Associations of circulating saturated long-chain fatty acids with risk of mild cognitive impairment and Alzheimer's disease in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort.

BACKGROUND: No study has examined the associations between peripheral saturated long-chain fatty acids (LCFAs) and conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD). This study aimed to examine whether circulating saturated LCFAs are associated with both risks of incident MCI from cognitively normal (CN) participants and incident AD progressed from MCI in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. METHODS: We conducted analysis of data from older adults aged 55-90 years who were recruited at 63 sites across the USA and Canada. We examined associations between circulating saturated LCFAs (i.e., C14:0, C16:0, C18:0, C20:0) and risk for incident MCI in CN participants, and incident AD progressed from MCI. FINDINGS: 829 participants who were enrolled in ADNI-1 had data on plasma saturated LCFAs, of which 618 AD-free participants were included in our analysis (226 with normal cognition and 392 with MCI; 60.2% were men). Cox proportional-hazards models were used to account for time-to-event/censor with a 48-month follow-up period for the primary analysis. Other than C20:0, saturated LCFAs were associated with an increased risk for AD among participants with MCI at baseline (Hazard ratios (HRs) = 1.3 to 2.2, P = 0.0005 to 0.003 in fully-adjusted models). No association of C20:0 with risk of AD among participants with MCI was observed. No associations were observed between saturated LCFAs and risk for MCI among participants with normal cognition. INTERPRETATION: Saturated LCFAs are associated with increased risk of progressing from MCI to AD. This finding holds the potential to facilitate precision prevention of AD among patients with MCI. FUNDING: National Institutes of Health.

Dietary calcium and magnesium intake and risk for incident dementia: The Shanghai Aging Study.

Introduction: Calcium (Ca), magnesium (Mg), or the calcium to magnesium (Ca:Mg) ratio may affect the risk of dementia via complex mechanisms. The aim of this study was to evaluate the association of dietary Ca, Mg, and Ca:Mg ratio with dementia risk at the prospective phase of the Shanghai Aging Study. Methods: We analyzed data from 1565 dementia-free participants living in an urban community who had measurements of dietary Ca and Mg intake derived from a food frequency questionnaire at baseline and incident dementia during follow-up. Results: Over the 5-year follow-up, 162 (10.4%) participants were diagnosed with incident dementia by Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria. Participants with the lowest tertile of dietary Ca (<339.1 mg/day) and Mg (<202.1 mg/day) had the highest incidence rates of dementia (3.3/100 person-years for Ca, 3.3/100 person-years for Mg) compared to those with higher Ca and Mg intake. In the subgroup with Ca:Mg ratios ≤ 1.69, Mg intake >267.5 mg/day was related to an increased risk for dementia (adjusted hazard ratio: 3.97, 95% confidence interval: 1.29-12.25). Conclusions: Our findings suggest that high dietary intake of Mg is associated with an increased risk of dementia mainly among older adults with low Ca:Mg intake ratios. Proper balance of Ca to Mg in the diet may be critical to the relationship between Mg intake and risk of dementia. Highlights: Participants with the lowest tertile of dietary calcium (Ca) and magnesium (Mg) had the highest incidence rates of dementia.In the subgroup with Ca:Mg ratios ≤1.69, Mg intake >267.5 mg/day was related to an increased risk for dementia.Balance of Ca to Mg in diet may be critical to the relationship between Mg intake and risk of dementia.

Smaller Head Circumference Combined with Lower Education Predicts High Risk of Incident Dementia: The Shanghai Aging Study.

INTRODUCTION: An important index of brain reserve is the maximal attained brain size, which can be estimated by measuring the head circumference (HC). We investigated the association of HC and education with incident dementia in a population-based study of Chinese older adults. METHODS: We conducted a prospective follow-up study of 1,659 non-demented participants with a mean age of 71.5 years. Characteristics and anthropometry of the participants were collected at baseline. Consensus diagnoses for dementia were made using DSM-IV criteria based on functional, neurological, and neuropsychological assessments. RESULTS: We identified 168 new-onset dementia cases after a mean of 5.2 years of follow-up. Participants with smaller HC combined with low educational attainment had a significantly higher risk of incident dementia than those with larger HC who had completed more than 12 years of education (adjusted hazard ratio 4.48, 95% CI 2.47-8.12). DISCUSSION/CONCLUSION: Our results suggest that smaller HC in combination with low education leads to a markedly increased risk of dementia.

