Cognitive Impairment and Dietary Habits Among Elders: The Velestino Study

Abstract

To investigate the association of dietary habits with cognitive function among elders (>65 years). Complete sociodemographic, dietary information, serum measurements, and Mini-Mental State Examination (MMSE) assessments were available for 237 elderly men and 320 women residing in Velestino, Greece (a rural Greek town). All models were adjusted for age, education, social activity, smoking, depression symptomatology (using the Geriatric Depression Scale), MedDietScore (range 0–55), and metabolic syndrome. About 49.8% men and 66.6% women had MMSE scores <24, with a mean MMSE score of 22.7±4.43 and 21.1±4.73, respectively. Adherence to the Mediterranean diet was moderate (mean MedDietScore of 34.1±3.25 in men and 35.1±2.48 in women). Indicative cognitive impairment (MMSE score <24) was positively associated with age and low education in women and with depressive symptoms, low education status, and low social activity in men. Adherence to the Mediterranean diet was positively associated with MMSE score in men (P=.02), but inversely associated in women (P=.04). Concerning the food groups studied, intake of pulses, nuts, and seeds was associated with lower likelihood of having MMSE score<24 in men (P=.04). Only the Mediterranean dietary pattern showed a significant association with MMSE score positive for cognitive impairment (i.e., protective in men, but not in women), while individual food groups or nutrients did not achieve significance. The latter findings support the role of whole diet in the prevention of mental disorders, and state a research hypothesis for a sex–diet interaction on cognitive function among elders.

Introduction

T he concept of cognitive impairment has become increasingly popular in recent years and also generated interest on the part of many research groups. A commonly agreed definition of cognitive impairment is a clinical syndrome that refers to nondemented persons with cognitive deficits (in memory, language, thinking, and judgment) measurable in some form or another, but that does not fulfill a diagnosis of dementia.¹ This condition was previously characterized as an early manifestation of the Alzheimer's disease or another dementia disorder and is thought to be a possible stage for early intervention and treatment.² Increases in life expectancy and improvements in the definition of the condition have led to higher numbers of seniors who meet the criteria for the diagnosis and also have revealed related social aspects of the problem.³

Specific dietary habits have been associated with significant reduction in total mortality, hence increased survival, and have consistently shown to be protective against coronary disease and many types of cancer.⁴ This association extends further to mental health, as it has been found that diet may play an important role in the causation and prevention of a wide range of cognitive disorders, including Alzheimer's.⁵ In particular, adherence to a well-known dietary pattern, the Mediterranean diet, has been associated with lower likelihood of developing such types of disorders. The typical Mediterranean diet includes high intake of vegetables, fruits and nuts, legumes, cereals, pulses, fish, and monounsaturated fat, with olive oil as the primary source; relatively low intakes of meat and dairy products; and moderate consumption of alcohol. Many of the components of the Mediterranean diet are related separately to a lower risk for cognitive disorders. The high antioxidant properties of the Mediterranean diet may partially explain the pathway by which this diet plays a protective role on human health.⁶ Despite strong indications suggesting that adherence to the Mediterranean diet is associated with a reduction in risk for mild cognitive impairment and with slower cognitive decline,^7,8 there are equally important studies that did not find significant correlation of the Mediterranean diet with cognitive function.^9,10

To contribute to this debate, in the context of the Velestino Study (a cross-sectional health and nutrition survey), the association of food groups' and nutrients' intake as well as adherence to the Mediterranean diet with Mini-Mental State Examination (MMSE)¹¹ score among elders living in Velestino, a small village in central Greece, was studied. In contrast with the vast majority of previous studies with samples originating from an urban population, in this work, the research hypothesis was examined in a rural population that was subject to various environmental and social factors. For example, Velestino's population has not been influenced very much by the Western lifestyle and has maintained many traditional habits, including a high adherence to the Mediterranean diet. The latter allowed a different approach to the research question that ultimately revealed a sex–diet association that has not been observed before.

