Abstract
Introduction: Objectives
Specific diets or lifestyles have an impact on cognitive function in previous studies. However, the association of the complex action of Chinese daily diets and lifestyle patterns with mild cognitive impairment (MCI) among elderly people had not been studied exactly. The aim of this study was to explore the association of dietary and lifestyle patterns with MCI among elderly people in Beijing.
Design
Population-based and case-control design.
Setting
The physical examination center in Xuanwu Hospital, Capital Medical University in Beijing.
Participants
A total of 404 subjects, aged 60 years old or above, with or without MCI.
Measurements
The Montreal cognitive assessment (MoCA) was used to screen the subjects with MCI. All subjects were required to complete a questionnaire which was comprised of their demographic information, health status, lifestyles, and food frequency questionnaire (FFQ). Binary multivariable logistic regression was used to evaluate the potential association between MCI and these factors.
Results
With adjustment for some factors,higher daily intake of eggs (OR, 0.975,95% CI, 0.959–0.992, P=.003) and marine products (OR, 0.96, 95% CI, 0.943–0.979, P=.000), longer time of watching TV (OR, 0.763, 95% CI, 0.628–0.928, P=.007), reading (OR, 0.540, 95% CI, 0.379–0.769, P=.001) and physical exercise (OR, 0.382, 95% CI, 0.185–0.789) had significantly decreased odds of suffering from MCI compared with the control group.
Conclusions
Our findings suggested that daily higher intake of eggs and marine products,watching TV, reading and physical exercise were associated with preventing the development of MCI in this population-based samples.
Key words: Dietary intake, lifestyle patterns, mild cognitive impairment, elderly people
Introduction
Mild cognitive impairment (MCI) is defined as a syndrome with cognitive decline more than expected for an individual’s age and education level but does not notably interfere with activities of daily life (1, 2). Subjects with MCI have a 10-fold increased risk of developing dementia at a rate of 10%–15% per year compared with 1%–2% per year in the general population (3). Early diagnosis and intervention of MCI could postpone or prevent the onset of subsequent dementia. It is critical to identify potentially protective factors for the development of MCI and progression to dementia.
Specific diets or lifestyles have an impact on cognitive function in recent studies (4, 5). Elderly people on a Mediterranean diet (MeDi) are reported to be less likely to develop MCI or progress from MCI to dementia (6, 7). A recent study in Chinese nonagenarians and centenarians, found that there were significant association between inadequate intake of legume and animal oil and the prevalence of MCI (8). Moreover, dietary and plant polyphenols exert neuroprotective effects on cognitive function (9). In a population-based case-control study, the presence of both physical exercise and computer use was associated with decreased odds of having MCI (10). However, these studies confirmed the effects of various specific dietary pattern or lifestyle pattern on MCI but did not explore the complex action of daily diets and lifestyle patterns. The aim of this study was to explore the effects of the complex action of daily diets and lifestyle patterns on MCI among elderly people in Beijing China, and find the potential protective factors for cognitive function in daily life. On the other hand, soybean isoflavone (SIF) as a natural polyphenol existing in soybean and the products are involved in daily diets in Chinese population. Our previous study demonstrated it could reduce cytokine cascade and inflammatory response induced by β-amyloid peptides(Aβ)1-42 or Aβ25-35 resulting in the improvement of spatial learning and memory ability impairment in the rats (11, 12). So we calculated the intake of SIF instead of legume in the present study to evaluate the effects of SIF on MCI.
Method
Study Design and Data collection
The study adopted population-based case-control design. Medical doctors with special training in dietary and lifestyle interview and evaluating of MCI interviewed the participants face-to-face from April to June 2013 in the physical examination center in Xuanwu Hospital, Capital Medical University in Beijing, China. A structured interview format was used to collect data of cognitive and dietary and lifestyle pattern in the last year. The results of the questionnaire and health examination were filled in the standard form. The subjects with Alzheimer’s disease (AD) or Parkinson’s disease (PD), or not completing the Montreal cognitive assessment (MoCA) test, or not able to have diet normally or <60 years old, or with long-term frequency antidepressants and CNS acting medications intake were excluded from the study.
