Mediterranean Diet Cognitive Function and Dementia a Systematic Review of the Evidence

Due to rapid population aging worldwide, wellness problems related to crumbling (including Alzheimer disease and dementia) are projected to add to the high clinical, social, and economic burden of caring for persons with dementia.¹ At that place is currently no cure for dementia, and available handling strategies offer mainly symptomatic benefits. Thus, strategies to forestall or filibuster onset of dementia by changes in lifestyle factors, such equally nutrition, are of import.

The Mediterranean nutrition has been associated with reduced risk for a wide range of age-related weather such as stroke, type ii diabetes, cardiovascular illness, and all-cause mortality.^2–5 The traditional Mediterranean diet refers to a multinutrient dietary profile characterized by high intake of fruits, vegetables, cereals, and legumes; low consumption of saturated fats with olive oil equally the main source of fatty; moderate consumption of fish; low to moderate intake of dairy products (in the course of yogurt and cheese); low consumption of red meat and meat products; and moderate amount of alcohol (especially wine) usually consumed during meals.^{half dozen} Recently, a number of narrative reviews take presented evidence for an clan betwixt a Mediterranean-type diet and decreased run a risk of dementia. Findings from prospective studies suggest that greater adherence to Mediterranean diet may be associated with slower cognitive decline and reduced gamble of Alzheimer disease.^7–9 In the calorie-free of these findings, it has been suggested that improving adherence to the Mediterranean diet may delay or forestall the onset of dementia.

To engagement, however, no systematic review has synthesized these findings. Our objective was to systematically review the literature to synthesize and evaluate available bear witness on the association between adherence to Mediterranean nutrition and cognitive function or dementia.

METHODS

Identification of Studies

A systematic review was conducted post-obit the general principles published by the United kingdom National Health Service Center for Reviews and Dissemination.¹⁰ We developed a predefined protocol following consultation with experts in the field (eAppendix, https://links.lww.com/EDE/A676).

Nosotros searched the following electronic databases for relevant studies from inception to Jan 2012: Medline, EMBASE, and PsycINFO (via Ovid); Science Commendation Index Expanded, Social Sciences Citation Index, Arts and Humanities Citation Index, Briefing Proceedings Commendation Index (via the Web of Science interface); the Health Direction Data Consortium, the Cumulative Index to Nursing and Allied Health Literature, and the Allied and Complementary Medicine Database (via the National Health Service evidence database); and the Cochrane Library of Systematic Reviews. The search strategies used text words and relevant indexing (MeSH terms) to capture studies investigating the clan between adherence to a Mediterranean diet and cognitive function and dementia. Search terms "Mediterranean diet," "cognition," "dementia," "Alzheimer," "memory," "mild cognitive impairment," and "neuropsychological tests" were keywords. The search strategy is shown in the eAppendix (https://links.lww.com/EDE/A676).

Forward and backwards citation searching was used to identify any additional relevant studies. The Athenaeum of Neurology (January 1990 to December 2011), the Journal of the American Medical Association (5 January 2000 to 11 January 2012), and the American Periodical of Clinical Nutrition (January 1990 to December 2011) were paw-searched, having been identified as particularly important journals in the field.

We performed internet searches for the following websites: Alzheimer's Society (www.alzheimers.org.uk/), Alzheimer'due south Disease Research (www.ahaf.org/alzheimers/), Alzheimer's Disease International (www.alz.co.uk/), Alzheimer'due south Research U.k. (world wide web.alzheimersresearchuk.org), and Alzheimer's Association (world wide web.alz.org/). The department of each website labeled "Research" or research-related tabs (eg, "enquiry portfolio," "researchers and professionals") was screened in detail on xvi January 2012. The corresponding authors of all included studies were contacted to identify whatsoever additional studies.