Material and Methods

Sampling procedure

During January 2005 through April 2006, all 858 permanent residents in the municipality of Velestino who where 65 years old and over were contacted by two physicians trained in field investigation (A.A. and K.-P.K.). Of the 858 elders, 557 (237 men and 320 women) agreed to participate in the study (65% participation rate) and provided an informed consent. Velestino is an ancient village, located in central Greece, with a mainly agricultural economy and ∼4000 inhabitants (census 2011).¹²

Participants were interviewed in person at their home or workplace. A precoded questionnaire was used that included quantitative or semiquantitative sections with questions about sociodemographic (i.e., age, sex, years of education, and participation in social activities), clinical (anthropometry, assessment of arterial blood pressure, and medical history of comorbidities), dietary, psychological (assessment of depressive symptoms and cognitive impairment), as well as other lifestyle characteristics (i.e., smoking and drinking habits). Morning, fasting (>12 h) blood and saliva samples were also drawn for biochemical and hormonal determinations. High-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, total cholesterol, triglycerides, and plasma glucose were determined (all in mg/dL) using standard procedures.

Assessment of cognitive impairment and depression symptoms

The translated and validated version of the MMSE questionnaire was used as an indicator of cognitive impairment. The MMSE includes eight main sections that evaluate functions regarding arithmetic, memory, and orientation abilities; individuals were asked to answer all of the questions in ∼10–15 min, and a score ranging 0–30 was then calculated. For the data analyses, participants were divided in two categories, those with an MMSE score ≥24 and those with a score <24, indicating cognitive impairment, according to the Greek validated version of MMSE.¹³ Additionally, the translated and validated version of the Geriatric Depression Scale (GDS-15) was also applied for the evaluation of depressive symptoms among the participants.¹⁴

Assessment of clinical and biological characteristics

Systolic and diastolic arterial blood pressure was measured by the two physicians, with the participant in a sitting position and calm. Metabolic syndrome was defined according to the International Diabetes Federation (IDF) definition¹⁵—waist circumference ≥94 cm for men and ≥80 cm for women, plus any two of the following four factors: triglycerides level ≥150 mg/dL or specific treatment for this lipid abnormality; HDL cholesterol <40 mg/dL for men and <50 mg/dL for women or specific treatment; systolic or diastolic blood pressures ≥130/85 mm Hg or treatment of previously diagnosed hypertension; fasting plasma glucose ≥100 mg/dL or previously diagnosed type 2 diabetes. Thus, these factors were evaluated to identify participants suffering from metabolic syndrome.

Dietary assessment

The EPIC–Greek Food Frequency Questionnaire provided by the Department of Hygiene, Epidemiology, and Medical Statistics was included in the study's questionnaire for dietary intake assessment. Specifically, the average frequency of consumption of 157 food items, per month, per week, or per day, was evaluated through a repeatable semiquantitative food frequency questionnaire¹⁶ that has been used by many European nutritional studies among their elderly populations.¹⁷ For the analysis, the frequency of consumption of various foods was quantified on a monthly basis, by multiplying the daily intake by 30 and the weekly by 4 and by assigning 0 to the food items that were rarely or never consumed. All the food items were then combined in basic food groups, namely: cereal and starchy roots; sugars and syrups; pulses, nuts, and seeds; vegetables and fruits; meats and meat products, fish, and shellfish; milk and dairy products; and added lipids (Table 1). This distribution into food groups is a variation of the scheme that has been proposed by Davidson and Passmore,¹⁸ and it is regularly used in nutritional epidemiology in Greece.¹⁹ Furthermore, the MedDietScore²⁰ was calculated from the dietary questionnaire to evaluate the level of adherence to the Mediterranean diet. MedDietScore is a large-scale dietary index that assigns scores from 0 to 5 or the opposite, in each of the 11 main food categories of the Mediterranean diet pyramid according to the rationale of this traditional dietary pattern (theoretical range 0–55); higher values of the reliable and repeatable MedDietScore tool suggest better adherence to the Mediterranean diet.²⁰

Table 1.

