Special Issue "Nutrition in Cognitive Impairment, Dementia, and Alzheimer's Disease"

A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Nutritional Epidemiology".

Deadline for manuscript submissions: closed (31 December 2020).

Special Issue Editor

Dr. Tatsuhiro Hisatsune
E-Mail Website
Guest Editor
Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo
Interests: brain aging; MCI; neuroinflammation; brain–gut interaction; neurovascular unit; human interventional study; RCT; psychometoric tests; MRI; surrogate markers; epidemiological study; functional peptides; polyphenols; Alzheimer’s disease model mice

Special Issue Information

Dear Colleagues,

Dementia is a major global health issue, since more than 10% of the elder population (>65 years old) is diagnosed with the syndrome in most of the recent epidemiologic studies. By 2050, more than 130 million people are estimated to have dementia worldwide. Alzheimer’s disease (AD) is the most frequent cause of dementia. Mild cognitive impairment (MCI) is an intermediate transitional stage between the cognitive normal and dementia. In AD, the accumulation of cerebral amyloid-beta has usually been occurring for more than 20 years before the onset of dementia. At the dementia stage, neuronal damage progresses together with the accumulation of tau protein. The necessity of targeting MCI or preclinical AD in clinical trials to prevent dementia is now widely recognized; however, no evidence of pharmacological treatments or cognitive training for preventing the development of dementia has been demonstrated. Under these circumstances, supplementation of food-derived materials attracts attention as potentially beneficial for reducing risks, and further research is needed. Nutritional substances present in food, such as functional peptides like imidazoledipeptides, polyphenols, and PFAs (DHA and EPA), have a potential protective effect on cognitive functions. On this topic, you are invited to submit proposals for manuscripts that fit the objectives and the topics of this Special Issue.

The objective of this proposed Special Issue on “Nutrition in Cognitive Impairment, Dementia, and Alzheimer's Disease” is to publish selected papers detailing specific aspects of nutrition that could play a role in protecting cognitive declines, both in normal elderly subjects, MCI, and in patients with dementia. Particularly, papers (reviews and/or clinical or experimental studies) dealing with the role of specific nutrients on cognitive function, and also contributions addressing their indirect effects through brain–gut interaction will be included.

Dr. Tatsuhiro Hisatsune
Guest Editor

Manuscript Submission Information

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Keywords

  • Brain aging
  • Neuroinflammation
  • Brain–gut interaction
  • Neurovascular unit
  • Human interventional study
  • Alzheimer’s disease
  • Clinical trials
  • Cognitive impairment
  • Dementia
  • Diet/dietary patterns
  • Micronutrients
  • Macronutrients
  • Nutrition
  • Functional peptides
  • Polyphenols
  • Observational studies

Published Papers (13 papers)

