Alzheimer Disease: Luchsinger JA

Luchsinger JA, Gustafson DR. · Gertrude H. Sergievsky Center, New York, NY 10032, USA. · J Alzheimers Dis. · Pubmed #19387106 links to  free full text

Abstract: This manuscript provides a comprehensive review of the epidemiologic evidence linking the continuum of adiposity and type 2 diabetes (T2D) with Alzheimer's disease (AD). The mechanisms relating adiposity and T2D to AD may include hyperinsulinemia, advanced products of glycosylation, cerebrovascular disease, and products of adipose tissue metabolism. Elevated adiposity in middle age is related to a higher risk of AD but the data on this association in old age is conflicting. Several studies have shown that hyperinsulinemia, a consequence of higher adiposity and insulin resistance, is also related to a higher risk of AD. Hyperinsulinemia is a risk factor for T2D, and numerous studies have shown a relation of T2D with higher AD risk. The implication of these associations is that a large proportion of the world population may be at increased risk of AD given the trends for increasing prevalence of overweight, obesity, hyperinsulinemia, and T2D. However these associations may present a unique opportunity for prevention and treatment of AD. Several studies in the prevention and treatment of T2D are currently conducting, or have planned, cognition ancillary studies. In addition, clinical trials using insulin sensitizers in the treatment or prevention of AD are under way.

Luchsinger JA, Gustafson DR. · Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, New York, USA. · Curr Opin Clin Nutr Metab Care. · Pubmed #19057182 No free full text.

Abstract: PURPOSE OF REVIEW: Alzheimer's disease is the most common form of dementia. There are no known preventive or curative measures. There is increasing evidence for the role of total adiposity, usually measured clinically as BMI, and central adiposity, in Alzheimer's disease. This topic is of enormous public health importance given the global epidemic of high adiposity and its consequences. RECENT FINDINGS: Salient publications in 2007 and 2008 showed that (a) central adiposity in middle age predicts dementia in old age; (b) the relation between high adiposity and dementia is attenuated with older age; (c) waist circumference in old age, a measure of central adiposity, may be a better predictor of dementia than BMI; (d) lower BMI predicts dementia in elderly people; and (e) weight loss may precede dementia diagnosis by decades, which may explain seemingly paradoxical findings. SUMMARY: The possibility that high adiposity increases Alzheimer's disease risk is alarming given global trends of overweight and obesity in the general population. However, prevention and manipulation of adiposity may also provide a means to prevent Alzheimer's disease. Treatment of weight loss in Alzheimer's disease may also be important but is beyond the score of this review.

Kalaria RN, Maestre GE, Arizaga R, Friedland RP, Galasko D, Hall K, Luchsinger JA, Ogunniyi A, Perry EK, Potocnik F, Prince M, Stewart R, Wimo A, Zhang ZX, Antuono P, Anonymous00415. · Institute for Ageing and Health, Newcastle General Hospital, Newcastle upon Tyne, UK. · Lancet Neurol. · Pubmed #18667359 No free full text.

Abstract: Despite mortality due to communicable diseases, poverty, and human conflicts, dementia incidence is destined to increase in the developing world in tandem with the ageing population. Current data from developing countries suggest that age-adjusted dementia prevalence estimates in 65 year olds are high (>or=5%) in certain Asian and Latin American countries, but consistently low (1-3%) in India and sub-Saharan Africa; Alzheimer's disease accounts for 60% whereas vascular dementia accounts for approximately 30% of the prevalence. Early-onset familial forms of dementia with single-gene defects occur in Latin America, Asia, and Africa. Illiteracy remains a risk factor for dementia. The APOE epsilon4 allele does not influence dementia progression in sub-Saharan Africans. Vascular factors, such as hypertension and type 2 diabetes, are likely to increase the burden of dementia. Use of traditional diets and medicinal plant extracts might aid prevention and treatment. Dementia costs in developing countries are estimated to be US$73 billion yearly, but care demands social protection, which seems scarce in these regions.