Classification into Food Groups of the Food Items Evaluated in the Food Frequency Questionnaire

Food group	Food item
Cereals and starchy roots	White bread, brown bread, traditional bread, rice, pasta, various breakfast cereals, trahana, cheese pie (1/2), meat pie (1/2), vegetable pie (1/2), pizza (1/2), pasticcio (1/2), potatoes
Sugars and syrups	Sugar, cookies, chocolate bars, wafers, baklava, kataifi and other Greek sweets with syrup, spoonful sweets (Greek delicacies), jellies, glaze fruits, cream pastries, pancakes with syrup, bonbons, honey, compote (1/2)
Pulses, nuts, and seeds	Dry beans, chick peas, peas, lentils, fava beans, dry broad beans, nuts
Vegetables and fruits	Raw tomatoes, cooked tomatoes, cucumbers, peppers, raw cabbage, cooked cabbage, lettuce, raw carrots, cooked carrots, zucchini, onions, green beans, eggplant, spinach, leeks, okra, dandelions, artichokes, fresh broad beans, cauliflower, broccoli, beets, mushrooms, courgette, vegetable pie (1/2), mousaka (1/2), watermelon, melon, mandarins, oranges, apples, peaches, pears, grapes, apricots, cherries, strawberries, bananas, figs, pineapple, grapefruit, fresh fruit juice, dried fruits, compote (1/2)
Meats and meat products	Pork, veal, beef, lamb, goat, chicken, turkey, ham, salami and sausages, liver and other entrails, eggs, meat pie (1/2), mousaka (1/2), pasticcio (1/2)
Fish and shellfish	Fish, shellfish
Milk and dairy products	Feta cheese, kasseri cheese, other cheese, whole milk, skim milk, full fat yogurt, reduced fat yogurt, milk pudding, rice milk pudding, ice cream, cheese pie (1/2), pizza (1/2)
Added lipids	Butter on bread, butter for cooking, margarine on bread, margarine for cooking, seed oils, olive oils, olives

1/2 indicates the cooked meals that were allocated to two food groups (one-half in each).

Total energy and nutrient intake were calculated using food composition tables based on the methodology that has been previously reported in detail.²¹ The macronutrients studied were protein, carbohydrates, and fat, while the micronutrients were carotene and retinol in micrograms as well as thiamin, riboflavin, nicotinic acid, vitamin C, vitamin B6, potassium, calcium, magnesium, phosphorus, iron, and zinc, all in milligrams.

Other measurements

Smoking habits (ever or never) were recorded. Education status was measured in years of school and classified into three categories (<6, 6–9, and >9 years). For the proxy of social activity, a score was created by adding the values of the variable “level of autonomy” (3 categories of self-help ability) plus the average time per day spent outside the home, in 3 categories, and then suboptimal activity was defined as the category with the lower values (<50%).

Bioethics

The study protocol was reviewed and approved by the Ethics Committee of the Athens University Medical School. All participants were informed about the aims of the study and gave their consent before the interview.

Statistical analyses

Categorical variables are presented by frequencies, while continuous variables by mean and standard deviation (SD), separately for those with MMSE score positive for cognitive impairment or not, as well as by sex. The stratified-by-sex analysis was performed because of the well-established differences in the MMSE score, as well as in the other variables, such as GDS and dietary habits, between men and women. The χ ² test, Fisher's exact test, or the t-test was used as appropriate. Subsequently, multiple logistic regression was performed, and odds ratios (OR) and 95% confidence intervals (95% CI) were calculated for MMSE score <24, indicative of cognitive impairment by the levels of various covariates (core model): that is, age (by 5-year increment), education (by one level more), social activity (suboptimal vs. optimal), smoking (ever vs. never), GDS (<7 vs. ≥7), and metabolic syndrome (yes vs. no). The MedDietScore (by 1/55 units increase), each of the food groups mentioned above (by one quintile increase), and the specified macronutrients and micronutrients (by 1 SD increase) were added in the core model alternatively (one each time). Furthermore, MMSE as a continuous outcome was also used in the analyses to confirm or refute the findings from the logistic regression analyses. For the models that included nutrients, the energy density adjustment method was applied. All statistical analyses were carried out using SAS software, version 9, for Windows 9 (SAS Institute, Inc., Cary, NC, USA).

