Supplementary materials for: Long term effects of cholinesterase inhibitors on cognitive decline and mortality

Objective: Cholinesterase inhibitors (ChEIs) are the mainstay treatment of
Alzheimer’s dementia (AD), but their long-term effectiveness is uncertain.
This study aims is to investigate whether ChEIs are associated with slower
cognitive decline in AD, and decreased risk of severe dementia or death.
Methods: AD patients from the Swedish Dementia Registry (SveDem) starting
on ChEIs within three months of the dementia diagnosis were included and
compared to non-treated AD patients. In a propensity score matched cohort,
the association between ChEI-use and cognitive trajectories assessed by
MMSE scores were examined with a mixed model, and severe dementia
(MMSE<10) or death as outcomes with Cox proportional hazards
models. Results: The matched cohort included 11,652 ChEI-use and 5,826
non-users. During an average of 5 years follow up, 255 cases developed
severe dementia and 6,055 (35%) died. ChEI-use was associated with higher
MMSE at each visit (0.13 MMSE points/year; 95% confidence interval-CI
0.06, 0.20). ChEI-use had a 27% lower risk of death (0.73; CI 0.69, 0.77)
compared with non-users. Galantamine was associated with lower risk of
death (0.71; CI 0.65, 0.76), lower risk of severe dementia (0.69; CI
0.47-1.00), and had the strongest effect on cognitive decline of all the
ChEIs (0.18 MMSE points/year, CI 0.07, 0.28). Conclusions: ChEIs are
associated with cognitive benefits which are modest but persist over time
and with reduced mortality risk, which could be explained partly by their
cognitive effects. Galantamine was the only ChEI demonstrating a
significant reduction in the risk of developing severe dementia.
Classification of Evidence: This study provides Class III evidence that
for patients with AD, ChEIs decrease long term cognitive decline and risk
of death, and that galantamine decreases the risk of severe dementia.