Dietary Patterns and Alzheimer’s Disease: An Updated Review Linking Nutrition to Neuroscience

Alzheimer’s disease (AD) is a growing concern for the aging population worldwide. With no current cure or reliable treatments available for AD, prevention is an important and growing area of research. A range of lifestyle and dietary patterns have been studied to identify the most effective preventive lifestyle changes against AD and related dementia (ADRD) pathology. Of these, the most studied dietary patterns are the Mediterranean, DASH, MIND, ketogenic, and modified Mediterranean-ketogenic diets. However, there are discrepancies in the reported benefits among studies examining these dietary patterns. We herein compile a narrative/literature review of existing clinical evidence on the association of these patterns with ADRD symptomology and contemplate their preventive/ameliorative effects on ADRD neuropathology in various clinical milieus. By and large, plant-based dietary patterns have been found to be relatively consistently and positively correlated with preventing and reducing the odds of ADRD. These impacts stem not only from the direct impact of specific dietary components within these patterns on the brain but also from indirect effects through decreasing the deleterious effects of ADRD risk factors, such as diabetes, obesity, and cardiovascular diseases. Importantly, other psychosocial factors influence dietary intake, such as the social connection, which may directly influence diet and lifestyle, thereby also impacting ADRD risk. To this end, prospective research on ADRD should include a holistic approach, including psychosocial considerations.


Introduction
Dementia is one of the most prevalent illnesses among older adults, with over 55 million people worldwide suffering from dementia. According to the World Health Organization (WHO), dementia is caused by diseases and injuries that affect the brain [1]. These diseases gradually destroy nerve cells and impair brain function over time, resulting in the deterioration of cognitive functioning beyond the normal effects of biological aging. This deterioration affects memory, thinking, processing speed, and the ability to engage in activities of daily living. Consequently, dementia leads to disability and an increasing level of dependency. Moreover, dementia imposes a significant physical, psychological, social, and economic burden on caregivers, families, and society. By 2030, the global population of older adults (aged ≥ 65 years old) is projected to reach 1 billion, accounting for 12% of the total population [2]. With an aging population, the rates of neurodegenerative diseases such as Alzheimer's disease (AD) and related dementias (ADRD) will continue to increase.

Impact of Mediterranean Diet on ADRD Progression
The Mediterranean diet (MedD), created by an American couple in the 1960s, is inspired by the eating habits of people in Greece, Southern Italy, and Spain in the 1940s and 1950s [45]. These habits involve a high consumption of olive oil, unrefined cereals, fruits, and vegetables; a moderate to high consumption of fish; a moderate consumption of dairy products (mostly cheese and yogurt); moderate wine consumption; and a low consumption of red meat products [12]. The MedD consists of nutrient-dense foods that have been recognized as beneficial for overall health and healthy brain aging [9]. It has been associated with a lower risk of conversion from mild cognitive impairment to dementia [46][47][48][49], a reduction in dementia incidence [46,[50][51][52][53][54][55][56], the maintenance of brain health [20,57], a lower risk of cognitive decline [41,[58][59][60][61][62][63], and better cognition [64,65]. However, some inconsistencies are observed among studies regarding the benefits of the MedD on cognition and cognitive aging, particularly with regard to ADRD. Some studies did not find significant associations between the MedD and a decrease in ADRD incidence and/or conversion from mild cognitive impairment to dementia, which may be attributed to recruiting participants from outside the Mediterranean area [21,56,[66][67][68][69][70][71][72][73][74]. There is evidence that