Results

The mean MMSE score was 22.7±4.43 in men and 21.1±4.73 in women (P=.0001). Of the 237 men and 320 women participated in this work, 49.8% of men and 66.6% of women had MMSE <24 (an indication of cognitive impairment). Participants' sociodemographic and dietary characteristics by levels of the MMSE scale are shown in Table 2. Although not accounting for mutual confounding, it seems that advanced age and lower education in both sexes, as well as depressive symptoms and low social activity only in men, were associated with a lower MMSE score. It is of interest that both men and women reported moderate adherence to the Mediterranean diet, since the average MedDietScore was about 35 out of 55 (i.e., 63% level of compete adherence to the traditional pattern). Moreover, MedDietScore was not associated with GDS (r=−0.10, P=.13 in men; r=−0.06, P=.30 in women), nor with years of school (parameter estimate=0.08, P=.77 in men; parameter estimate=0.09, P=.75 in women; as derived from linear regression).

Table 2.

Distribution of Sociodemographic, Lifestyle, and Dietary Characteristics of the Velestino Study for 237 Men and 320 Women, by MMSE Score

	Men					Women
	MMSE<24		MMSE≥24			MMSE<24		MMSE≥24
Variable	N	%	N	%	P-value	N	%	N	%	P-value
Age (years)					.13^*					.0001^*
65–69	16	13.6	25	21.0		35	16.4	50	46.7
70–74	28	23.7	33	27.7		66	31.0	31	29.0
75–79	35	29.7	25	21.0		54	25.4	15	14.0
80+	39	33.0	36	30.3		58	27.2	11	10.3
Education (years)					.0001^*					.001^*
<6	89	75.4	52	43.7		164	77.0	63	58.9
6–8	26	22.0	47	39.5		47	22.1	37	34.6
9+	3	2.6	20	16.8		2	0.9	7	6.5
Suboptimal social activity	31	26.3	16	13.5	.01^*	106	49.8	45	42.1	.19^*
Ever smoking	74	62.7	77	64.7	.74^*	2	0.9	3	2.8	.34^**
GDS score					.001^*					.53^*
0–6 (low)	62	52.5	87	73.1		76	35.7	42	39.3
7+ (high)	56	47.5	32	26.9		137	64.3	65	60.7
Metabolic syndrome	59	50.0	63	52.9	.65^*	143	67.1	64	59.8	.20^*

	Mean±SD	Mean±SD		Mean±SD	Mean±SD
MedDietScore (0–55)	34.1±3.25	35.1±2.48	.01	34.9±2.57	34.5±2.91	.27
Cereals and starchy roots	95.0±33.02	96.7±25.76	.64	97.5±30.83	92.1±36.64	.19
Sugars and syrups	72.5±54.14	67.9±46.94	.49	70.1±54.31	64.3±50.82	.36
Pulses, nuts, and seeds	7.4±5.73	11.0±11.50	.003	7.8±10.75	6.6±5.10	.16
Vegetables and fruits	183.3±96.74	195.2±97.13	.35	174.0±86.38	174.4±96.71	.97
Meats and meat products	24.0±14.67	22.0±10.25	.23	18.8±11.47	19.8±12.27	.48
Fish and shellfish	4.4±3.06	4.8±3.65	.35	3.4±2.65	3.6±2.64	.42
Milk and dairy products	60.3±33.40	53.0±29.90	.08	47.4±31.60	47.9±34.34	.88
Added lipids	15.4±20.11	15.3±19.70	.97	12.8±16.63	11.4±14.18	.45
Energy intake (kcal)	2673.0±1019.30	2632.1±929.61	.75	2561.5±990.41	2433.6±961.29	.27
Carbohydrates (g)	422.6±166.45	416.0±159.68	.76	420.2±166.68	393.9±162.18	.18
Protein (g)	82.5±28.84	81.0±23.57	.67	75.5±24.34	74.8±28.59	.83
Total fat (g)	100.1±52.70	96.5±51.34	.59	93.7±53.29	90.2±46.06	.57
Saturated fat (g)	26.6±20.51	23.5±15.93	.19	25.9±18.40	23.7±16.75	.29
Monosaturated fat (g)	30.2±17.53	30.0±18.09	.94	29.6±18.63	27.3±15.55	.24
Polysaturated fat (g)	10.9±9.33	11.1±9.93	.86	11.7±9.87	10.5±8.01	.26

P-values derived from t-test, except those indicated otherwise which were derived from ^* χ ² or ^**Fisher's exact test.

