Treatment of a Whole Population Sample of Alzheimer’s Disease with Donepezil over a 4-Year Period: Lessons Learned

Abstract

Background: In the UK it is recommended that acetylcholinesterase inhibitors be restricted to patients with moderate Alzheimer’s disease, and progress monitored within specialist clinics. Objective: To describe a cohort of patients with Alzheimer’s disease from a whole city population treated with donepezil, and to analyse outcomes over 4 years. Methods: Historical cohort design: 88 patients recruited 1997–1998, assessed at baseline with 4-year follow-up, using an agreed protocol and validated measures: survival, retention in treatment, cognition, non-cognitive symptoms, weight change, carer stress. Results: 64.7% remained on treatment beyond 6 months, 57.9% beyond 1 year and 12.5% beyond 4 years. 56% remained alive at 4 years – almost twice the number predicted. Mean MMSE score amongst patients in treatment did not deteriorate over 4 years. Survival, retention in treatment, maintenance/improvement of cognition was greater with high baseline MMSE. Non-cognitive symptoms, carer stress and weight change remained low throughout. Conclusions: A minority of people with dementia from the population (88 of potential 2,000 at outset, 11 by 4 years) received treatment. Benefits for individuals were confirmed, especially for those with mild impairment. Expenditure on medication was modest in a population context. These findings question recent guidance from the National Institute for Clinical Excellence, which would restrict therapy to patients with moderate cognitive impairment.

Predictive Value of Platelet Activation for the Rate of Cognitive Decline in Alzheimer's Disease Patients

“…Platelet activation and cognitive decline in AD K Stellos et al present with a better or unchanged MMSE score after a 1-year follow-up period (Clark et al, 1999). Moreover, patients treated with a ChEI may score higher in MMSE after 1 year compared with placebo (Lyle et al, 2008). For instance, in the Penn Hospital cohort, 72% of survivors treated with a ChEI showed a cognitive improvement after 1-year follow-up and even 47% at the end of the second year (Lyle et al, 2008).…”

“…Moreover, patients treated with a ChEI may score higher in MMSE after 1 year compared with placebo (Lyle et al, 2008). For instance, in the Penn Hospital cohort, 72% of survivors treated with a ChEI showed a cognitive improvement after 1-year follow-up and even 47% at the end of the second year (Lyle et al, 2008). Nevertheless, the differential mechanism leading to a cognitive decline or improvement in patients with AD is not fully understood.…”

Longitudinal Associations between Survival in Alzheimer's Disease and Cholinesterase Inhibitor Use, Progression, and Community-Based Services

“…These drugs may improve or stabilize some of the symptoms of AD for a limited period of 6-12 months on average [5]. Moreover, long-term observational studies of AD have described the benefits of ChEI on cognition [6,7] and function [8,9] over several years. We observed slower disease progression in patients with a higher cognitive or ADL ability at the start of therapy [9,10], which suggests advantages of early initiation of ChEIs.…”

Adherence to Cholinesterase Inhibitors in Alzheimer's Disease: A Review

“…Sustained use of these agents for 3 or more months may delay the worsening of cognitive, functional and behavioural symptoms of AD [5,7]. However, treatment management is a major challenge in AD, with non-adherence to treatment often a barrier to effective therapy [8,9]. …”