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Long‐Term Effect of Acetylcholinesterase Inhibitors on Behavioral and Psychological Symptoms of Dementia

ABSTRACT

Objective

Behavioral and psychological symptoms of dementia (BPSD) are critical aspects of the clinical presentation of dementia. There is no universally accepted approach for the managment of BPSD, currently based first on a non-pharmacological and subsequently on a pharmacological approach. We explored the potential effect of long-term treatment with acetylcholinesterase inhibitors (AChEI) on BPSD severity over time.

Methods

The initial sample included 4032 older patients with mild-moderate dementia (Alzhemier’s disease – AD, Lewy body dementia – LBD, or vascular dementias – VaD) from the National Alzheimer’s Coordinating Center Uniform Data Set (NACC UDS). After propensity score matching, a cohort of 1408 patients (704 treated with AChEI = AChEI+ and 704 not treated = AChEI−) was generated. The mean age was 73.2 years (females: 50.4%). The mean follow-up duration was 4.3 ± 1.6 years (range: 2.2–8.3 years). Patients were evaluated at baseline, T1 (2 years), T2 (4 years), T3 (6.2 years), and T4 (8.1 years). BPSD severity was assessed by Neuropsychiatric Inventory (NPI-Q).

Results

The baseline mean NPI-Q severity score was 1.33. At T4, the score increased to 1.41 in AChEI− patients (+6% from baseline), while it decreased to 1.26 in AChEI+ (−6%) (all p < 0.01 from T1 to T4). As regards the NPI-Q sub-items, six of them (hallucinations, agitation/aggression, depression/dysphoria, anxiety, disinhibition and irritability/lability) exhibited significant differences over time (all p < 0.01) in favor of the AChEI + group (stabilization or improvement). Similar trends were observed when LOAD, LBD and VaD were considered separately. In contrast, for five domains (delusions, elation/euphoria, motor disturbances, night-time behaviors, and appetite/eating changes) no differences were observed.

Conclusions

Our study supports the potential role for AChEI in BPSD management, demonstrating a trend toward symptoms stabilization or improvement in patients with mild-moderate dementia. Although the effects were not uniform across all NPI-Q domains, and the limitations of the study, our results reinforces the relevance of AChEI in the comprehensive treatment of dementia.

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Posted in: Journal Article Abstracts on 02/13/2026 | Link to this post on IFP |
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