Nikolaos Scarmeas

Mediterranean Diet and Risk for Alzheimer's Disease

Previous research in Alzheimers disease (AD) has focused on individual dietary components. There is converging evidence that composite dietary patterns such as the Mediterranean diet (MeDi) is related to lower risk for cardiovascular disease, several forms of cancer, and overall mortality. We sought to investigate the association between MeDi and risk for AD.

Physical Activity, Diet, and Risk of Alzheimer Disease

CONTEXT Both higher adherence to a Mediterranean-type diet and more physical activity have been independently associated with lower Alzheimer disease (AD) risk but their combined association has not been investigated. OBJECTIVE To investigate the combined association of diet and physical activity with AD risk. DESIGN, SETTING, AND PATIENTS Prospective cohort study of 2 cohorts comprising 1880 community-dwelling elders without dementia living in New York, New York, with both diet and physical activity information available. Standardized neurological and neuropsychological measures were administered approximately every 1.5 years from 1992 through 2006. Adherence to a Mediterranean-type diet (scale of 0-9; trichotomized into low, middle, or high; and dichotomized into low or high) and physical activity (sum of weekly participation in various physical activities, weighted by the type of physical activity [light, moderate, vigorous]; trichotomized into no physical activity, some, or much; and dichotomized into low or high), separately and combined, were the main predictors in Cox models. Models were adjusted for cohort, age, sex, ethnicity, education, apolipoprotein E genotype, caloric intake, body mass index, smoking status, depression, leisure activities, a comorbidity index, and baseline Clinical Dementia Rating score. MAIN OUTCOME MEASURE Time to incident AD. RESULTS A total of 282 incident AD cases occurred during a mean (SD) of 5.4 (3.3) years of follow-up. When considered simultaneously, both Mediterranean-type diet adherence (compared with low diet score, hazard ratio [HR] for middle diet score was 0.98 [95% confidence interval {CI}, 0.72-1.33]; the HR for high diet score was 0.60 [95% CI, 0.42-0.87]; P = .008 for trend) and physical activity (compared with no physical activity, the HR for some physical activity was 0.75 [95% CI, 0.54-1.04]; the HR for much physical activity was 0.67 [95% CI, 0.47-0.95]; P = .03 for trend) were associated with lower AD risk. Compared with individuals neither adhering to the diet nor participating in physical activity (low diet score and no physical activity; absolute AD risk of 19%), those both adhering to the diet and participating in physical activity (high diet score and high physical activity) had a lower risk of AD (absolute risk, 12%; HR, 0.65 [95% CI, 0.44-0.96]; P = .03 for trend). CONCLUSION In this study, both higher Mediterranean-type diet adherence and higher physical activity were independently associated with reduced risk for AD.

Influence of leisure activity on the incidence of Alzheimer’s Disease

Objective: To determine whether leisure activities modify the risk for incident dementia. Background: Although high educational and occupational attainments have been associated with reduced risk of incident dementia, the relation between leisure activities and dementia risk has not been adequately investigated. Methods: A total of 1,772 nondemented individuals aged 65 years or older, living in northern Manhattan, New York, were identified and followed longitudinally in a community-based cohort incidence study. Subjects’ leisure activities at baseline were assessed, annual examinations with the same standardized neurologic and neuropsychological measures were performed for up to 7 years (mean 2.9 years), and incident dementia was assessed as the main outcome measure. Cox proportional hazards models, adjusting for age, ethnic group, education, and occupation, were used to estimate the relative risk (RR) of incident dementia associated with high leisure activities. Results: Of the 1,772 subjects, 207 became demented. The risk of dementia was decreased in subjects with high leisure activities (RR, 0.62; 95% CI 0.46 to 0.83). The association of high leisure with decreased RR of incident dementia was present even when baseline cognitive performance, health limitations interfering with desired leisure activities, cerebrovascular disease, and depression were considered. Conclusions: The data suggest that engagement in leisure activities may reduce the risk of incident dementia, possibly by providing a reserve that delays the onset of clinical manifestations of the disease.

