The average lifespan in humans is reaching its limit. Resultantly, the need for intervention strategies to relieve age-related cognitive decline and neurodegenerative disorders has never been more prevalent. Alzheimer's disease (AD) is now the leading cause of dementia and death among all the age-related illnesses. It is a progressive neurodegenerative disorder characterized by the accumulation of amyloid (A)-prone fragments and phosphorylated tau clustered in different parts of the brain. Unfortunately, most research studies of possible AD therapies have failed to produce beneficial results on cognitive health in the last decades. As Alzheimer's is a heterogeneous disorder, limited administration of a single action procedure may thus only support a small subgroup of people. Thus, it is plausible that dietary strategies derived from natural food compounds have earned significant attention lately in reversing the cognitive impairment caused by AD or other age-related diseases.
According to a clinical study performed on an animal model of AD in 2015, the polyphenolic extract of blueberries and grapes (PEBG) fed to mice showed promising results in the improvement of spatial working memory. The major focus of conducting this trial was to determine whether if PEBG can help boost memory performance by the brain-derived neurotrophic factor (BENF), a protein that helps in the growth of neurons. Supplementations of a high polyphenolic diet of grapes and berries were fed to 12-month-old mice with major symptoms of Alzheimer's. The main components of the diet were Catechins, epicatechins and gallic acid, the clinical trials on mice were continued to be observed for nearly four months. The supplemental doses were ranged from 500-2500 mg/kg. Meanwhile, the mice were analyzed for various behavioral aspects, like explanatory, anxiety, memory, and motor performances. After the trial period of 122 days, the results were evaluated. It was shown that, although supplementation of PEBG did not have a much thorough effect on beta-amyloid and tau biomarkers, it significantly enhanced object recognition in mice and improved memory performance without modifying levels of anxiety or motor activities. Also, senior citizens with age-related cognitive decline demonstrated significant improvement in their cognitive skills and memory performances after ingesting polyphenol-rich foods, like grapes or blueberry juices. (Alexandrea Dal-Pan, Stephanie. D, Phillippe Barossa et al., 2017)
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In another 6.5-year trial conducted, known as PREDIMED (Prevention with the Mediterranean Diet) it was revealed that the consumption of Med Diet supplemented with extra virgin olive oil or raw nuts, resulted in improved cognitive abilities as compared with the group who just consumed a low-fat diet. The study proposed the objective that the Mediterranean Diet had a more significant effect on cognition than a controlled low-fat diet. This randomized trial was done with senior citizens, between the ages of 55-80 years. After the participants were assessed in accordance to inclusion-exclusion criteria, the eligible sample population were given one of the three dietary plans; one Mediterranean diet that was supplemented with 1 liter of extra virgin olive oil per week, another one was the same Mediterranean diet but this time supplemented with about 30g of mixed nuts, the last diet was the standard low-fat diet. The sample groups were asked to come for a series of cognitive tests after the completion of an average of 6.5 years follows up. After several neurological tests including, CDT (Clock Drawing Test), MMSE (Mini-Mental State Examination), etc, the scores were analyzed and it was concluded that consumers of MedDiet either enhanced with extra virgin olive oil or mixed nuts, had better scores, in comparison with the ones who consumed the controlled low-fat diet. These findings of Elena. H, Pedro. C strengthened the evidence that MedDiet has protective effects on cognitive or neurological health. (Elena. H, Pedro. C, Estefan is Toledo et al., 2015)
An additional study with a similar objective found out that increasing constancy to the Mediterranean diet was associated with lower risks of Mild cognitive impairment and Alzheimer’s disease. The main focus of this study was to determine if there was any relation between the two variables namely; Cognitive impairment and the Mediterranean diet. The results were analyses with the help of MeDi scores (0-9). These scores not only encouraged the evidence of a strong link between Med Diet and cognitive health, but it also showed that adherence to this dietary lifestyle also slowed down the conversion of mild cognitive impairment to Alzheimer’s disease, thus suggesting that it could help in reducing the overall risk of Alzheimer’s disease. (Balwinder Singh, Ajay. K et al., 2014)