Study Pick

Studies were included if they examined the association of a defined score used to measure adherence to the Mediterranean diet and included cognitive function or dementia every bit outcomes. At that place was no restriction in study design or language of publication. Conference abstracts were included if there were sufficient details to allow appraisal of written report quality. We excluded studies evaluating adherence to a recommended guideline, to a dietary pattern other than a Mediterranean diet, or to private components and not Mediterranean diet as a whole. We also excluded letters and editorials that did not include original research findings. The titles and abstracts retrieved by the electronic searches were screened independently by two reviewers (I.L. and M.Southward.).The full text of potentially relevant papers was retrieved and screened in the same way. Whatever discrepancies were resolved through discussion with a third reviewer (D.J.L.).

Data Extraction and Quality Assessment

A customized information extraction form was adult, airplane pilot tested on three included studies, and refined accordingly. Data on study and participant characteristics, exposure, method of cognitive assessment, and relevant outcomes were independently extracted past two reviewers (I.L. and M.S.). We contacted one author who provided numerical data and clarification for two studies (1 published article and one conference abstract).¹¹ ^, ¹² The quality of the design and reporting of included studies were independently assessed by two reviewers (I.L. and 1000.S.), using custom checklists for the appraisal of observational studies and randomized trials (eAppendix, https://links.lww.com/EDE/A676). These checklists were derived from existing widely used questionnaires^13–15 and included items addressing issues related to population, recruitment, assessment of exposure and outcome, confounding, and statistical analyses. Discrepancies were resolved by give-and-take with a third reviewer (J.T.-C.) where necessary.

RESULTS

Study Characteristics

The combination of searches yielded a total of 719 references. Duplicates were excluded (northward = 195). Championship and abstract screening resulted in the exclusion of further 508 papers. Full texts of the remaining 16 papers were obtained for detailed review. Four papers were excluded following full text screening: a book chapter, a narrative review, and two studies that focused on specific components of the Mediterranean diet instead of the dietary pattern as a whole. This left 12 papers eligible for inclusion (Figure).

F1-1 — Figure:
Flowchart of choice process of studies included in the review.

Table ane describes the characteristics of the 12 papers (seven unique cohorts). All had been published from 2006 onwards. Two were conducted in Mediterranean countries (French republic and Greece),^xvi ^, ¹⁷ three in Australia,¹¹ ^, ¹² ^, ¹⁸ and the rest in the United States.^19–25 Eight had a longitudinal design, one was a single-blind randomized trial with follow-upwards subsequently only ten days, one was a nested case-control study, and iii reported both cross-sectional and longitudinal findings. V of the papers were based on participants of two related cohort studies recruited in 1992 and 1999 as function of the Washington Heights-Inwood Columbia Aging Project.^20–23 ^, ²⁵ Most studies included both sexes with the proportion of women being slightly higher in all merely 1 written report. Several studies were based on samples of community-abode older adults 65 years old and to a higher place at baseline; one study focused on people aged 70–89 years²⁴ and two recruited participants aged threescore to 64 years;^xi ^, ¹² the randomized trial included just young women (hateful historic period= 21.1 years).¹⁸ Sample size ranged from 25 to 3790 subjects, whereas mean follow-upwardly ranged from 10 days to 8.0 years.

T1-1 — Table 1:
Characteristics of Included Studies

Adherence to Mediterranean Diet

All studies used variations of a food frequency questionnaire to appraise average dietary intake for the year preceding the study. The number of food questionnaire items ranged from 61 to 236 and provided details about foods, beverages, and consumption frequency, usual portion sizes, and cooking style. Most of the studies (10 papers) calculated caloric intake (kcal) converted into daily gram intakes for each of the 7 food groups considered characteristic of the Mediterranean dietary pattern: fruits, vegetables, cereals, legumes, dairy, fish, and meat. The dietary profile also included calculation of fat intake (using the ratio of daily intake of monounsaturated fats to saturated fats) and nomenclature of booze consumption. Sexual practice-specific median cut points were used to assign a value of 0 or ane to each of these 9 dietary components. Calculation the value assigned to each component generated a total Mediterranean Diet score, ranging from 0 to 9, where higher scores represented better adherence.