The questionnaire included demographics (e.g., age, gender, education), lifestyle (e.g., physical exercises, smoking, alcohol consumption), self-reported disease status (e.g., hypertension, diabetes, coronary heart disease or cerebrovascular disease) and food frequency questionnaire (FFQ). All participants filled out the FFQ about the frequencies of each food item and the frequency units (day, week, month, year or never) based on 11 food categories grain, meat (pork, beef and mutton), eggs, milk and milk products, marine products, vegetables, fruits, legumes, fungi, nuts and teas. The 11 kinds of food categories were based on the Chinese Food Guide Pagoda which is extensively used for dietary guidelines for Chinese residents. Moreover, 9 food items were listed in the legume section, including soybean milk, soybean curd, semi-congealed jellied bean curd, soybean, soybean sprout, dried bean curd, skin of soybean milk, bean curd sheet rolls and fermented bean curd. We calculated the quantity of total SIF intake based on the quantity of legumes intake and SIF content in the foods according to China Food Composition or prior studies (13).
Evaluation of MCI
MCI was evaluated with MoCA. The cut-off score being used for screening MCI in some developed countries is 25/26. However, a study based on the Chinese population suggests relatively lower cut-offs, which vary by education. The proposed cut-offs show high sensitivity and specificity for MCI and dementia in the Chinese population (14). We used the cut-offs from this study with 12/13 for illiterate individuals, 18/19 for individuals with ≤6 years of education, and 23/24 for individuals with more than 6 years of education or higher. Based on the cut-offs, we divided participants into two groups: MCI group and control group. If the participants were presumed MCI according MoCA we would arranged them to go to see the neurologist who would defined MCI ultimately according additional cognitive assessments including Clinical Dementia Rating (CDR), Neuropsychiatric Inventory(NPI) and Hamilton(HAMD)/Geriatric Depression Scale (GDS) and development of the disease.
Statistical Analysis
Data was analyzed with the software SPSS 13.0. All clinical continuous variables are presented as means ± standard deviation (M ± s.d.). Gender, educational level, current smoker, alcohol consumption, smoking history, suffering from chronic diseases (including hypertension, diabetes, coronary heart disease and cerebrovascular disease) were presented as category variables. Significance of the difference between the two groups was analyzed by using Independent-Samples t test for continuous variables; and Chi-square or Fisher’s exact test was used for category variables. Binary multivariable logistic regression was performed to evaluate the association between potential dietary and lifestyle patterns risk factors and MCI. We calculated odds ratio (OR) and the 95% confidence interval (CI). Statistical testing was performed at the conventional 2-tailed α=0.05.
Results
Social demographic characteristics
There were 404 of participants, including 98 (24.26%) subjects with MCI, and 306 (75.74%) cognitively normal subjects. The median age is 76 (range from 60 to 90). Table 1 and Table 2 show the social demographic characteristics, health status, dietary and lifestyle patterns of the study population for elderly people with and without MCI in univariate analysis.
Table 1.
