History of vascular disease and mild parkinsonian signs in community-dwelling elderly individuals

Background: Mild parkinsonian signs (MPS) are commonly found during the clinical examination of older people. These signs could reflect the accumulation of vascular pathological changes in the brain. If the etiology were vascular, one could hypothesize that individuals with MPS would be more likely to have systemic vascular disease than would their counterparts without these signs. Objectives: To examine whether MPS are associated with a history of vascular disease and whether certain MPS (rigidity, changes in axial function) are more strongly associated with a history of vascular disease than are other MPS (tremor). Methods: Evaluation of older people without dementia in Washington Heights-Inwood, northern Manhattan, NY. The presence of vascular diseases was assessed with a structured health interview. Results: Mild parkinsonian signs were present in 375 (16.4%) of 2286 participants without dementia. Diabetes mellitus, heart disease, peripheral vascular disease, and stroke were more prevalent in participants with MPS than without MPS, whereas nonvascular diseases (cancer, thyroid disease) were not. In a logistic regression analysis that adjusted for age, sex, education, and depressive symptoms, the number of vascular diseases was associated with MPS (odds ratio, 1.31 [95% confidence interval, 1.18-1.46]; P<.001). The combination of diabetes mellitus and heart disease increased the odds of MPS by 70% and the combination of these with stroke increased the odds by 332%. Conclusions: The presence of MPS in elderly individuals might reflect, in part, the accumulation of vascular pathological changes in the basal ganglia or white matter regions caused by preventable vascular diseases. Prospective and pathological studies are needed to further explore this finding

Mediterranean Diet, Inflammatory and Metabolic Biomarkers, and Risk of Alzheimer's Disease

We aimed to investigate the association between adherence to the Mediterranean diet (MeDi) and Alzheimer's disease (AD) risk in a prospective study. Specifically, we analyzed reduced inflammation and improved metabolic profile as a potential medium through which the MeDi reduced the risk of AD. During a 4-year follow-up, 118 incident AD cases were identified among the 1219 non-demented elderly (age ⩾ 65) subjects who provided dietary information and blood samples at baseline. We used high-sensitivity C-reactive protein (hsCRP) as an index of systemic inflammation, and fasting insulin and adiponectin as indexes of metabolic profile. We investigated whether there was a change in the association between MeDi and incident AD risk when the biomarkers were introduced into multivariable adjusted COX models. Better adherence to MeDi was associated with lower level of hsCRP (p =0.003), but not fasting insulin or adiponectin. Better adherence to MeDi was significantly associated with lower risk for AD: compared to those in the lowest tertile of MeDi, subjects in the highest tertile had a 34% less risk of developing AD (p-for-trend =0.04). Introduction of the hsCRP, fasting insulin, adiponectin, or combinations of them into the COX model did not change the magnitude of the association between MeDi and incident AD. Ultimately, the favorable association between better adherence to MeDi and lower risk of AD did not seem to be mediated by hsCRP, fasting insulin, or adiponectin. Other aspects of inflammatory and metabolic pathways not captured by these biomarkers, or non-inflammatory or non-metabolic pathways, may be relevant to the MeDi-AD association

Mediterranean Diet, Inflammatory and Metabolic Biomarkers, and Risk of Alzheimer's Disease

We aimed to investigate the association between adherence to the Mediterranean diet (MeDi) and Alzheimer's disease (AD) risk in a prospective study. Specifically, we analyzed reduced inflammation and improved metabolic profile as a potential medium through which the MeDi reduced the risk of AD. During a 4-year follow-up, 118 incident AD cases were identified among the 1219 non-demented elderly (age ⩾ 65) subjects who provided dietary information and blood samples at baseline. We used high-sensitivity C-reactive protein (hsCRP) as an index of systemic inflammation, and fasting insulin and adiponectin as indexes of metabolic profile. We investigated whether there was a change in the association between MeDi and incident AD risk when the biomarkers were introduced into multivariable adjusted COX models. Better adherence to MeDi was associated with lower level of hsCRP (p =0.003), but not fasting insulin or adiponectin. Better adherence to MeDi was significantly associated with lower risk for AD: compared to those in the lowest tertile of MeDi, subjects in the highest tertile had a 34% less risk of developing AD (p-for-trend =0.04). Introduction of the hsCRP, fasting insulin, adiponectin, or combinations of them into the COX model did not change the magnitude of the association between MeDi and incident AD. Ultimately, the favorable association between better adherence to MeDi and lower risk of AD did not seem to be mediated by hsCRP, fasting insulin, or adiponectin. Other aspects of inflammatory and metabolic pathways not captured by these biomarkers, or non-inflammatory or non-metabolic pathways, may be relevant to the MeDi-AD association

