Thursday, June 23, 2011

Donepezil for language dysfunction in Alzheimer's disease


Progressive language impairment is among the primary components of cognitive decline in Alzheimer's disease (AD). Because expressive and receptive language helps maintain emotional connection to caregivers and supports management of AD functional needs, language plays a critical role in patients' emotional and physical health. Using data from a large prospective clinical trial comparing two doses of donepezil in patients with moderate to severe AD, we performed a post hoc analysis to determine whether a higher dose of donepezil was associated with greater benefits in language function.


In the original randomized, double-blind clinical trial, 1467 patients with moderate to severe AD (baseline Mini-Mental State Examination [MMSE] scores 0-20) were randomized 2:1 to receive donepezil 23 mg/d or to continue on donepezil 10 mg/d for 24 weeks. In this post hoc analysis, the Severe Impairment Battery language (SIB-L) scale and a new 21-item SIB-derived language scale (the SIB[lang]) were used to explore differences in language function between the treatment groups. Correlations between SIB-L and SIB[lang] scores and scores on the severe version of the Alzheimer's Disease Cooperative Study-Activities of Daily Living inventory (ADCS-ADL-sev), the Clinician's Interview-Based Impression of Severity/Change-plus caregiver input (CIBIS/CIBIC-plus), and the MMSE were also investigated.


At Week 24, treatment with donepezil 23 mg/d was associated with an improvement in language in the full intention-to-treat (ITT) population, whereas language function declined with donepezil 10 mg/d (SIB-L treatment difference 0.8, P = 0.0013; SIB[lang] treatment difference 0.8, P = 0.0009). Similar results were observed in a cohort of patients with more severe baseline disease (MMSE, 0-16). At baseline and Week 24, correlations between the SIB-derived language scales and the ADCS-ADL-sev and CIBIC-plus were moderate, but were stronger between the language scales and MMSE.


Patients with moderate to severe AD receiving donepezil 23 mg/d showed greater language benefits compared with those receiving 10 mg/d, as measured by SIB-derived language assessments. Increasing the dose of donepezil to 23 mg/d may provide language benefits in patients with moderate to severe AD, for whom preservation of language abilities is especially critical. identifier: NCT00478205.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

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