Impact of Mediterranean Diet on ADRD Progression
The Mediterranean diet (MedD), created by an American couple in the 1960s, is inspired by the eating habits of people in Greece, Southern Italy, and Spain in the 1940s and 1950s [45]. These habits involve a high consumption of olive oil, unrefined cereals, fruits, and vegetables; a moderate to high consumption of fish; a moderate consumption of dairy products (mostly cheese and yogurt); moderate wine consumption; and a low consumption of red meat products [12]. The MedD consists of nutrient-dense foods that have been recognized as beneficial for overall health and healthy brain aging [9]. It has been associated with a lower risk of conversion from mild cognitive impairment to dementia [46][47][48][49], a reduction in dementia incidence [46,[50][51][52][53][54][55][56], the maintenance of brain health [20,57], a lower risk of cognitive decline [41,[58][59][60][61][62][63], and better cognition [64,65]. However, some inconsistencies are observed among studies regarding the benefits of the MedD on cognition and cognitive aging, particularly with regard to ADRD. Some studies did not find significant associations between the MedD and a decrease in ADRD incidence and/or conversion from mild cognitive impairment to dementia, which may be attributed to recruiting participants from outside the Mediterranean area [21,56,[66][67][68][69][70][71][72][73][74]. There is evidence that the benefits of the MedD may be more prominent among individuals who have adhered to the MedD throughout their lives and reside in the Mediterranean region compared to those who adopt this dietary pattern later in life [75]. Another factor contributing to the contradictory results is the variation in the qualitative and quantitative food components prescribed in different studies. For example, some studies grouped all polyunsaturated fatty acids together, while others focused solely on olive oil. Additionally, the quantities of different components of the diet vary among studies. A randomized study, for instance, examined the impact of the MedD supplemented with olive oil or nuts and identified a significant improvement in global cognition and/or specific cognitive domains among a Spanish population with cardiovascular risk factors over a period of 6.5 years [76]. Furthermore, there is considerable variation in the scoring systems used across different studies, which can lead to disparities in estimating nutrient intake and compliance with the MedD [77]. It is important to consider potential sources of discrepancies in research findings, which may stem from differences in the studied populations, including factors such as gender (males or females only), the presence of obesity or cardiovascular diseases, and the duration of the studies. The timing of dietary adherence, whether it occurs during midlife or late life, also needs careful consideration. Table 1 provides a compilation of observational, longitudinal, and intervention studies conducted in the past 10 years examining the MedD and its association with ADRD risk factors.
In addition to cognitive outcomes associated with ADRD risk, recent research has examined the effect of the MedD on AD biomarkers, specifically β-amyloid and phosphorylated tau tangles. In a systematic review and meta-analysis conducted by Hill et al. [78], it was concluded that adherence to a Mediterranean-style dietary pattern was associated with a reduction in AD biomarkers (β-amyloid and tau tangle) and subsequent pathology. Specifically, in the latest published study by Agarwal et al. [79], which involved autopsied older adults, higher scores of adherence to the MedD were significantly associated with lower global AD pathology (p = 0.039). Even after adjusting the models for other covariates, such as physical activity, smoking, and vascular disease burden, the association remained significant (p = 0.027). When excluding the dietary assessments from the last year of life of the participants to account for events that might have altered their diet, greater overall adherence to the MedD for almost a decade remained significantly associated with reduced global AD pathology and β-amyloid load. Furthermore, the MedD has shown potential in reducing the incidence of ADRD through its beneficial effects on blood pressure [80], mitochondrial structure and function [81], the preservation of white matter microstructure [82,83], the induction of cerebral blood flow [81], cortical thickness [84], and the accumulation of white matter hyperintensities [85]. The MedD can also act through a variety of mechanisms, including antiinflammatory, antioxidant, and lipid-lowering actions [86,87], as well as its favorable impact on cardiovascular risk factors [87][88][89]. MedD has also been associated with higher total brain volume and cortical thickness and lower white matter hyperintensities [84,[90][91][92][93]. All these factors can contribute to reducing ADRD ( Figure 2).
MedD adherence associated with less brain atrophy, with an effect similar to 5 years of aging.

NS
Cognitive performance (global cognition score based on immediate and delayed recall, backward counting, and serial seven subtraction) Association between the MedD and MIND diets and cognition in a nationally representative population of older U.S. adults.
Higher tertile of A-MedD score significantly associated with better cognitive performance and lower risk of poor cognitive performance.
Age, gender, race, low education attainment, current smoking, obesity, total wealth, hypertension, diabetes mellitus, physical inactivity, depression, and total energy intake. [65] Cross-sectional US Association of adherence to an a priori defined MedD and its components with dementia and specific aspects of cognitive function in a representative population cohort in Greece.
Continuous A-MedD score and A-MedD score quartile significantly associated with lower risk of dementia. A-MedD score significantly associated with composite z-score, memory, language, and executive functioning but not with visuospatial perception.
Age, gender, education, number of clinical comorbidities, and energy intake. [52] Cross-sectional US Clinically and cognitively normal participants who were enrolled in observational brain imaging studies n = 116 ( After adjustment with all covariates, a significant effect of MedD score on the volume of the dentate gyrus.