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Research

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Article
Brain Training and Sulforaphane Intake Interventions Separately Improve Cognitive Performance in Healthy Older Adults, Whereas a Combination of These Interventions Does Not Have More Beneficial Effects: Evidence from a Randomized Controlled Trial
Nutrients 2021, 13(2), 352; https://doi.org/10.3390/nu13020352 - 25 Jan 2021
Cited by 2 | Viewed by 1221
Abstract
Background: Earlier studies have demonstrated that a single-domain intervention, such as a brain-training (BT) game alone and a sulforaphane (SFN) intake, positively affects cognition. This study examined whether a combined BT and SFN intake intervention has beneficial effects on cognitive function in older [...] Read more.
Background: Earlier studies have demonstrated that a single-domain intervention, such as a brain-training (BT) game alone and a sulforaphane (SFN) intake, positively affects cognition. This study examined whether a combined BT and SFN intake intervention has beneficial effects on cognitive function in older adults. Methods: In a 12-week double-blinded randomized control trial, 144 older adults were randomly assigned to one of four groups: BT with SFN (BT-S), BT with placebo (BT-P), active control game (AT) with SFN (AT-S), and active control game with placebo (AT-P). We used Brain Age in BT and Tetris in AT. Participants were asked to play BT or AT for 15 min a day for 12 weeks while taking a supplement (SFN or placebo). We measured several cognitive functions before and after the intervention period. Results: The BT (BT-S and BT-P) groups showed more improvement in processing speed than the active control groups (AT-S and AT-P). The SFN intake (BT-S and AT-S) groups recorded significant improvements in processing speed and working memory performance unlike the placebo intake groups (BT-P and AT-P). However, we did not find any evidence of the combined intervention’s beneficial effects on cognition. Discussion: We discussed a mechanism to improve cognitive functions in the BT and SFN alone interventions. Full article
(This article belongs to the Special Issue Nutrition in Cognitive Impairment, Dementia, and Alzheimer's Disease)
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Article
Consumption of Oleic Acid on the Preservation of Cognitive Functions in Japanese Elderly Individuals
Nutrients 2021, 13(2), 284; https://doi.org/10.3390/nu13020284 - 20 Jan 2021
Cited by 3 | Viewed by 1259
Abstract
We recruited 154 community-dwelling elderly individuals and conducted a cohort study to find out the nutrient intake that is suitable for maintaining cognitive function in Japanese elders. Cognitive function was evaluated by the two functional tests, the Montreal Cognitive Assessment (MoCA) and Wechsler [...] Read more.
We recruited 154 community-dwelling elderly individuals and conducted a cohort study to find out the nutrient intake that is suitable for maintaining cognitive function in Japanese elders. Cognitive function was evaluated by the two functional tests, the Montreal Cognitive Assessment (MoCA) and Wechsler Memory Scale-Delayed Recall (WMS-DR), and daily nutrient intake was estimated from a Brief-type Self-administered Diet History Questionnaire (BDHQ). By a multiple regression analysis, among the four major nutrients (protein, fat, carbohydrate and ash), we detected a significant correlation between the score of cognitive functions assessed by both MoCA and WMS-DR and daily consumption of fat (p = 0.0317 and p = 0.0111, respectively). Among categories of fatty acid, we found a significant correlation between the score of both MoCA and WMS-DR and consumption of monounsaturated fatty acid (MUFA) (p = 0.0157 and p = 0.0136, respectively). Finally, among MUFAs, we observed a significant correlation between the score of both MoCA and WMS-DR and consumption of oleic acid (p = 0.0405 and p = 0.0165, respectively). From these observations, we can propose that daily consumption of fat, especially in oleic acid, has a beneficial effect against cognitive decline in community-dwelling Japanese elderly individuals. Full article
(This article belongs to the Special Issue Nutrition in Cognitive Impairment, Dementia, and Alzheimer's Disease)
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Article
Effects of Matcha Green Tea Powder on Cognitive Functions of Community-Dwelling Elderly Individuals
Nutrients 2020, 12(12), 3639; https://doi.org/10.3390/nu12123639 - 26 Nov 2020
Cited by 3 | Viewed by 2829
Abstract
Matcha Green Tea Powder contains a variety of active ingredients beneficial to health, such as tea catechins, lutein and vitamin K. It is also known that these ingredients confer benefits upon cognitive functions of elderly people. Therefore, we aimed to investigate the relationship [...] Read more.