Adherence to a Mediterranean Diet, Cognitive Decline, and Risk of Dementia

CONTEXT Higher adherence to a Mediterranean-type diet is linked to lower risk for mortality and chronic diseases, but its association with cognitive decline is unclear. OBJECTIVE To investigate the association of a Mediterranean diet with change in cognitive performance and risk for dementia in elderly French persons. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study of 1410 adults (> or = 65 years) from Bordeaux, France, included in the Three-City cohort in 2001-2002 and reexamined at least once over 5 years. Adherence to a Mediterranean diet (scored as 0 to 9) was computed from a food frequency questionnaire and 24-hour recall. MAIN OUTCOME MEASURES Cognitive performance was assessed on 4 neuropsychological tests: the Mini-Mental State Examination (MMSE), Isaacs Set Test (IST), Benton Visual Retention Test (BVRT), and Free and Cued Selective Reminding Test (FCSRT). Incident cases of dementia (n = 99) were validated by an independent expert committee of neurologists. RESULTS Adjusting for age, sex, education, marital status, energy intake, physical activity, depressive symptomatology, taking 5 medications/d or more, apolipoprotein E genotype, cardiovascular risk factors, and stroke, higher Mediterranean diet score was associated with fewer MMSE errors (beta = -0.006; 95% confidence interval [CI], -0.01 to -0.0003; P = .04 for 1 point of the Mediterranean diet score). Performance on the IST, BVRT, or FCSRT over time was not significantly associated with Mediterranean diet adherence. Greater adherence as a categorical variable (score 6-9) was not significantly associated with fewer MMSE errors and better FCSRT scores in the entire cohort, but among individuals who remained free from dementia over 5 years, the association for the highest compared with the lowest group was significant (adjusted for all factors, for MMSE: beta = -0.03; 95% CI, -0.05 to -0.001; P = .04; for FCSRT: beta = 0.21; 95% CI, 0.008 to 0.41; P =.04). Mediterranean diet adherence was not associated with the risk for incident dementia (fully adjusted model: hazard ratio, 1.12; 95% CI, 0.60 to 2.10; P = .72), although power to detect a difference was limited. CONCLUSIONS Higher adherence to a Mediterranean diet was associated with slower MMSE cognitive decline but not consistently with other cognitive tests. Higher adherence was not associated with risk for incident dementia.

Mediterranean Diet and Mild Cognitive Impairment

BACKGROUND Higher adherence to the Mediterranean diet (MeDi) may protect from Alzheimer disease (AD), but its association with mild cognitive impairment (MCI) has not been explored. OBJECTIVE To investigate the association between the MeDi and MCI. DESIGN, SETTING, AND PATIENTS In a multiethnic community study in New York, we used Cox proportional hazards to investigate the association between adherence to the MeDi (0-9 scale; higher scores indicate higher adherence) and (1) the incidence of MCI and (2) the progression from MCI to AD. All of the models were adjusted for cohort, age, sex, ethnicity, education, APOE genotype, caloric intake, body mass index, and duration between baseline dietary assessment and baseline diagnosis. MAIN OUTCOME MEASURES Incidence of MCI and progression from MCI to AD. RESULTS There were 1393 cognitively normal participants, 275 of whom developed MCI during a mean (SD) follow-up of 4.5 (2.7) years (range, 0.9-16.4 years). Compared with subjects in the lowest MeDi adherence tertile, subjects in the middle tertile had 17% less risk (hazard ratio [HR] = 0.83; 95% confidence interval [CI], 0.62-1.12; P = .24) of developing MCI and those in the highest tertile had 28% less risk (HR = 0.72; 95% CI, 0.52-1.00; P = .05) of developing MCI (trend HR = 0.85; 95% CI, 0.72-1.00; P for trend = .05). There were 482 subjects with MCI, 106 of whom developed AD during a mean (SD) follow-up of 4.3 (2.7) years (range, 1.0-13.8 years). Compared with subjects in the lowest MeDi adherence tertile, subjects in the middle tertile had 45% less risk (HR = 0.55; 95% CI, 0.34-0.90; P = .01) of developing AD and those in the highest tertile had 48% less risk (HR = 0.52; 95% CI, 0.30-0.91; P = .02) of developing AD (trend HR = 0.71; 95% CI, 0.53-0.95; P for trend = .02). CONCLUSIONS Higher adherence to the MeDi is associated with a trend for reduced risk of developing MCI and with reduced risk of MCI conversion to AD.

Cognitive Reserve and Lifestyle

The concept of cognitive reserve (CR) suggests that innate intelligence or aspects of life experience like educational or occupational attainments may supply reserve, in the form of a set of skills or repertoires that allows some people to cope with progressing Alzheimer’s disease (AD) pathology better than others. There is epidemiological evidence that lifestyle characterized by engagement in leisure activities of intellectual and social nature is associated with slower cognitive decline in healthy elderly and may reduce the risk of incident dementia. There is also evidence from functional imaging studies that subjects engaging in such leisure activities can clinically tolerate more AD pathology. It is possible that aspects of life experience like engagement in leisure activities may result in functionally more efficient cognitive networks and therefore provide a CR that delays the onset of clinical manifestations of dementia.