Impact of DASH Diet on ADRD Progression
The Dietary Approaches to Stop Hypertension (DASH) diet is a dietary pattern that aims at preventing and treating hypertension and improving cardiovascular health [110]. The DASH diet shares several similarities with the MedD, as both encourage a high intake of plant-based foods. However, the DASH diet also emphasizes the low consumption and/or limitation of dietary sodium, sweetened beverages, and red meats, and it does not recommend alcohol [12]. Similar to the MedD, the DASH diet has been shown to prevent several cardiovascular risk factors, including high blood pressure and LDL cholesterol, which are associated with the development of dementia and particularly ADRD. Additionally, the DASH diet can modulate oxidative stress, inflammation, and insulin resistance, which are involved in the pathological process of ADRD ( Figure 2) [111]. Long-term adherence to the DASH diet has been associated with better cognitive function. For example, this association was found in older American women participating in a six-year follow-up study from the Nurses' Health study [112], as well as in an observational study spanning 11 years involving older adult men and women in the Cache County Memory Study [104], and in participants of the Memory and Aging Project over 4.1 years, who exhibited slower rates of cognitive decline [58]. However, a cross-sectional study focusing on sedentary adults with cognitive impairment and cardiovascular disease risks reported mixed results regarding cognitive functions. While high adherence to the DASH diet was associated with better verbal memory, it had no effect on executive function, processing speed, or visual memory [102]. Another randomized trial concluded that combining the DASH diet with weight management significantly improved executive function and memory/learning (p = 0.008). When the DASH diet was implemented alone, it showed an improvement in psychomotor speed (p = 0.036) for hypertensive overweight adults in the U.S. after a 4-month intervention [103]. In the same study, when combining the DASH diet intervention with weight management, greater improvements were observed in executive function, memory, learning (p = 0.008), and psychomotor speed (p = 0.023).
Discrepancies have been reported, as other studies have not found a significant association between the DASH diet and cognition. For instance, a prospective longitudinal study among older women in the Women's Health Initiative Memory Study by Haring et al. [73] concluded that the DASH diet had no significant association with cognitive decline, nor did a high DASH score have an impact on cognitive decline in older community participants (both men and women) in other longitudinal studies [41,113,114]. Another six-month randomized controlled trial with sedentary men and women concluded that the DASH diet alone did not improve cognitive impairment (p = 0.059), but when combined with aerobic exercise, a considerable improvement in executive function (p = 0.012) was observed [115]. These results suggest that the DASH diet, when combined with other nondietary interventions, possibly synergistically, provides a neuroprotective effect. Table 2 summarizes the different clinical trials investigating the relationship between the DASH diet and ADRD and cognition in the last 10 years. The observed discrepancies in Table 2 may be attributed to differences in study design (RCT vs. observational or cross-sectional), the number and variety of participants (e.g., men only, specific age group, obese or lean individuals), the scoring systems used to define adherence to the DASH diet, and the food products considered in each study. Overall, while the existing evidence hints that the DASH diet might be beneficial for cognitive functioning, further research is needed to validate these findings and demonstrate the benefits of DASH for ADRD progression and risk. Higher quintile compared to lower one of DASH score associated with better average cognition but not significantly associated with rate of change in cognitive function.
Age, gender, education, BMI, frequency of moderate physical activity, multivitamin and mineral supplement use, history of drinking and smoking, and history of diabetes, heart attack, or stroke. [104] Longitudinal US