MMSE, Mini-Mental State Examination; GDS, Geriatric Depression Scale.

As mentioned above, residual confounding may exist; thus, multiple logistic regression analysis was then applied (Table 3). As shown, women of older age and less educated, as well as men with depressive symptoms, low education status, and low social activity, were more likely to report cognitive impairment expressed as MMSE score <24. Adherence to the Mediterranean diet was positively associated with MMSE score in men, although an inverse association was observed in women. Concerning the food groups studied, in men, intake of pulses, nuts, and seeds was associated with lower likelihood of having an MMSE score positive for cognitive impairment; conversely, intake of milk and dairy products was associated, without being statistically significant, with higher likelihood of cognitive impairment. In women, none of the food groups studied was associated with the presence of cognitive impairment (Table 3). The analysis of the MMSE as a continuous outcome yielded similar results with the aforementioned analysis (data not shown).

Table 3.

Multiple Logistic Regression–Derived Odds Ratios and 95% Confidence Intervals for Cognitive Impairment Expressed as MMSE Score <24 by Sociodemographic, Lifestyle, and Dietary Characteristics

	Men (n=237)			Women (n=320)
Variable	OR	95% CI	P-value	OR	95% CI	P-value
Core model
Age, by 5 years more	1.01	0.77–1.32	.97	1.98	1.53–2.56	.0001
GDS, 0–6 vs. 7+	2.23	1.23–4.05	.01	0.84	0.49–1.43	.51
Education, by 1 level more	0.29	0.18–0.47	.0001	0.43	0.26–0.70	.001
Social activity, suboptimal vs. optimal	0.43	0.20–0.92	.03	0.88	0.52–1.49	.64
Smoking, ever vs. never	0.72	0.40–1.31	.28	0.54	0.07–4.14	.55
Metabolic syndrome, yes vs. no	1.09	0.62–1.93	.77	1.12	0.66–1.90	.68
Additional alternatively introduced variable (by one quintile more)
MedDietScore (by 1/55 unit)	0.88	0.80–0.98	.02	1.11	1.00–1.22	.04
Cereals and starchy roots^a	0.99	0.80–1.23	.94	1.01	0.83–1.22	.95
Sugars and syrups^a	1.03	0.83–1.27	.82	1.08	0.90–1.31	.39
Pulses, nuts and seeds^a	0.79	0.64–0.99	.04	0.97	0.80–1.17	.75
Vegetables and fruits^a	1.14	0.90–1.44	.28	1.01	0.81–1.26	.92
Meat and meat products^a	1.03	0.84–1.27	.75	0.96	0.81–1.16	.70
Fish and shellfish^a	0.99	0.75–1.32	.96	0.91	0.71–1.16	.45
Milk and dairy products^a	1.20	0.97–1.48	.10	1.04	0.87–1.24	.67
Added lipids^a	1.02	0.84–1.24	.85	1.00	0.85–1.20	.92
Total energy intake	1.05	0.86–1.29	.63	1.12	0.93–1.35	.22

Each food group was adjusted for the core model variables and MedDietScore.

OR, odds ratio; CI, confidence interval; GDS, geriatric depression scale.

Furthermore, regarding nutrient consumption, elderly men with an MMSE score <24 also had increased intake of protein as well as total fat, without reaching the statistically significant level (OR=1.36 [95% CI 0.92–2.02], OR=1.56 [95% CI 0.89–2.72], respectively). The same was evident for saturated fatty acid intake (OR=1.39 [95% CI 0.90–2.15]). Concerning micronutrients, only for retinol, riboflavin, and calcium intake, suggestive evidence for higher likelihood of having MMSE score positive for cognitive impairment was found, only in men (Table 4). Analysis of MMSE score as a continuous outcome derived approximately the same results. When the analysis was focused on those with low education status, that is, <6 years of school, no significant associations were observed.

Table 4.

