Cholinesterase inhibitors for gait, balance, and fall in Parkinson disease: a meta-analysis

Gait disturbance and imbalance are the major symptoms of Parkinson disease (PD), with fall being the most undesirable consequence. However, few effective evidence-based treatments are available for alleviating these symptoms and preventing falls. Cholinesterase inhibitors (ChEIs) are a well-established treatment for PD dementia with possible impacts on gait, balance, and fall reduction. The present study involved a meta-analysis of randomized controlled trials (RCTs) to investigate the effects of ChEIs on gait, balance, and fall in patients with PD. We searched for studies using the PubMed, Embase, and Web of Science databases. The major outcomes were effects on gait parameters, balance, and fall. This study was registered with PROSPERO (CRD42021254733). Five RCTs were included in the present meta-analysis. ChEIs did not significantly increase gait speed in PD patients (mean difference [MD]: 0.03 m/s, 95% confidence interval [CI]: −0.02 to 0.07, p = 0.29). However, ChEI treatment significantly decreased step or stride variability during the single task (standard MD: −0.43, 95% CI = −0.79 to −0.06, p = 0.02). Regarding fall and balance, trending but nonsignificant beneficial effects were observed with ChEI treatment. In conclusion, although ChEI treatment did not significantly improve gait speed and reduce fall, it can significantly reduce step or stride variability. Considering that gait disorder is a challenging issue in patients with PD and that ChEIs are generally tolerable, the present meta-analysis may provide more evidence for the benefit of ChEIs on PD gait disturbance as an alternative treatment consideration.

Cholinesterase inhibitors for the treatment of dementia: real-life data in Hungary

Dementia is one of the leading causes of death and disability in older population. Previous reports have shown that antidementia medications are associated with longer survival; nonetheless, the prevalence of their use and the compliance with them are quite different worldwide. There is hardly any available information about the pharmacoepidemiology of these drugs in the Eastern-European region; we aimed to analyze the use of cholinesterase inhibitors (ChEis) for the treatment of dementia to provide real-life information from the Eastern European region. All medical and medication prescription reports of the in- and outpatient specialist services collected in the NEUROHUN database in Hungary were analyzed between 2013 and 2016. Survival, adherence, and persistence values were calculated. 8803 patients were treated with ChEis during the study period, which was only 14.5% of the diagnosed demented patients. The survival of treated patients (more than 4 years) was significantly longer than patients without ChEi treatment (2.50 years). The best compliance was observed with rivastigmine patch. Choosing the appropriate medication as soon as possible after the dementia diagnosis may lead to increased life expectancy.

Pre-Stroke Cholinesterase Inhibitor Treatment Is Beneficially Associated with Functional Outcome in Patients with Acute Ischemic Stroke and Pre-Stroke Dementia: The Fukuoka Stroke Registry

Introduction: Pre-stroke dementia is significantly associated with poor stroke outcome. Cholinesterase inhibitors (ChEIs) might reduce the risk of stroke in patients with dementia. However, the association between pre-stroke ChEI treatment and stroke outcome remains unresolved. Therefore, we aimed to determine this association in patients with acute ischemic stroke and pre-stroke dementia. Methods: We enrolled 805 patients with pre-stroke dementia among 13,167 with ischemic stroke within 7 days of onset who were registered in the Fukuoka Stroke Registry between June 2007 and May 2019 and were independent in basic activities of daily living (ADLs) before admission. Primary and secondary study outcomes were poor functional outcome (modified Rankin Scale [mRS] score: 3–6) at 3 months after stroke onset and neurological deterioration (≥2-point increase in the NIH Stroke Scale [NIHSS] during hospitalization), respectively. Logistic regression analysis was used to evaluate associations between pre-stroke ChEI treatment and study outcomes. To improve covariate imbalance, we further conducted a propensity score (PS)-matched cohort study. Results: Among the participants, 212 (26.3%) had pre-stroke ChEI treatment. Treatment was negatively associated with poor functional outcome (odds ratio: 0.68 [95% confidence interval: 0.46–0.99]) and neurological deterioration (0.52 [0.31–0.88]) after adjusting for potential confounding factors. In the PS-matched cohort study, the same trends were observed between pre-stroke ChEI treatment and poor functional outcome (0.61 [0.40–0.92]) and between the treatment and neurological deterioration (0.47 [0.25–0.86]). Conclusions: Our findings suggest that pre-stroke ChEI treatment is associated with reduced risks for poor functional outcome and neurological deterioration after acute ischemic stroke in patients with pre-stroke dementia who are independent in basic ADLs before the onset of stroke.

Short-Term Response to Cholinesterase Inhibitors in Alzheimer’s Disease Delays Time to Nursing Home Placement

Background: A varying response to cholinesterase inhibitor (ChEI) treatment has been reported among patients with Alzheimer’s disease (AD). Whether the individual-specific response directly affects time to nursing home placement (NHP) was not investigated. Objective: We examined the relationship between the 6-month response to ChEI and institutionalization. Methods: In a prospective, observational, multicenter study, 881 outpatients with a clinical AD diagnosis and a Mini-Mental State Examination score of 10-26 at the start of ChEI therapy (baseline) were included. The participants were evaluated using cognitive, global, and activities of daily living (ADL) scales at baseline and semiannually over 3 years. The date of NHP was recorded. Results: During the study, 213 patients (24%) were admitted to nursing homes. The mean ± standard deviation time from baseline (AD diagnosis) to NHP was 20.8 ± 9.3 months. After 6 months of ChEI treatment, the improved/unchanged individuals had longer time to NHP than those who worsened. The prolonged time to NHP was 3 months for cognitive response (P=0.022), 4 months for global response (P=0.004), 6 months for basic ADL response (P<0.001), and 8 months for response in all three scales (P<0.001). No differences were detected between the improved and unchanged groups in any scales. Conclusion: Patients who exhibit a positive short-term response to ChEI can expect to stay in their own home for 3-8 months longer. These findings underline the importance of a comprehensive clinical examination including various assessment scales to evaluate treatment response and provide a more accurate prognosis.

Initial cognitive response to cholinesterase inhibitors and subsequent long-term course in patients with mild Alzheimer's disease

ABSTRACTBackground:Some guidelines recommend to discontinue treatment with cholinesterase inhibitors (ChEIs) in patients with Alzheimer's disease (AD) without an initial response to ChEI treatment. Evidence supporting this recommendation, however, is limited. This study aimed to investigate the relation between the initial cognitive response to ChEI treatment and the subsequent long-term course of cognition of AD patients.Methods:The Frisian Alzheimer's Disease Cohort study is a retrospective longitudinal study of 576 community-dwelling AD patients treated with ChEIs in a “real-life” setting at a large memory clinic. A repeated measures analysis using a marginal model (population based averaged model) was applied to investigate whether there is a difference in the subsequent long-term course of cognition (Mini-Mental State Examination (MMSE)) between initial non-responders and responders. Absence of an initial response was defined as a lower MMSE score after the first six months of treatment compared to baseline, a positive response as the same or a higher MMSE score.Results:At baseline, median age was 80 years and the median MMSE score 23. Non-responders showed a slower rate of cognitive decline in the three subsequent years than responders, with a mean annual MMSE decline of 0.9 points versus 1.2 points, respectively (p < 0.0001).Conclusions:Our results suggest that it is not appropriate to discontinue ChEI treatment solely based on the absence of an initial cognitive response.