Obstructive sleep apnea and longitudinal Alzheimer's disease biomarker changes.

STUDY OBJECTIVES: To determine the effect of self-reported clinical diagnosis of obstructive sleep apnea (OSA) on longitudinal changes in brain amyloid PET and CSF biomarkers (Aß42, T-tau, and P-tau) in cognitively normal (NL), mild cognitive impairment (MCI), and Alzheimer's disease (AD) elderly. METHODS: Longitudinal study with mean follow-up time of 2.52 ± 0.51 years. Data were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Participants included 516 NL, 798 MCI, and 325 AD elderly. Main outcomes were annual rate of change in brain amyloid burden (i.e. longitudinal increases in florbetapir PET uptake or decreases in CSF Aß42 levels); and tau protein aggregation (i.e. longitudinal increases in CSF total tau [T-tau] and phosphorylated tau [P-tau]). Adjusted multilevel mixed effects linear regression models with randomly varying intercepts and slopes was used to test whether the rate of biomarker change differed between participants with and without OSA. RESULTS: In NL and MCI groups, OSA+ subjects experienced faster annual increase in florbetapir uptake (B = .06, 95% CI = .02, .11 and B = .08, 95% CI = .05, .12, respectively) and decrease in CSF Aß42 levels (B = -2.71, 95% CI = -3.11, -2.35 and B = -2.62, 95% CI = -3.23, -2.03, respectively); as well as increases in CSF T-tau (B = 3.68, 95% CI = 3.31, 4.07 and B = 2.21, 95% CI = 1.58, 2.86, respectively) and P-tau (B = 1.221, 95% CI = 1.02, 1.42 and B = 1.74, 95% CI = 1.22, 2.27, respectively); compared with OSA- participants. No significant variations in the biomarker changes over time were seen in the AD group. CONCLUSIONS: In both NL and MCI, elderly, clinical interventions aimed to treat OSA are needed to test if OSA treatment may affect the progression of cognitive impairment due to AD.

Occupational Characteristics and Patterns as Risk Factors for Parkinson's Disease: A Case Control Study.

BACKGROUND: Associations have been reported between the risk of Parkinson's disease (PD) and employment in certain fields. Most studies have focused on toxic exposures as potential causal explanations. However, PD also has been associated with personality characteristics that may influence occupational choices and patterns. OBJECTIVE: This study evaluates the role of personality as indicated by occupational choices and employment patterns in the risk for PD. METHODS: In-person interviews were conducted to assess occupational histories and early-adult personality indicators among 89 PD patients and 99 controls. RESULTS: PD cases had fewer lifetime jobs than controls (mean for cases = 4.38 ± 2.20; mean for controls = 5.00 ± 2.26; p = 0.03). Among women, PD was positively associated with more complex work with people (OR = 1.45, 95% CI 1.12-1.89), representing a 95% increased risk for PD comparing women with the greatest complexity of work with those requiring the least complexity of work with people. Women PD cases also performed less complex work with things compared with controls (OR = 0.69 (95% CI 0.53-0.90)), translating into a 13-fold increased risk for PD among women whose work involved the least complex work with things compared with the most. The numbers of jobs and job types were associated with taking more activity risks as a young-adult (r = 0.19, p = 0.02; r = 0.26, p = 0.001, respectively). CONCLUSIONS: Cases with PD held fewer lifetime jobs compared with controls. Occupational complexity was associated with the risk for PD among women, but not men. Further consideration of the possible influence of personality on occupational choices is warranted.

Prevalence of mild cognitive impairment in an urban community in China: a cross-sectional analysis of the Shanghai Aging Study.