Social demographic information, health status, dietary and lifestyles of the study population for elderly people with and without MCI in univariate analysis, continuous variables, aged 60+, in Beijing, China
| Control group M ± s.d | MCI group M ± s.d | |
|---|---|---|
| Age (years) | 71.20 ± 7.31 | 84.63 ± 3.12* |
| BMI (kg/m2) | 25.48 ± 3.51 | 25.33 ± 3.56 |
| GLU (mmol/L) | 5.73±1.36 | 6.10±2.62 |
| TC (mmol/L) | 4.93±0.94 | 4.80±1.10 |
| TG (mmol/L) | 1.52±0.70 | 1.49±1.26 |
| HDL (mmol/L) | 1.50±0.36 | 1.45±0.37 |
| LDL (mmol/L) | 2.96±0.80 | 2.80±0.84 |
| ALT (IU/L) | 19.46±9.44 | 17.94±5.84 |
| AST (IU/L) | 21.75±4.93 | 21.64±5.01 |
| Intake(g/d) | ||
| SIF | 23.22±1.09 | 18.49±1.58* |
| Grain | 262.07±10.49 | 283.44±24.76 |
| Meat | 52.54±3.42 | 45.75±3.90 |
| Eggs | 44.48±1.72 | 35.46±1.99* |
| Milk | 203.17±7.78 | 183.44±14.51 |
| fish and shrimp | 40.43±2.10 | 25.16±1.22* |
| vegetables | 361.07±14.33 | 301.31±20.01* |
| fruit | 254.66±11.30 | 243.70±17.62 |
| fungi | 45.04±4.21 | 42.88±4.65 |
| nuts | 48.07±3.40 | 48.00±6.39 |
| teas | 10.04±0.72 | 10.11±1.46 |
| Watching TV(h/d) | 1.58±1.08 | 1.26±0.63* |
| Reading(h/d) |
2.74±1.52 |
2.15±1.35* |
Note: Data was analyzed with the software SPSS 13.0 (SPSS Inc, Chicago, USA) by using Independent-Samples t test. *=Compared with control group P<0.05. Abbreviation: Body mass index, BMI; Plasma glucose, GLU; Total cholesterol, TC; Triglycerides, TG; high-density lipoprotein, HDL; low-density lipoprotein, LDL; alanine transarninase, ALT; aspartate aminotransferase, AST.
Table 2.
Social demographic information, lifestyle and health status of the study population for elderly people with and without MCI in univariate analysis, category variables, aged 60+, in Beijing, China
| Control group | MCI group | ||||
|---|---|---|---|---|---|
| N | % | N | % | ||
| Gender | Male | 148 | 75.13% | 49 | 24.87% |
| Female | 158 | 76.34% | 49 | 23.67% | |
| Hypertension | No | 144 | 47.1% | 42 | 42.9% |
| Yes | 162 | 52.9% | 56 | 57.1% | |
| Diabetes | No | 261 | 85.3% | 75 | 76.5% |
| Yes | 45 | 14.7% | 23 | 23.5%* | |
| Coronary Heart Disease | No | 265 | 86.6% | 76 | 77.6% |
| Yes | 41 | 13.4% | 22 | 22.4%* | |
| Cerebrovascular disease | No | 288 | 94.1% | 86 | 87.8% |
| Yes | 18 | 5.9% | 12 | 12.2%* | |
| Smoking | No | 263 | 85.9% | 75 | 76.5% |
| Yes | 43 | 14.1% | 23 | 23.5%* | |
| Alcohol consumption | No | 232 | 75.8% | 78 | 79.6% |
| Yes | 74 | 24.2% | 20 | 20.4% | |
| Physical exercises | No | 265 | 86.6% | 76 | 77.6% |
| Yes |
41 |
13.4% |
22 |
22.4%* |
|
Notes: Data was analyzed with the software SPSS 13.0 (SPSS Inc, Chicago, USA) by using Chi-square or Fisher’s exact test. *=compared with control group P<0.05.
Association of the complex action of dietary and lifestyle patterns with MCI
The results of the multivariable logistic regression analysis suggest a significant association between MCI and dietary and lifestyle patterns after adjusting by gender, age, educational level, chronic disease, body mass index (BMI), fasting plasma glucose (GLU), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), alanine transarninase (ALT) and, aspartate aminotransferase (AST) in baseline dietary assessment. We found that higher daily intake of eggs (OR, 0.975, 95% CI, 0.959-0.992, P=.003) and marine products (OR, 0.961, 95% CI, 0.943-0.979, P=.000), longer time of watching TV (OR, 0.763, 95% CI, 0.628-0.928, P=.007) and reading (OR, 0.540, 95% CI, 0.379-0.769, P=.001) physical exercise (OR, 0.382, 95% CI, 0.185-0.789) had significantly decreased odds ratio of suffering from MCI compared with the control group (Table 3).
Table 3.