Matcha Green Tea Powder contains a variety of active ingredients beneficial to health, such as tea catechins, lutein and vitamin K. It is also known that these ingredients confer benefits upon cognitive functions of elderly people. Therefore, we aimed to investigate the relationship between a daily supplementation of Matcha and the change in cognitive functions of community-dwelling elderly people. A randomized, double-blind, placebo-controlled 12-week trial was performed. Sixty-one participants were recruited and randomly assigned to receive test drink containing 3 g powder from fresh Matcha or placebo powder per day. Changes in cognitive function were assessed utilizing a psychometric test battery. Daily food intake was assessed by a Brief-type Self-administered Diet History Questionnaire (BDHQ). In the gender-specific analysis, a significant cognitive enhancement was observed in the Montreal Cognitive Assessment (MoCA) score in the active group of women. In dietary analysis, we found a significant inverse correlation between consumption of vitamin K in daily diet, excluding test drinks, and change in MoCA. The present study suggests that daily supplementation of Matcha Green Tea Powder has protective effects against cognitive decline in community-dwelling elderly women. Full article
(This article belongs to the Special Issue Nutrition in Cognitive Impairment, Dementia, and Alzheimer's Disease)
Article
High Glycemic Load Is Associated with Cognitive Decline in Apolipoprotein E ε4 Allele Carriers
Nutrients 2020, 12(12), 3619; https://doi.org/10.3390/nu12123619 - 25 Nov 2020
Viewed by 824
Abstract
Recent evidence suggests that a high glycemic load (GL) diet is a risk factor for dementia, especially among apolipoprotein E ε4 allele (APOE4) carriers, while its association with cognitive decline is poorly known. Here, we investigated the association of high-GL meals [...] Read more.
Recent evidence suggests that a high glycemic load (GL) diet is a risk factor for dementia, especially among apolipoprotein E ε4 allele (APOE4) carriers, while its association with cognitive decline is poorly known. Here, we investigated the association of high-GL meals with cognitive decline in older adults during a 12-year follow-up, according to their APOE4 carrier status. We used random-effect models and data from 2539 elderly participants from the Three-City study who completed a food frequency questionnaire (FFQ) to longitudinally assess the association of GL with changes in different cognitive domains (verbal fluency, visual memory, attention, visual motor processing speed, episodic memory). In APOE4 carriers, afternoon snack with high GL was significantly associated with cognitive decline in visual memory, episodic memory, and global cognition compared with APOE4 non-carriers. This study suggests a detrimental association between a high-GL diet and cognitive decline. The promotion of a low GL diet as a target to prevent cognitive decline in high-risk populations deserves more research. Full article
(This article belongs to the Special Issue Nutrition in Cognitive Impairment, Dementia, and Alzheimer's Disease)
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Article
Sex-Specific Effects of Chronic Creatine Supplementation on Hippocampal-Mediated Spatial Cognition in the 3xTg Mouse Model of Alzheimer’s Disease
Nutrients 2020, 12(11), 3589; https://doi.org/10.3390/nu12113589 - 23 Nov 2020
Cited by 3 | Viewed by 950
Abstract
The creatine (Cr) energy system has been implicated in Alzheimer’s disease (AD), including reductions in brain phosphoCr and Cr kinase, yet no studies have examined the neurobehavioral effects of Cr supplementation in AD, including the 3xTg mouse model. This studied investigated the effects [...] Read more.
The creatine (Cr) energy system has been implicated in Alzheimer’s disease (AD), including reductions in brain phosphoCr and Cr kinase, yet no studies have examined the neurobehavioral effects of Cr supplementation in AD, including the 3xTg mouse model. This studied investigated the effects of Cr supplementation on spatial cognition, plasticity- and disease-related protein levels, and mitochondrial function in the 3xTg hippocampus. Here, 3xTg mice were fed a control or Cr-supplemented (3% Cr (w/w)) diet for 8–9 weeks and tested in the Morris water maze. Mitochondrial oxygen consumption (Seahorse) and protein levels (Western blots) were measured in the hippocampus in subsets of mice. Overall, 3xTg females exhibited impaired memory as compared to males. In females, Cr supplementation decreased escape latency and was associated with increased spatial search strategy use. In males, Cr supplementation decreased the use of spatial search strategies. Pilot data indicated mitochondrial enhancements with Cr supplementation in both sexes. In females, Cr supplementation increased CREB phosphorylation and levels of IκB (NF-κB suppressor), CaMKII, PSD-95, and high-molecular-weight amyloid β (Aβ) species, whereas Aβ trimers were reduced. These data suggest a beneficial preventative effect of Cr supplementation in females and warrant caution against Cr supplementation in males in the AD-like brain. Full article