Multiple Logistic Regression-Derived Odds Ratios and 95% Confidence Interval for Cognitive Impairment Expressed as MMSE Score <24 by Macro- and Various Micronutrients with Increment of One Standard Deviation

	Men			Women
Model for:	OR	95% CI	P-value	OR	95% CI	P-value
Protein (g)	1.36	0.92–2.02	.13	0.88	0.56–1.37	.57
Carbohydrates (g)	0.68	0.36–1.27	.22	1.02	0.54–1.91	.96
Total fat (g)	1.56	0.89–2.72	.12	0.95	0.59–1.51	.82
Saturated fat (g)	1.39	0.90–2.15	.14	0.94	0.60–1.47	.78
Monosaturated fat (g)	1.13	0.70–1.81	.62	1.26	0.86–1.86	.24
Polysaturated fat (g)	1.03	0.71–1.49	.88	1.21	0.89–1.66	.23
Fiber (g)	0.91	0.63–1.31	.61	1.14	0.77–1.68	.53
Retinol (μg)	1.22	0.91–1.64	.19	0.90	0.70–1.17	.43
Carotene (μg)	0.95	0.68–1.34	.77	0.91	0.66–1.26	.56
Thiamin (mg)	1.05	0.76–1.44	.78	1.16	0.80–1.70	.43
Riboflavin (mg)	1.37	0.94–2.00	.10	0.94	0.65–1.38	.77
Nicotinic acid (mg)	1.11	0.74–1.68	.61	1.28	0.80–2.04	.30
Vitamin C (mg)	0.98	0.71–1.35	.89	1.01	0.74–1.38	.97
Vitamin B6 (mg)	1.06	0.75–1.50	.74	1.08	0.73–1.60	.71
Sodium (mg)	1.07	0.76–1.52	.69	1.00	0.69–1.45	.99
Potassium (mg)	1.05	0.71–1.55	.81	1.02	0.67–1.55	.95
Calcium (mg)	1.38	0.96–2.00	.08	0.84	0.59–1.19	.32
Magnesium (mg)	0.91	0.59–1.40	.67	1.21	0.79–1.86	.39
Phosphorus (mg)	1.17	0.80–1.71	.43	1.11	0.74–1.67	.60
Iron (mg)	0.91	0.60–1.37	.64	1.05	0.68–1.62	.82
Zinc (mg)	1.15	0.82–1.62	.42	0.96	0.65–1.42	.84

All models were adjusted for the core variables (see Table 3) and total energy intake.

No significant association was observed between the levels of the blood lipids (total cholesterol, HDL, LDL, and triglycerides) and MMSE score (data not shown).

Discussion

In this population-based, cross-sectional survey, 50% of elderly men and 67% of elderly women were defined as having MMSE scores positive for cognitive impairment. These rates were much greater than those presented by other similar studies,²² although it has been reported that the prevalence of mild cognitive impairment varies widely among different populations, as well as within each population. However, at this point, it should be mentioned that the MMSE score is not sufficient for a definite diagnosis of mild cognitive impairment, as it requires more examinations, longer surveillance, and clinical evaluation by physician. Also, a significant proportion of the participants (i.e., 26%) was older than 80 years and had low education, and this may partially explain the increased rates observed in this work. Cognitive impairment was positively associated with advanced age and low education in women and with depression symptomatology, low education status, and low social activity in men. Concerning the food groups and nutrients studied, higher intake of pulses, nuts, and seeds was associated with lower likelihood of having an MMSE score positive for cognitive impairment, whereas suggestive evidence only in men linked consumption of milk and dairy products to higher likelihood of having an MMSE score <24. The suggestive evidence for positive association with calcium intake in men further supported the latter. The statistical significance of these results could be reduced if correction for multiple comparisons is applied. Adherence to the Mediterranean diet was inversely associated with an MMSE score indicative of cognitive impairment in men, but it was positively associated in women, revealing potential behavioral differences and exposures between sexes. Despite the limitations of the cross-sectional nature of the present work, the reported findings revealed high rates of the MMSE score in the elderly population studied, as well as the role of some food groups in relation to this disorder. These findings share considerable public health messages about the actions that need to be taken to prevent cognitive impairment among elders, with diet seeming to play a modest role.