Luchsinger JA. · Taub Institute for Research of Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA. · Eur J Pharmacol. · Pubmed #18384771 links to  free full text

Abstract: The objective of this manuscript is to provide a comprehensive review of the epidemiologic evidence linking the continuum of adiposity, hyperinsulinemia, and diabetes with Alzheimer's disease. The mechanisms for these associations remain to be elucidated, but may include direct actions from insulin, advanced products of glycosilation, cerebrovascular disease, and products of adipose tissue metabolism. Elevated adiposity in middle age is related to a higher risk of Alzheimer's disease. The evidence relating adiposity in old age to Alzheimer's disease is conflicting. Several studies have shown that hyperinsulinemia, a consequence of higher adiposity and insulin resistance, is also related to a higher risk of Alzheimer's disease. Hyperinsulinemia is a risk factor for diabetes, and numerous studies have shown a relation of diabetes with higher Alzheimer's disease risk. Most studies fail the take into account the continuum linking these risk factors which may result in underestimation of their importance in Alzheimer's disease. The implication of these associations is that a large proportion of the world population may be at increased risk of Alzheimer's disease given the trends for increasing prevalence of overweight, obesity, hyperinsulinemia, and diabetes. However, if proven causal, these associations also present a unique opportunity for prevention and treatment of Alzheimer's disease.

Luchsinger JA, Noble JM, Scarmeas N. · Taub Institute for Research of Alzheimer's Disease and the Aging Brain, Columbia University, PH9E-105, 630 West 168th Street, New York, NY 10032, USA. · Curr Neurol Neurosci Rep. · Pubmed #17764625 No free full text.

Abstract: Alzheimer's disease (AD) is increasing in prevalence. There are no known preventive or curative measures. There is evidence that oxidative stress, homo-cysteine-related vitamins, fats, and alcohol have a role in the pathogenesis of AD. Some epidemiologic studies suggest that higher dietary intake of antioxidants, vitamins B(6), B(12), and folate, unsaturated fatty acids, and fish are related to a lower risk of AD, but reports are inconsistent. Modest to moderate alcohol intake, particularly wine, may be related to a lower risk of AD. The Mediterranean diet may also be related to lower AD risk. However, randomized clinical trials of supplements of vitamins E, B(12), B(6), and folate have shown no cognitive benefit, and randomized trials for other nutrients or diets in AD are not available. The existing evidence does not support the recommendation of specific supplements, foods, or diets for the prevention of AD.

Luchsinger JA, Mayeux R. · Taub Institute for Research of Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA. · Curr Alzheimer Res. · Pubmed #17430235 links to  free full text

Abstract: The objective of this manuscript is to provide a comprehensive review of the relation between adiposity and Alzheimer's disease (AD), its potential mechanisms, and issues in its study. Adiposity represents the body fat tissue content. When the degree of adiposity increases it can be defined as being overweight or obese by measures such as the body mass index. Being overweight or obese is a cause of hyperinsulinemia and diabetes, both of which are risk factors for AD. However, the epidemiologic evidence linking the degree of adiposity and AD is conflicting. Traditional adiposity measures such as body mass index have decreased validity in the elderly. Increased adiposity in early or middle adult life leads to hyperinsulinemia which may lead to diabetes later in life. Thus, the timing of ascertainment of adiposity and its related factors is critical in understanding how it might fit into the pathogenesis of AD. We believe that the most plausible mechanism relating adiposity to AD is hyperinsulinemia, but it is unclear whether specific products of adipose tissue also have a role. Being overweight or obese is increasing in children and adults, thus understanding the association between adiposity and AD has important public health implications.

Luchsinger JA, Mayeux R. · Taub Institute for Research of Alzheimer's Disease and the Aging Brain, Division of General Medicine, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, USA. · Lancet Neurol. · Pubmed #15380154 No free full text.

