Neuroprotective effects of combined therapy with memantine, donepezil, and vitamin D in ovariectomized female mice subjected to dementia model

Vieira, Ana Daniela Coutinho; Medeiros, Eduarda Behenck; Zabot, Gabriel Casagrande; Pereira, Nathalia de Souza; Nascimento, Natália Baltazar do; Lidio, Adrielly Vargas; Scheffer, Ândrea Kohlrausch; Rempel, Lisienny Campoli Tono; Macarini, Bárbara Machado Naspolini; Costa, Maiara de Aguiar da; Gonçalves, Cinara L.; Kucharska, Ewa; Rodrigues, Matheus Scarpatto; Moreira, José Cláudio Fonseca; Oliveira, Jade de; Budni, Josiane

doi:10.1016/j.pnpbp.2022.110653

Cited by 5 publications

(3 citation statements)

References 100 publications

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“…First, it has been shown that there are differences in brain structure and function between men and women, with the hippocampus and gray matter regions being larger in women than in men ( Cosgrove et al, 2007 ). The expression of presynaptic and postsynaptic proteins in the hippocampus is affected by fluctuations in estrogen levels, which have a direct impact on cognition ( Vieira et al, 2023 ). Decreasing estrogen levels or menopause in women may lead to the onset or worsening of cognitive deficits and the development of dementia ( Davey, 2017 ; Vieira et al, 2023 ).…”

Section: Discussionmentioning

confidence: 99%

“…The expression of presynaptic and postsynaptic proteins in the hippocampus is affected by fluctuations in estrogen levels, which have a direct impact on cognition ( Vieira et al, 2023 ). Decreasing estrogen levels or menopause in women may lead to the onset or worsening of cognitive deficits and the development of dementia ( Davey, 2017 ; Vieira et al, 2023 ). In addition, the ratio of the volume of distribution to the bioavailability of donepezil is greater in women than in men, and the peak concentrations of memantine are greater in women than in men ( Ovejero-Benito et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

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Adverse event profile of memantine and donepezil combination therapy: a real-world pharmacovigilance analysis based on FDA adverse event reporting system (FAERS) data from 2004 to 2023

Yang,

Wei,

Tian

et al. 2024

Front. Pharmacol.

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BackgroundDonepezil in combination with memantine is a widely used clinical therapy for moderate to severe dementia. However, real-world population data on the long-term safety of donepezil in combination with memantine are incomplete and variable. Therefore, the aim of this study was to analyze the adverse events (AEs) of donepezil in combination with memantine according to US Food and Drug Administration Adverse Event Reporting System (FAERS) data to provide evidence for the safety monitoring of this therapy.MethodsWe retrospectively analyzed reports of AEs associated with the combination of donepezil and memantine from 2004 to 2023 extracted from the FAERS database. Whether there was a significant association between donepezil and memantine combination therapy and AEs was assessed using four disproportionality analysis methods, namely, the reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker methods. To further investigate potential safety issues, we also analyzed differences and similarities in the time of onset and incidence of AEs stratified by sex and differences and similarities in the incidence of AEs stratified by age.ResultsOf the 2,400 adverse drug reaction (ADR) reports in which the combination of donepezil and memantine was the primary suspected drug, most of the affected patients were female (54.96%) and older than 65 years of age (79.08%). We identified 22 different system organ classes covering 100 AEs, including some common AEs such as dizziness and electrocardiogram PR prolongation; fall, pleurothotonus and myoclonus were AEs that were not listed on the drug label. Moreover, we obtained 88 reports of AEs in men and 100 reports of AEs in women; somnolence was a common AE in both men and women and was more common in women, whereas pleurothotonus was a more common AE in men. In addition, we analyzed 12 AEs in patients younger than 18 years, 16 in patients between 18 and 65 years, and 113 in patients older than 65 years. The three age groups had distinctive AEs, but lethargy was the common AE among all age groups. Finally, the median time to AE onset was 19 days in all cases. In both men and women, most AEs occurred within a month of starting donepezil plus memantine, but some continued after a year of treatment.ConclusionOur study identified potential and new AEs of donepezil in combination with memantine; some of these AEs were the same as in the specification, and some of the AE signals were not shown in the specification. In addition, there were sex and age differences in some of the AEs. Therefore, our findings may provide valuable insights for further studies on the safety of donepezil and memantine combination therapy, which are expected to contribute to the safe use of this therapy in clinical practice.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Adverse event profile of memantine and donepezil combination therapy: a real-world pharmacovigilance analysis based on FDA adverse event reporting system (FAERS) data from 2004 to 2023

Yang,

Wei,

Tian

et al. 2024

Front. Pharmacol.