(This article belongs to the Special Issue Nutrition in Cognitive Impairment, Dementia, and Alzheimer's Disease)
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Article
The Different Relationship between Homocysteine and Uric Acid Levels with Respect to the MTHFR C677T Polymorphism According to Gender in Patients with Cognitive Impairment
Nutrients 2020, 12(4), 1147; https://doi.org/10.3390/nu12041147 - 19 Apr 2020
Viewed by 1213
Abstract
In an elderly population with cognitive impairment, we investigated the association between serum uric acid (sUA) and serum homocysteine (sHcy), known risk factors for cerebrovascular disease. We also investigated the potential effect of the C677T polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR) [...] Read more.
In an elderly population with cognitive impairment, we investigated the association between serum uric acid (sUA) and serum homocysteine (sHcy), known risk factors for cerebrovascular disease. We also investigated the potential effect of the C677T polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR) to the sUA level in different dementia types. Participants underwent a battery of tests including measurements of sUA, sHcy, folic acid, and vitamin B12 as well as genotyping of the MTHFR locus. Data from 861 subjects (597 females to 264 males) were retrospectively analyzed. Subjects with hyperhomocysteinemia had lower serum folic acid and vitamin B12 and higher sUA than those with normal sHcy. sUA was significantly associated with serum creatinine, HbA1c, and sHcy regardless of gender. The TT genotype was found to be associated with hyperhomocysteinemia in both genders (p = 0.001). The levels of hyperlipidemia, sHcy, and sUA differed according to dementia subtypes. High sUA were associated with hyperhomocystenemia in TT genotype only in dementia with vascular lesion. This study reveals that sUA is positively associated with sHcy. We speculate that the two markers synergistically increase cerebrovascular burden and suggested that dietary intervention for sUA and sHcy would be helpful for cognitive decline with vascular lesion. Full article
(This article belongs to the Special Issue Nutrition in Cognitive Impairment, Dementia, and Alzheimer's Disease)
Article
The Effects of a 6-Month High Dose Omega-3 and Omega-6 Polyunsaturated Fatty Acids and Antioxidant Vitamins Supplementation on Cognitive Function and Functional Capacity in Older Adults with Mild Cognitive Impairment
Nutrients 2020, 12(2), 325; https://doi.org/10.3390/nu12020325 - 26 Jan 2020
Cited by 10 | Viewed by 3529
Abstract
The aim of the present study was to examine the effects of a high-dose omega-3 and omega-6 fatty acids supplementation, in combination with antioxidant vitamins, on cognitive function and functional capacity of older adults with mild cognitive impairment (MCI), over a 6-month period [...] Read more.
The aim of the present study was to examine the effects of a high-dose omega-3 and omega-6 fatty acids supplementation, in combination with antioxidant vitamins, on cognitive function and functional capacity of older adults with mild cognitive impairment (MCI), over a 6-month period in a randomized, double-blind, placebo-controlled trial. Forty-six older adults with MCI (age: 78.8 ± 7.3 years) were randomized 1:1 to receive either a 20 mL dose of a formula containing a mixture of omega-3 (810 mg Eicosapentaenoic acid and 4140 mg Docosahexaenoic acid) and omega-6 fatty acids (1800 mg gamma-Linolenic acid and 3150 mg Linoleic acid) (1:1 w/w), with 0.6 mg vitamin A, vitamin E (22 mg) plus pure γ-tocopherol (760 mg), or 20 mL placebo containing olive oil. Participants completed assessments of cognitive function, functional capacity, body composition and various aspects of quality of life at baseline and following three and six months of supplementation. Thirty-six participants completed the study (eighteen from each group). A significant interaction between supplementation and time was found on cognitive function (Addenbrooke’s Cognitive Examination -Revised (ACE-R), Mini-Mental State Examination (MMSE) and Stroop Color and Word Test (STROOP) color test; p < 0.001, p = 0.011 and p = 0.037, respectively), functional capacity (6-min walk test and sit-to-stand-60; p = 0.028 and p = 0.032, respectively), fatigue (p < 0.001), physical health (p = 0.007), and daily sleepiness (p = 0.007)—showing a favorable improvement for the participants receiving the supplement. The results indicate that this nutritional modality could be promising for reducing cognitive and functional decline in the elderly with MCI. Full article
(This article belongs to the Special Issue Nutrition in Cognitive Impairment, Dementia, and Alzheimer's Disease)
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Review

