The effect of combination pretreatment of donepezil and environmental enrichment on memory deficits in amyloid-beta-induced Alzheimer-like rat model

Gholami, Jamileh; Negah, Sajad Sahab; Rajabian, Arezoo; Saburi, Ehsan; Hajali, Vahid

doi:10.1016/j.bbrep.2022.101392

Cited by 2 publications

(4 citation statements)

References 65 publications

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“…This finding is in accord with another study showing that both physical activity and cognitive stimulation can restore spatial memory, recognition, and motor deficits in the Tg4-42 AD mouse model [60]. Alzheimer's rats that had both EE and donepezil showed significant improvement in performance on the Morris Water Maze tests compared to having either EE or donepezil alone, or neither [65].…”

Section: Alzheimer's Disease and Dementiasupporting

confidence: 91%

Digital Therapeutics for Improving Effectiveness of Pharmaceutical Drugs and Biological Products: Preclinical and Clinical Studies Supporting Development of Drug + Digital Combination Therapies for Chronic Diseases

Biskupiak,

Ha,

Rohaj

et al. 2024

JCM

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Limitations of pharmaceutical drugs and biologics for chronic diseases (e.g., medication non-adherence, adverse effects, toxicity, or inadequate efficacy) can be mitigated by mobile medical apps, known as digital therapeutics (DTx). Authorization of adjunct DTx by the US Food and Drug Administration and draft guidelines on “prescription drug use-related software” illustrate opportunities to create drug + digital combination therapies, ultimately leading towards drug–device combination products (DTx has a status of medical devices). Digital interventions (mobile, web-based, virtual reality, and video game applications) demonstrate clinically meaningful benefits for people living with Alzheimer’s disease, dementia, rheumatoid arthritis, cancer, chronic pain, epilepsy, depression, and anxiety. In the respective animal disease models, preclinical studies on environmental enrichment and other non-pharmacological modalities (physical activity, social interactions, learning, and music) as surrogates for DTx “active ingredients” also show improved outcomes. In this narrative review, we discuss how drug + digital combination therapies can impact translational research, drug discovery and development, generic drug repurposing, and gene therapies. Market-driven incentives to create drug–device combination products are illustrated by Humira® (adalimumab) facing a “patent-cliff” competition with cheaper and more effective biosimilars seamlessly integrated with DTx. In conclusion, pharma and biotech companies, patients, and healthcare professionals will benefit from accelerating integration of digital interventions with pharmacotherapies.

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Section: Alzheimer's Disease and Dementiasupporting

confidence: 91%

Digital Therapeutics for Improving Effectiveness of Pharmaceutical Drugs and Biological Products: Preclinical and Clinical Studies Supporting Development of Drug + Digital Combination Therapies for Chronic Diseases

Biskupiak,

Ha,

Rohaj

et al. 2024

JCM

View full text Add to dashboard Cite

show abstract

“…Some experimenters have recognized that EE alone is not sufficient to produce the desired widespread improvement in cognitive function and pathology in AD and have used other therapies alongside enrichment to assess their combined effect. Studies combining EE with drug therapies, such as memantine, an N-methyl-D-aspartate receptor antagonist, donepezil, an acetylcholinesterase inhibitor, magnesium-L-threonate, an ingestible method to increase essential magnesium in the brain, or Bifidobacterium breve probiotic, have shown that the drug or EE alone can produce some benefits, but when combined there is improvement in learning and memory or more long-term effects [112][113][114][115]. Combination therapy using EE and caffeine was not as robust, with individual therapies having nearly equal effects as combined therapies [116].…”

Section: Roles Of Enrichment In Animal Models Of Alzheimer's Diseasementioning

confidence: 99%

“…Combined treatment only was able to restore spatial memory and elevate BDNF to control levels [115] Environmental Enrichment with Memantine SAMP8 (male-mouse)…”

Section: Improved Motor Skills Mildly Improved Inflammationmentioning

confidence: 99%

“…Studies examining the hormonal aspect of stress (HS) and its relationship to AD have concluded that glucocorticoids can lead to increased soluble Aβ and impair fear recall, while CRF and its receptor, corticotrophin-releasing factor receptor-1, are involved in the process of ptau phosphorylation [115,119,123,128,151]. Other studies have examined alternate styles of stressors, including maternal separation (MS) and psychosocial stress (PS), and found that these stressors lead to worsened spatial memory, increased levels of stress hormones, increased inflammation, and increased Aβ and ptau in AD animals [125,126,[165][166][167].…”

Section: Roles Of Stress In Animal Models Of Alzheimer's Diseasementioning

confidence: 99%

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Life Experience Matters: Enrichment and Stress Can Influence the Likelihood of Developing Alzheimer’s Disease via Gut Microbiome

et al. 2023

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Alzheimer’s disease (AD) is a chronic neurodegenerative disease, characterized by the presence of β-amyloid (Aβ) plaques and neurofibrillary tangles (NFTs) formed from abnormally phosphorylated tau proteins (ptau). To date, there is no cure for AD. Earlier therapeutic efforts have focused on the clinical stages of AD. Despite paramount efforts and costs, pharmaceutical interventions including antibody therapies targeting Aβ have largely failed. This highlights the need to alternate treatment strategies and a shift of focus to early pre-clinical stages. Approximately 25–40% of AD cases can be attributed to environmental factors including chronic stress. Gut dysbiosis has been associated with stress and the pathogenesis of AD and can increase both Aβ and NFTs in animal models of the disease. Both stress and enrichment have been shown to alter AD progression and gut health. Targeting stress-induced gut dysbiosis through probiotic supplementation could provide a promising intervention to delay disease progression. In this review, we discuss the effects of stress, enrichment, and gut dysbiosis in AD models and the promising evidence from probiotic intervention studies.

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The effect of combination pretreatment of donepezil and environmental enrichment on memory deficits in amyloid-beta-induced Alzheimer-like rat model

Cited by 2 publications

References 65 publications

Digital Therapeutics for Improving Effectiveness of Pharmaceutical Drugs and Biological Products: Preclinical and Clinical Studies Supporting Development of Drug + Digital Combination Therapies for Chronic Diseases

Digital Therapeutics for Improving Effectiveness of Pharmaceutical Drugs and Biological Products: Preclinical and Clinical Studies Supporting Development of Drug + Digital Combination Therapies for Chronic Diseases

Life Experience Matters: Enrichment and Stress Can Influence the Likelihood of Developing Alzheimer’s Disease via Gut Microbiome

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