BACKGROUND: Substantial variations in the prevalence of mild cognitive impairment (MCI) have been reported, although mostly in Western countries. Less is known about MCI in the Chinese population. METHODS: We clinically and neuropsychologically evaluated 3141 community residents ≥60 years of age. Diagnoses of MCI and its subtypes were made using standard criteria via consensus diagnosis. RESULTS: Among 2985 nondemented individuals, 601 were diagnosed with MCI, resulting in a prevalence of 20.1% for total MCI, 13.2% for amnestic MCI (aMCI), and 7.0% for non-amnestic MCI (naMCI). The proportions of MCI subtypes were: aMCI single domain (SD), 38.9%; aMCI multiple domains (MD), 26.5%; naMCI-SD, 25.0%; and naMCI-MD, 9.6%. The prevalence of aMCI-MD increased rapidly with age in women APOE ε4 carriers (from 60 to 69 years to ≥80 years, 3.1%-33.3%, P < .001). CONCLUSIONS: Our findings suggest that 20% of Chinese elderly are affected by MCI. Prospective studies in China are needed to examine progression to dementia and related risk factors.

The Shanghai Aging Study: study design, baseline characteristics, and prevalence of dementia.

BACKGROUND: To establish a prospective cohort to enumerate the prevalence, incidence and risk factors for dementia and mild cognitive impairment (MCI) among residents aged ≥60 in an urban community of Shanghai, China. METHODS: Participants received clinical evaluations including physical measurements, demographic and lifestyle questionnaires, physical and neurologic examinations, and neuropsychological testing. Urine and blood samples were collected, aliquoted, and stored. DNA was extracted for Apolipoprotein (APOE) genotyping. Diagnoses of dementia and MCI were made using standard criteria via consensus diagnosis. RESULTS: Among 3,141 participants aged ≥60, 1,438 (45.8%) were men. The average age of participants was 72.3 years (SD 8.1), and they had an average of 11.6 years (SD 4.4) of education. The most common chronic disease of participants was hypertension (56.4%). The frequencies of APOE-​ε2, ε3 and ε4 were 7.9, 82.7 and 9.4%, respectively. We diagnosed 156 (5.0%, 95% CI 4.3-5.8%) participants with dementia. The prevalence rates of Alzheimer's disease and vascular dementia were 3.6% (95% CI 3.0-4.3%) and 0.8% (95% CI 0.5-1.1%). CONCLUSIONS: The Shanghai Aging Study is the first prospective community-based cohort study of cognitive impairment in China, with a comparable study design, procedures, and diagnostic criteria for dementia and MCI to most previous cohort studies in developed countries.

Bilingualism delays age at onset of dementia, independent of education and immigration status.

Editors' Note: Mortimer argues that important confounding variables may have biased the conclusion by Alladi et al. on the role of bilingualism in delaying the onset of dementia. Following Mortimer's comments, Alladi et al. conducted additional analysis of their data to support their conclusion. The attitude of "close enough" is not appropriate when determining brain death. Stadlan comments and supports Frank's call for action regarding this sensitive issue.

Dementia: a barrier to receiving percutaneous coronary intervention for elderly patients with ST-elevated myocardial infarction.

OBJECTIVE: Percutaneous coronary intervention (PCI) is the first line of treatment for ST-elevated myocardial infarction (STEMI). This study evaluates the role of dementia in diagnostic cardiac catheterization (to receive PCI) in STEMI patients ≥65 years old admitted to high annual volume PCI hospitals. METHODS: Participants were registered in Florida's comprehensive inpatient surveillance system for the years 2006-2007 with principal diagnosis of STEMI. Dementia was defined using ICD-9 codes for presenile, senile, and Alzheimer's type dementia. RESULTS: Data from 8331 STEMI patients were used. Of these, 77.2% were catheterized, 67.2% received PCI, and 9.3% had coronary artery bypass graft (CABG). The mean age of the cohort was 76.3 years (SD 7.8 years.); with 43.3% female, 83.4% white, 4.6% black, and 12% Hispanic/other. Of the 248 (3%) patients with dementia, 42% were catheterized. After adjustment for age, gender, and race/ethnicity, patients with dementia were less likely to be catheterized (RR 0.30, 95% CI 0.30-0.50) than non-demented patients. However, among patients who were catheterized, there was no difference in the use of PCI or CABG for patients with versus without dementia (p = 0.56). Of those with dementia, being older and arriving to the hospital in the afternoon were associated with lower likelihood of being catheterized (RR 0.08, 95% CI 0.02-0.28, and RR 0.30, 95% CI 0.10-0.88, respectively). However, having hyperlipidemia increased the probability of catheterization (RR 3.60, 95% CI 1.86-6.98). CONCLUSION: ST-elevated myocardial infarction patients with dementia were much less likely to receive diagnostic cardiac catheterization, thereby limiting the possibility for receiving optimal care including PCI or CABG.