To observe the effects of the Mediterranean diet, either with high adherence or low adherence, on Alzheimer’s disease, a 3-year study was conducted at New York University, in 2018. The basic purpose of this research was to determine the effect of the Mediterranean diet on biomarkers of Alzheimer’s disease, specifically the beta-amyloid marker. About 82 participants were selected for the study, out of this about 12 were excluded mid-study, due to absence in follow-ups, incomplete questionnaires, or other medical problems. The baseline ages for the eligibility of participants was 50 years or above. The current dietary history and future dietary information of the sample population were collected via food frequency questionnaires developed by Harvard. The foods were combined to form 30 food groups, their average consumption was calculated, and MeDi scores were generated. A greater MeDi score between 5-9, indicated higher adherence while poor MeDi scores between 0-4 showed lower adherence. After 3 years, the final results of the study concluded that at the start of the study, the participants showed low CMRglc rates (reflects neural dysfunction) and high beta-amyloid deposition. Abnormalities in biomarker's changes in Alzheimer’s disease appeared after one and a half years of following this diet. Finally, the combined results stated that high adherence to the Mediterranean diet may help protect against Alzheimer’s and aging of the brain for further 3.5 years, and also that dietary changes may indeed affect the progression of Alzheimer’s, with a lowered risk of having dementia. (Valentina Berti, Michelle Walters, Joanna Sterling et al., 2018)
For a more microscopic approach between the relationship of Diet and Alzheimer’s or Dementia, several researchers carried out a study in January 2020, with the major objective of determining the interactions of underlying protein, which results in neuropsychological symptoms in those with dementia or Alzheimer’s. Data from several participants and previous researches were gathered, entered into a computer system, and integrated using the DAVID database (provides proper tools for processing the true biological meaning of large genomic networks). The results showed that the basic pathological cause of Alzheimer’s is the disrupted synaptic distribution which leads to loss of synapses, hence behavioral difficulties in people with Alzheimer’s. This in turn is caused by unique proteins that are categorized into two functional categories; the first ones are proteins involved in phosphorylation, while the other ones are chaperones. The main reason behind including this research was that a more clear view of the pathology of Alzheimer’s may lead to better insight for further dietary-based researches for both Dementia and Alzheimer’s. (Yimin Mao, Daniel. W, Rachel. M et al., 2020)
Furthermore, another study was undertaken to evaluate the effects of polyphenols on the aging brain and Alzheimer’s. Researchers like Sebastian, Heike, Sabine, etc collected several available studies and trials, to provide a better understanding of the polyphenolic mechanisms which provide protective or even reversible effects for neurological conditions, such as Alzheimer’s. A polyphenol-rich diet is abundant in flavonoids, mainly curcumin, flavanols, hydroxyl tyrosol, anthocyanin, terpenes, etc. The conclusive discussion suggested that consumption of anthocyanin, lead to reduced semantic interference in memory. Also, the ingestion of tea polyphenols was associated with reduced cognitive decline. Several studies also evidenced that G. Biloba (herb) was found to reduce neurogenesis and lower impaired nutrigenomics. Further, there is much evidence that supports the protective effects of polyphenols on cognition. (Sebastian. S, Heike Asseburg, Sabine. K et al., 2012)