Abstract: Alzheimer's disease (AD) is increasing in prevalence, and environmental risk factors have not been identified with certainty. There is evidence that oxidative stress, homocysteine-related vitamins, fats, and alcohol have a role in the pathogenesis of AD. Few large epidemiological studies have explored the associations between nutrients and AD, and there has been only one trial of vitamin E in the prevention of AD. Some studies suggest that high intake of vitamins C, E, B6, and B12, and folate, unsaturated fatty acids, and fish are related to a low risk of AD, but reports are inconsistent. Modest to moderate alcohol intake, particularly wine, may be related to a low risk of AD. Available data do not permit definitive conclusions regarding diet and AD or specific recommendations on diet modification for the prevention of AD.

Luchsinger JA, Mayeux R. · Taub Institute for Research of Alzheimer's Disease and the Aging Brain, Columbia University, PH9E-105, 630 West 168th Street, New York, NY 10032, USA. · Curr Atheroscler Rep. · Pubmed #15191699 No free full text.

Abstract: Alzheimer's disease is a devastating condition that is increasing in prevalence. No known prevention or cure exists for Alzheimer's disease. Cardiovascular risk factors are prevalent and increase in the elderly, and there have been conflicting reports of associations between modifiable cardiovascular risk factors and Alzheimer's disease. The mechanisms for these associations are uncertain, but they are likely to be the result of a combination of direct and cerebrovascular disease-related mechanisms. From this standpoint, diabetes and hyperinsulinemia seem to have the strongest evidence from laboratory, clinical, and epidemiologic studies. Studies have also indicated that hypertension, hyperlipidemia, hyperhomocysteinemia, and smoking are potentially important risk factors for Alzheimer's disease.

Helzner EP, Luchsinger JA, Scarmeas N, Cosentino S, Brickman AM, Glymour MM, Stern Y. · Gertrude H. Sergievsky Center, Columbia University Medical Center, NY, New York, USA. · Arch Neurol. · Pubmed #19273753 No free full text.

Abstract: 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.

Fitzpatrick AL, Kuller LH, Lopez OL, Diehr P, O'Meara ES, Longstreth WT, Luchsinger JA. · Department of Epidemiology, University of Washington, Collaborative Health Studies Coordinating Center, Seattle, 98115, USA. · Arch Neurol. · Pubmed #19273752 No free full text.

Abstract: BACKGROUND: While high adiposity in middle age appears to be related to greater dementia risk, studies exploring this association in the elderly are conflicting. OBJECTIVE: To evaluate associations between midlife and late-life obesity and risk of dementia. DESIGN: Prospective study with mean follow-up of 5.4 years (1992-1994 through 1999). SETTING: Community-dwelling sample in 4 US sites recruited from Medicare eligibility files. PARTICIPANTS: A total of 2798 adults without dementia (mean age, 74.7 years; 59.1% women) participating in the Cardiovascular Health Study who underwent magnetic resonance imaging were measured for height and weight at baseline at age 65 years or older (late life), and self-reported weight at age 50 years (midlife). Body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) was calculated at both times. MAIN OUTCOME MEASURES: Dementia, Alzheimer disease, and vascular dementia classified by a multidisciplinary committee using standardized criteria. RESULTS: Classification resulted in 480 persons with incident dementia, 245 with Alzheimer disease (no vascular dementia), and 213 with vascular dementia (with or without Alzheimer disease). In evaluations of midlife obesity, an increased risk of dementia was found for obese (BMI >30) vs normal-weight (BMI 20-25) persons, adjusted for demographics (hazard ratio [HR], 1.39; 95% confidence interval [CI], 1.03-1.87) and for cardiovascular risk factors (1.36; 0.94-1.95). The risk estimates were reversed in assessments of late-life BMI. Underweight persons (BMI <20) had an increased risk of dementia (1.62; 1.02-2.64), whereas being overweight (BMI >25-30) was not associated (0.92; 0.72-1.18) and being obese reduced the risk of dementia (0.63; 0.44-0.91) compared with those with normal BMI. CONCLUSION: These results help explain the "obesity paradox" as differences in dementia risk across time are consistent with physical changes in the trajectory toward disability.