Impact of MIND Diet on ADRD Progression
The MIND diet, which stands for Mediterranean-DASH Intervention for Neurogenerative Delay, combines elements from both the Mediterranean and DASH diets, with a specific focus on dietary components with neuroprotective effects [12]. Unlike the Mediterranean diet, the MIND diet emphasizes the consumption of berries and green leafy vegetables rather than a high intake of fruits. Numerous observational studies and clinical trials have examined the impact of the MIND diet on ADRD progression (Table 3), and all of these studies suggest a positive association with better cognition [20,41,100,[116][117][118][119], lower risks of cognitive impairment [74], and a reduced risk of developing AD [100]. An observational study conducted by Morris et al. [100] over an average of 4.7 years highlighted that high adherence to the MIND diet was associated with less cognitive decline compared to low adherence (p < 0.0001), suggesting that the MIND diet may slow the rate of cognitive decline. Another cross-sectional study involving older U.S. citizens found that higher adherence to the MIND diet was associated with improved cognitive function in a dose-response manner (p < 0.001) [65]. Long-term adherence to the MIND diet was associated with moderately improved verbal memory in later life over a 12.9-year follow-up [120], and a longitudinal study with a 12-year follow-up concluded that the MIND diet reduced the risk of cognitive decline by 53% [74]. Additionally, a study on older adults with a 6-year follow-up on MIND diet adherence showed that a one-point increase in the MIND diet score was associated with a 14% reduction in the risk of subjective memory complaints [121]. Furthermore, a study on older adults highlighted a strong and significant association between MIND diet adherence and better cognitive functioning, even among those diagnosed with AD before or after death [122]. A systematic search conducted by Chu et al. [12] concluded that higher adherence to the MIND diet may be associated with a lower incidence of cognitive impairment and AD, while the MedD appears to provide greater neuroprotection against ADRD. Huang et al. [123] attempted to establish a Chinese version of the MIND diet that aligned with Chinese dietary characteristics and culture while also being more affordable. Moderate and high adherence to the developed Chinese MIND diet were both associated with lower odds of cognitive impairment and IADL disability (0.81 and 0.6, respectively), even after adjusting for covariates. In a recent study by Agarwal et al. [79], higher MIND diet scores were negatively correlated with lower global AD pathology (p = 0.047), and this association remained significant even after adjusting for other covariates (p = 0.047). Participants who had a one-unit higher MIND diet score showed amyloid loads similar to those of individuals who were four years younger [79]. This effect persisted even after adjusting for other lifestyle factors and the burden of vascular disease. A randomized controlled trial conducted over 3 months with a MIND diet intervention for postmenopausal women demonstrated a significant improvement in working memory and verbal recognition [124]. However, combining the MIND diet with different lifestyle components, particularly physical activity, may be more effective in slowing ADRD progression when diagnosed early, as indicated by a cross-sectional study involving both physical activity and the MIND diet in an older adult population [125]. Overall, the current evidence indicates that the MIND diet may be associated with a reduced risk of ADRD and slowed ADRD progression.  Gender, age, race, low education attainment, current smoking, obesity, total wealth, hypertension, diabetes mellitus, physical inactivity, depression, and total energy intake. [65]   Association between the MIND diet and measures of brain volume, silent brain infarcts (SBIs), or brain atrophy in the community-based Framingham Heart Study Higher MIND diet scores associated with better global cognitive function, verbal memory, visual memory, processing speed, and verbal comprehension/reasoning and with larger total brain volume following adjustments.
Higher MIND diet scores not associated with other brain MRI measures or cognitive decline.
Age, gender, presence of APOE ε4 allele, total energy intake, education, the time interval between completion of the FFQ and the measurement of the neuropsychological and MRI outcomes, BMI, physical activity, smoking status, cardiometabolic factors, and high level of depressive symptoms. [117]  Relationship between MIND diet and cognitive function and its decline among middle-aged and older adults Higher MIND diet scores were significantly associated with better global cognitive function. Each increment of 3 points in MIND diet score has adjusted difference in global cognitive function z-score approximately equivalent to being one year younger in age.
In the meta-analysis of 26,103 participants, 1 standardized deviation MIND score increment associated with 0.042-unit higher global cognitive function z-score and 0.014-unit slower annual cognitive decline.
Age, gender, education, annual household income per capita, residence, region, smoking, alcohol drinking, BMI, total energy intake, physical activity, history of chronic diseases included self-reported hypertension, diabetes, and myocardial infarction diagnosis, and use of antihypertensive and anti-diabetic medications.

