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Nutrition-Based Approaches in Clinical Trials Targeting Cognitive Function: Highlights of the CTAD 2020.
Giudici, KV
The journal of prevention of Alzheimer's disease. 2021;(2):118-122
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Abstract
The Clinical Trials on Alzheimer's Disease (CTAD) 2020 conference was the stage for researchers from all over the world to present their recent and ongoing research focused on potential Alzheimer's disease (AD) treatments and prevention of cognitive decline. Among a varied range of topics, nutritional aspects arose as possibilities of treatments towards the promotion of a healthy aging. Among the discussed themes, supplementation of omega-3 polyunsaturated fatty acids and multi-nutrient approaches were presented, suggesting that long-term supplementation (i.e., over 3 years) might be needed for observing positive effects on cognitive performance. Trials testing ketogenic agents and carbohydrate-restricted diet were also presented and showed promising effects on improving cognitive function of mild-cognitive impaired (MCI) and pre-diabetic individuals, respectively, in a short-term way (i.e. after 3 to 6 months). The combination of some of the nutritional approaches with physical activity interventions raises the question on whether they would individually perform in a similar way. Promising therapies involving nutrition appear to be safe and well tolerated by volunteers. Failures on achieving positive findings raise questions on whether they were driven by specific characteristics of the studied populations, insufficient doses or duration of treatment. Notwithstanding, current evidence on the applicability of nutrition-based approaches as AD treatments are encouraging but demand further research on the topic.
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Potential effect of herbal antidepressants on cognitive deficit: Pharmacological activity and possible molecular mechanism.
Li, JM, Zhao, Y, Sun, Y, Kong, LD
Journal of ethnopharmacology. 2020;:112830
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Cognitive symptom is a "core" symptom of major depressive disorder (MDD) patients with clear deficit in memory, social and occupational function, and may persist during the remitting phase. Therefore, the remission of cognitive symptom has been considered as one of the main objectives in the treatment of MDD. Herbal antidepressants have been used to treat MDD, and there has been great advances in the understanding of the ability of these herbs to improve cognitive deficit linked to brain injury and various diseases including depression, Alzheimer disease, diabetes and age-related disorders. This systematic review summarizes the evidence from preclinical studies and clinical trials of herbal antidepressants with positive effects on cognitive deficit. The potential mechanisms by which herbal antidepressants prevent cognitive deficit are also reviewed. This review will facilitate further research and applications. MATERIALS AND METHODS We conducted an open-ended, English restricted search of MEDLINE (PubMed), Web of Science and Scopus for all available articles published or online before 31 December 2019, using terms pertaining to medical herb/phytomedicine/phytochemical/Chinese medicine and depression/major depressive disorder/antidepressant and/or cognitive impairment/cognitive deficit/cognitive dysfunction. RESULTS 7 prescriptions, more than 30 individual herbs and 50 phytochemicals from China, Japan, Korea and India with positive effects on the depressive state and cognitive deficit are reviewed herein. The evidence from preclinical studies and clinical trials proves that these herbal antidepressants exhibit positive effects on one or more aspects of cognitive defect including spatial, episodic, aversive, and short- and long-term memory. The action mode of the improvement of cognitive deficit by these herbal antidepressants is mediated mainly through two pathways. One pathway is to promote hippocampal neurogenesis through activating brain derived neurotrophic factor-tropomyosin-related kinase B signaling. The other pathway is to prevent neuronal apoptosis through the inhibition of neuro-inflammation and neuro-oxidation. CONCLUSION These herbal antidepressants, having potential therapy for cognitive deficit, may prevent pathological processes of neurodegenerative diseases. Furthermore, these herbal medicines should provide a treasure trove, which will accelerate the development of new antidepressants that can effectively improve cognitive symptom in MDD. Studies on their molecular mechanisms may provide more potential targets and therapeutic approaches for new drug discovery.
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Phosphodiesterase as a Target for Cognition Enhancement in Schizophrenia.