Scarmeas N, Stern Y, Mayeux R, Manly JJ, Schupf N, Luchsinger JA. · Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA. · Arch Neurol. · Pubmed #19204158 links to  free full text

Abstract: 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.

Luchsinger JA, Tang MX, Miller J, Green R, Mayeux R. · Taub Institute for Research of Alzheimer's Disease and the aging Brain, Columbia University, New York, NY, USA. · J Nutr Health Aging. · Pubmed #18953463 No free full text.

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Luchsinger JA, Honig LS, Tang MX, Devanand DP. · Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, USA. · Int J Geriatr Psychiatry. · Pubmed #18327871 links to  free full text

Abstract: BACKGROUND: Depressive symptoms in the elderly are associated with an increased Alzheimer's disease (AD) risk. We sought to determine whether the association between depressive symptoms and AD is explained by a history of vascular risk factors and stroke. METHODS: Five hundred and twenty-six elderly persons from New York City without dementia at baseline were followed for a mean of 5 years. Depressive symptoms were assessed using the 17-item Hamilton Depression Rating Scale (HAM). Incident AD was ascertained using standard criteria. Diabetes, hypertension, heart disease, current smoking and stroke were ascertained by self-report. Proportional hazards regression was used to relate HAM scores to incident AD. RESULTS: HAM scores were higher in persons with hypertension, heart disease, and stroke, which in turn were related to higher AD risk. AD risk increased with increasing HAM scores as a continuous logarithmically transformed variable (HR for one point increase=1.4; 95% CI=1.1,1.8) and as a categorical variable (HR for HAM >or= 10=3.4; 95% CI=1.5,8.1; p for trend=0.004 with HAM=0 as the reference). These results were virtually unchanged after adjustment for vascular risk factors and stroke, individually (HR for HAM >or= 10=3.4; 95% CI=1.5,8.1; p for trend = 0.004), and in a composite measure (HR for HAM >or= 10=3.0; 95% CI=1.2,7.8; p for trend=0.02). CONCLUSION: The prospective relation between depressive symptoms and AD is not explained by a history of vascular risk factors and stroke, suggesting that other mechanisms may account for this association.

Reitz C, Tang MX, Manly J, Schupf N, Mayeux R, Luchsinger JA. · Gertrude H. Sergievsky Center, Mailman School of Public Health, Columbia University College of Physicians and Surgeons, New York, N.Y., USA. · Dement Geriatr Cogn Disord. · Pubmed #18264008 No free full text.

Abstract: BACKGROUND: There are conflicting data relating plasma lipids to the risk of Alzheimer's disease (AD). We explored the association of plasma lipids to mild cognitive impairment (MCI), a transitional stage between normal cognition and dementia, in a prospective community-based cohort study among randomly sampled Medicare recipients > or =65 years. Baseline data were collected from 1992 to 1994, follow-up data were collected at 18-month intervals. METHODS: Multivariate proportional hazards regression was used to relate plasma lipid levels to incident total MCI, amnestic MCI and nonamnestic MCI in 854 persons without MCI or dementia at baseline. RESULTS: There were 324 cases of incident MCI, 153 cases of amnestic MCI and 171 cases of nonamnestic MCI during 4,189 person-years of follow-up. Higher levels of total cholesterol and LDL were associated with a decreased risk of total MCI in models adjusting for age and sex. However, these associations were attenuated after adjusting for ethnicity, education, APOEepsilon4 and vascular risk factors. There was no association between lipids and the risk of amnestic or nonamnestic MCI, and there was no effect of lipid-lowering treatment on MCI risk. CONCLUSIONS: Plasma lipid levels or lipid-lowering treatment in the elderly are not associated with the risk of MCI.

