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All that follows is from Mediterranean Diet, Ketogenic Diet or MIND Diet for Aging Populations with Cognitive Decline: A Systematic Review. [PubMed Review] [Full-Text HTML] [Full-TextPDF]. Life (Basel). 2023 Jan; 13(1): 173. Published online 2023 Jan 6. doi: 10.3390/life13010173
Abstract
(1) Background: Compelling evidence shows that dietary patterns can slow the rate of cognitive decline, suggesting diet is a promising preventive measure against dementia. (2) Objective: This systematic review summarizes the evidence of three dietary patterns, the Mediterranean diet, the ketogenic diet and the MIND diet, for the prevention of cognitive decline. (3) Methods: A systematic search was conducted in major electronic databases (PubMed, ScienceDirect and Web of Science) up until 31 January 2022, using the key search terms “Mediterranean diet”, “ketogenic diet”, “MIND diet”, “dementia”, “cognition” and “aging”. A statistical analysis was performed using RoB 2 and the Jadad scale to assess the risk of bias and methodological quality in randomized controlled trials. (4) Results: Only RCTs were included in this study; there were eleven studies (n = 2609 participants) of the Mediterranean diet, seven studies (n = 313) of the ketogenic diet and one study (n = 37) of the MIND diet. The participants’ cognitive statuses were normal in seven studies, ten studies included patients with mild cognitive impairments and two studies included Alzheimer’s disease patients. (5) Conclusion: All three dietary interventions have been shown to slow the rate of cognitive decline in the included studies. The Mediterranean diet was shown to be beneficial for global cognition after 10 weeks of adherence, the ketogenic diet had a beneficial effect for patients with diabetes mellitus and improved verbal recognition, while the MIND diet showed benefits in obese patients, improving working memory, verbal recognition, memory and attention.
Keywords: Alzheimer’s disease; MIND diet; Mediterranean diet; aging; dementia; ketogenic diet; mild cognitive impairment; systematic review.
1. Introduction
Dementia is the seventh leading cause of death worldwide, affecting approximately 55 million people; in the next decade, the number of dementia patients worldwide is estimated to increase by 50% [1]. The most common cause of dementia is Alzheimer’s disease (AD). The strongest genetic risk factor for AD is carrying the ε4 allele of the Apolipoprotein E (APOE) [2,3]. About 25% of the general population has at least one ε4 allele, with a three-fold increased risk of AD for heterozygotes and a nearly 15-fold increased risk for homozygotes [2]. Current pharmacological treatments for AD and dementia have proven to be ineffective [4]. Hence research efforts have shifted towards non-pharmacological treatments, especially in the earlier stages of dementia, and towards prevention strategies [5,6].
MeDi is a dietary pattern that is common in countries bordering the Mediterranean Sea and is characterized by a high intake of plant-based food products, including fruits, vegetables, legumes, nuts and seeds, and whole grains. Olive oil is the principal fat used and is also added liberally to salads and meals. Fish and red wine are consumed in moderate amounts, while red meat, confectionery and highly processed foods are consumed infrequently [14]. Adherence to a MeDi has been associated with a reduced rate of cognitive decline in AD [15], improved overall cognition and episodic memory, and a lower risk of cognitive impairment and neurodegenerative diseases [16]. Oxidative stress and inflammation are known to exert significant deleterious effects on cognitive decline and brain ageing [17]. The bioactive dietary constituents of the MeDi, including phenolic compounds, have been shown to reduce neuroinflammation due to antioxidant actions [18]. Furthermore, MeDi adherence has been correlated with a reduced risk of coronary heart disease, hypertension, diabetes mellitus (DM), dyslipidemia and metabolic syndrome, which are all also associated with MCI, dementia and AD risks [19].
Although there is no strict definition of the MeDi [20], there are multiple scoring systems developed to measure MeDi adherence. The initial MeDi score of eight food items developed by Trichopoulou and colleagues [21] was revised to include fish as a ninth food item [22]. In this nine-point MeDi score, one point is given for above average consumption of each food item, ranging from the minimum, 0, to the maximum, 9. This approach has been further investigated by Martínez-González and colleagues using a Mediterranean Diet Adherence Screener (MEDAS), which initially included nine food items [23] and was then further revised to include fourteen food items [24]. This 14-point MeDi screening score ranges from the minimum, 0, to the maximum, 14, and one point for each consumed food item is given. A more detailed 55-point MeDi score has been developed by Panagiotakos and colleagues, taking 11 food items into account and distributing five points for each food item adhering to the MeDi, ranging from the minimum, 0, to the maximum, 55 [25]. Another approach is the Mediterranean Adequacy Index (MAI) which considers 18 food groups and their energy percentages of the total calorie intake [26]. To calculate the MAI, the sum of the energy percentages of ten typical MeDi food groups are divided by the sum of the energy percentages of eight non-typical MeDi food groups. All these scoring tools have been proven indispensable in evaluating one’s adherence to the MeDi and associated health benefits.
Previous systematic reviews and meta-analyses provide consistent evidence that MeDi adherence is associated with improved outcomes in cognitive function and performance as well as a reduction in cognitive decline compared to patients who do not follow a MeDi-type pattern [27,28,29].