Adjusted odds ratios for the association between MCI and complex action of dietary and lifestyle patterns among people aged 60+, Beijing, China
| β | Wals χ2 | OR | 95% CI. | P | ||
|---|---|---|---|---|---|---|
| Lower limit | Upper limit | |||||
| Physical exercises | -.961 | 6.764 | .382 | .185 | .789 | .009 |
| Watching TV(h/d) | -.270 | 7.341 | .763 | .628 | .928 | .007 |
| Reading(h/d) | -.616 | 11.651 | .540 | .379 | .769 | .001 |
| Eggs intake | -.025 | 8.692 | .975 | .959 | .992 | .003 |
| marine products |
-.040 |
16.929 |
.961 |
.943 |
.979 |
.000 |
Notes: Binary multivariable logistic regression was performed. Statistical testing was performed at the conventional 2-tailed α=0.05.OR=Odds ratio; CI=confidence interval. Only significant predictors are presented. Variables adjusted in the model include gender, age, educational level, chronic disease (including hypertension, diabetes, coronary heart disease and cerebrovascular disease), body mass index (BMI), fasting plasma glucose (GLU), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), alanine transarninase (ALT) and aspartate aminotransferase (AST).
Discussion
This survey showed that the prevalence of MCI (24.26%) in this population-based sample was higher than a study in Xi’an in China (18.2%) (15) and a pooled analysis of 22 studies in China which described a pooled prevalence of MCI of 12.7% among older individuals (16). But this prevalence of MCI was approximate to other population-based studies conducted in Malaysia (21.1%) (17) and Beijing (20.8%) (18). The results may be due to higher median age of 76 years old in this study. The incidence of MCI was increased with age. Lai Kuan Lee (17) found that the prevalence of MCI in 60-74 years old group (19.8%) was significantly higher than that in >75 years old group and this tendency was consistent with the present study. We found that the age of MCI group was higher than that of control group (84.63±3.12 vs 71.20±7.31, P<0.05). Furthermore, the variability of the study design, selection of neuropsychological test, sample size, geographical boundaries and participant background, et al, would affect the results.
In this population-based case-control study, we examined associations of the Chinese daily diet and lifestyle patterns with MCI incidence among elderly people. The present results showed that the mean daily intakes of eggs, marine products, vegetables and SIF were significantly lower in participants with MCI than in controls through univariate analysis (P < 0.05) (table 1). These results were consistent with other’s studies. A systematic review and Meta-analysis indicated that higher adherence to the MeDi, which is characterized by a high intake of vegetables, legumes, fruits, cereals, and unsaturated fatty acids (mostly in the form of olive oil), moderate to high intake of fish, low to moderate intake of dairy products, low intake of meat, and saturated fatty acids, and a regular but moderate intake of alcohol (19, 20), were associated with reduced risk of MCI and AD. A long-term intervention with an EVOO-rich MedDiet resulted in a better cognitive function in comparison with a control diet (21). The subjects in the highest MeDi tertile had 33% less risk of cognitive impairment (MCI or AD) as compared to the lowest MeDi score tertile. Among cognitively normal individuals, higher adherence to the MeDi was associated with a reduced risk of MCI and AD (22). These findings suggested that adequacy intake of eggs, marine product, vegetables, and soybean isoflavone rich diet would be likely to prevent the development of MCI.
Evidence from population-based longitudinal epidemiologic studies suggested that moderate exercise and physical activity are associated with a lower risk of dementia which is the severity progression of MCI (3, 23). A few studies have also reported the independent association of physical exercise with decreased odds of suffering from MCI. Engaging in computer use, playing games, reading books, participating in craft activities (quilting, knitting,et al), and watching less television (TV) were associated with decreased odds of having MCI (24, 25). We found that the time spent on watching TV and reading in subjects with MCI was shorter than controls and the ratio of doing physical exercises was lower in MCI group than that in control group, but the ratio of smoking was higher in MCI group than that in control group through univariate analysis (P < 0.05).
