Targeting impaired nutrient sensing with repurposed therapeutics to prevent or treat age-related cognitive decline and dementia: A systematic review.
Ageing Res Rev
; 67: 101302, 2021 05.
Article
in English
| MEDLINE | ID: covidwho-1454005
ABSTRACT
BACKGROUND:
Dementia 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.AIMS:
This 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.METHODS:
PubMed, 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.RESULTS:
Out 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.CONCLUSIONS:
Modulation 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.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Dementia
/
Alzheimer Disease
/
Cognitive Dysfunction
Type of study:
Prognostic study
/
Reviews
/
Systematic review/Meta Analysis
Limits:
Aged
/
Humans
Language:
English
Journal:
Ageing Res Rev
Journal subject:
Geriatrics
Year:
2021
Document Type:
Article
Affiliation country:
J.arr.2021.101302
Similar
MEDLINE
...
LILACS
LIS