The association of physical and mental health with sexual activity in older adults in a retirement community.

INTRODUCTION: Understanding sexual behavior is important when evaluating the health needs of older adults. Little research has addressed the effect of specific health conditions on sexual inactivity in this growing population. AIM: The study aims to assess the association of mental and physical health conditions with sexual inactivity among adults 55 and older living in The Villages, Florida. METHODS: Exposure data for 22 self-reported health conditions were assessed in relation to sexual inactivity in 22,654 participants ages 55 and older, including 1,879 participants over age 80 in a community-based cross-sectional study. Logistic regression analyses were conducted separately for men and women to evaluate the likelihood of being sexually active for each health condition. Covariates included age, race, education, income, self-reported overall health, and marital status. MAIN OUTCOME MEASURES: The odds ratio and 95% confidence intervals for sexual activity status were calculated separately for men and women. RESULTS: Fifty-five percent of men and 45% of women reported being sexually active. Significant positive correlates of sexual activity included walking at least 1-2 times per week, participating in at least two registered clubs, engaging in physical and social activities, no tobacco use, fewer medications, increased alcohol consumption, and reporting a good quality of life, psychological well-being, or social support. Sexual inactivity was significantly related to cancer, bladder/bowl problems, major surgery, poor vision, mental health conditions, and cardiovascular disease and its risk factors including diabetes, hypertension, and high cholesterol. Additional associations with sexual inactivity included hearing loss and dementia for men, and dermatologic conditions, problems with the joints, bone or back, gastrointestinal problems, alcohol misuse, chronic wound care, and gum disease in women. CONCLUSIONS: Mental and physical health conditions have very similar associations with sexual inactivity in men and women. Increased sexual activity was associated with positive physical, social, and emotional health indicators.

Associations of welding and manganese exposure with Parkinson disease: review and meta-analysis.

OBJECTIVE: To examine associations of welding and manganese exposure with Parkinson disease (PD) using meta-analyses of data from cohort, case-control, and mortality studies. METHODS: Epidemiologic studies related to welding or manganese exposure and PD were identified in a PubMed search, article references, published reviews, and abstracts. Inclusion criteria were 1) cohort, case-control, or mortality study with relative risk (RR), odds ratio (OR), or mortality OR (MOR) and 95 confidence intervals (95% CI); 2) RR, OR, and MOR matched or adjusted for age and sex; 3) valid study design and analysis. When participants of a study were a subgroup of those in a larger study, only results of the larger study were included to assure independence of datasets. Pooled RR/OR estimates and 95% CIs were obtained using random effects models; heterogeneity of study effects were evaluated using the Q statistic and I(2) index in fixed effect models. RESULTS: Thirteen studies met inclusion criteria for the welding meta-analysis and 3 studies for the manganese exposure meta-analysis. The pooled RR for the association between welding and PD for all study designs was 0.86 (95% CI 0.80-0.92), with absence of between-study heterogeneity (I(2) = 0.0). Effect measures for cohort, case-control, and mortality studies were similar (0.91, 0.82, 0.87). For the association between manganese exposure and PD, the pooled OR was 0.76 (95% CI 0.41-1.42). CONCLUSIONS: Welding and manganese exposure are not associated with increased PD risk. Possible explanations for the inverse association between welding and PD include confounding by smoking, healthy worker effect, and hormesis.