Mediterranean Diet and Alzheimer Disease Mortality

BACKGROUND: We previously reported that the Mediterranean diet (MeDi) is related to lower risk for Alzheimer disease (AD). Whether MeDi is associated with subsequent AD course and outcomes has not been investigated. OBJECTIVES: To examine the association between MeDi and mortality in patients with AD. METHODS: A total of 192 community-based individuals in New York who were diagnosed with AD were prospectively followed every 1.5 years. Adherence to the MeDi (0- to 9-point scale with higher scores indicating higher adherence) was the main predictor of mortality in Cox models that were adjusted for period of recruitment, age, gender, ethnicity, education, APOE genotype, caloric intake, smoking, and body mass index. RESULTS: Eighty-five patients with AD (44%) died during the course of 4.4 (+/-3.6, 0.2 to 13.6) years of follow-up. In unadjusted models, higher adherence to MeDi was associated with lower mortality risk (for each additional MeDi point hazard ratio 0.79; 95% CI 0.69 to 0.91; p = 0.001). This result remained significant after controlling for all covariates (0.76; 0.65 to 0.89; p = 0.001). In adjusted models, as compared with AD patients at the lowest MeDi adherence tertile, those at the middle tertile had lower mortality risk (0.65; 0.38 to 1.09; 1.33 years' longer survival), whereas subjects at the highest tertile had an even lower risk (0.27; 0.10 to 0.69; 3.91 years' longer survival; p for trend = 0.003). CONCLUSION: Adherence to the Mediterranean diet (MeDi) may affect not only risk for Alzheimer disease (AD) but also subsequent disease course: Higher adherence to the MeDi is associated with lower mortality in AD. The gradual reduction in mortality risk for higher MeDi adherence tertiles suggests a possible dose-response effect

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 ≥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, ω-3 polyunsaturated fatty acids, ω-6 polyunsaturated fatty acids, vitamin E, vitamin B12, 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 and Risk for Alzheimer's Disease

OBJECTIVE: Previous research in Alzheimer's 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. METHODS: A total of 2,258 community-based nondemented individuals in New York were prospectively evaluated every 1.5 years. Adherence to the MeDi (zero- to nine-point scale with higher scores indicating higher adherence) was the main predictor in models that were adjusted for cohort, age, sex, ethnicity, education, apolipoprotein E genotype, caloric intake, smoking, medical comorbidity index, and body mass index. RESULTS: There were 262 incident AD cases during the course of 4 (+/-3.0; range, 0.2-13.9) years of follow-up. Higher adherence to the MeDi was associated with lower risk for AD (hazard ratio, 0.91; 95% confidence interval, 0.83-0.98; p = 0.015). Compared with subjects in the lowest MeDi tertile, subjects in the middle MeDi tertile had a hazard ratio of 0.85 (95% confidence interval, 0.63-1.16) and those at the highest tertile had a hazard ratio of 0.60 (95% confidence interval, 0.42-0.87) for AD (p for trend = 0.007). INTERPRETATION: We conclude that higher adherence to the MeDi is associated with a reduction in risk for AD. Ann Neurol 2006

Mild parkinsonian signs and plasma homocysteine concentration in community-dwelling elderly individuals

Objective: To determine whether plasma homocysteine (Hcy) concentration is associated with mild parkinsonian signs (MPS) in community-dwelling elderly individuals. Design: Cross-sectional analyses of a population-based cohort study. Setting: Washington Heights–Inwood, New York. Patients: Persons without dementia 65 years and older. Main Outcome: Measure Participants underwent an abbreviated motor portion of the Unified Parkinson's Disease Rating Scale. Each participant was assigned an MPS score (range, 0-40). The Hcy concentration was measured from plasma. All analyses were cross-sectional. Results: There were 369 participants (mean ± SD age, 77.8 ± 6.0 years; mean ± SD MPS score, 1.51 ± 2.55; mean ± SD plasma Hcy concentration, 17.3 ± 6.5 μmol/L). Mean ± SD MPS scores in plasma Hcy concentration quintiles were as follows: lowest quintile, 1.15 ± 1.77; second quintile, 1.18 ± 1.88; third quintile, 1.64 ± 2.93; fourth quintile, 1.45 ± 2.17; and highest quintile, 2.12 ± 3.49 (84.3% higher than 1.15) (P = .02). In an unadjusted linear regression model, plasma Hcy concentration was associated with log MPS score (dependent variable) (P = .008). In a linear regression model that adjusted for confounding variables, plasma Hcy concentration was associated with log MPS score (P = .04). Conclusions: These data indicate that MPS are associated with higher plasma Hcy concentrations. Prospective neuroimaging as well as clinical-pathological studies would further our understanding of several mechanisms that could underlie the observed association

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

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

The Relationship of Hypertension in the Elderly to AD, Vascular Dementia, and Cognitive Function

Background: Hypertension at the age of 45 to 50 years may predispose to AD later in life. It is not known whether hypertension after age 65 years also contributes to AD risk, and its effect on cognitive function is also not fully understood. Methods: Data were analyzed from 1,259 Medicare recipients free of dementia in a longitudinal study covering a 7-year period (1991 to 1998). The effect of hypertension was first examined in relationship to the risk for incident AD and then to incident vascular dementia (VaD) using Cox proportional hazards models. Changes in performance over time on tasks of memory, language, and visuospatial/cognitive function were compared in those with and without hypertension using generalized estimating equations. Results: Of the 1,259 subjects, 731 (58.1%) had a history of hypertension associated with diabetes, stroke, and heart disease. A history of hypertension was not associated with an increased risk for AD (rate ratio [RR] 0.9, 95% CI 0.7 to 1.3) but was associated with an increased risk for VaD (1.8 [1.0 to 3.2]). Hypertension was not associated with changes in memory, language, and general cognitive function in normal individuals over time. Compared with individuals with neither hypertension nor heart disease, those with hypertension or heart disease alone had no increase in risk for VaD. However, when both were present, there was a threefold increase in risk for VaD. A sixfold increase in risk was observed when both hypertension and diabetes were present. Conclusions: Hypertension after age 65 years is not associated with AD and does not adversely affect memory, language, or general cognitive function. A history of hypertension may be an antecedent to VaD, particularly in the presence of heart disease or diabetes