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Review
Potential of Caffeine in Alzheimer’s Disease—A Review of Experimental Studies
Nutrients 2021, 13(2), 537; https://doi.org/10.3390/nu13020537 - 06 Feb 2021
Cited by 5 | Viewed by 1988
Abstract
Alzheimer’s disease (AD) is the most common type of dementia leading to progressive memory loss and cognitive impairment. Considering that pharmacological treatment options for AD are few and not satisfactory, increasing attention is being paid to dietary components that may affect the development [...] Read more.
Alzheimer’s disease (AD) is the most common type of dementia leading to progressive memory loss and cognitive impairment. Considering that pharmacological treatment options for AD are few and not satisfactory, increasing attention is being paid to dietary components that may affect the development of the disease. Such a dietary component may be caffeine contained in coffee, tea or energy drinks. Although epidemiological data suggest that caffeine intake may counteract the development of cognitive impairment, results of those studies are not conclusive. The aim of the present study is to review the existing experimental studies on the efficacy of caffeine against AD and AD-related cognitive impairment, focusing on the proposed protective mechanisms of action. In conclusion, the reports of studies on experimental AD models generally supported the notion that caffeine may exert some beneficial effects in AD. However, further studies are necessary to elucidate the role of caffeine in the effects of its sources on cognition and possibly AD risk. Full article
(This article belongs to the Special Issue Nutrition in Cognitive Impairment, Dementia, and Alzheimer's Disease)
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Review
Influence of Imidazole-Dipeptides on Cognitive Status and Preservation in Elders: A Narrative Review
Nutrients 2021, 13(2), 397; https://doi.org/10.3390/nu13020397 - 27 Jan 2021
Cited by 1 | Viewed by 1024
Abstract
The worldwide increase in the number of patients with dementia is becoming a growing problem, while Alzheimer’s disease (AD), a primary neurodegenerative disorder, accounts for more than 70% of all dementia cases. Research on the prevention or reduction of AD occurrence through food [...] Read more.
The worldwide increase in the number of patients with dementia is becoming a growing problem, while Alzheimer’s disease (AD), a primary neurodegenerative disorder, accounts for more than 70% of all dementia cases. Research on the prevention or reduction of AD occurrence through food ingredients has been widely conducted. In particular, histidine-containing dipeptides, also known as imidazole dipeptides derived from meat, have received much attention. Imidazole dipeptides are abundant in meats such as poultry, fish, and pork. As evidenced by data from recent human intervention trials conducted worldwide, daily supplementation of carnosine and anserine, which are both imidazole dipeptides, can improve memory loss in the elderly and reduce the risk of developing AD. This article also summarizes the latest researches on the biochemical properties of imidazole dipeptides and their effects on animal models associated with age-related cognitive decline. In this review, we focus on the results of human intervention studies using supplements of poultry-derived imidazole dipeptides, including anserine and carnosine, affecting the preservation of cognitive function in the elderly, and discuss how imidazole dipeptides act in the brain to prevent age-related cognitive decline and the onset of dementia. Full article
(This article belongs to the Special Issue Nutrition in Cognitive Impairment, Dementia, and Alzheimer's Disease)
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Review
The Role of Natural Antioxidants in the Prevention of Dementia—Where Do We Stand and Future Perspectives
Nutrients 2021, 13(2), 282; https://doi.org/10.3390/nu13020282 - 20 Jan 2021
Cited by 3 | Viewed by 1209
Abstract
Dementia, and especially Alzheimer’s disease (AD), puts significant burden on global healthcare expenditure through its increasing prevalence. Research has convincingly demonstrated the implication of oxidative stress in the pathogenesis of dementia as well as of the conditions which increase the risk of developing [...] Read more.
Dementia, and especially Alzheimer’s disease (AD), puts significant burden on global healthcare expenditure through its increasing prevalence. Research has convincingly demonstrated the implication of oxidative stress in the pathogenesis of dementia as well as of the conditions which increase the risk of developing dementia. However, drugs which target single pathways have so far failed in providing significant neuroprotection. Natural antioxidants, due to their effects in multiple pathways through which oxidative stress leads to neurodegeneration and triggers neuroinflammation, could prove valuable weapons in our fight against dementia. Although efficient in vitro and in animal models of AD, natural antioxidants in human trials have many drawbacks related to the limited bioavailability, unknown optimal dose, or proper timing of the treatment. Nonetheless, trials evaluating several of these natural compounds are ongoing, as are attempts to modify these compounds to achieve improved bioavailability. Full article
(This article belongs to the Special Issue Nutrition in Cognitive Impairment, Dementia, and Alzheimer's Disease)
