, even after consideration of differences in initial dementia severity. In the differential diagnosis of dementia with parkinsonism, LB disease in its various forms, including AD with LB, is the principal diagnostic consideration. Future studies of parkinsonism in AD should employ standardized clinical rating scales and should exclude patients on neuroleptics or analyze their results separately. Investigators should report frequencies for individual parkinsonian signs in addition to the overall prevalence of EPS to facilitate meaningful comparisons across studies.