Abstract
IntroductionKnowledge of longitudinal progression in mild Alzheimer’s disease (AD) is required for the evaluation of disease-modifying therapies. Our aim was to observe the effects of long-term cholinesterase inhibitor (ChEI) therapy in mild AD patients in a routine clinical setting.MethodsThis was a prospective, open-label, non-randomized, multicenter study of ChEI treatment (donepezil, rivastigmine or galantamine) conducted during clinical practice. The 734 mild AD patients (Mini-Mental State Examination (MMSE) score 20 to 26) were assessed at baseline and then semi-annually over three years. Outcome measures included the MMSE, Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog), Clinician’s Interview-Based Impression of Change (CIBIC) and Instrumental Activities of Daily Living (IADL) scale.ResultsAfter three years of ChEI therapy, 31% (MMSE) and 33% (ADAS-cog) of the patients showed improved/unchanged cognitive ability, 33% showed improved/unchanged global performance and 14% showed improved/unchanged IADL capacity. Higher mean dose of ChEI and lower educational level were both predictors of more positive longitudinal cognitive and functional outcomes. Older participants and those with a better IADL score at baseline exhibited a slower rate of cognitive decline, whereas younger participants and those with higher cognitive status showed more preserved IADL ability over time. Gender and apolipoprotein E (APOE) genotype showed inconsistent results. Prediction models using the abovementioned scales are presented.ConclusionsIn naturalistic mild AD patients, a marked deterioration in IADL compared with cognitive and global long-term outcomes was observed, indicating the importance of functional assessments during the early stages of the disease. The participants’ time on ChEI treatment before inclusion in studies of new therapies might affect their rate of decline and thus the comparisons of changes in scores between various studies. An increased understanding of expected disease progression in different domains and potential predictors of disease progression is essential for assessment of future therapies in AD.
Highlights
Knowledge of longitudinal progression in mild Alzheimer’s disease (AD) is required for the evaluation of disease-modifying therapies
Our study demonstrated that individuals with higher cognitive status at the start of cholinesterase inhibitor (ChEI) therapy showed greater preserved instrumental activities of daily living (IADL) capacity over time and that those with a better IADL score at baseline exhibited a slower rate of cognitive decline
In conclusion, an investigation of disease progression in different domains was described in this mild AD study
Summary
Knowledge of longitudinal progression in mild Alzheimer’s disease (AD) is required for the evaluation of disease-modifying therapies. Our aim was to observe the effects of long-term cholinesterase inhibitor (ChEI) therapy in mild AD patients in a routine clinical setting. The main treatment for mild-to-moderate AD is acetylcholinesterase inhibitors (ChEI), which have shown positive symptomatic effects on cognition and function compared with a placebo in randomized clinical trials [2]. Using pooled data from the two phase 3 passive immunization trials of solanezumab, the analyses demonstrated a significant slowing of cognitive decline and a trend towards slower deterioration in instrumental activities of daily living (IADL) after 80 weeks among individuals with mild but not moderate AD [5]. A six-month randomized trial of mild AD patients showed that souvenaid, a medical food product containing precursors and other specific nutrients required to enhance synapse formation, significantly increased memory performance in comparison with a placebo [6]
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