Review
Vitamins in Alzheimer’s Disease—Review of the Latest Reports
Nutrients 2020, 12(11), 3458; https://doi.org/10.3390/nu12113458 - 11 Nov 2020
Cited by 4 | Viewed by 1138
Abstract
Alzheimer’s disease (AD) is the most common form of dementia, and the aging of the population means that the number of cases is successively increasing. The cause of the disease has not been established, but it is suggested that many factors affect it, [...] Read more.
Alzheimer’s disease (AD) is the most common form of dementia, and the aging of the population means that the number of cases is successively increasing. The cause of the disease has not been established, but it is suggested that many factors affect it, including nutritional aspects. As part of the work, the PubMed database has been searched, beginning from 2005, for terms related to key nutritional aspects. A diet rich in antioxidant vitamins can improve the cognitive functions of patients. Thanks to an adequate intake of B vitamins, homocysteine levels are reduced, which indirectly protects against the development of the disease. A properly balanced diet, as well as the use of appropriate supplementation, can contribute to improving the clinical condition of patients with AD. Full article
(This article belongs to the Special Issue Nutrition in Cognitive Impairment, Dementia, and Alzheimer's Disease)
Review
Influence of the Mediterranean and Ketogenic Diets on Cognitive Status and Decline: A Narrative Review
Nutrients 2020, 12(4), 1019; https://doi.org/10.3390/nu12041019 - 08 Apr 2020
Cited by 17 | Viewed by 5149
Abstract
Alzheimer’s disease (AD) is the most common form of senile dementia, accounting for up to 70% of dementia cases. AD is a slowly progressive disease, which causes global mental deterioration by affecting various cognitive areas. A growing body of evidence has demonstrated that [...] Read more.
Alzheimer’s disease (AD) is the most common form of senile dementia, accounting for up to 70% of dementia cases. AD is a slowly progressive disease, which causes global mental deterioration by affecting various cognitive areas. A growing body of evidence has demonstrated that lifestyle habits and nutritional patterns could delay the natural course of the neurodegeneration process. There is no single dietary pattern unequivocally proven to prevent AD. Nevertheless, epidemiological data suggest that by adopting several dietary habits, especially if accompanied with a healthy lifestyle, the negative consequences of AD could potentially be delayed. Alongside with others, two specific eating patterns have been well investigated concerning their potential beneficial effect on cognitive status: the Mediterranean diet (MedDi) and the Ketogenic Diet (KD). Despite the different underlying mechanisms, both of them have demonstrated a fairly profitable role in reducing or delaying cognitive impairment. The aim of the present narrative review is to overview the existing research on the efficacy of MedDi and KD against AD-related cognitive decline, focusing on the proposed protective mechanisms of action. Although the current knowledge on this complex topic does not allow us, at this point, to make exhaustive conclusions, this information could be of help in order to better characterize the possible role of MedDi and KD as nonpharmacological therapies in the treatment of AD and, more generically, of neurodegenerative disorders. Full article
(This article belongs to the Special Issue Nutrition in Cognitive Impairment, Dementia, and Alzheimer's Disease)
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Review
Neuroprotective Effects of Choline and Other Methyl Donors
Nutrients 2019, 11(12), 2995; https://doi.org/10.3390/nu11122995 - 06 Dec 2019
Cited by 19 | Viewed by 2713
Abstract
Recent evidence suggests that physical and mental health are influenced by an intricate interaction between genes and environment. Environmental factors have been shown to modulate neuronal gene expression and function by epigenetic mechanisms. Exposure to these factors including nutrients during sensitive periods of [...] Read more.
Recent evidence suggests that physical and mental health are influenced by an intricate interaction between genes and environment. Environmental factors have been shown to modulate neuronal gene expression and function by epigenetic mechanisms. Exposure to these factors including nutrients during sensitive periods of life could program brain development and have long-lasting effects on mental health. Studies have shown that early nutritional intervention that includes methyl-donors improves cognitive functions throughout life. Choline is a micronutrient and a methyl donor that is required for normal brain growth and development. It plays a pivotal role in maintaining structural and functional integrity of cellular membranes. It also regulates cholinergic signaling in the brain via the synthesis of acetylcholine. Via its metabolites, it participates in pathways that regulate methylation of genes related to memory and cognitive functions at different stages of development. Choline-related functions have been dysregulated in some neurodegenerative diseases suggesting choline role in influencing mental health across the lifespan. Full article
(This article belongs to the Special Issue Nutrition in Cognitive Impairment, Dementia, and Alzheimer's Disease)
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