Al-Nema, MY, Gaurav, A
Current topics in medicinal chemistry. 2020;(26):2404-2421
Abstract
Schizophrenia is a severe mental disorder that affects more than 1% of the population worldwide. Dopamine system dysfunction and alterations in glutamatergic neurotransmission are strongly implicated in the aetiology of schizophrenia. To date, antipsychotic drugs are the only available treatment for the symptoms of schizophrenia. These medications, which act as D2-receptor antagonist, adequately address the positive symptoms of the disease, but they fail to improve the negative symptoms and cognitive impairment. In schizophrenia, cognitive impairment is a core feature of the disorder. Therefore, the treatment of cognitive impairment and the other symptoms related to schizophrenia remains a significant unmet medical need. Currently, phosphodiesterases (PDEs) are considered the best drug target for the treatment of schizophrenia since many PDE subfamilies are abundant in the brain regions that are relevant to cognition. Thus, this review aims to illustrate the mechanism of PDEs in treating the symptoms of schizophrenia and summarises the encouraging results of PDE inhibitors as anti-schizophrenic drugs in preclinical and clinical studies.
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MIND not Mediterranean diet related to 12-year incidence of cognitive impairment in an Australian longitudinal cohort study.
Hosking, DE, Eramudugolla, R, Cherbuin, N, Anstey, KJ
Alzheimer's & dementia : the journal of the Alzheimer's Association. 2019;(4):581-589
Abstract
INTRODUCTION Associations between the Mediterranean-DASH diet Intervention for Neurological Delay (MIND) diet and incidence of cognitive impairment have not been evaluated outside the United States. METHODS We investigated MIND and Mediterranean diet relations with 12-year incidence of Alzheimer's disease/Vascular dementia (National Institute of Neurological Disorders criteria) and mild cognitive impairment (Winbald criteria) in the Personality and Total Health (PATH) Through Life cohort (n = 1220) set in Canberra, Australia: wave-1 2001-2002; wave-2 2005-2006; wave-3 2009-2010; and wave-4 2013-2014. MIND diet and two alternate Mediterranean diet scores were calculated from the baseline food frequency questionnaire responses. Higher dietary scores signified greater adherence. RESULTS In adjusted logistic regression models, MIND diet (OR = 0.47, 95% CI 0.24, 0.91), but not Mediterranean diet, was associated with reduced odds of 12-year cognitive impairment. DISCUSSION Preliminary evidence suggests that protective effects of the MIND diet are geographically generalizable. Additional prospective studies are needed in diverse samples to determine the relative effects of the MIND and the Mediterranean diets against cognitive decline.
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Homocysteine: A modifiable culprit of cognitive impairment for us to conquer?
Ji, Y, Lyu, P, Jin, W, Li, X, Li, X, Dong, Y
Journal of the neurological sciences. 2019;:128-136
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.
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The Role of Nutrition in Cognitive Function and Brain Ageing in the Elderly.
Gardener, SL, Rainey-Smith, SR
Current nutrition reports. 2018;(3):139-149
Abstract
PURPOSE OF REVIEW The purposes of this review were to examine literature published over the last 5 years and to evaluate the role of nutrition in cognitive function and brain ageing, focussing on the Mediterranean diet (MeDi), Dietary Approaches to Stop Hypertension (DASH), and Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diets. RECENT FINDINGS Results suggest that higher adherence to a healthy dietary pattern is associated with preservation of brain structure and function as well as slower cognitive decline, with the MIND diet substantially slowing cognitive decline, over and above the MeDi and DASH diets. Whilst results to-date suggest adherence to a healthy diet, such as the MeDi, DASH, or MIND, is an important modifiable risk factor in the quest to develop strategies aimed at increasing likelihood of healthy brain ageing, further work is required to develop dietary guidelines with the greatest potential benefit for public health; a research topic of increasing importance as the world's population ages.
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Diet, nutrition and the ageing brain: current evidence and new directions.
