Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Jul 16;12(1):12214.
doi: 10.1038/s41598-022-16476-w.

Acetyl-cholinesterase-inhibitors slow cognitive decline and decrease overall mortality in older patients with dementia

Marco Zuin  1 , Antonio Cherubini  2 , Stefano Volpato  3 , Luigi Ferrucci  4 , Giovanni Zuliani  5
Affiliations

Acetyl-cholinesterase-inhibitors slow cognitive decline and decrease overall mortality in older patients with dementia

Marco Zuin et al. Sci Rep. .

Abstract

We evaluated the effect of Acetyl-cholinesterase-inhibitors (AChEIs) on cognitive decline and overall survival in a large sample of older patients with late onset Alzheimer's disease (LOAD), vascular dementia (VD) or Lewy body disease (LBD) from a real world setting. Patients with dementia enrolled between 2005 and 2020 by the "Alzheimer's Disease Research Centers" were analysed; the mean follow-up period was 7.9 years. A 1:1 propensity score matching was performed generating a cohort of 1.572 patients (786 treated [AChEIs +] and 786 not treated [AChEIs-] with AChEIs. The MMSE score was almost stable during the first 6 years of follow up in AChEIs + and then declined, while in AChEIs- it progressively declined so that at the end of follow-up (13.6 years) the average decrease in MMSE was 10.8 points in AChEIs- compared with 5.4 points in AChEIs + (p < 0.001). This trend was driven by LOAD (Δ-MMSE:-10.8 vs. -5.7 points; p < 0.001), although a similar effect was observed in VD (Δ-MMSE:-11.6 vs. -8.8; p < 0.001). No effect on cognitive status was found in LBD. At multivariate Cox regression analysis (adjusted for age, gender, dependency level and depression) a strong association between AChEIs therapy and lower all-cause mortality was observed (H.R.:0.59; 95%CI: 0.53-0.66); this was confirmed also in analyses separately conducted in LOAD, VD and LBD. Among older people with dementia, treatment with AChEIs was associated with a slower cognitive decline and with reduced mortality, after a mean follow-up of almost eight years. Our data support the effectiveness of AChEIs in older patients affected by these types of dementia.

PubMed Disclaimer

Conflict of interest statement

AC reports personal fees from Nestle, personal fees from Bristol Myers Squibb and payment /honoraria from MSD, outside the submitted work; SV reports Consulting fees from Angelini SPA and Payment/honoraria from Abbot Vifor, outside from the submitted work. MZ, GZ and LF have no conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Flow chart of the study.
Figure 2
Figure 2
Mini Mental State Examination (MMSE) score during follow-up in all patients with dementia (A), LOAD (B), and vascular dementia (C) according to treatment with AChEIs. ***p < 0.001 for trend (Adjusted curves–for propensity score matched cohorts).
Figure 3
Figure 3
Cumulative survival (Cox multivariate regression analysis) after propensity score matching in patients with dementia treated or not treated with AChEIs: (A) all patients; (B) LOAD; (C): vascular dementia.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Mattiuzzi C, Lippi G. Worldwide disease epidemiology in the older persons. Eur. Geriatr. Med. 2020;11:147–153. doi: 10.1007/s41999-019-00265-2. - DOI - PubMed
    1. Arvanitakis Z, Shah RC, Bennett DA. Diagnosit and management of dementia: Review. JAMA. 2019;322:15891599. - PMC - PubMed
    1. Takeda A, Loveman E, Clegg A, Kirby J, Picot J, Payne E, Green C. A systematic review of the clinical effectiveness of donepezil, rivastigmine and galantamine on cognition, quality of life and adverse events in Alzheimer's disease. Int. J. Geriatr. Psychiatry. 2006;21:17–28. doi: 10.1002/gps.1402. - DOI - PubMed
    1. Marucci G, Buccioni M, Ben DD, Lambertucci C, Volpini R, Amenta F. Efficacy of acetylcholinesterase inhibitors in Alzheimer's disease. Neuropharmacology. 2020 doi: 10.1016/j.neuropharm.2020.108352. - DOI - PubMed
    1. Wilkinson DG, Francis PT, Schwam E, Payne-Parrish J. Cholinesterase inhibitors used in the treatment of Alzheimer's disease: the relationship between pharmacological effects and clinical efficacy. Drugs Aging. 2004;21:453–478. doi: 10.2165/00002512-200421070-00004. - DOI - PubMed

Publication types

Grants and funding