Association Between Functional Impairment, Depression, and Extrapyramidal Signs in Neuroleptic-Free Patients With Alzheimer Disease

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Extrapyramidal signs (EPSs) are commonly observed in patients with Alzheimer disease (AD). We report here the base rate of EPS in a large cohort of patients with AD who were not receiving neuroleptic drugs, and the associations of EPS with functional outcomes and depressive symptoms.


In a consortium involving 56 clinics, we recruited 2614 patients with AD. We estimated basic activities of daily living (ADL) and instrumental ADL by the Barthel index and the Seoul-Instrumental Activities of Daily Living (S-IADL) scales, respectively. Depressive symptoms were assessed using the 15-item Geriatric Depression Scale (GDS-15). The EPS group was defined by the presence of at least 1 EPS based on a focused neurologic examination.


The prevalence of EPS-positive patients was 12%. These had lower Korean version of the Mini-Mental State Examination (K-MMSE) scores than the EPS-negative cases (P < .001). After controlling for demographic, medical, radiological, genetic, and cognitive (K-MMSE) factors, the proportion of patients with impaired ADL was significantly higher in the EPS group than in the non-EPS group (P < .001, odds ratio = 1.90, 95% confidence interval, 1.45–2.48, and logistic regression). The S-IADL scores were significantly higher in the EPS group than this in the non-EPS group (P < .001, regression coefficient = 3.19, and median regression). The GDS-15 scores were higher in the EPS group (P = .04, regression coefficient = 0.89, and median regression).


The presence of EPS in patients with AD who were not receiving neuroleptic drugs was associated with more impaired basic and instrumental ADL functioning and with greater depression symptoms.

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