The Nun Study: risk factors for pathology and clinical-pathologic correlations.

The Nun Study was the first cohort study to enroll and follow a large, well-defined population that included demented and non-demented participants, all of whom agreed to donate their brains for research. The inclusion of systematic neuropathologic analysis in this study has resulted in a greater understanding of the role of Alzheimer and vascular pathology in the expression of memory deficits and dementia and has provided data showing that biomarkers for the pathology may be evident many decades earlier in adult life. Findings related to neuropathology in this study have included the following: (1) Although clinical outcomes were strongly correlated with Alzheimer neuropathology, about one-third of the participants fulfilling criteria for neuropathologic Alzheimer's disease (AD) were not demented at the time of death. (2) Brain infarcts by themselves had little effect on cognitive status, but played an important role in increasing the risk of dementia associated with Alzheimer pathology. (3) Hippocampal volume was strongly correlated with Braak neurofibrillary stage even in participants with normal cognitive function. (4) A linguistic characteristic of essays written in early adult life, idea density, had a strong association with not only clinical outcomes in late life, but the severity of Alzheimer neuropathology as well. (5) The effect of apolipoprotein E-e4 on dementia was mediated through Alzheimer, but not vascular pathology.

Changes in brain volume and cognition in a randomized trial of exercise and social interaction in a community-based sample of non-demented Chinese elders.

Physical exercise has been shown to increase brain volume and improve cognition in randomized trials of non-demented elderly. Although greater social engagement was found to reduce dementia risk in observational studies, randomized trials of social interventions have not been reported. A representative sample of 120 elderly from Shanghai, China was randomized to four groups (Tai Chi, Walking, Social Interaction, No Intervention) for 40 weeks. Two MRIs were obtained, one before the intervention period, the other after. A neuropsychological battery was administered at baseline, 20 weeks, and 40 weeks. Comparison of changes in brain volumes in intervention groups with the No Intervention group were assessed by t-tests. Time-intervention group interactions for neuropsychological measures were evaluated with repeated-measures mixed models. Compared to the No Intervention group, significant increases in brain volume were seen in the Tai Chi and Social Intervention groups (p < 0.05). Improvements also were observed in several neuropsychological measures in the Tai Chi group, including the Mattis Dementia Rating Scale score (p = 0.004), the Trailmaking Test A (p = 0.002) and B (p = 0.0002), the Auditory Verbal Learning Test (p = 0.009), and verbal fluency for animals (p = 0.01). The Social Interaction group showed improvement on some, but fewer neuropsychological indices. No differences were observed between the Walking and No Intervention groups. The findings differ from previous clinical trials in showing increases in brain volume and improvements in cognition with a largely non-aerobic exercise (Tai Chi). In addition, intellectual stimulation through social interaction was associated with increases in brain volume as well as with some cognitive improvements.

Work-related stress may increase the risk of vascular dementia.

OBJECTIVES: To examine job control, job demands, social support at work, and job strain (ratio of demands to control) in relation to risk of any dementia, Alzheimer's disease (AD), and vascular dementia (VaD). DESIGN: Cohort study. SETTING: The population-based Study of Dementia in Swedish Twins. PARTICIPANTS: Two hundred fifty-seven people with dementia (167 AD, 46 VaD) and 9,849 without. MEASUREMENTS: Dementia diagnoses were based on telephone screening for cognitive impairment followed by in-person clinical examination. An established job exposure matrix was matched to main occupation categories to measure work characteristics. RESULTS: In generalized estimating equations (adjusted for the inclusion of complete twin pairs), lower job control was associated with greater risk of any dementia (odds ratio (OR) = 1.17, 95% confidence interval (CI) = 1.04-1.31) and VaD specifically (OR = 1.39, 95% CI = 1.07-1.81). Lower social support at work was associated with greater risk of dementia (OR = 1.15, 95% CI = 1.03-1.28), AD (OR = 1.14, 95% CI = 1.00-1.31), and VaD (OR = 1.28, 95% CI = 1.02-1.60). Greater job strain was associated with greater risk of VaD only (OR = 1.28, 95% CI = 1.02-1.60), especially in combination with low social support (OR = 1.35, 95% CI = 1.11-1.64). Age, sex, and education were controlled for. Work complexity, manual work, and vascular disease did not explain the results. No differences in work-related stress scores were observed in the 54 twin pairs discordant for dementia, although only two pairs included a twin with VaD. CONCLUSION: Work-related stress, including low job control and low social support at work, may increase the risk of dementia, particularly VaD. Modification to work environment, including attention to social context and provision of meaningful roles for employees, may contribute to efforts to promote cognitive health.