Impact of Ketogenic Diet on ADRD Progression
The ketogenic diet is characterized by high fat and low carbohydrate intake, which promotes ketone production for energy [12]. This diet has been successfully used to treat patients with refractory epilepsy [129], and growing evidence indicates that it may have benefits for cognitive functioning. In a recent case study conducted by Morrill and Gibas [130], the ketogenic diet was found to increase cognitive assessment scores in ApoE4-positive patients with mild AD. Chu et al. [12] extensively reviewed human studies linking the ketogenic diet to cognitive impairment and ADRD development. Out of the 15 identified studies, 14 indicated a significant improvement in cognitive function when ketogenic diets or ketone supplements were administrated to patients with mild cognitive impairment, mild-to-moderate AD, or AD. Grammatikopoulou et al. [131] identified 10 randomized controlled trials that focused on the impact of ketogenic therapies on improving cognitive function and delaying AD progression. The beneficial effects of the ketogenic diet were observed both after acute consumption and with long-term adherence, particularly in participants with mild cognitive impairment. One characteristic of the ketogenic diet is its level of restrictiveness compared to other 'healthy' diets, such as the Mediterranean, MIND, and DASH diets [12]. Individuals adhering to the ketogenic diet often experience adverse gastrointestinal events and hypoglycemic episodes during the initial phase [132]. Additionally, long-term compliance with the ketogenic diet presents challenges. For instance, for older adults with mild cognitive impairment or established ADRD health conditions, a drastic shift toward a high-fat dietary pattern can have detrimental effects on their cardiovascular health [12,130]. The potential benefits identified in current studies suggest that more research is needed to evaluate the long-term benefits and side effects, as well as research addressing adherence to this more restrictive eating pattern. It is important to note that, to the best of our knowledge, there are no large-scale RCTs examining ketogenic diet and cognition, so more research is needed in this area.

Impact of Modified Mediterranean-Ketogenic Diet on ADRD Progression
To meet the dietary requirements of the late-middle-aged population and mitigate the potential negative consequences of long-term adherence to the ketogenic diet, Taylor et al. [133] proposed making the ketogenic diet nutritionally dense. This led to the development of a new diet called the modified Mediterranean-ketogenic diet (MMKD), which combines key elements of the Mediterranean and ketogenic diets. The target macronutrient composition of the MMKD is approximately 5-10% carbohydrate, 60-65% fat, and 30% protein as a percentage of total caloric intake [134]. The diet encourages the consumption of protein sources low in saturated fats, such as fish and lean meats, along with healthy fats, with a particular emphasis on extra virgin olive oil as the main source of fats. It also promotes the intake of fruits, vegetables, and whole grains within certain limits and allows for the consumption of one glass of wine per day [135]. Since the MMKD is relatively new, a few studies have investigated its relationship with AD progression (Table 4). In a pilot study, Nagpal et al. [136] highlighted that the MMKD can modulate the gut microbiome and metabolites, which are associated with improved AD biomarkers in the cerebrospinal fluid. However, they reported an increase in cerebrospinal fluid Aβ42 but a decrease in tau at the end of the 6-week intervention. Similar observations were made in a randomized controlled trial conducted by Neth et al. [135]. A 12-week intervention with MMKD resulted in improved cognitive function and everyday functioning [137]. In a crossover trial investigating the impact of MMKD, a decrease in adiposity was found to be correlated with a similar decrease in cerebrospinal fluid biomarkers [134]. The latest review conducted by Wang et al. [138] addresses different diet patterns and individual food product intake and their respective impacts on ADRD. However, conducting more studies with a large number of participants will help uncover the hidden mechanisms and better understand the impacts of MMKD on individuals with mild cognitive impairment or ADRD. in body fat on the MMKD related to changes in Aβ biomarkers.
Age and diet order [134] ACE

Impact of Vegetarian Diet on ADRD Progression
A vegetarian diet is not just a plant-based diet that restricts animal products but is also characterized by a low consumption of saturated fat and a high intake of vegetables, fruits, whole grains, legumes, nuts and seeds, dairy products, and/or eggs [139,140]. The extent to which this diet includes discretionary foods, such as sugar-sweetened beverages, desserts, and potato chips, determines its classification as a 'healthy' plant-based food pattern [141]. The vegetarian diet has been associated with a lower risk of several chronic diseases and may have the potential to reduce the risk of cardiometabolic and neurodegenerative diseases ( Figure 2) [142]. Despite the increasing number of individuals globally adopting a vegetarian diet, only a few studies have specifically investigated the relationship between this dietary pattern and cognitive impairment, particularly ADRD ( Table 5). The Adventist Health Study-2 included older adults who followed a vegetarian or non-vegetarian diet. This cohort demonstrated that vegetarians had higher adherence to their dietary patterns constantly over decades, which was associated with better memory and language abilities [143]. Liu et al. [141] assessed the difference in cognition among different races and dietary patterns. They found that a healthy plant-based diet was associated with significantly slower rates of decline in global cognition (p = 0.032), perceptual speed (p = 0.04), and episodic memory (p = 0.04), specifically in African American participants. A large study conducted in Taiwan concluded that vegetarians had a reduced risk of developing dementia compared to non-vegetarians [144]. Despite the limited number of studies on vegetarian diets, existing evidence suggests that such diets may have a beneficial impact on slowing the progression of cognitive decline. The vegetarian diet is rich in nutrients known for their anti-inflammatory and antioxidant activities. However, it is important to note that patients with cognitive impairment and ADRD may still require a certain intake of animal-derived products, especially meat [145,146]. Indeed, older adults have high protein needs, which will present a challenge when restricting animal product consumption to adhere to a vegetarian diet. These products ensure an important supply of B vitamins that are highly and strictly related to AD development and progression [146].