Reitz C, Tang MX, Manly J, Mayeux R, Luchsinger JA. · The Gertrude H Sergievsky Center, Columbia University Medical Center, Columbia University, New York, NY 10706, USA. · Arch Neurol. · Pubmed #18071036 links to  free full text

Abstract: OBJECTIVE: To explore whether hypertension is associated with the risk of mild cognitive impairment (MCI), an intermediate stage of dementia, because there are conflicting data relating hypertension to the risk of Alzheimer disease. DESIGN AND SETTING: Prospective community-based cohort study conducted in northern Manhattan. Multivariate proportional hazards regression analyses were used, relating hypertension to incident all-cause MCI, amnestic MCI, and nonamnestic MCI in 918 persons without prevalent MCI at baseline followed up for a mean of 4.7 years. RESULTS: There were 334 cases of incident MCI, 160 cases of amnestic MCI, and 174 cases of nonamnestic MCI during 4337 person-years of follow-up. Hypertension was associated with an increased risk of all-cause MCI (hazard ratio, 1.40; 95% confidence interval, 1.06-1.77; P = .02) and nonamnestic MCI (hazard ratio, 1.70; 95% confidence interval, 1.13-2.42; P = .009) after adjusting for age and sex. Both associations were slightly attenuated in models additionally adjusting for stroke and other vascular risk factors. There was no association between hypertension and the risk of amnestic MCI (hazard ratio, 1.10; 95% confidence interval, 0.79-1.63; P = .49). Consistent with this association, hypertension was related with the slope of change in an executive ability score, but not with memory or language score. There was no effect modification of the association between hypertension and MCI by APOEepsilon4 genotype or use of antihypertensive medication. CONCLUSIONS: A history of hypertension is related to a higher risk of MCI. The association seems to be stronger with the nonamnestic than the amnestic type of MCI in the elderly. These findings suggest that prevention and treatment of hypertension may have an important impact in lowering the risk of cognitive impairment.

Scarmeas N, Luchsinger JA, Mayeux R, Stern Y. · Taub Institute for Research in Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032, USA. · Neurology. · Pubmed #17846408 links to  free full text

Abstract: 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.

Luchsinger JA, Tang MX, Mayeux R. · Taub University in Alzheimer's Disease and the aging Brain, Columbia University, New York, NY, USA. · J Nutr Health Aging. · Pubmed #17508100 No free full text.

Abstract: OBJECTIVE: to explore the relation of glycemic load (GL) with Alzheimer's disease (AD) risk. DESIGN: Cohort study. SETTING: Cohort of elderly subjects in New York City. PARTICIPANTS: 939 persons 65 years and older without dementia followed for an average of 6.3 years. MEASUREMENTS: Glycemic index, carbohydrate and calorie intake were measured using a semi-quantitative food frequency questionnaire (SFFQ). GL was calculated as the product of carbohydrate intake and glycemic index and adjusted for energy intake. AD was ascertained with standard research criteria. RESULTS: Cox regression was used to relate GL quartiles to AD using time from SFFQ to AD as the time-to-event variable. There was no association between GL and AD after adjustment for age, gender, education, ethnic group, and presence of diabetes. There was no evidence of modification by age, gender, APOE-e4, and presence of diabetes. The only dietary variable associated with a higher risk of AD was total calories (HR of AD for a one-log unit increase =2.2; 95% CI: 1.4,3.5) after adjustment for age, gender, ethnic group, education, diabetes, and APOE-e4. CONCLUSION: GL is not associated with a higher risk of AD in the elderly. Our data does not support the popular practice of low carbohydrate diets for the prevention of AD in the elderly.