However, it was well known that the presence of MCI was determined by interaction of varied daily diets and lifestyle patterns. In order to evaluate the complex action of dietary and lifestyle patterns affecting MCI in this population sample, we adjusted by gender, age, educational level, chronic non-communicable disease (including hypertension, diabetes, coronary heart disease and cerebrovascular disease), BMI, GLU, TC, TG, HDL, LDL, ALT, AST and performed binary multivariable logistic regression. The results indicated a significant association between the incidence of MCI and some of dietary and lifestyle patterns. The mean daily intake of eggs and marine products was significantly lower in participants with MCI than in controls (OR, 0.975, 95% CI, 0.959-0.992, P=.003; OR, 0.961, 95% CI, 0.943-0.979, P=.000). The mean time of watching TV and reading was significantly lower in participants with MCI than in controls (OR, 0.763, 95% CI, 0.628-0.928, P=.007; OR, 0.540, 95% CI, 0.379-0.769, P=.001). Participants who engaged in physical exercise had significantly decreased odds ratio of having MCI (OR [95% CI], 0.382[0.185-0.789]) compared with the reference group. These results suggested that in this population sample higher intake of eggs and marine products, watching TV, reading and physical exercise were associated with decreased OR of developing MCI through interacting with dietary and lifestyle patterns. A study suggested the potential role of docosahexaenoic acid (DHA)-concentrated fish oil supplementation to improve memory function in MCI subjects (26). In the present study, the result that higher intake of marine products was associated with decreased OR of MCI maybe attributed to DHA concentrated in marine products. As well known, physical exercises make limps more agilely which potentially make for prevent the development of MCI. This was consistent with Boripuntakul’s recent study which suggest that individuals with MCI have reduced balance control when undertaking a challenging walking task such as gait initiation, and this is exacerbated with an added cognitive task (27). While we presumed watching TV and reading improve cognitive performance through training the brain thinking actively. Future studies should prospectively focus on these issues.
There were some limitations in the study including the lack of longitudinal follow up and no imaging or other biomarker confirmation of prodromal AD. We will think highly of this limitations and make an effort to avoid them in our following study.
Conclusion
Our findings observed from this population-based sample suggested that intake of adequate eggs and marine products, watching TV, reading and physical exercise would likely to reduce the risk of developing MCI.
Acknowledgements: This work was supported by the grants from National Natural Science Foundation of China (No. 81172661 and No. 81330065). Xia Zhao contributed to the specific implementation of the questionnaire and interview, Evaluation of MCI, data analysis and the drafting of the paper; Linhong Yuan and Lingli Feng contributed to training of the personnel and data collection; Yuandi Xi, Huanling Yu, Weiwei Ma and Dandi Zhang contributed to interview of the participants. Rong Xiao designed and organized the study. The authors have no conflicts of interest to declare.
Ethical Standards: This study was approved by the School of Public Health, Capital Medical University institutional review board #1 (IRB00009511) and written informed consent was obtained from all participants (also from their legal proxies). The documents of the participants were only used in this study and the private information of the participants would not be revealed to public. The study comply with the current laws of China.