Previous reports of the association between Mediterranean diet and mild cognitive impairment have been equivocal. In two large prospective studies, Scarmeas et al. ⁷ and Féart et al. ⁸ found that higher adherence to the Mediterranean diet was associated with a reduced risk for developing mild cognitive impairment and reduced risk for conversion to Alzheimer's disease. In contrast, a prospective study in Greece⁹ also using the MMSE in a large sample of older adults reported only suggestive evidence of an inverse association between adherence to the Mediterranean diet and cognitive impairment. In addition, Cherbuin et al. ¹⁰ found no relationship between Mediterranean diet and cognitive impairment. Regarding macronutrient intake, high levels of protein intake, total fat, and saturated fatty acids seem to increase the likelihood of having an MMSE score positive for cognitive impairment.²³ The differences in the reported association of the Mediterranean diet with cognitive impairment between the studies could be attributed to the dietary intake differences between the studied populations (in the present work, a moderate adherence was reported by the entity of the participants), the differences in composition of the Mediterranean diet and the food quality between countries, including the origin of the aliments and the cooking style, the differences in the population sample (i.e., multiracial population in the U.S. cohort), and perhaps due to the size of the sample. It is of interest that the inverse association observed in men was not confirmed in women, a fact that cannot easily be interpreted. Possibly, the much higher rate of MMSE score and the lower education status in women as compared with men, together with the moderate adherence to the Mediterranean diet, may have confounded the association observed in men. Specifically, it could be speculated that very low education status, especially of women, led to higher misreporting of foods consumed as compared with men, and in accordance with the increased mental decline, women (even with low MMSE) reported what they should have eaten (i.e., healthy foods) and not what they actually did. Moreover, only some food consumption, that is, pulses, nuts, and seeds, was associated with lower likelihood of cognitive impairment, whereas intake of milk and dairy products tended to be related to higher likelihood of this disorder. The latter revealed the very modest effect of diet on cognitive impairment in the studied population of older adults, in contrast with some recent studies that suggested strong relationships. These results suggest that it's not the individual components of a diet but the whole-diet pattern and the synergistic effect between the various food groups that influences cognitive function. It is more likely to assume that the protective effect of the Mediterranean dietary pattern against cognitive impairment in men is not attributed to one specific food group, but to the consumption of all beneficial food groups and the avoidance of all “detrimental” food groups that are consistent with the dietary pattern. This is in accordance to the opinion stated by several nutritionists during the past years that the overall dietary habits matter in exploring the relationships between diet and chronic diseases, and not consumption of individual foods per se.⁴ Most of the typical foods that comprise the Mediterranean Diet, such as olive oil, nuts, vegetables, legumes, fish, and wine, have been associated with a favorable health outcome and a better quality of life, not only for their unique effects, but also for their synergistic actions. Particularly, olive oil is a major component of the diet, and it contains abundant monounsaturated fatty acids (MUFA), mostly oleic acid, and, depending on the degree of refinement, variable proportions of bioactive micronutrients, such as phytosterols, vitamin E, and phenolic compounds.²⁴ The majority of fruits and vegetables are rich in flavonoids; more specifically, greens contain a great variety of flavones and flavonols, and in the case of grapes, anthocyanidins such as quercetin and kaempherol are present in large quantities. The above-mentioned substances, among other micronutrients, give the Mediterranean foods a high antioxidant capacity that counteracts the oxidative stress responsible for many chronic illnesses, with dementia being one of them.