Reitz C, Brickman AM, Luchsinger JA, Wu WE, Small SA, Tang MX. · Gertrude H. Sergievsky Center, Columbia University, New York, NY 10032, USA. · Am J Geriatr Cardiol. · Pubmed #17483671 links to  free full text

Abstract: The authors compared the frequency of structural and functional heart abnormalities assessed using transthoracic echocardiography among persons with Alzheimer's disease, vascular dementia, stroke, and healthy control subjects. Compared with controls, patients with Alzheimer's disease were more likely to have aortic valve thickening, aortic valve regurgitation, left ventricular wall motion abnormalities, left ventricular hypertrophy, and reduced ejection fraction. Persons with vascular dementia were more likely to have aortic valve regurgitation, but mitral valve thickening and tricuspid valve regurgitation were also more frequent. In the absence of dementia, persons with stroke differed from controls by more frequent mitral valve calcifications. With the increasing prevalence of Alzheimer's disease and vascular dementia, clinicians have to be more attentive to the presence of structural heart disease and its complications in persons with these conditions.

Luchsinger JA, Reitz C, Patel B, Tang MX, Manly JJ, Mayeux R. · Department of Medicine, Taub Institute for Research of Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY 10032, USA. · Arch Neurol. · Pubmed #17420320 links to  free full text

Abstract: BACKGROUND: Type 2 diabetes mellitus is an important risk factor for Alzheimer disease and is more prevalent in elderly minority persons compared with non-Hispanic white persons. OBJECTIVE: To determine whether diabetes is related to a higher risk of mild cognitive impairment (MCI), a transitional stage between normal cognition and Alzheimer disease, in a multiethnic cohort with a high prevalence of diabetes. DESIGN: Longitudinal cohort study. SETTING: Northern Manhattan in New York, NY. PARTICIPANTS: We studied persons without prevalent MCI or dementia at baseline and with at least 1 follow-up interval. Of 1772 participants with a complete neuropsychological evaluation, 339 (19.1%) were excluded because of prevalent dementia, 304 were excluded because of prevalent MCI (17.2%), and 211 were excluded because of loss to follow-up (11.9%), resulting in a final sample of 918 participants for longitudinal analyses. MAIN OUTCOME MEASURES: We related diabetes defined by self-report to incident all-cause MCI, amnestic MCI, and nonamnestic MCI. We conducted multivariate analyses with proportional hazards regression adjusting for age, sex, years of education, ethnic group, apolipoprotein E (APOE) epsilon4 allele, hypertension, low-density lipoprotein level, current smoking, heart disease, and stroke. RESULTS: A total of 334 persons had incident MCI, 160 (47.9%) had amnestic MCI, and 174 (52.1%) had nonamnestic MCI. Diabetes was related to a significantly higher risk of all-cause MCI and amnestic MCI after adjustment for all covariates. Diabetes was also related to a higher risk of nonamnestic MCI, but this association was appreciably attenuated after adjustment for socioeconomic variables and vascular risk factors. The risk of MCI attributable to diabetes was 8.8% for the whole sample and was higher for African American persons (8.4%) and Hispanic persons (11.0%) compared with non-Hispanic white persons (4.6%), reflecting the higher prevalence of diabetes in minority populations in the United States. CONCLUSION: Diabetes is related to a higher risk of amnestic MCI in a population with a high prevalence of this disorder.

Luchsinger JA, Patel B, Tang MX, Schupf N, Mayeux R. · Taub Institute for Research of Alzheimer's Disease and the Aging Brain, Columbia University, 630 W 168th St, New York, NY 10032, USA. · Arch Neurol. · Pubmed #17353383 links to  free full text

