Antioxidants and Dementia Risk: Consideration through a Cerebrovascular Perspective

Abstract

A number of natural and chemical compounds that exert anti-oxidative properties are demonstrated to be beneficial for brain and cognitive function, and some are reported to reduce the risk of dementia. However, the detailed mechanisms by which those anti-oxidative compounds show positive effects on cognition and dementia are still unclear. An emerging body of evidence suggests that the integrity of the cerebrovascular blood-brain barrier (BBB) is centrally involved in the onset and progression of cognitive impairment and dementia. While recent studies revealed that some anti-oxidative agents appear to be protective against the disruption of BBB integrity and structure, few studies considered the neuroprotective effects of antioxidants in the context of cerebrovascular integrity. Therefore, in this review, we examine the mechanistic insights of antioxidants as a pleiotropic agent for cognitive impairment and dementia through a cerebrovascular axis by primarily focusing on the current available data from physiological studies. Conclusively, there is a compelling body of evidence that suggest antioxidants may prevent cognitive decline and dementia by protecting the integrity and function of BBB and, indeed, further studies are needed to directly examine these effects in addition to underlying molecular mechanisms.

Does Vitamin C Influence Neurodegenerative Diseases and Psychiatric Disorders?

“…Besides the presented roles, Vit C has also been suggested to prevent neurodegenerative changes and cognitive decline by protecting blood–brain barrier (BBB) integrity [ 68 ].…”

Vitamin C, Aging and Alzheimer’s Disease

“…So far, scant investigations have explored the effects of anti-oxidative vitamins on dementia through the cerebrovascular axis [ 95 ]. The study of Kook et al [ 87 ] recently reported that high-dose supplementation of AA reduced amyloidosis in AD mice (5XFAD) via the reduction of BBB disruption and mitochondrial alteration [ 96 ].…”

“…To date, AA seems to offer neuroprotection by restoring BBB integrity. However, further investigations should focus on simultaneously testing brain neuroprotective effects and BBB protective effects of antioxidants [ 95 ]. AA seems to possess both types of neuroprotection and could be further tested as a targeted dual agent for preventing cognitive decline.…”

“…Several cross-sectional studies have demonstrated a lower CSF-to-plasma AA ratio in AD patients compared to controls. In particular, recent findings [ 95 ] suggest that maintenance of a high CSF-to-plasma AA ratio is important in preventing cognitive decline in AD and that BBB impairment unfavorably affects this ratio. However, whether the AA transport carrier dysfunction (SVCT2) or the disturbed BBB integrity is responsible for it, is still a matter of debate.…”

Traditional Chinese Medicine Might Reduce Risk of Dementia in Patients with Parkinson’s disease: A Population-based Nested Case-control Study

“…Previous studies demonstrated that natural compounds, which act as antioxidative, have positive effects on neuroprotection. [13] Some TCM contain contributing factors as mentioned above on preventing dementia, such as AChE inhibitors and neuronal injury inhibitors. Part of the TCM also exhibit anti-in ammation, anti-hypertension, anti-hyperlipidemia, anti-diabetes, and anticonvulsion characteristics.…”