Impact of Vegan Diet on ADRD Progression
What distinguishes the vegan diet from plant-based and vegetarian diets is that it excludes all animal products, not just meat. In fact, the vegan diet is not only free of meat but also eliminates all animal-derived products. When compared to an omnivorous diet, the vegan diet is richer in fiber, polyunsaturated fatty acids, and vitamins [147][148][149]. These individual components can potentially slow down AD pathophysiology. Despite the suspected beneficial impacts on AD, no studies have been conducted to investigate the specific impact of a vegan diet. However, it is important to pay special attention to the long-term effects of a vegan diet, as it may lead to deficiencies in essential micronutrients such as vitamin B12 and vitamin D. These deficiencies are closely associated with the development and progression of ADRD [150].

Impact of Specific Dietary Patterns on ADRD Prevention
The multiple dietary patterns reviewed here have shown potential for slowing the progression of ADRD and may also play a preventive role. However, it is important to determine when to start adhering to these dietary patterns, given that ADRD symptoms may manifest decades after the onset of brain changes. Current research evidence suggests that the first prodromal symptoms, such as changes in the synapse number, nutritional status, cognitive level, and neuropathological changes in the central nervous system, appear around the age of 50 years. Therefore, the ideal age to start taking preventive actions and implementing diet interventions seems to be around 50-60 years old or earlier, with impacts being assessed starting from 70 years old. This is due to the prevalence of long-term interventions rather than the acute effects of consumption on ADRD prevention. As a result, most proposed research studies target participants between the age of 50 and 70 years who do not show any symptoms of cognitive impairment but carry one or several risk factors. Some researchers recommend that dietary interventions last 4-8 years to enable long-term adherence effects to accumulate [151]. To make dietary patterns effective in preventing neurodegenerative diseases, the interventions need to be balanced and meet the dietary requirements of the target population. They should help maintain proper blood pressure and optimal cholesterol, glucose, and homocysteine levels. The proposed diet should also prevent overweight and obesity, which are increasing risk factors for AD [152]. The following sections present the dietary patterns that have been studied and linked to ADRD prevention (Figures 1 and 2).

Impact of Mediterranean Diet on ADRD Prevention
Given the extensive research on the MedD in the management of ADRD, it is reasonable to explore whether it has the potential to prevent the onset of this disease as well. In a study conducted by Hoscheidt et al. [153], normal cognitive participants who adhered to the MedD showed a decrease in Aβ 40 levels and a shift in the Aβ 42/40 ratio, indicating a decreased risk of AD development. The results of an epidemiological study conducted by Andreu-Reinon et al. [87] suggest that over a 20-year follow-up period, participants with high adherence to the MedD had a 20% lower risk of dementia compared to those with low adherence. In fact, every 2-point increase in MedD adherence provided an 8% lower risk of developing AD. However, when examining the linear or non-linear trends between adherence to MedD and AD, no statistically significant associations were reported (p = 0.196, p = 0.353). Similarly, the studies conducted by Féart et al. [154] and Hu et al. [155] found no statistically significant association between adherence to the MedD and the incidence of ADRD (p = 0.72). High adherence to the MedD was not associated with a decreased risk of ADRD after 4.1 years of follow-up in an older French population [154] or after 12 years of follow-up in an older Swedish population [72]. On the other hand, the results of the Washington Heights-Inwood Columbia Aging Project conducted by Scarmeas et al. [50] concluded that a one-point increase in the MedD scale decreased the risk of ADRD by 9%. The latest meta-analysis performed by Solch et al. [9] demonstrated a 32% decreased risk of developing ADRD when adhering to the MedD compared to low adherence, with low heterogeneity between studies. The observed beneficial effects of the MedD are attributed to its anti-inflammatory and antioxidant capacities, as well as its high fiber and polyphenol contents, which impact the gut microbiota ( Figure 2) [156,157]. The reported discrepancies may be attributed to variations in scoring systems used to define diet adherence, differences in the selected populations' age, and differences in risk factors for developing AD, as well as the duration of the follow-up and the lack of an AD diagnosis at the beginning of the study period. Despite the reported non-significant effects on ADRD prevention, it is still plausible that some protection is provided through the various mechanisms mentioned earlier. To arrive at evidence-based conclusions, it is imperative to conduct numerous clinical trials, particularly randomized controlled trials, that examine the impact of adherence to the MedD on various AD biomarkers and imaging. Additionally, long-term observational studies starting with a middle-aged population and following them for 12-15+ years are necessary.