Abstract: BACKGROUND: Studies relating adiposity to dementia are conflicting. We explored the associations of body mass index (BMI), (calculated as weight in kilograms divided by the square of height in meters) waist circumference, and weight change to dementia, probable Alzheimer disease, and dementia associated with stroke (DAS). DESIGN: Persons without dementia were followed up for 5 years; 893 persons had BMI data, 907 had waist circumference data, and 709 had a second weight measurement. Dementia was ascertained using standard methods. Cox proportional hazards regression was used for analyses using follow-up as time to event, adjusting for demographics and apolipoprotein E-epsilon4 status. RESULTS: Compared with persons in the first quartile of BMI, persons in the third quartile had a lower dementia and Alzheimer disease risk and persons in the second quartile had a lower DAS risk. The association between BMI and dementia resembled a U shape in those younger than 76 years, while dementia risk decreased with higher BMI in those 76 years and older. The fourth quartile of waist circumference was related to a higher DAS risk in the whole sample, and to dementia and Alzheimer disease in persons younger than 76 years. Weight loss was related to a higher dementia and DAS risk, and weight gain was related to a higher DAS risk only. CONCLUSIONS: The prospective association between adiposity and dementia differs depending on the anthropometric measure used, and is modified by age. This may explain previous conflicting reports.

Reitz C, Patel B, Tang MX, Manly J, Mayeux R, Luchsinger JA. · The Gertrude H. Sergievsky Center, Columbia University College of Physicians and Surgeons, New York, NY, USA. · J Neurol Sci. · Pubmed #17328914 No free full text.

Abstract: BACKGROUND: Vascular risk factors increase the risk of Alzheimer's disease (AD). The mechanisms for these associations are unclear, and may be due to misdiagnosis of a vascular dementia syndrome as AD. OBJECTIVE: To examine differences in neuropsychological profile among persons diagnosed clinically with AD with and without vascular risk factors or stroke. METHODS: Community based cohort study. Individual and composite scores of neuropsychological tests at the time of clinical diagnosis of incident AD were compared among 243 persons with and without vascular risk factors or stroke. RESULTS: Among subjects with incident AD, diabetes was associated with lower performance in Delayed Recall of the Selective Reminding Test (SRT), while persons diagnosed with hypertension scored lower in consistent long term recall (CLTR) of the SRT and current smokers scored lower in Category Fluency. None of the risk factors was associated with differences in composite scores in memory, abstract/visuospatial or language domain, nor was the number of risk factors per person. Persons with stroke had a higher delayed recall score at the time of AD diagnosis. CONCLUSION: The presence of vascular risk factors among persons with clinically diagnosed AD was associated with subtle differences in neuropsychological profile at the time of diagnosis. This study needs to be replicated in samples with brain imaging, a comprehensive executive abilities battery, and pathological diagnosis of AD.

Luchsinger JA, Tang MX, Miller J, Green R, Mayeux R. · Taub Institute for Research of Alzheimer's Disease and the Aging Brain, Joseph P. Mailman School of Public Health, Columbia University, New York, NY, USA. · Arch Neurol. · Pubmed #17210813 links to  free full text

Abstract: BACKGROUND: Higher intake of folate and vitamins B6 (pyridoxine hydrochloride) and B12 (cyanocobalamin) may decrease the risk of Alzheimer disease (AD) through the lowering of homocysteine levels. OBJECTIVE: To relate intake of folate and vitamins B6 and B12 to AD risk. DESIGN AND PATIENTS: We followed up 965 persons 65 years or older without dementia at baseline for a mean +/- SD period of 6.1 +/- 3.3 person-years after the administration of a semiquantitative food frequency questionnaire. Total, dietary, and supplement intake of folate and vitamins B6 and B12 and kilocalorie intake were estimated from the questionnaire responses. We related energy-adjusted intake of folate and vitamins B6 and B12 to incident AD using the Cox proportional hazards regression model. MAIN OUTCOME MEASURE: Incident AD. RESULTS: We found 192 cases of incident AD. The highest quartile of total folate intake was related to a lower risk of AD (hazard ratio, 0.5; 95% confidence interval, 0.3-0.9; P=.02 for trend) after adjustment for age, sex, education, ethnic group, the epsilon4 allele of apolipoprotein E, diabetes mellitus, hypertension, current smoking, heart disease, stroke, and vitamin B6 and B12 levels. Vitamin B6 and B12 levels were not related to the risk of AD. CONCLUSIONS: Higher folate intake may decrease the risk of AD independent of other risk factors and levels of vitamins B6 and B12. These results require confirmation with clinical trials.

