Extrapyramidal signs in patients with probable Alzheimer disease

Objective: To examine whether extrapyramidal signs (EPSs) were associated with more rapid progression of Alzheimer disease (AD). Design: Cross-sectional with longitudinal follow-up and the likelihood of arriving at 4 end points: Mini-Mental State Examination score of less than 9, Blessed Dementia Rating Scale score for activities of daily living of 15 or more, institutionalization, and death using a proportional hazard model with 6 variables: overall EPSs, bradykinesia, tremors, abnormal gait, cogwheel rigidity, and postural instability. Setting: Multidisciplinary behavioral neurology research clinic. Patients: We examined the individual EPS characteristics of 164 patients with mild-moderately probable AD, free of neuroleptic medication, participating in a longitudinal study of dementia. Results: Patients with AD with EPSs (n = 51 [31%]) were older (P > .001) and had lower Mini-Mental State Examination scores (P = .003) than those without EPSs at study entry. Bradykinesia was present in 35 (69%) of the 51 patients with EPSs, abnormal gait in 18 (35%), rigidity in 10 (20%), postural instability in 10 (20%), tremors in 7 (14%), and oral-mandibular dyskinesia in 2 (4%). Using proportional hazard analysis with time-dependent covariates for overall EPSs and individual EPSs, adjusted by age at study entry, education, Mini-Mental State Examination score, and Blessed Dementia Rating Scale score for activities of daily living, the development of EPSs was associated with time to institutionalization (P < .001) but not with cognitive leg, Mini-Mental State Examination score < 9) or functional leg, Blessed Dementia Rating Scale score greater than or equal to 15) decline or death. However, when we examined severity of the EPSs, as measured by the New York University Parkinson's Disease Scale, the development of EPSs was associated with functional decline (p = .005). Of the individual EPSs, rigidity predicted death (P < .001) and institutionalization (P = .03), whereas tremors pre dieted functional decline (P = .02). Conclusions: In this cohort, the presence or absence of EPSs is related to time to institutionalization, but not to severe cognitive or functional impairment or death. However, when severity of the extrapyramidal phenomenon is taken into account, EPSs are related to functional decline. Further, it appears that a subgroup of patients with AD with EPSs, where cogwheel rigidity and tremors are the core signs, can have a worse outcome.