In a pilot study, conducted in 2018 in Spain, it was observed that the use of coconut oil was associated with improved problem solving and enhanced memory. Moreover, the positive effects were much more prevalent in women than in men. This study was carried to detect the additional effects of the Mediterranean diet when supplemented with coconut oil instead of extra virgin olive oil and also to determine its beneficial functions in several variables; age, gender, stage of Alzheimer’s. For this purpose, 44 participants were selected mostly belonging to senior citizen houses. All 44 participants had Alzheimer’s and they have divided into two homogeneous groups; the first 22 participants were those who consumed a Mediterranean diet supplemented with coconut oil, while the remaining 22 were the control group. Before assigning the diet, four tests were conducted to assess the participants: Benton Temporal Orientation Test, Clock Drawing Test, Categorical Verbal Fluency Test, and lastly the Free and Cued Selective Reminding Test. After evaluation, the case sample was told to follow the Mediterranean diet along with 40 ml of coconut oil (first 20 ml during breakfast and remaining 20 ml during lunch) for 21 days continuously, while the control group was asked to consume just the typical Mediterranean diet, without any supplementation. After the said period of 21 days, and several follow-ups, the results were analyzed. They showed that there was more improvement in memories, both episodic and semantic, and also in problem-solving, for those who took coconut oil as a supplementation in contrast to the control group who did not. Not only this, but this study also provided evidence for the MCFA-based ketogenic diets, for its protective functions in various neurodegenerative diseases, such as Parkinson’s disease, Epilepsy, and Sclerosis. (Jose Enrique, Maria. P, David Sancho et al., 2018)
For another dietary pattern, also known as the DASH diet (Dietary Approaches to Stop Hypertension) a randomized control trial took place for about 4 years, unraveling major opportunities for the implementation of this dietary pattern in several other conditions in the upcoming future. The study showed that the DASH diet was a highly assessable and more economically friendly diet. Its beneficial effects were not only limited to hypertension only, but they branched to a much more diverse array of health conditions, some of them are different types of CVDs or Alzheimer’s, etc. Although more trials are needed to know exactly the effects the DASH diet has on Alzheimer’s, one thing is for sure that this study evidence that the DASH diet may become a convenience for those suffering from both, financial difficulties as well as Alzheimer’s disease. (Dori Steinberg, Laura. S, Gary. G et al., 2017)
To examine the combined effect of both the Mediterranean diet and the DASH diet, a study was conducted in 2014. Its major objective was to determine the effect of both dietary patterns on cognitive decline in older people. This cohort study comprised of eight hundred twenty-six participants, who aged 80 years or above. The majority of the participants were females with more than 14 years of education. Most of the participants belonged to an ongoing study MAP, Memory and Aging Project, which was initiated in 1997. The sample population was asked to fill a modified food frequency questionnaire which was based on MAP, containing 144 food items. They were asked to fill in their usual, routinely consumption. After this, two different dietary patterns were assigned to people, one of which was the Mediterranean diet it had 10 food groups, along with alcohol intake, while the DASH diet had 7 food groups. Three components were the same in both diets, the energy intake was from total fat, or saturated fat and some mg of sodium per day were ingested. Scores were set, for the DASH diet (0 – 10), and the Mediterranean diet (0 – 55), out of which the maximum score could be 55. Meanwhile, cognitive functioning was annually assessed by 19 different tests, mainly for memory and visuospatial ability. The results presented a mean DASH score of 4.1, while the Mediterranean score counted a maximum of 31.3, along with lowering cognitive score from 0.12 to negative 0.08 (normal ranges 3.23 to negative 1.60). This study evidenced the support of the alternate hypothesis, that both DASH and the Mediterranean diet are linked with lowering rates of cognitive decline. (Christy. C, Hong Li, Yamin, et al., 2014)
This study was carried out to analyze the relation of the MIND diet and the reduced incidence of Alzheimer’s disease. The study population consisted of 923 volunteers between the ages of 58-98 years, residing in old homes or retirement centers. The participants were asked to fill the Food Frequency Questionnaires before the study and were also clinically assessed. (According to the diagnostic criteria; 144 cases of Alzheimer’s and 14 cases of non-Alzheimer’s dementia were reported). Other variables like BMI, physical activity, hypertension were also assessed. Participants were asked to consume (Fruits 3-4 servings/day), (High Dairy 2+ servings/day), (High Starch 2 servings/day), (1 fish meal/week) and overall (>6 meals/week). The diet scores were computed, according to the filled FFQs and servings were devised. This dietary pattern was observed over the period of 12 months and the MIND score was analyzed and correlated with both the Mediterranean and DASH diet scores. The results suggested that high adherence to all 3 dietary patterns individually is found to have an inverse relation to Alzheimer’s, but moderate adherence to the MIND diet could support the lowered risk of Alzheimer’s as well. (Martha Clare Morris et al., 2015)