2. Materials and Methods
2.1. Literature Selection Criteria
A systematic literature search was conducted in the electronic databases of PubMed, ScienceDirect and Web of Science. Publications including search terms of dietary interventions and cognitive status were selected for review, specifically MeDi, KD, MIND diets, cognition, aging, dementia, AD and MCI.
2.2. Eligibility Criteria
Primarily, randomized controlled trials (RCT) with patients over 40 years old were included in this systematic review. For inclusion, all studies needed to report cognitive outcomes measured by at least one cognitive assessment tool after a period following each diet. All three criteria: dietary intervention, measurement of diet and measurement of cognitive status, had to be met in all the selected publications.
2.3. Study Selection
The online service of Rayyan was used for blinding the reviewers and the selection of the studies to be included [50].
2.3.1. Outcomes
The primary outcome of the reviewed studies was the assessment of cognitive status in relation to dietary intervention. Cognitive status refers to patient being cognitively normal, or having MCI or dementia, as in AD. Assessment of cognitive status includes a variety of cognitive test batteries, most commonly the Mini Mental Status Examination (MMSE) [51] and the Montreal Cognitive Assessment (MoCA) [52].
2.3.2. Data Extraction
When available, the following data were extracted from each study: (1) study design; (2) number of participants; (3) gender of participants; (4) age of participants; (5) cognitive status of participants at baseline; (6) cognitive test batteries; (7) duration of intervention; (8) outcomes of the study; (9) statistical significance of outcomes; (10) details of dietary intervention; (11) country of study; (12) health status of participants and other diseases; and (13) diet adherence.
2.3.3. Quality Assessment
The quality assessment of all the included studies is described in the Supplementary Materials.
2.3.4. Data Synthesis
A meta-analysis was considered but it could not be performed due to the wide variation in the cognitive assessment tools used in the different studies that precluded the synthesis of the extracted data.
3. Results
The three types of dietary interventions, the MeD*i, KD** and MIND diets, were reviewed separately. No study was found to compare the outcome of the three diets in cognition.
*Mediterranean Diet (MeDi)
Table 1 and Table 2 show the quality assessment of included studies. Table 3 shows the main characteristics of the 11 MeDi studies, all of which were published between 2000 and 2021. The period of the MeDi interventions varied between 4 weeks and 6.5 years. The total number of participants was 2609; in five studies the participants had normal cognitive function, in two studies the participants were diagnosed with MCI, one study had mixed participants with normal cognition and participants with MCI, and one study had participants diagnosed with MCI in Parkinson’s Disease (PD). All but one study reported beneficial effects of the MeDi intervention on cognitive function, reaching statistical significance for at least one cognitive test in a subgroup of participants. The shortest one with a 4-week intervention did not report significant benefits of the MeDi on cognition.
**Ketogenic Diet (KD)
In total, 1632 publications were identified that referred to the KD. The flow chart of the literature search is presented in Figure 2. After removing 113 duplicates, 1519 studies were screened and assessed for eligibility. Next, 1481 of the 1519 articles were excluded after reading the titles and abstracts, and the remaining 38 full-text articles were estimated for their eligibility. Eventually, seven studies were included, all published between 2000 and 2021. Table 4 and Table 5 show the quality assessment of included studies, as shown in Table 6.
***MIND Diet
In total, 6764 publications were identified (PubMed: 110, ScienceDirect: 6472, Web of Science: 182). Additionally, 13 studies were identified by another systematic review [48]. After removing 94 duplicates, 6683 articles were screened and assessed for eligibility, of which 6652 were excluded by screening the abstracts. The remaining 31 articles were retrieved and their full texts were screened, after which 30 articles were excluded. Only one study was included in the final review. Table 7 and Table 8 show the quality assessment of the included study, as presented in Table 9. The flow chart of the literature search is presented in Figure 3.
Strengths and Limitations
The present systematic review does not come without limitations. The number of databases searched was restricted to three: PubMed, ScienceDirect and Web of Science. The publications selected were restricted to the English language. Only one RCT could be found on the MIND diet as an intervention study. The data in the selected publications were too diverse, particularly those regarding the cognitive status of the intervention groups and the multiplicity of the neurocognitive tests used, for a meta-analysis to be conducted.
As for its strengths, however, this systematic review is the first to undertake a synthesized review of multiple dietary interventions for dementia prevention. No time restrictions were set in our database searches. The authors are health professionals covering different disciplines, including dieticians, medical doctors and pharmacists.
5. Conclusions
As this systematic review shows, dietary interventions can be beneficial in maintaining cognitive health, they can be integrated in the everyday practice of prevention clinics and be considered in national prevention programs. An individualised dietary intervention is proposed for each patient, according to an individual’s overall health status and personal characteristics, and the recommendation of a specific diet without considering the patient’s specific needs should be avoided.
Supplementary Materials
The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/life13010173/s1, Table S1: PRISMA 2020 item checklist; Table S2: PRISMA 2020 for Abstracts checklist; Table S3: Search strings used in the systematic reviews. Reference [101] was cited in the supplementary materials.