A similar approach using 5-bespeak increments for daily or weekly consumption of 10 food groups and alcohol was adopted in the Chicago Health and Aging Projection (CHAP) study for the calculation of the Mediterranean nutrition score on a scale from 0 to 45.¹⁹ The randomized trial considered adherence to Mediterranean nutrition successful if 80% or more of the meals and snacks reported in a food diary completed past participants were in accordance with the Mediterranean dietary pattern. Adherence was quantified either every bit a continuous score (0–ix points or 0–45) or tertile-defined categories (low, center, high), whereas some studies (north = 6) reported analyses in both forms. X studies reported a mean score of adherence to Mediterranean nutrition. However, directly numerical comparisons beyond studies are problematic as they used unlike dietary indexes to assess adherence. The mean level of adherence to Mediterranean diet was low to moderate across studies. This was truthful even for the populations from the 2 Mediterranean countries, where fewer than one-tertiary of the participants had high adherence (scores six–ix) (eTable, https://links.lww.com/EDE/A676).

Relevant Outcomes

Measures of cognitive functioning were identified in eight publications, balmy cognitive impairment in four papers, and dementia in 7 studies (five of which focused specifically on Alzheimer disease). No studies examined other primal dementia subtypes (such equally vascular dementia or Lewy body dementia).

All but 1¹⁷ of the studies performed cerebral assessments prospectively. The majority of studies utilized information from neuropsychological batteries that produced a composite cognitive score for each participant, whereas five administered the Mini-Mental State Exam exam (MMSE) as office of their neuropsychological cess.¹¹ ^, ¹² ^, ¹⁶ ^, ¹⁷ ^, ¹⁹ Assessments likewise included memory (short- and long-term), linguistic communication (comprehension, naming, fluency), executive part, visual-spatial skills, orientation, and abstract reasoning and construction (copying and matching). For one report, the MMSE was the sole measure out of cerebral function.¹⁷ Longitudinal studies examining mild cerebral impairment^xi ^, ¹² ^, ²² ^, ²⁴ and dementia risk¹⁶ ^, ^twenty–24 adopted a stepwise process to evaluate global cognitive function and detect balmy cerebral damage or dementia. The whole study population was screened, with more detailed test of participants suspected of having cerebral damage or dementia.

Quality Assessment

Overall the quality of included papers was moderate (Table 2). Follow-upwardly time and sample size in some studies may accept been bereft to discover outcomes of interest,¹¹ ^, ^xvi ^, ¹⁷ ^, ²⁴ with power calculations reported in only three studies.¹⁶ ^, ²¹ ^, ²⁴ Participants were representative of the populations from which they were drawn in nine studies (representing five unique cohorts), and their characteristics were described clearly in the majority of them. X studies did non utilise standardized median cut points for each food component, and the diet score was calculated in a study-specific way. Reporting of variables related to nutrition adherence and statistical analyses was often inadequate. There was corking variability in the instruments used for cognitive cess, making studies hard to compare. This was especially true for the diagnosis of balmy cognitive impairment and global cognition scores.

T2-1 — Table 2:
Quality Cess of Included Studies

Adherence to Mediterranean Diet and Cognitive Function

Both studies with cantankerous-sectional information showed evidence of a positive association betwixt Mediterranean diet adherence and cerebral function.¹⁹ ^, ²³ 3 of six studies¹¹ ^, ¹² ^, ¹⁶ ^, ¹⁷ ^, ¹⁹ ^, ²⁰ that examined prospectively the relationship of Mediterranean diet adherence with cognitive decline suggested that greater adherence was associated with reduced reject. Results from the studies conducted in Mediterranean countries were inconsistent.^xvi ^, ¹⁷ The randomized trial¹⁸ found that compared with the control group, participants assigned to follow the Mediterranean diet over 10 days improved on only one of the 14 tasks used to assess changes in cognitive function, the Corsi Block Task (spatial working retentiveness). The treatment group as well showed slower reaction times on the numeric working memory and discussion recognition job (Table 3).

