Highlights
- •Homocysteine metabolism and the detrimental effects caused by its abnormal elevation
- •The research status of the association between homocysteine and cognitive impairment
- •Improvement of randomized controlled trials exploring the possible causative status of homocysteine in dementia
Abstract
Background
Cognitive impairment, including mild cognitive impairment and its progressive deterioration
to dementia, results in great hazards to the patient and the surrounding society.
While some of the risk factors are unmodifiable, such as age, lower educational attainment,
and genetic factors, another proposed one-homocysteine, an amino acid produced in
the methylation cycle of protein metabolism is modifiable by cheap and easily accessible
B-vitamins treatments in medical practice.
Objective and methods
To investigate the relationship between homocysteine and cognitive impairment, elucidate
the underlying pathophysiological mechanisms and exploit any potential therapeutic
values of homocysteine-lowering treatments in prevention and/or treatment in cognitive
decline, we searched on the PUBMED databases surrounding around the physiological
homocysteine metabolism, detrimental effects of abnormal homocysteine concentrations
on the brain, and review observational and interventional experiments to date estimating
the relationship between homocysteine and cognitive impairment with relatively powerful
evidence.
Results
Intrinsic and environmental factors help maintain the normal homocysteine concentrations,
and pathological homocysteine concentrations exert adverse effects mediated by cellular
and vascular pathways. Although many observational studies have suggested a causal
link between hyperhomocysteinemia and cognitive impairment, the majority of randomized
controlled trials failed to observe marked benefits on cognition by homocysteine-lowering
treatments using B-vitamins, partly arising from some design limitations including:
not identifying individuals at earlier stages of cognitive impairment who are most
likely to benefit, overlooking any latent safety hazards of multiple vitamin supplementation,
lack of sensitive and domain-specific cognitive tests, and interference of other underappreciated
factors.
Conclusion
More studies are required to better explain the related pathophysiological mechanisms,
improve experimental methods, and investigate the preventive or/and therapeutic effects
of homocysteine-lowering strategies on cognitive impairment.
Keywords
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Article info
Publication history
Published online: July 15, 2019
Accepted:
July 11,
2019
Received in revised form:
July 10,
2019
Received:
January 6,
2019
Identification
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© 2019 Elsevier B.V. All rights reserved.