After the evidence supported positive effects of both the DASH diet and Mediterranean diet, nonpharmaceutical treatment approaches received a lot of attention in Alzheimer’s research, this leads to the creation of a new hybrid diet, named MIND diet (Mediterranean-DASH Intervention for Neurodegenerative Delay). The purpose of this study was to evaluate which of the MIND diet components, are more responsible for its beneficial effect on cognition. In this clinical study, it was seen that MIND dust consumption resulted in an overall reduction of Alzheimer’s by 53 percent, all while significantly lowering cognitive decline. These effects were mainly caused by the combined functions of both diets like antioxidant activity, anti-atherogenic activity, anti-inflammatory activity, and cognitive enhancing functions of both Mediterranean and DASH diet. (Syed Harris Omar, 2019)
A recent cohort study of 2019, was carried out to determine other additional effects of MIND diet on cognitive health, after a stroke. About a hundred participants were selected, eligibility criteria were based on fulfilling assessment forms, cognitive tests and also had a history of stroke. The participants were asked to follow the MIND diet, which included the consumption of vegetables, nuts, poultry, berries, and olive oil, along with reducing the consumption of fried and sugary foods. MIND scores of the sample population were computed and analyzed, the results once again were concluded in favor of the MIND diet, stating its inverse relation to cognitive health not only for Alzheimer’s but those who also suffered from a stroke. It also stated that the MIND diet is more superior than other diets when it comes to nonpharmaceutical treatment options. (L. Cherian, Y. Wang et al., 2019)
In another 12 week study conducted of the MIND diet in collaboration with speed process training, was checked in low educated population, to determine its additive effects on cognition. The participants were aged 60 years or above, with education as low as 10th grader, and self-reported diagnosis of Alzheimer’s or Dementia. The study population was to select seven food items/week, each serving designed specifically to provide a minimum of 1000 mg of polyphenols. They were also given IPad with 12-week application access to mind training games and much more. After the period of 12 weeks, the participants were assessed by filling the FFQs and cognitive tests. Also, this was the very first study to incorporate high polyphenol intake along with speed cognitive testing, the results not only showed positive impact but also paves way for future research possibilities for both Alzheimer’s and Dementia, as a nonpharmaceutical approach for therapeutic purposes. (Daniel O. Clark et al., 2019)
Lastly, another study was performed in 2018, to determine the effects of the high polyphenolic MIND diet, mainly on neuropsychic symptoms that come with Alzheimer’s. The main purpose was to evaluate the role of MIND diet on depression, in comparison with the Mediterranean diet. The participants were selected from several follow-ups, who were depression-free. Food consumption was noted and analyzed to produce MIND diet scores, and it was found out that the Mediterranean diet had high adherence towards lowered depression risk than the MIND diet. (Maira Bes. R, Gina. S et al., 2018)
In light of this researches, it is strongly evidenced that the consumption of either the Mediterranean diet or the DASH diet is beneficial in reducing Alzheimer’s. Still, not many studies were conducted to focus on the newly developed hybrid MIND diet, there are still a lot of questions about its effectiveness on Alzheimer’s, about its additional effects on the brain, what type of polyphenol is behind its effects and much more. This study is designed to fulfill these gaps and to establish a more clear understanding of its components and the relationship of this hybrid diet with Alzheimer’s.
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