T3-1 — Table 3:
Results of Included Studies for the Association Between Adherence to Mediterranean Diet and Cognitive Decline or Cerebral Performance

Adherence to Mediterranean Nutrition and Mild Cerebral Impairment

Four studies investigated the relationship between adherence to Mediterranean nutrition and mild cognitive impairment using both the continuous score and the tertile-defined categories of adherence (Table four). Studies examining risk of mild cerebral impairment by unit increase on the Mediterranean Nutrition score (0–9) gave inconsistent results.^xi ^, ¹² ^, ²² The ii studies²² ^, ²⁴ that examined balmy cognitive harm hazard across Mediterranean Diet tertiles found similar results with hazard ratios for the highest tertile compared with the lowest ranging from 0.72 (95% confidence interval [CI] = 0.52–i.00) to 0.75 (95% CI = 0.46–1.21).

T4-1 — Tabular array four:
Results of Included Studies for the Clan Between Adherence to Mediterranean Nutrition and Balmy Cognitive Impairment

Adherence to Mediterranean Diet and Dementia

Ii studies that examined incidence of all-cause dementia in relation to Mediterranean diet adherence had inconsistent results¹⁶ ^, ²⁴ (Table 5). All four prospective studies of Alzheimer disease run a risk from the Columbia Aging Project (following older adults for various fourth dimension intervals betwixt 1992 through 2006) found a favorable association with the Mediterranean dietary design. Reduced gamble of developing Alzheimer disease across studies ranged from 34% to 40% for nondemented persons in the highest tertile of adherence compared with the everyman (0–3).^20–23 Moreover, an 11% reduction in the hazard of balmy cognitive impairment converting to Alzheimer disease was observed for each unit increase in the Mediterranean nutrition score. This was specially true for persons with nonamnestic impairment.²² Greater adherence to Mediterranean diet was also associated with lower chance for Alzheimer disease prevalence in the example-control written report nested within the original cohort.²⁵

T5-1 — Table 5:
Results of Included Studies for the Association Betwixt Adherence to Mediterranean Nutrition and Dementia or Alzheimer Disease (AD)

DISCUSSION

We identified 12 papers reporting an clan between adherence to Mediterranean nutrition and cognitive function or dementia. Adherence to the Mediterranean diet may be associated with lower rates of cerebral decline. Our analysis also shows an emerging relationship betwixt higher adherence and reduced chance for Alzheimer affliction. The benefits of Mediterranean diet adherence were especially evident in studies with mean baseline ages to a higher place 75 years, possibly because the college chance of incident cognitive problems in this historic period group made it easier to detect differences in outcomes between those who consumed a Mediterranean diet and those who did not.

Evidence is accumulating for the effectiveness of the Mediterranean dietary pattern on the prevention of various age-related diseases, including dementia. Narrative reviews have suggested that stricter adherence to Mediterranean diet is associated with slower cerebral decline and reduced gamble of Alzheimer disease. In a recent meta-analysis, a ii-signal increase in the Mediterranean diet adherence calibration was associated with 13% reduction in the incidence of neurodegenerative diseases (take a chance ratio = 0.87 [95% CI = 0.81–0.94]).²⁶ The meta-assay combined dementia with other degenerative diseases such as Parkinson's disease; our systematic review is the first to address the association between adherence to Mediterranean diet and dementia specifically and includes more contempo studies.

