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. 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.

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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

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