Short-Term Response to Cholinesterase Inhibitors in Alzheimer's Disease Delays Time to Nursing Home Placement

Abstract

Background: A varying response to cholinesterase inhibitor (ChEI) treatment has been reported among patients with Alzheimer's disease (AD). Whether the individual-specific response directly affects time to nursing home placement (NHP) was not investigated.

Objective: We examined the relationship between the 6-month response to ChEI and institutionalization.

Methods: In a prospective, observational, multicenter study, 881 outpatients with a clinical AD diagnosis and a Mini-Mental State Examination score of 10-26 at the start of ChEI therapy (baseline) were included. The participants were evaluated using cognitive, global, and activities of daily living (ADL) scales at baseline and semiannually over 3 years. The date of NHP was recorded.

Results: During the study, 213 patients (24%) were admitted to nursing homes. The mean ± standard deviation time from baseline (AD diagnosis) to NHP was 20.8 ± 9.3 months. After 6 months of ChEI treatment, the improved/unchanged individuals had longer time to NHP than those who worsened. The prolonged time to NHP was 3 months for cognitive response (P=0.022), 4 months for global response (P=0.004), 6 months for basic ADL response (P<0.001), and 8 months for response in all three scales (P<0.001). No differences were detected between the improved and unchanged groups in any scales.

Conclusion: Patients who exhibit a positive short-term response to ChEI can expect to stay in their own home for 3-8 months longer. These findings underline the importance of a comprehensive clinical examination including various assessment scales to evaluate treatment response and provide a more accurate prognosis.

Keywords: Alzheimer's disease; activities of daily living; cholinesterase inhibitors; cognition; nursing home placement; predictors; statistical models; treatment effect..

Fig. (1)

Time from the start of ChEI therapy (baseline) to the endpoint NHP. (A) Kaplan-Meier graph of the distribution of time from baseline to NHP according to cognitive response to ChEI after 6 months of treatment. A log-rank test showed a longer time to NHP for the improved/unchanged SATS participants (P < 0.001). (B) Kaplan-Meier graph of the distribution of time from baseline to NHP according to global response to ChEI after 6 months of therapy. A log-rank test demonstrated a longer time to NHP for the improved/unchanged patients (P < 0.001). (C) Kaplan-Meier graph of the distribution of time from baseline to NHP according to IADL response to ChEI after 6 months of treatment. A log-rank test exhibited a longer time to NHP for the improved/unchanged group (P = 0.017). (D) Kaplan-Meier graph of the distribution of time from baseline to NHP according to basic ADL response to ChEI after 6 months of therapy. A log-rank test showed a longer time to NHP for the improved/unchanged individuals (P < 0.001). ADL, activities of daily living; ChEI, cholinesterase inhibitor; CIBIC, Clinician Interview-Based Impression of Change; IADL, Instrumental Activities of Daily Living scale; MMSE, Mini-Mental State Examination; NHP, nursing home placement; PSMS, Physical Self-Maintenance Scale; SATS, Swedish Alzheimer Treatment Study.

Fig. (2)

Time from the start of ChEI treatment to the endpoint NHP. Kaplan-Meier graph of the distribution of time from baseline to NHP according to improvement/no change after 6 months of therapy as measured by the number of assessment scales (MMSE, CIBIC, IADL, and PSMS). A log-rank test demonstrated a relationship between the SATS patients’ number of scales with positive response to ChEI and delays in the time to NHP (P < 0.001). All pairwise comparisons were significant (0.001 < P ≤ 0.039), except for the combination of “improvement/no change on three of the scales—improvement/no change on all four scales.” ChEI, cholinesterase inhibitor; CIBIC, Clinician Interview-Based Impression of Change; IADL, Instrumental Activities of Daily Living scale; MMSE, Mini-Mental State Examination; NHP, nursing home placement; PSMS, Physical Self-Maintenance Scale; SATS, Swedish Alzheimer Treatment Study.