In that location has been a focus on individual components of the Mediterranean diet, such as ω-3 fatty acids²⁷ or olive oil every bit the principal source of monounsaturated fats²⁸ and their neuroprotective properties. Indeed, separate analyses for certain nutrient groups in two of the studies found that high vegetable intake and loftier lipids ratio (monounsaturated fat plus polyunsaturated fatty in relation to saturated fat) were associated with a reduced hazard for mild cognitive impairment,²⁴ whereas moderate wine consumption was associated with reduced rates of cerebral decline.¹⁹ Although the advantages of Mediterranean diet are relevant for not-Mediterranean populations,²⁹ it is often argued that studies are not always comparable because there are substantial differences in dietary limerick amidst countries. A more detailed examination reveals this is especially truthful for fat acids.¹¹ ^, ¹⁷ ^, ²⁰ Although olive oil is the authentication of Mediterranean diet, differences in the origin of monounsaturated fats or cooking style (eg, baked vs. fried) could partly explain these inconsistencies.^eleven ^, ³⁰ Studies comparing types of olive oil ended that compared with refined oil, virgin olive oil (rich in phenolic content) has additional anti-inflammatory and antioxidant properties beneficial to cellular part and cardiovascular health.³¹

Potential Underlying Mechanisms

The Mediterranean diet may exert its effects on cognitive health through multiple biologic mechanisms. Relationships with reduced risk of coronary heart disease, hypertension, diabetes,⁵ ^, ³² ^, ³³ dyslipidemia, and metabolic syndrome³⁴ have been observed, and these atmospheric condition have likewise been associated with balmy cognitive impairment, dementia, or Alzheimer illness. Higher adherence may too facilitate metabolic control because it has been related to improved insulin sensitivity and glucose metabolism.³⁵ Furthermore, oxidative stress increases with age and results in oxidative damage—a land often observed in the brain of patients with Alzheimer disease.³⁶ Typical components of the Mediterranean nutrition (namely fruits, vegetables, wine, and virgin olive oil) are rich in antioxidants such as vitamin C and E, carotenoids, and flavonoids.^37–39 Decreased oxidative stress establish in people adhering to a Mediterranean-type diet could partially explain their lowered risk for dementia.⁴⁰ Neurons are protected against oxidative stress by neurotrophins (bones proteins) such as the brain-derived neurotrophic factor, and there is some evidence that Mediterranean nutrition may increase plasma brain-derived neurotrophic factor concentrations.⁴¹ Neurotransmitter synthesis, synaptic plasticity, and cell metabolism are influenced by vitamin C and B complex vitamin intake.⁴² Inflammatory processes have also been suggested for Alzheimer pathogenesis. College concentrations of C-reactive poly peptide, a nonspecific mark of inflammation, take been associated with increased gamble for cognitive decline, Alzheimer disease, and vascular dementia,⁴³ whereas ameliorate adherence to Mediterranean diet has been associated with lower levels of C-reactive protein.⁴⁴ The ATTICA study⁴⁴ also found that interleukin levels were reduced by 17%, and at that place were beneficial changes in other markers involved in inflammation and coagulation processes including homocysteine, white blood jail cell count, and fibrinogen.