Food Combination and Alzheimer Disease Risk: A Protective Diet

OBJECTIVE To assess the association between food combination and Alzheimer disease (AD) risk. Because foods are not consumed in isolation, dietary pattern (DP) analysis of food combination, taking into account the interactions among food components, may offer methodological advantages. DESIGN Prospective cohort study. SETTING Northern Manhattan, New York, New York. PATIENTS OR OTHER PARTICIPANTS Two thousand one hundred forty-eight community-based elderly subjects (aged > or = 65 years) without dementia in New York provided dietary information and were prospectively evaluated with the same standardized neurological and neuropsychological measures approximately every 1.5 years. Using reduced rank regression, we calculated DPs based on their ability to explain variation in 7 potentially AD-related nutrients: saturated fatty acids, monounsaturated fatty acids, omega-3 polyunsaturated fatty acids, omega-6 polyunsaturated fatty acids, vitamin E, vitamin B(12), and folate. The associations of reduced rank regression-derived DPs with AD risk were then examined using a Cox proportional hazards model. Main Outcome Measure Incident AD risk. RESULTS Two hundred fifty-three subjects developed AD during a follow-up of 3.9 years. We identified a DP strongly associated with lower AD risk: compared with subjects in the lowest tertile of adherence to this pattern, the AD hazard ratio (95% confidence interval) for subjects in the highest DP tertile was 0.62 (0.43-0.89) after multivariable adjustment (P for trend = .01). This DP was characterized by higher intakes of salad dressing, nuts, fish, tomatoes, poultry, cruciferous vegetables, fruits, and dark and green leafy vegetables and a lower intake of high-fat dairy products, red meat, organ meat, and butter. CONCLUSION Simultaneous consideration of previous knowledge regarding potentially AD-related nutrients and multiple food groups can aid in identifying food combinations that are associated with AD risk.

Mediterranean diet, stroke, cognitive impairment, and depression: A meta‐analysis

This meta‐analysis aims to quantitatively synthesize all studies that examine the association between adherence to a Mediterranean diet and risk of stroke, depression, cognitive impairment, and Parkinson disease.

Contribution of Vascular Risk Factors to the Progression in Alzheimer Disease

BACKGROUND Vascular factors including medical history (heart disease, stroke, diabetes, and hypertension), smoking, and prediagnosis blood lipid measurements (cholesterol: total, high-density lipoprotein, low-density lipoprotein [LDL-C], and triglyceride concentrations) may be predictors for progression of Alzheimer disease (AD). OBJECTIVE To determine whether prediagnosis vascular risk factors are associated with progression of AD. DESIGN Inception cohort followed up longitudinally for a mean of 3.5 (up to 10.2) years. SETTING Washington Heights/Inwood Columbia Aging Project, New York, New York. Patients One hundred fifty-six patients with incident AD (mean age at diagnosis, 83 years). Main Outcome Measure Change in a composite score of cognitive ability from diagnosis onward. RESULTS In generalized estimating equation models (adjusted for age, race/ethnicity, and years of education), higher cholesterol (total cholesterol and LDL-C) concentrations and history of diabetes were associated with faster cognitive decline. Each 10-U increase in cholesterol and LDL-C was associated with a 0.10-SD decrease in cognitive score per year of follow-up (P < .001 for total cholesterol; P = .001 for LDL-C). High-density lipoprotein cholesterol and triglyceride concentrations were not associated with rate of decline. A history of diabetes was associated with an additional 0.05-SD decrease in cognitive score per year (P = .05). History of heart disease and stroke were associated with cognitive decline only in carriers of the apolipoprotein E epsilon4 (APOE-epsilon4) gene. In a final generalized estimating equation model that included high-density lipoprotein cholesterol and LDL-C concentrations and history of diabetes, only higher LDL-C was independently associated with faster cognitive decline. CONCLUSION Higher prediagnosis total cholesterol and LDL-C concentrations and history of diabetes were associated with faster cognitive decline in patients with incident AD, which provides further evidence for the role of vascular risk factors in the course of AD.

Education and rates of cognitive decline in incident Alzheimer’s disease

Background: Some (but not all) epidemiological studies have noted faster rates of progression in high education patients with Alzheimer’s disease (AD), which has been attributed to harbouring/tolerating a higher pathological burden at the time of clinical dementia for subjects with higher education. We wanted to assess the relationship between education and rates of decline in AD. Methods: During the course of a community based multiethnic prospective cohort study of individuals aged ⩾65 years living in New York, 312 patients were diagnosed with incident AD and were followed overall for 5.6 (up to 13.3) years. The subjects received an average of 3.7 (up to 9) neuropsychological assessments consisting of 12 individual tests. With the aid of a normative sample, a standardised composite cognitive score as well as individual cognitive domain scores were calculated. Generalised estimating equation models were used to examine the association between education and rates of cognitive decline. Results: Composite cognitive performance declined by 9% of a standard deviation per year. Rates of decline before and after AD incidence were similar. For each additional year of education there was 0.3% standard deviation lower composite cognitive performance for each year of follow up. The association between higher education and faster decline was noted primarily in the executive speed (0.6%) and memory (0.5%) cognitive domains and was present over and above age, gender, ethnicity, differential baseline cognitive performance, depression, and vascular comorbidity. Conclusions: We conclude that higher education AD patients experience faster cognitive decline.