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“…Our 1-year supplementation with the nutritional blend, however, did not mitigate the increase in plasma GFAP over time. Investigations on the effects of nutrient supplementation on GFAP are still scarce in literature, but there is evidence linking vitamin D (55) and EPA (56) supplementation with inhibition of glial activation in rodents. Future studies on the topic are hence encouraged.…”

Section: Discussionmentioning

confidence: 99%

Effect of a 1-Year Nutritional Blend Supplementation on Plasma p-tau181 and GFAP Levels among Community-Dwelling Older Adults: A Secondary Analysis of the Nolan Trial

Giudici¹,

Barreto²,

Guyonnet³

et al. 2023

J Aging Res & Lifestyle

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B A C K G R O U N D : O b s e r v a t i o n a l s t u d i e s a n d s o m e randomized controlled trials have suggested that nutritional supplementation could be a possible intervention pathway to prevent cognitive decline and Alzheimer's disease (AD). As measuring amyloid-β and tau pathophysiology by positron emission tomography (PET) or cerebrospinal fluid (CSF) analyses may be perceived as complex, plasma versions of such biomarkers have emerged as more accessible alternatives with comparable capacity of predicting cognitive impairment. OBJECTIVES: This study aimed to evaluate the effect of a 1-year intervention with a nutritional blend on plasma p-tau181 and glial fibrillary acidic protein (GFAP) levels in communitydwelling older adults. Effects were further assessed in exploratory analyses within sub-cohorts stratified according to p-tau status (with the third tertile considered as high: ≥15.1 pg/ mL) and to apolipoprotein E (APOE) ε4 allele status. METHODS: A total of 289 participants ≥70 years (56.4% female, mean age 78.1 years, SD=4.7) of the randomized, double-blind, multicenter, placebo-controlled Nolan trial had their plasma p-tau181 assessed, and daily took either a nutritional blend (composed of thiamin, riboflavin, niacin, pantothenic acid, pyridoxine, biotin, folic acid, cobalamin, vitamin E, vitamin C, vitamin D, choline, selenium, citrulline, eicosapentaenoic acid -EPA, and docosahexaenoic acid -DHA) or placebo for 1 year. RESULTS: After 1-year, both groups presented a significant increase in plasma p-tau181 and GFAP values, with no effect of the intervention (p-tau181 between-group difference: 0.27pg/mL, 95%CI: -0.95, 1.48; p=0.665; GFAP between-group difference: -3.28 pg/mL, 95%CI: -17.25, 10.69; p=0.644). P-tauand APOE ε4-stratified analyses provided similar findings. CONCLUSIONS: In community-dwelling older adults, we observed an increase in plasma p-tau181 and GFAP levels that was not different between the supplementation groups after one year.

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Emerging paradigms in Alzheimer's therapy

Preethy H,

Rajendran,

Sukumar

et al. 2024

European Journal of Pharmacology

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Neuroprotective effects of combined therapy with memantine, donepezil, and vitamin D in ovariectomized female mice subjected to dementia model

Cited by 5 publications

References 100 publications

Adverse event profile of memantine and donepezil combination therapy: a real-world pharmacovigilance analysis based on FDA adverse event reporting system (FAERS) data from 2004 to 2023

Adverse event profile of memantine and donepezil combination therapy: a real-world pharmacovigilance analysis based on FDA adverse event reporting system (FAERS) data from 2004 to 2023

Effect of a 1-Year Nutritional Blend Supplementation on Plasma p-tau181 and GFAP Levels among Community-Dwelling Older Adults: A Secondary Analysis of the Nolan Trial

Emerging paradigms in Alzheimer's therapy

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