Intermittent Fasting: a Promising Approach for Preventing Vascular Dementia
Journal: 2020/August - Atherosclerosis
Abstract:
Vascular dementia is the most common neuropsychiatric syndrome and is characterized by synaptic dysfunction, neuroinflammation, and cognitive dysfunction. Vascular dementia is associated with various environmental, genetic, and lifestyle risk factors. Recent research has focused on the association between vascular dementia and dietary patterns, suggesting that dietary regulation leads to better control of energy metabolism, improvements in brain insulin resistance, and the suppression of neuroinflammation. Intermittent fasting is a calorie-restriction method known to be more effective in promoting fat loss and regulating the impairment of glucose metabolism as compared with other dietary restriction regimens. Herein, the authors review the effects of intermittent fasting with regard to vascular dementia based on recent evidence and propose that intermittent fasting could be a therapeutic approach for ameliorating vascular dementia pathology and preventing its onset.
Keywords: Cognitive function; Intermittent fasting; Vascular dementia.
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J Lipid Atheroscler 8(1): 1-7

Intermittent Fasting: a Promising Approach for Preventing Vascular Dementia

1. Intermittent fasting: focus on neuroinflammation

A previous study demonstrated that caloric restriction reduces the production of reactive oxygen species and promotes antioxidant responses such as nuclear factor-erythroid 2 signaling.26 Additionally, calorie restriction reduces DNA damage by attenuating telomere erosion through regulating nuclear factor kappa B in inflammatory signaling and the production of proinflammatory mediator C-reactive proteins.27 In particular, intermittent fasting reduces the levels of proinflammatory cytokines including interleukin (IL)-1β and IL-18 in the brain.27 One study reported that intermittent fasting decreases the production of IL-1α, IL-1β, and tumor necrosis factor-α under lipopolysaccharide-induced inflammatory conditions and increases the production of brain-derived neurotrophic factor in the hippocampus.28 Furthermore, intermittent fasting has been reported to improve cognitive decline by downregulating inflammatory responses.29 Intermittent fasting controls inflammatory pathways and contributes to hippocampal neuronal function, relating to memory,30 and inhibits neuronal cell apoptosis by controlling autophagic flux.31

2. Intermittent fasting: focus on neurotransmitters and synaptic plasticity

Neurotransmitters, including glutamate, are involved in synaptic plasticity and contribute to neuronal circuitry.32 Fasting may activate cAMP responsive element binding signaling in hippocampal and entorhinal cortical neurons involved in synaptic function and memory formation.33 In particular, intermittent fasting boosts hippocampal plasticity and mitochondrial function via calcium signaling.34 Intermittent fasting also contributes to neuronal synaptic plasticity by controlling the secretion of neurotransmitters including serotonin, noradrenaline, and dopamine.35 Intermittent fasting additionally improves the impairment of synaptic plasticity in hippocampal neurons36 and enhances autonomic synaptic plasticity,37 subsequently rescuing cognitive impairment.38

3. Intermittent fasting: focus on vascular function

Cerebrovascular dysfunction is commonly exhibited in patients with dementia.39 It leads to neuroinflammation and oxidative stress in the brain and causes neuronal damage; provokes BBB breakdown; and triggers amyloid plaque production by boosting the amyloid precursor protein (APP) cleavage enzyme, beta-secretase, and tau protein phosphorylation.40 A recent study demonstrated that arterial stiffness (or high-pulse wave velocity) could promote the increase of amyloid beta deposition and exacerbate cognitive decline.41 Additionally, neurovascular coupling is impaired in AD, and abnormal blood flow leads to an imbalance between neural activity and glucose metabolism in the brain.42 Calorie restriction has been reported to decrease the risk for atherosclerosis and reduce BP and triglyceride levels in blood vessels.43 Previous research has demonstrated that intermittent fasting improves endothelial dysfunction and attenuates the risk for cardiovascular diseases.44 Intermittent fasting has been found to improve endothelial vasorelaxation and stabilize high BP.45 A few studies have reported dramatic decreases in BP values after intermittent fasting46 as well as improvement in vascular function.47

4. Intermittent fasting: focus on insulin resistance and neurogenesis

Intermittent fasting leads to a decrease in insulin-like growth factor 1 expression and a consequent reduction in glucose levels.30 Additionally, intermittent fasting enhances insulin sensitivity in neurons and ameliorates dysfunction in glucose metabolism.48 Neurogenesis describes the process where new neurons are generated to replace injured neurons in the subventricular and subgranular zones of the hippocampus.49 In dementia, the process of neurogenesis is impaired and, consequently, cognitive impairment occurs.49 In AD, the excessive accumulation of APP triggers a decrease in neurogenesis in both the dentate gyrus and subventricular zone.50 Intermittent fasting enhances hippocampal neurogenesis51 and reduces brain damage by generating new neurons in response to oxidative stress.52

Department of Anatomy, Chonnam National University Medical School, Gwangju, Korea.
Department of Biochemistry, Chonnam National University, Gwangju, Korea.
Corresponding author.
Correspondence to Juhyun Song. Department of Anatomy, Chonnam National University Medical School, 160 Baekseo-ro, Dong-gu, Gwangju 61469, Korea. rk.ca.mannohc@gnosnuyhuj
Correspondence to Juhyun Song. Department of Anatomy, Chonnam National University Medical School, 160 Baekseo-ro, Dong-gu, Gwangju 61469, Korea. rk.ca.mannohc@gnosnuyhuj
Received 2018 Dec 15; Revised 2019 Jan 30; Accepted 2019 Mar 22.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Vascular dementia is the most common neuropsychiatric syndrome and is characterized by synaptic dysfunction, neuroinflammation, and cognitive dysfunction. Vascular dementia is associated with various environmental, genetic, and lifestyle risk factors. Recent research has focused on the association between vascular dementia and dietary patterns, suggesting that dietary regulation leads to better control of energy metabolism, improvements in brain insulin resistance, and the suppression of neuroinflammation. Intermittent fasting is a calorie-restriction method known to be more effective in promoting fat loss and regulating the impairment of glucose metabolism as compared with other dietary restriction regimens. Herein, the authors review the effects of intermittent fasting with regard to vascular dementia based on recent evidence and propose that intermittent fasting could be a therapeutic approach for ameliorating vascular dementia pathology and preventing its onset.

Keywords: Intermittent fasting, Vascular dementia, Cognitive function
Abstract

Footnotes

Funding: This study was supported by funded by grants (2016R1D1A1B03930394 to Juhyun Song) of the Basic Science Research Program through the National Research Foundation of Korea (NRF).

Conflict of Interest: The authors have no conflicts of interest to declare.

Footnotes

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