Impact of DASH Diet on ADRD Prevention
There is only one longitudinal study focusing on adherence to the DASH diet and its implication in the development of ADRD in U.S. participants [100]. The study concluded that high adherence to the DASH diet decreases the risk of developing AD by 39%. The observed positive impacts are expected to be the result of long-time use, particularly before the first symptoms appear [158]. To reach a unanimous conclusion about the prevention of ADRD development through the DASH diet, several studies are required, with a special focus on early adherence (in the middle-aged population) and long-term follow-ups (12-15+ years).

Impact of MIND Diet on ADRD Prevention
Only one longitudinal study conducted in an older adult population from the Memory and Aging Project evaluated the relationship between the MIND diet and the prevention of ADRD [100]. The study observed a 53% lower risk of ADRD after a 4.5-year follow-up period. Furthermore, moderate adherence to the MIND diet resulted in a 35% decrease in the risk of developing AD. Undoubtedly, more studies need to be conducted to arrive at evidence-based conclusions regarding the potential beneficial effects of the MIND diet, including the examination of adherence beginning in middle age.

Discussion
Across the literature, there is relatively strong evidence that adherence to the MedD, DASH, MIND, and MMKD diets may reduce the risk of developing ADRD and slow the rate of decline. These diets may be particularly beneficial for cognitive health based on common factors, such as increased polyunsaturated fat, higher fiber, and nutrients and compounds that have neuroprotective properties. Multiple studies have provided evidence linking the intake of certain nutrients common in these diets to preventive or therapeutic effects on AD specifically [12]. For instance, polyphenols have shown the ability to promote cognitive well-being through several pathways. They can improve cerebral blood flow, reduce oxidative stress, decrease neuroinflammation, enhance neurogenesis, and promote neuroplasticity. [159][160][161][162]. Whole grains, through their cardiometabolic and gastrointestinal benefits, as evidenced by the gut microbiota-brain axis, also contribute to cognitive improvement [136,163]. Omega-3 polyunsaturated fatty acids, especially those derived from marine sources, as well as mono-and polyunsaturated fatty acids found in nuts, contribute to brain protection through various effects, including anti-inflammatory action, blood pressure reduction, and endothelial enhancement [164][165][166]. Vitamins, such as B9, B12, and E, have been associated with neurogenesis in adults due to their antioxidant effects [167][168][169]. Many of these nutrients operate through mechanistic pathways that are associated with reducing metabolic syndromes, such as lowering blood pressure, decreasing insulin resistance, and reducing blood sugar and triglyceride levels, resulting in enhanced cognitive health [170][171][172][173]. It is also important to address the appropriate proportions of these nutrient intakes within the suggested dietary patterns. Furthermore, upcoming randomized controlled trials should focus on assessing the intake of these elements within these dietary patterns and their impact on ADRD progression and prevention, as their beneficial effects may be associated with their combined consumption rather than their individual intake. In addition, the amounts of deleterious foods and drinks, such as highly processed meat, refined grains, refined sugars, and beverages with high refined sugar content, need to be monitored in the proposed dietary patterns to be studied, as these products have been significantly linked to an increased risk of cognitive impairment and ADRD. Consuming them alongside the proposed diet may decrease the effectiveness of the studied dietary pattern and its components.