References
- 1.Suzana S, Lai Kuan L, Norfadilah R, et al. Association between vitamin A, vitamin E and apolipoprotein E status with mild cognitive impairment among elderly people in low-cost residential areas. Nutritional Neuroscience. 2013;16:6–12. doi: 10.1179/1476830512Y.0000000013. [DOI] [PubMed] [Google Scholar]
- 2.Gauthier S, Reisberg B, Zaudig M, et al. Mild cognitive impairment. Lancet. 2006;267:1262–1270. doi: 10.1016/S0140-6736(06)68542-5. 10.1016/S0140-6736(06)68542-5 [DOI] [PubMed] [Google Scholar]
- 3.Geda YE, Ragossnig M, Roberts LA, et al. Caloric Intake, Aging, and Mild Cognitive Impairment: A Population-Based Study. J Alzheimers Dis 34: 501–507. [DOI] [PMC free article] [PubMed]
- 4.Balion C, Griffith LE, Strifler L, et al. Vitamin D, cognition, and dementia: a systematic review and analysis. Neurology. 2012;79:1397–1405. doi: 10.1212/WNL.0b013e31826c197f. 10.1212/WNL.0b013e31826c197f PMCID 3448747; PubMed PMID: 23008220. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Anweiler C, Llewellyn CJ, Beauchet O. Low serum vitamin D concentrations in Alzheimer's disease: a systematic review and meta-analysis. J. Alzheimers Dis. 2012;33:659–674. doi: 10.3233/JAD-2012-121432. [DOI] [PubMed] [Google Scholar]
- 6.Roberts RO, Geda YE, Cerhan JR, et al. Vegetables, unsaturated fats, moderate alcohol intake and mild cognitive impairment. Dement Geriatr Cogn Disord. 2010;29:413–423. doi: 10.1159/000305099. 10.1159/000305099 PMCID 2889256; PubMed PMID: 20502015. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Davey DA. Alzheimer's disease, dementia, mild cognitive impairment and the menopause: a ‘window of opportunity'. Women's Health. 2013:279–290. doi: 10.2217/whe.13.22. [DOI] [PubMed] [Google Scholar]
- 8.Wang Z, Dong B, Zeng G, et al. Is there an association between mild cognitive impairment and dietary pattern in chinese elderly? Results from a cross-sectional. population study. BMC Public Health. 2010;10:595–607. doi: 10.1186/1471-2458-10-595. 10.1186/1471-2458-10-595 PMCID 3091557; PubMed PMID: 20932304. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Henderson VW, John JA, Hodis HN, et al. Long-term soy isoflavone supplementation and cognition in women: a randomized, controlled trial. Neurology. 2012;78:1841–1848. doi: 10.1212/WNL.0b013e318258f822. 10.1212/WNL.0b013e318258f822 PMCID 3369523; PubMed PMID: 22665144. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Geda YE, Silber TC, Roberts RO, et al. Computer Activities, Physical Exercise, Aging, and Mild Cognitive Impairment: A Population-Based Study. Mayo Clin Proc. 2012;87:437–442. doi: 10.1016/j.mayocp.2011.12.020. 10.1016/j.mayocp.2011.12.020 PMCID 3538471; PubMed PMID: 22560523. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Ding BJ, Ma WW, He LL, et al. Soybean isoflavone alleviates ß-amyloid 1-42 induced inflammatory response to improve learning and memory ability by down regulation of Toll-like receptor 4 expression and nuclear factor-γB activity in rats. Int. J. Devl Neuroscience. 2011;29:537–542. doi: 10.1016/j.ijdevneu.2011.04.002. 10.1016/j.ijdevneu.2011.04.002 [DOI] [PubMed] [Google Scholar]
- 12.Yuan L, Zhou X, Li D, et al. Pattern recognition receptors involved in the inflammatory attenuating effects of soybean isoflavone in ß-amyloid peptides 1-42 treated rats. Neurosci Lett. 2012;506:266–270. doi: 10.1016/j.neulet.2011.11.020. 10.1016/j.neulet.2011.11.020 PubMed PMID: 22133809. [DOI] [PubMed] [Google Scholar]
- 13.Yang YX, Wang GY, Pan XC. China Food Composition. 2nd ed. Peking University Medical Press. Beijing.