Methodological Considerations

Eleven out of the 12 papers were observational and cannot be used to confirm whether the association is causal. However, the cohort studies with long follow-upward periods and large samples propose an association between Mediterranean diet adherence and reduced take a chance of cognitive decline and Alzheimer disease.²¹ ^, ²² Findings in relation to Alzheimer disease chance, still, are all based on analyses conducted inside a single projection (Columbia). The limerick of the cohort was multiethnic with a loftier proportion of African-Americans and Caribbean Hispanics. Previous research has demonstrated increased Alzheimer disease and vascular dementia incidence rates in these ethnic groups (although these results remain controversial),⁴⁵ ^, ⁴⁶ and farther replication may analyze a potential association with ethnicity. Show supported by well-designed, long-term randomized trials that can manipulate dietary intake co-ordinate to specific dietary patterns and appraise changes in cognitive part will strengthen findings and clarify trends identified in the systematic review. The one randomized trial in the review had several of import limitations (express dietary assessment method, only ten days follow-up, recruitment through snowballing, limited to women, and pocket-size sample size), which may have biased the results and limited its external validity. Present study designs do non permit the determination of causal relationships, just at to the lowest degree suggest that higher adherence to the Mediterranean nutrition influences cognitive outcomes. The contrary could also be true: people may experience changes in appetite, nutrient preferences, and eating habits both before diagnosis and every bit part of dementia itself.⁴⁷ ^, ⁴⁸ To address this possibility, several studies excluded persons with dementia or Alzheimer disease from the dietary analyses and used multiple dietary assessments to investigate adherence stability over time.¹⁶ ^, ^19–21 Cerebral pass up and Alzheimer disease processes may start several years—even decades—before the onset of symptoms. Observing middle-aged adults with long-term adherence to Mediterranean diet could enable a more in-depth understanding of the relationship with noesis and dementia subtypes and perhaps indicate an optimum time window when dietary interventions would be nearly benign for changing the course of the affliction.⁴⁹

Comparing outcomes is challenging because a variety of tools was used to assess cognitive function in the diverse studies. In that location are besides issues related to the measurement of adherence, such as the use of food frequency questionnaires with various number of items and the study-specific cutoffs for dietary intake and score adding, that limit comparability and increase the risk of misclassification bias. The rather small proportion of persons with high adherence to Mediterranean diet, either measured on a continuous score or in tertile-defined categories, as well as the limited cases (≤100) identified in some studies, may take limited statistical power to notice an association with incident mild cognitive harm or dementia.

Regarding statistical analyses, diverse methods were applied to estimate changes in cognition, whereas each written report used a different set of factors to adjust for potential confounders (see Tables1 and 3). Merely two papers written report boosted analyses in an attempt to reduce bias due to confounding (ie, propensity scores),²¹ ^, ²⁴ and residual confounding cannot be excluded. For example, depressive symptoms have been related to cognitive harm and dementia, and adherence to the Mediterranean dietary design has been associated with reduced gamble of low (four studies adjusted for depression; encounter Table one).⁵⁰ ^, ⁵¹ It is also possible that older people post-obit a Mediterranean-blazon diet may by and large lead a healthier lifestyle, which in plow protects them from dementia. Finally, missing-data details were underreported and were limited to comparisons of characteristics between those who were and were not lost to follow-up. Complete instance analysis was generally used; only 1 out of 12 papers reported imputation of missing values in some covariates for the analyses of adjusted models.²¹

The current analysis has several advantages over previous reviews. It is the first systematic review to address the association between adherence to the Mediterranean dietary pattern and cognitive function and dementia. Second, this review was conducted using a predefined protocol and applying specific inclusion and exclusion criteria, without restrictions in study pattern or language of publication. We practical an extensive search strategy combining a diversity of different methods to identify relevant papers and data extraction, and quality assessments were performed independently by two reviewers. Thus, we are confident that we accept identified the currently available testify. However, the substantial variability in methods of cognitive assessment and statistical analyses used meant the findings were not uniform for meta-analysis. Farther studies adopting more coherent and uniform methodology and analyses would allow for better quantification of the clan of Mediterranean diet adherence with cognitive function and dementia.

Boosted studies are too warranted to clarify the association with additional cardinal dementia subtypes (notably vascular dementia and dementia with Lewy bodies) and to clarify the mechanisms by which adherence to a Mediterranean diet may protect confronting dementia. Long-term randomized controlled trials promoting adherence to a Mediterranean diet may aid establish whether improved adherence helps to forestall or filibuster the onset of Alzheimer disease and dementia.

ACKNOWLEDGMENTS

We give thanks Alison Bethel (Information Specialist, PenTAG, University of Exeter Medical School) for her communication regarding the search strategy. We acknowledge funding from the National Institute for Wellness Research Collaborations for Leadership in Applied Health Inquiry and Care.

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