Language impairment in Alzheimer's disease and benefits of acetylcholinesterase inhibitors

Abstract

Alzheimer's disease is characterized by progressively worsening deficits in several cognitive domains, including language. Language impairment in Alzheimer's disease primarily occurs because of decline in semantic and pragmatic levels of language processing. Given the centrality of language to cognitive function, a number of language-specific scales have been developed to assess language deficits throughout progression of the disease and to evaluate the effects of pharmacotherapy on language function. Trials of acetylcholinesterase inhibitors, used for the treatment of clinical symptoms of Alzheimer's disease, have generally focused on overall cognitive effects. However, in the current report, we review data indicating specific beneficial effects of acetylcholinesterase inhibitors on language abilities in patients with Alzheimer's disease, with a particular focus on outcomes among patients in the moderate and severe disease stages, during which communication is at risk and preservation is particularly important.

Keywords: Alzheimer’s disease; clinical trials; cognition; communication; donepezil; language.

Figure 1

Symptom progression in Alzheimer’s disease. Note: Modified from Feldman HH, Woodward M. The staging and assessment of moderate to severe Alzheimer’s disease. Neurology. 2005;65:S10–S17. With permission from Wolters Kluwer Health.Abbreviations: AD, Alzheimer’s disease; MMSE, Mini-Mental State Examination; MCI, mild cognitive impairment; BADL, basic activities of daily living.

Figure 2

Effect of donepezil 23 mg/day on language function after 24 weeks of treatment in patients with moderate to severe Alzheimer’s disease. Mean change in LS from baseline to week 24 in SIB-L scores (A) and 21-item SIB-derived language subscale scores (B). Note: ©2011 Springer. Reproduced with permission from Ferris SH, Schmitt FA, Saxton J, et al. Analyzing the impact of 23 mg/day donepezil on language dysfunction in moderate to severe Alzheimer’s disease. Alzheimers Res Ther. 2011;3(3):22.Abbreviations: LS, least squares; SIB-L, Severe Impairment Battery language scale; MMSE, Mini-Mental State Examination; SE, standard error of the mean.

Figure 3

Effect of rivastigmine on language function after 26 weeks of treatment in patients with mild to moderate Alzheimer’s disease. Notes: Mean changes from baseline on ADAS-cog subscale scores at week 26 (intention-to-treat population). *P < 0.0001; ^†P < 0.001 versus placebo; ^‡P < 0.001 versus 1 to 4 mg/day rivastigmine capsule.Reproduced from Farlow MR, Cummings JL, Olin JT, Meng X. Effects of oral rivastigmine on cognitive domains in mild-to-moderate Alzheimer’s disease. Am J Alzheimers Dis Other Demen. 2010;25(4):347–352. With permission from Sage publications.Abbreviation: ADAS-cog, cognitive subscale of the Alzheimer’s Disease Assessment Scale.

Figure 4

Effect of galantamine on language function after 26 weeks of treatment in patients with severe Alzheimer’s disease. Notes: Change from baseline in SIB subscale scores at week 26 in intention-to-treat population. Bars indicate 95% confidence interval for comparison with baseline. *P = 0.006; ^†P = 0.010; ^‡P = 0.002 versus placebo.Reproduced from Burns A, Bernabei R, Bullock R, et al. Safety and efficacy of galantamine (Reminyl) in severe Alzheimer’s disease (the SERAD study): a randomised, placebo-controlled, double-blind trial. Lancet Neurol 2009;8(1):39–47. With permission from Elsevier Ltd.Abbreviation: SIB, Severe Impairment Battery.