High normal fasting blood glucose is associated with dementia in Chinese elderly.

BACKGROUND: Diabetes is a risk factor for mild cognitive impairment (MCI) and dementia. However, the association between high normal fasting blood glucose (FBG) and dementia has not been studied. METHODS: Polytomous logistic regression was used to assess the association of dementia and MCI with FBG in an age- and sex-matched sample of 32 dementia patients, 27 amnestic MCI (aMCI) patients, and 31 normal controls (NC). Analyses were repeated for those with normal FBG. Correlations between FBG and cognitive test scores were obtained. RESULTS: Controlling for age, gender, education, body mass index, Hachinski Ischemic Score, magnetic resonance imaging (MRI) stroke, and normalized brain, hippocampal, and white matter hyperintensity MRI volumes; higher FBG was associated with dementia versus aMCI status (OR = 3.13; 95% CI, 1.28-7.69). This association remained (OR = 7.75; 95% CI, 1.10-55.56) when analyses were restricted to subjects with normal FBG. When dementia patients were compared with NC adjusting for age, gender, and education, a significant association with FBG also was seen (OR = 1.83; 95% CI, 1.09-3.08), but it was lost when vascular covariates were added to the model. FBG was not associated with aMCI status versus NC. Higher FBG was correlated with poorer performance on the Trailmaking Test Part B (P = .003). The percentage of dementia patients with high normal FBG (90%) was significantly higher than that of aMCI patients with high normal FBG (32.9%) (χ(2) = 13.9, P < .001). CONCLUSIONS: Higher FBG was associated with dementia (vs. aMCI) independent of vascular risk factors and MRI indicators of vascular disease, and remained a significant risk factor when analyses were restricted to subjects with normal FBG. The results of this cross-sectional study suggest that a high normal level of FBG may be a risk factor for dementia.

Brain structure and cerebrovascular risk in cognitively impaired patients: Shanghai Community Brain Health Initiative-pilot phase.

OBJECTIVE: To investigate the associations among brain morphologic changes as seen on magnetic resonance imaging (MRI), cerebrovascular risk (CVR), and clinical diagnosis and cognition in elderly patients with mild cognitive impairment and dementia living in urban Shanghai. DESIGN: Cross-sectional study performed from May 1, 2007, to November 31, 2008. SETTING: Memory Disorders Clinic of the Huashan Hospital and the Shanghai community. PARTICIPANTS: Ninety-six older people: 32 with normal cognition (NC), 30 with amnestic mild cognitive impairment (aMCI), and 34 with dementia. MAIN OUTCOME MEASURES: For each patient, we administered a neurologic and physical examination, neuropsychological evaluation, and brain MRI and genotyped the apolipoprotein E-ε4 (APOE-ε4) gene. The volumes determined by MRI were assessed using a semiautomatic method. RESULTS: Brain volume was significantly smaller in the dementia patients compared with the NC (P < .001) and aMCI patients (P = .04). Hippocampal volume (HV) was lower and white matter hyperintensity (WMH) volume was higher in those with aMCI (HV: P = .03; WMH volume: P = .04) and dementia (HV: P < .001; WMH volume: P = .002) compared with NC participants. The presence of APOE-ε4 was significantly associated with reduced HV (P = .02). Systolic blood pressure was positively associated with CVR score (P = .04); diastolic blood pressure (P = .02) and CVR score (P = .04) were positively associated with WMH volume. The WMH volume (P = .03) and CVR score (P = .03) were higher among dementia patients compared with NC participants. CONCLUSIONS: Brain structure changes seen on MRI were significantly associated with clinical diagnosis. In addition, blood pressure was highly associated with CVR score and WMH volume. These results suggest that MRI is a valuable measure of brain injury in a Chinese cohort and can serve to assess the effects of various degenerative and cerebrovascular diseases.