Moore, K, Hughes, CF, Ward, M, Hoey, L, McNulty, H
The Proceedings of the Nutrition Society. 2018;(2):152-163
Abstract
Globally populations are ageing. By 2050, it is estimated that there will be two billion people aged 60 years or over, of which 131 million are projected to be affected by dementia, while depression is predicted to be the second leading cause of disability worldwide by 2020. Preventing or delaying the onset of these disorders should therefore be a public health priority. There is some evidence linking certain dietary patterns, particularly the Mediterranean diet, with a reduced risk of dementia and depression. Specific dietary components have also been investigated in relation to brain health, with emerging evidence supporting protective roles for n-3 PUFA, polyphenols, vitamin D and B-vitamins. At this time, the totality of evidence is strongest in support of a role for folate and the metabolically related B-vitamins (vitamin B12, vitamin B6 and riboflavin) in slowing the progression of cognitive decline and possibly reducing the risk of depression in ageing. Future studies incorporating new technologies, such as MRI and magnetoencephalography, offer much promise in identifying effective nutrition interventions that could reduce the risk of cognitive and mental disorders. This review will explore the ageing brain and the emerging evidence linking diet and specific nutrients with cognitive function and depression in ageing, with the potential to develop strategies that could improve quality of life in our ageing population.
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Cerebellar injury in preterm infants.
Tam, EWY
Handbook of clinical neurology. 2018;:49-59
Abstract
Although preterm birth is best known to result in adverse neurodevelopmental outcomes through injury of the supratentorial structures, including intraventricular hemorrhage and periventricular leukomalacia, the cerebellum has become increasingly recognized as an important target for injury and adverse motor and cognitive outcomes. Undergoing the most dramatic growth during the preterm period, the cerebellum is vulnerable to large and small hemorrhages, as well as hypoplasia resulting from a number of potentially modifiable risk factors. These factors include contact with intraventricular blood, crossed cerebrocerebellar diaschisis, postnatal glucocorticoid exposure, pain and opioid exposure, nutrition and somatic growth, cardiorespiratory factors, and socioeconomic status. Strategies targeting these factors may result in prevention of the motor and cognitive deficits seen after cerebellar hemorrhage or hypoplasia.
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The possible factors affecting microglial activation in cases of obesity with cognitive dysfunction.
Chunchai, T, Chattipakorn, N, Chattipakorn, SC
Metabolic brain disease. 2018;(3):615-635
Abstract
Obesity has reached epidemic proportions in many countries around the world. Several studies have reported that obesity can lead to the development of cognitive decline. There is increasing evidence to demonstrate that microglia play a crucial role in cognitive decline in cases of obesity, Alzheimer's disease and also in the aging process. Although there have been several studies into microglia over the past decades, the mechanistic link between microglia and cognitive decline in obese models is still not fully understood. In this review, the current available evidence from both in vitro and in vivo investigations regarding the association between the alteration in microglial activity in different obese models with respect to cognition are included. The metabolite profiles from obesity, adiposity, dietary and hormone affected microglial activation and its function in the brain are comprehensively summarized. In addition, the possible roles of microglial activation in relation to cognitive dysfunction are also presented and discussed. To ensure a balanced perspective controversial reports regarding these issues are included and discussed.
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Adherence to Mediterranean diet and risk of developing cognitive disorders: An updated systematic review and meta-analysis of prospective cohort studies.
Wu, L, Sun, D
Scientific reports. 2017;:41317
Abstract
Recent articles have presented inconsistent findings on the impact of Mediterranean diet in the occurrence of cognitive disorders; therefore, we performed an updated systematic review and meta-analysis to evaluate the potential association and dose-response pattern with accumulating evidence. We searched the PubMed and the Embase for the records relevant to this topic. A generic inverse-variance method was used to pool the outcome data for continuous variable, and categories of high vs. low, median vs. low of Mediterranean diet score with a random-effects model. Generalized least-squares trend estimation model was used to estimate the potential dose-response patterns of Mediterranean diet score on incident cognitive disorders. We identified 9 cohort studies involving 34,168 participants. Compared with the lowest category, the pooled analysis showed that the highest Mediterranean diet score was inversely associated with the developing of cognitive disorders, and the pooled RR (95% CI) was 0.79 (0.70, 0.90). Mediterranean diet score of the median category was not significantly associated with cognitive disorders. Dose-response analysis indicated a trend of an approximately linear relationship of the Mediterranean diet score with the incident risk of cognitive disorders. Further studies of randomized controlled trials are warranted to confirm the observed association in different populations.