Several possible mechanisms have been proposed associating the Mediterranean diet, as well as specific foods or nutrients, with cognitive function, though many of them remain under investigation. High oxidative stress has been implicated in the development of cognitive impairment, and certain components of the Mediterranean diet, such as fruits, vegetables, and seeds, are rich in flavonoids, vitamin E, and other antioxidant substances that may reduce the oxidative stress in the brain.²⁵ Other typical Mediterranean elements, such as olive oil, are known to possess antioxidant properties due to their high mean content in phenols.²⁶ Considering that inflammatory pathways participate in the pathogenesis of cognitive impairment,²⁷ and combining this fact with the reports that the Mediterranean diet lowers C-reactive protein and interleukin-6 levels²⁸ via multiple pathways,²⁹ a possible explanation is suggested. On the contrary, there are studies reporting no association between the Mediterranean diet and inflammatory markers.³⁰ Vascular mechanisms also contribute in the development of cognitive impairment, but this field remains yet under investigation. In addition, the influence of the Mediterranean diet may interact with other factors that favorably affect cognitive function, such as social activity and psychological disorders. In the present work, depressive symptomatology, as well as suboptimal social activity, was associated with adherence to the Mediterranean diet in men. Regarding the food groups studied, pulses, seeds, and nuts are rich in a variety of nutrients, such as unsaturated fatty acids, ω-3 fatty acids, antioxidants, and other vitamins that have been linked with a reduced likelihood of cognitive impairment, especially among elderly.³¹ In contrast, the association of milk and dairy product intake with a higher likelihood of cognitive impairment could, at least partially, be due to the high total and saturated fat content of these foods.^32,33 However, several studies have reported opposite results regarding high dairy product intake, possibly by modifying vascular factors linked to detrimental brain changes.³⁴

The variation in sex-specific rates of mental disorders that was observed in this study has already been previously reported by others,^35,36 with a general tendency for higher prevalence of cognitive impairment in women, particularly in the 80+ age group. Responsible for these sex differences might be biological differences, or differences in behavior and exposures,³⁷ such as differences in the dietary patterns and other social behaviors, which are not unusual in rural populations. Moreover, the association of cognitive impairment with advanced age and low level of education is well known^7,9 and confirmed in the present work, too. In the present work, the percentage of participants with adequate years of school (i.e., >9 years) was almost threefold in those with MMSE score ≥24 as compared with the rest (i.e., those with possible cognitive impairment). Lastly, the high rates of low education status found in this survey (a common phenomenon in Greek people of this age group³⁸) may also explain, at least in part, the high number of MMSE scores indicative of cognitive impairment observed in the study.

Limitations and strengths

The present work has several limitations, but also strengths. The cross-sectional design had inherent limitations that do not allow for causal interpretations, but only to state research hypotheses. The issue of reverse causation due to the synchronous assessment of the dietary habits and the cognitive function cannot be entirely excluded, meaning that the cognitive status has altered the dietary habits instead of the opposite. The misreport could have been further intensified by the recall bias that is probable in similar studies and by the relatively low education level of the population. However, previous studies found that an adherence to the Mediterranean diet was quite diachronic,³⁹ making improbable any change in the reported habits. Moreover, other variables that were not examined, such as physical activity, might have contributed in the interpretation of the present results, though they were indirectly calculated through the social activity index.

Among the study's strengths was its high quality of the retrieved data that were derived from face-to-face interviews by two experienced physicians who were familiar with the studied population is strength of the present work. Moreover, the Food Frequency Questionnaire and the MedDietScore that were used, as well as the MMSE and the GDS scales, have been previously validated for the referent population and used widely in epidemiological studies. Nevertheless, it must be mentioned that these questionnaires are used for screening purposes, rather than tools for an in-depth clinical analysis. Furthermore, the fact that the target of the study was the entirety of the elderly population of the town and the achievement of this goal to its greatest possible extent offered conclusive results for this specific population.

Conclusion

It was revealed that a dietary pattern close to the Mediterranean diet was inversely associated with MMSE score in men, suggesting an indication of cognitive impairment, but not in women, extending the protective role of this already-known healthy diet on mental decline, too. However, the latter also states a hypothesis for residual confounding with regard to sex in the investigated relationship. Additionally, the study of individual foods and nutrients on cognitive impairment showed poor results. The latter findings underline the role of whole diet in the prevention of mental disorders, and state a research hypothesis for a sex–diet interaction on cognitive function among elders. In addition, the promotion of a healthy diet is essential in all age groups, and the low rates of adherence to the traditional Mediterranean diet observed here should urge public health policy makers about this situation, especially in a Mediterranean population.

Footnotes

Acknowledgments

The authors thank the participants of the Velestino Study, the Velestino Municipality, and the Onassis Foundation; without their support, this survey would never have been done.

Author Disclosure Statement

No competing financial interests exist.

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