Comparative efficacy and safety of cognitive enhancers for treating vascular cognitive impairment: systematic review and Bayesian network meta-analysis

Abstract

Objective: To assess and compare the clinical efficacy and safety of cognitive enhancers (donepezil, galantamine, rivastigmine, and memantine) on cognition, behavior, function, and global status in patients with vascular cognitive impairment. Data sources: The initial literature search was performed with PubMed, EMBASE, the Cochrane Methodology Register, the Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing & Allied Health (CINAHL) from inception to January 2018 for studies regarding donepezil, galantamine, rivastigmine, and memantine for treatment of vascular cognitive impairment. Data selection: Randomized controlled trials on donepezil, galantamine, rivastigmine, and memantine as monotherapy in the treatment of vascular cognitive impairment were included. A Bayesian network meta-analysis was conducted. Outcome measures: Efficacy was assessed by changes in scores of the Alzheimer’s Disease Assessment Scale, cognitive subscale, Mini-Mental State Examination, Neuropsychiatric Inventory scores and Clinician’s Interview-Based Impression of Change Scale Plus Caregiver’s Input, Activities of Daily Living, the Clinical Dementia Rating scale. Safety was evaluated by mortality, total adverse events (TAEs), serious adverse events (SAEs), nausea, vomiting. diarrhea, or cerebrovascular accidents (CVAs). Results: After screening 1717 citations, 12 randomized controlled trials were included. Donepezil and rivastigmine (mean difference (e) = –0.77, 95% confidence interval (CI): 0.25–1.32; MD = 1.05, 95% CI : 0.18–1.79) were significantly more effective than placebo in reducing Mini-Mental State Examination scores. Donepezil, galantamine, and memantine ( MD = –1.30, 95% CI : –2.27 to –0.42; MD = –1.67, 95% CI : –3.36 to –0.06; MD = –2.27, 95% CI : –3.91 to –0.53) showed superior benefits on the Alzheimer’s Disease Assessment Scale–cognitive scores compared with placebo. Memantine ( MD = 2.71, 95% CI : 1.05–7.29) improved global status (Clinician’s Interview-Based Impression of Change Scale Plus Caregiver’s Input) more than the placebo. Safety results revealed that donepezil 10 mg (odds ratio ( OR ) = 3.04, 95% CI : 1.86–5.41) contributed to higer risk of adverse events than placebo. Galantamine ( OR = 5.64, 95% CI : 1.31–26.71) increased the risk of nausea. Rivastigmine ( OR = 16.80, 95% CI : 1.78–319.26) increased the risk of vomiting. No agents displayed a significant risk of serious adverse events, mortality, cerebrovascular accidents, or d...

Roles of glutamate receptors in a novel in vitro model of early, comorbid cerebrovascular, and Alzheimer’s diseases

“…However, clinical benefits of memantine are highly variable and have been questioned in several meta-analytic reviews, particularly for cases classified as mild AD (Blanco-Silvente et al, 2018;Folch et al, 2018;McShane et al, 2019). A similar case is verified for patients diagnosed with vascular cognitive impairment (Farooq, Min, Goshgarian, & Gorelick, 2017;Jin & Liu, 2019). The contrast between retrospective meta-analyses of large cohorts of patients and the sporadic reports of clinical benefit of memantine may be a consequence of preclinical models that do not represent the majority of patients of rather complex maladies such as coexisting cerebrovascular and Alzheimer diseases (Yassi et al, 2020).…”

Cholinesterase inhibitors and memantine for the treatment of Alzheimer and non-Alzheimer dementias

“…Patients with donepezil (5 and 10 mg) or galantamine (16 and 24 mg) therapy showed improvement in cognitive tests, while rivastigmine had no substantial effect on cognition 25 . Examining a wider range of outcomes, the meta-analysis of Jin and Liu 26 found, that the effect of ChEis on cognitive functions was similar, but without improvement on ADL and BPSD domains. The clinical heterogeneity of VaD limits the general validity of outcome data, the effect of treatment on specific patients or subgroups might be different.…”

Vascular cognitive impairment and chronic cerebral ischemia (dyscirculatory encephalopathy)

“…Противодементные средства (ингибитор ацетилхолинэстераз, мемантин) эффективны при деменции альцгеймеровского типа, а также при сочетании СКН и БА [55,56]. На основании систематического анализа противодементные средства расцениваются как препараты выбора для улучшения когнитивных функций при СКН, при этом отмечается положительное влияние акатинола мемантина в отношении функционального состояния пациентов [57].…”