Parameters Affecting Food Intake in Older Adults
Older adults often have unique dietary needs and preferences. The quality and quantity of their dietary intake are impacted by various parameters, such as physiological, economic, and societal factors, which can become more pronounced with age [174]. Some of these factors are personal, encompassing sociodemographic and psychosocial aspects, as well as lifestyle factors [175][176][177]. In fact, diet quality has been strongly linked to marital status and living arrangement. Living with a partner or in a community allows older adults to have some social support and share food [178]. Furthermore, emerging evidence shows that the association between dietary elements and neurocognition depends on socioeconomic status, with the effects of diet being more pronounced in people with low socioeconomic status [179,180]. At the same time, older adults are subject to some conditions impacting their food intake, namely, loss of sensory perceptions (olfaction, taste bud loss, salivation decrease), poor oral health, and particularly mastication difficulties, which represent barriers to diet variety and a healthy diet. ADRD in particular can lead to sensory changes that can also lead to reduced appetite. Further, certain medications and medical treatments can increase deficiencies of some nutrients, which must be emphasized in their diet. Likewise, most older adults suffer dexterity loss with aging, which can lead to practical challenges related to cooking and food preparation [181].

Other Parameters Important for ADRD
Conducting research to understand how to prevent AD is valuable. It is a part of the science of risk reduction, aiming to gather evidence on noteworthy lifestyle changes. According to the Centers for Disease Control and Prevention, healthy lifestyle habits such as regular exercise and blood pressure management are among the noticeable factors that can lower the risk of dementia. Similarly, adopting healthy habits that reduce the prevalence of cancer, diabetes, and heart diseases may also be beneficial in preventing cognitive decline. Given the specific nature of neurodegenerative diseases, other factors should also be taken into consideration for daily habits, such as not smoking, stress reduction, and engaging in mental and physical activities [152]. Emerging evidence highlights that three lifestyle components, namely, social, mental, and physical factors, are inversely correlated with the risk and incidence of ADRD. In this context, maintaining a lifestyle with high levels of physical, mental, and social activities stands out as one of the important factors contributing to enhancing the quality and expectancy of life. Enhanced psychosocial engagement, in turn, lowers the risk of dementia and neurocognitive impairment in ADRD [182]. Additionally, other factors are associated with cognitive impairment and ADRD, such as marital status and frequent social contacts. Maintaining frequent social contacts can be achieved through numerous activities, including participating in social activities, having a larger social network, and receiving greater social support, thus promoting social engagement [183]. These social parameters vary among individuals as personal attributes, and they are highly affected by the place of residence of older adults. In recent years, there has been a growing interest in the new concept of lifestyle medicine, which is associated with optimal brain health and healthy aging. This concept is based on six pillars, namely, consuming whole foods and following plant-based dietary patterns, maintaining physical activity, managing stress through non-pharmaceutical means, avoiding risky substances, ensuring good-quality sleep, and maintaining social connections [184]. Indeed, the Western lifestyle is characterized by a sedentary nature, with sedentarity or physical inactivity defined as engaging in less than 30 min of moderate-intensity physical activity on a minimum of 5 days per week or at least 20 min of vigorous-intensity physical activity on a minimum of 3 days per week [185]. Research has shown that leading an active lifestyle is inversely related to the risk of cognitive decline, with aerobic exercise training being the most widely studied form of physical activity in relation to neurocognitive function and aging [186,187]. Simultaneously, other studies have highlighted the importance of participating in leisure activities and how it can result in better diet quality for older adults [188]. Ultimately, it has been found that multidomain programs, which include interventions related to diet, nutrition, exercise, neurocognitive exercises, and social activities, yield better outcomes in slowing down disease progression compared to single-domain interventions [189].

Conclusions
Considering the rapidly growing number of people with or at risk of developing ADRD in the upcoming decades, it is crucial to find low-cost and effective ways to prevent and/or ameliorate the development and progression of these diseases. Diet, indeed, appears to be one of the most important modifiable factors that influence ADRD risk. Despite the discrepancies revealed in this review due to differences in study populations, associated risk factors, geographical regions, and scoring methods, plant-based dietary patterns generally show a positive correlation with a reduction in AD advancement and the lowering of its incidence. The MedD, DASH, MIND, and MMKD diets have the greatest efficacy for their neuroprotective benefits. The precise cellular and molecular pathways underlying and mediating the preventive and ameliorative effects of these diets on ADRD are still unclear and need to be elucidated through prospective clinical and mechanistic studies. For future studies, it is advisable to consider holistic approaches that not only incorporate dietary patterns but also encompass factors related to physical, social, economic, and mental health components.