Scarmeas N, Stern Y, Mayeux R, Luchsinger JA. · Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY 10032, USA. · Arch Neurol. · Pubmed #17030648 links to  free full text

Abstract: OBJECTIVES: To examine the association between the Mediterranean diet (MeDi) and Alzheimer disease (AD) in a different AD population and to investigate possible mediation by vascular pathways. Design, Setting, Patients, and MAIN OUTCOME MEASURES: A case-control study nested within a community-based cohort in New York, NY. Adherence to the MeDi (0- to 9-point scale with higher scores indicating higher adherence) was the main predictor of AD status (194 patients with AD vs 1790 nondemented subjects) in logistic regression models that were adjusted for cohort, age, sex, ethnicity, education, apolipoprotein E genotype, caloric intake, smoking, medical comorbidity index, and body mass index (calculated as weight in kilograms divided by height in meters squared). We investigated whether there was attenuation of the association between MeDi and AD when vascular variables (stroke, diabetes mellitus, hypertension, heart disease, lipid levels) were simultaneously introduced in the models (which would constitute evidence of mediation). RESULTS: Higher adherence to the MeDi was associated with lower risk for AD (odds ratio, 0.76; 95% confidence interval, 0.67-0.87; P<.001). Compared with subjects in the lowest MeDi tertile, subjects in the middle MeDi tertile had an odds ratio of 0.47 (95% confidence interval, 0.29-0.76) and those at the highest tertile an odds ratio of 0.32 (95% confidence interval, 0.17-0.59) for AD (P for trend <.001). Introduction of the vascular variables in the model did not change the magnitude of the association. CONCLUSIONS: We note once more that higher adherence to the MeDi is associated with a reduced risk for AD. The association does not seem to be mediated by vascular comorbidity. This could be the result of either other biological mechanisms (oxidative or inflammatory) being implicated or measurement error of the vascular variables.

Scarmeas N, Stern Y, Tang MX, Mayeux R, Luchsinger JA. · Taub Institute for Research in Alzheimer's Disease and the Aging Brain, New York, NY 10032, USA. · Ann Neurol. · Pubmed #16622828 No free full text.

Abstract: 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.

Luchsinger JA, Reitz C, Honig LS, Tang MX, Shea S, Mayeux R. · Taub Institute for Research of Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, USA. · Neurology. · Pubmed #16116114 links to  free full text

Abstract: BACKGROUND: The prevalence of Alzheimer disease (AD) is increasing in the elderly, and vascular risk factors may increase its risk. OBJECTIVE: To explore the association of the aggregation of vascular risk factors with AD. METHODS: The authors followed 1,138 individuals without dementia at baseline (mean age 76.2) for a mean of 5.5 years. The presence of vascular risk factors was related to incident possible and probable AD. RESULTS: Four risk factors (diabetes, hypertension, heart disease, and current smoking) were associated with a higher risk of AD (p < 0.10) when analyzed individually. The risk of AD increased with the number of risk factors (diabetes + hypertension + heart disease + current smoking). The adjusted hazards ratio of probable AD for the presence of three or more risk factors was 3.4 (95% CI: 1.8, 6.3; p for trend < 0.0001) compared with no risk factors. Diabetes and current smoking were the strongest risk factors in isolation or in clusters, but hypertension and heart disease were also related to a higher risk of AD when clustered with diabetes, smoking, or each other. CONCLUSIONS: The risk of Alzheimer disease (AD) increased with the number of vascular risk factors. Diabetes and current smoking were the strongest risk factors, but clusters including hypertension and heart disease also increased the risk of AD. These associations are unlikely to be explained by misclassification of the outcome, given strong associations when only probable AD is considered.