Effects of apolipoprotein E-epsilon4 and -epsilon2 in amnestic mild cognitive impairment and dementia in Shanghai: SCOBHI-P.

OBJECTIVE: To determine apolipoprotein E (APOE)-epsilon4 and -epsilon2 frequencies and risk of mild cognitive impairment (MCI) and dementia in Shanghai, China. METHODS: A total of 34 MCI and 34 dementia cases were recruited from an urban Memory Disorders Clinic and 32 controls were recruited from a residential community served by the clinic. Apolipoprotein E was genotyped using standard methods. RESULTS: Among controls, frequencies were epsilon2, 0.11; epsilon3, 0.84; and epsilon4, 0.05; among MCI, 0.05, 0.77, and 0.18; and for dementia, 0.02, 0.84, and 0.15, respectively. In education-adjusted models, the odds ratio (OR) = 5.6 for dementia (95% CI = 1.09-29.3) and 4.7 for MCI (95% CI = 0.90-25.2) associated with any epsilon4 allele. The epsilon2 allele was inversely associated with dementia (OR = 0.12, 95% CI = 0.013-0.997) and MCI (OR = 0.38, 95% CI = 0.08-1.61). CONCLUSIONS: APOE-epsilon4 increases and -epsilon2 decreases the risk of dementia vs normal cognition. Similar trends were observed for amnestic mild cognitive impairment (aMCI).

Midlife fruit and vegetable consumption and risk of dementia in later life in Swedish twins.

OBJECTIVE: Diet may be associated with risk of dementia and Alzheimer disease (AD). The authors examined the association between fruit and vegetable consumption in midlife and risk for all types of dementia and AD. METHODS: Participants were 3,779 members of the Swedish Twin Registry who completed a diet questionnaire approximately 30 years before cognitive screening and full clinical evaluation for dementia as part of the study of dementia in Swedish Twins (HARMONY) study. Among the participants, 355 twins were diagnosed with dementia. Among these, 81 twin pairs were discordant for dementia (50 discordant for AD). Data were analyzed with logistic regression for the entire sample using generalized estimating equations to adjust for relatedness of twins and with conditional logistic regression for the co-twin control design. RESULTS: In fully adjusted models, a medium or great proportion of fruits and vegetables in the diet, compared with no or small, was associated with a decreased risk of dementia and AD. This effect was observed among women and those with angina. Similar, but nonsignificant, odds ratios were found in the co-twin control analyses. CONCLUSION: The findings suggest that higher fruit and vegetable consumption may reduce the risk of dementia, especially among women and those with angina pectoris in midlife.

The effect of APOE-epsilon4 on dementia is mediated by Alzheimer neuropathology.

The degree to which the association of epsilon4 with dementia is mediated by AD lesions in comparison with vascular lesions is controversial. The present study was undertaken to determine the roles of Alzheimer disease (AD) and vascular pathology in mediating the effect of apolipoprotein E (APOE)-epsilon4 alleles on dementia. Clinicopathologic correlations were studied in 267 Catholic sisters participating in the Nun Study. The extent to which AD and vascular pathologies mediated the effect of APOEepsilon4 on dementia was investigated using multiple logistic regression. Adjusted for age at death and education, possession of 1 or more epsilon4 alleles was an important risk factor for dementia (odds ratio=2.98; 95% confidence interval, 1.62-5.48). This association was lost (odds ratio=1.38; 95% confidence interval, 0.68-2.80) when an index of the severity of AD-related neuropathology was added to the model, but changed little when measures of the severity of vascular pathology were added. The findings suggest that the effect of epsilon4 on dementia is mediated by the severity of AD pathology. Although infarcts and atherosclerosis contribute to the occurrence of dementia, this contribution seems unrelated to APOE genotype.