Targeting impaired nutrient sensing with repurposed therapeutics to prevent or treat age-related cognitive decline and dementia: A systematic review |
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| Institution: | 1. Department of Medicine and Aged Care, @AgeMelbourne, Royal Melbourne Hospital, University of Melbourne, Victoria, Australia;2. University Hospital Geelong, Barwon Health, Melbourne, Victoria, Australia;3. Centre for Quantitative Neuroimaging, Department of Radiology, Royal Melbourne Hospital, University of Melbourne, Victoria, Australia;4. North West Mental Health, Melbourne Health, Melbourne, Victoria, Australia;5. Older Persons Mental Health Service, Canberra Health Services, Canberra, ACT, Australia;6. Healthy Longevity Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore;7. Centre for Healthy Longevity, National University Health System, Singapore;8. Singapore Institute of Clinical Sciences, A?STAR, Singapore;9. Academic Unit for Psychiatry of Old Age, Department of Psychiatry, University of Melbourne, Melbourne, Victoria, Australia;10. Department of Human Movement Sciences, @AgeAmsterdam, Amsterdam Movement Sciences, Vrije Universiteit, Amsterdam, The Netherlands;1. Department of Medicine and Aged Care, @AgeMelbourne, Royal Melbourne Hospital, University of Melbourne, Victoria, Australia;2. University Hospital Geelong, Barwon Health, Melbourne, Victoria, Australia;3. Centre for Quantitative Neuroimaging, Department of Radiology, Royal Melbourne Hospital, University of Melbourne, Victoria, Australia;4. North West Mental Health, Melbourne Health, Melbourne, Victoria, Australia;5. Older Persons Mental Health Service, Canberra Health Services, Canberra, ACT, Australia;6. Healthy Longevity Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore;7. Centre for Healthy Longevity, National University Health System, Singapore;8. Singapore Institute of Clinical Sciences, A?STAR, Singapore;9. Academic Unit for Psychiatry of Old Age, Department of Psychiatry, University of Melbourne, Melbourne, Victoria, Australia;10. Department of Human Movement Sciences, @AgeAmsterdam, Amsterdam Movement Sciences, Vrije Universiteit, Amsterdam, The Netherlands |
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| Abstract: | BackgroundDementia is a debilitating syndrome that significantly impacts individuals over the age of 65 years. There are currently no disease-modifying treatments for dementia. Impairment of nutrient sensing pathways has been implicated in the pathogenesis of dementia, and may offer a novel treatment approach for dementia.AimsThis systematic review collates all available evidence for Food and Drug Administration (FDA)-approved therapeutics that modify nutrient sensing in the context of preventing cognitive decline or improving cognition in ageing, mild cognitive impairment (MCI), and dementia populations.MethodsPubMed, Embase and Web of Science databases were searched using key search terms focusing on available therapeutics such as ‘metformin’, ‘GLP1’, ‘insulin’ and the dementias including ‘Alzheimer’s disease’ and ‘Parkinson’s disease’. Articles were screened using Covidence systematic review software (Veritas Health Innovation, Melbourne, Australia). The risk of bias was assessed using the Cochrane Risk of Bias tool v 2.0 for human studies and SYRCLE’s risk of bias tool for animal studies.ResultsOut of 2619 articles, 114 were included describing 31 different ‘modulation of nutrient sensing pathway’ therapeutics, 13 of which specifically were utilized in human interventional trials for normal ageing or dementia. Growth hormone secretagogues improved cognitive outcomes in human mild cognitive impairment, and potentially normal ageing populations. In animals, all investigated therapeutic classes exhibited some cognitive benefits in dementia models. While the risk of bias was relatively low in human studies, this risk in animal studies was largely unclear.ConclusionsModulation of nutrient sensing pathway therapeutics, particularly growth hormone secretagogues, have the potential to improve cognitive outcomes. Overall, there is a clear lack of translation from animal models to human populations. |
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| Keywords: | Aging Dementia Cognition Therapeutics Organic chemicals Clinical trial |
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