Cholinesterase inhibitors, cognitive decline, major cardiovascular events, and mortality in dementia with Lewy bodies
Hong Xu, Daniel Ferreira, Elisabet Londos, Maria Eriksdotter- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
- Geriatrics and Gerontology
- Neurology (clinical)
- Developmental Neuroscience
- Health Policy
- Epidemiology
Abstract
Background
Cholinesterase inhibitors (ChEIs) are approved pharmacological treatment in Alzheimer’s dementia (AD) and dementia with Lewy bodies (DLB). Recent studies showed that ChEI‐use is associated with decreased risk of cardiovascular events and death in AD. This study explores the long‐term effects of ChEIs on cognition, the risk for hospitalization of major cardiovascular events and death in patients with DLB.
Method
We included DLB patients with mild‐moderate dementia(defined as Mini Mental State Examination(MMSE)≥10 points) from the Swedish Dementia Registry(SveDem). Patients starting on ChEI within 90 days of diagnosis were compared to patients with DLB not receiving ChEI. Major cardiovascular events(MACE) were defined as the composite of hospitalization of myocardial infarction or congestive heart failure or stroke. In an inverse probability of treatment weighting cohort, the association between ChEI‐use and cognitive trajectories were examined with mixed models and the risks of MACE or death with Cox models with balancing 45 confounders.
Result
893 ChEI‐use and 305 non‐users were included. The most frequently used ChEIs was rivastigmine(69%), followed by donepezil(21%) and galantamine(10%). There was no difference in MMSE scores between the two ChEI groups at baseline after weighting. During a median follow up time of 3.2 years (interquartile range1.7‐4.3), ChEI‐users showed slower cognitive decline (‐1.4 MMSE points/year, 95%confidence interval CI ‐1.8, ‐1.0) compared to non‐users (‐2.8 MMSE points/year, ‐3.9, ‐1.9). Of the ChEIs, galantamine was associated with the slowest cognitive decline (‐0.9 MMSE points/year, ‐1.8, ‐0.1). During follow up, 120(10%) events of MACE occurred, along with 666(56%) deaths. Compared to non‐users, ChEI‐use was not associated with risk for hospitalization for MACE (adjusted hazard ratio(aHR)0.89; 95% CI 0.43‐1.82) or risk of death (aHR 1.09; 0.87‐1.37).
Conclusion
In patients with DLB, ChEI‐use was associated with slower cognitive decline over 3.2 years on average, where galantamine presented the strongest effect. This may be explained by its modulatory effect on nicotinic receptors as well as its inhibitory effect on acetylcholinesterase. Interestingly, in contrast to our previous findings in AD, ChEI‐treatment in DLB was not associated with reduced MACE or mortality risk, which might be related with the more prominent autonomic dysfunction in DLB than in AD.