Initial cognitive response to cholinesterase inhibitors and subsequent long-term course in patients with mild Alzheimer's disease

Background: Some guidelines recommend to discontinue treatment with cholinesterase inhibitors (ChEIs) in patients with Alzheimer's disease (AD) without an initial response to ChEI treatment. Evidence supporting this recommendation, however, is limited. This study aimed to investigate the relation between the initial cognitive response to ChEI treatment and the subsequent long-term course of cognition of AD patients. Methods: The Frisian Alzheimer's Disease Cohort study is a retrospective longitudinal study of 576 community-dwelling AD patients treated with ChEIs in a "real-life" setting at a large memory clinic. A repeated measures analysis using a marginal model (population based averaged model) was applied to investigate whether there is a difference in the subsequent long-term course of cognition (Mini-Mental State Examination (MMSE)) between initial non-responders and responders. Absence of an initial response was defined as a lower MMSE score after the first six months of treatment compared to baseline, a positive response as the same or a higher MMSE score. Results: At baseline, median age was 80 years and the median MMSE score 23. Non-responders showed a slower rate of cognitive decline in the three subsequent years than responders, with a mean annual MMSE decline of 0.9 points versus 1.2 points, respectively (p < 0.0001). Conclusions: Our results suggest that it is not appropriate to discontinue ChEI treatment solely based on the absence of an initial cognitive response.