- 14.Lu J, Li D, Li F, et al. Montreal cognitive assessment in detecting cognitive impairment in Chinese elderly individuals: A population-based study. Journal of Geriatric Psychiatry and Neurology. 2011;24:184–190. doi: 10.1177/0891988711422528. 10.1177/0891988711422528 PubMed PMID: 22228824. [DOI] [PubMed] [Google Scholar]
- 15.Su X, Shang L, Xu QL, et al. Prevalence and Predictors of Mild Cognitive Impairment in Xi'an: A Community-Based Study among the Elders. PLoS One. 2014;9:83217. doi: 10.1371/journal.pone.0083217. 10.1371/journal.pone.0083217 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Nie H, Xu Y, Liu B, et al. The prevalence of mild cognitive impairment about elderly population in China: a meta-analysis. Int J Geriatr Psychiatry. 2011;26:558–563. doi: 10.1002/gps.2579. 10.1002/gps.2579 PubMed PMID: 20878675. [DOI] [PubMed] [Google Scholar]
- 17.Lee LK, Shahar S, Chin AV, et al. Prevalence of gender disparities and predictors affecting the occurrence of mild cognitive impairment (MCI) Arch Gerontol Geriatr. 2012;54:185–191. doi: 10.1016/j.archger.2011.03.015. 10.1016/j.archger.2011.03.015 PubMed PMID: 21546098. [DOI] [PubMed] [Google Scholar]
- 18.Jia J, Zhou A, Wei C, et al. The prevalence of mild cognitive impairment and its etiological subtypes in elderly Chinese. Alzheimers Dement. 2014 doi: 10.1016/j.jalz.2013.09.008. [DOI] [PubMed] [Google Scholar]
- 19.Trichopoulou A, Costacou T, Bamia C, et al. Adherence to a Mediterranean diet and survival in a Greek population. N Engl J Med. 2003;348:2599–2608. doi: 10.1056/NEJMoa025039. 10.1056/NEJMoa025039 PubMed PMID: 12826634. [DOI] [PubMed] [Google Scholar]
- 20.Willett WC, Sacks F, Trichopoulou A, et al. Mediterranean diet pyramid: a cultural model for healthy eating. Am J Clin Nutr. 1995;61:1402S–1406S. doi: 10.1093/ajcn/61.6.1402S. PubMed PMID: 7754995. [DOI] [PubMed] [Google Scholar]
- 21.Martínez-Lapiscina EH, Clavero P, Toledo E, et al. Virgin olive oil supplementation and long-term cognition: the PREDIMED-NAVARRA randomized, trial. J Nutr Health Aging. 2013;17(6):544–552. doi: 10.1007/s12603-013-0027-6. 10.1007/s12603-013-0027-6 PubMed PMID: 23732551. [DOI] [PubMed] [Google Scholar]
- 22.Singh B, Parsaik AK, Mielke MM, et al. Association of Mediterranean Diet with Mild Cognitive Impairment and Alzheimer's Disease: A Systematic Review and Meta-Analysis. J Alzheimers Dis. 2014;39:271–282. doi: 10.3233/JAD-130830. PMCID 3946820; PubMed PMID: 24164735. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Solfrizzi V, Capurso C, D'Introno A, et al. Lifestyle-related factors in predementia and dementia syndromes. Expert Rev Neurother. 2008;8:133–158. doi: 10.1586/14737175.8.1.133. 10.1586/14737175.8.1.133 PubMed PMID: 18088206. [DOI] [PubMed] [Google Scholar]
- 24.Geda YE, Roberts RO, Knopman DS, et al. Physical exercise, aging, and mild cognitive impairment: a population-based study. Arch Neurol. 2010;67:80–86. doi: 10.1001/archneurol.2009.297. PMCID 2919839; PubMed PMID: 20065133. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Geda YE, Topazian HM, Lewis RA, et al. Engaging in cognitive activities, aging, and mild cognitive impairment: a population-based study. J Neuropsychiatry Clin Neurosci. 2011;23:149–154. doi: 10.1176/appi.neuropsych.23.2.149. 10.1176/jnp.23.2.jnp149 PMCID 3204924; PubMed PMID: 21677242. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Lee LK, Shahar S, Chin AV, Yusoff NA. Docosahexaenoic acid-concentrated fish oil supplementation in subjects with mild cognitive impairment (MCI): a 12-month randomised, double-blind, placebo-controlled trial. Psychopharmacology (Berl) 2012;225(3):605–612. doi: 10.1007/s00213-012-2848-0. 10.1007/s00213-012-2848-0 [DOI] [PubMed] [Google Scholar]
- 27.Boripuntakul S, Lord SR, Brodie MA, et al. Spatial variability during gait initiation while dual tasking is increased in individuals with mild cognitive impairment. J Nutr Health Aging. 2014;18(3):307–312. doi: 10.1007/s12603-013-0390-3. 10.1007/s12603-013-0390-3 PubMed PMID: 24626760. [DOI] [PubMed] [Google Scholar]
