José A. Luchsinger

Impact of Plasma Lipids and Time on Memory Performance in Healthy Elderly without Dementia

Objective: To examine the association of plasma lipid levels to changes in cognitive function in elderly subjects without dementia. Methods: The authors examined changes in performance in tests of memory, visuospatial/cognitive, and language abilities in 1,147 elderly individuals without dementia or cognitive impairment at baseline followed for 7 years using generalized estimating equations. Results: Performance in all cognitive domains declined significantly over time, while there was no association between levels of any plasma lipid or lipid lowering treatment and memory, cognitive/visuospatial, or language performance at any interval. Higher age at baseline was related to lower scores in all three domains at each interval, while higher education and white ethnicity were associated with higher scores in all domains. Analyses relating plasma lipids to performance in color trails tests using proportional hazards regression showed no association. In subsequent analyses excluding subjects with incident dementia, memory performance declined over time, while cognitive/visuospatial and language performance did not. Higher plasma high density lipoprotein and total cholesterol were associated with higher scores in language performance at baseline; this domain declined faster among individuals with higher total cholesterol, but this result was not significant after taking multiple comparisons into account. Plasma triglycerides, low density lipoprotein, or treatment with lipid lowering agents were not associated with changes in cognitive performance. Conclusions: Plasma lipid levels or treatment with lipid lowering agents in the elderly were not associated with changes in cognitive function.

Type 2 Diabetes and Late-Onset Alzheimer’s Disease

Background/Aims: To confirm in a cohort recruited in 1999–2001 our finding in a cohort recruited in 1992–1994 relating type 2 diabetes (T2D) to late-onset Alzheimer’s disease (LOAD). Methods: Participants were 1,488 persons aged 65 years and older without dementia at baseline from New York City. T2D was ascertained by self-report. Dementia and LOAD were ascertained by standard research procedures. Proportional hazard regression was used for analyses relating T2D and LOAD. Results: The prevalence of T2D was 17%. There were 161 cases of dementia and 149 cases of LOAD. T2D was related to dementia (hazard ratio = 1.7; 95% confidence interval = 1.4–2.9) and LOAD (1.6; 1.0–2.6) after adjustment for age, sex, education, ethnic group and apolipoprotein E Ε4. This association was weaker when only AD – excluding cases of mixed dementia – was considered (hazard ratio = 1.3; 95% confidence interval = 0.8–2.2). Conclusion: T2D is associated with LOAD. Cerebrovascular disease may be an important mediator.

Mediterranean Diet and Magnetic Resonance Imaging–Assessed Cerebrovascular Disease

Cerebrovascular disease is 1 of the possible mechanisms of the previously reported relationship between Mediterranean‐type diet (MeDi) and Alzheimers disease (AD). We sought to investigate the association between MeDi and MRI infarcts.

Physical Activity and Alzheimer Disease Course

OBJECTIVES To examine the association between physical activity (PA) and Alzheimer disease (AD) course. BACKGROUND PA has been related to lower risk for AD. Whether PA is associated with subsequent AD course has not been investigated. METHODS In a population-based study of individuals aged 65 years and older in New York who were prospectively followed up with standard neurologic and neuropsychological evaluations (every ~1.5 years), 357 participants i) were nondemented at baseline and ii) were diagnosed with AD during follow-up (incident AD). PA (sum of participation in a variety of physical activities, weighted by the type of activity [light, moderate, and severe]) obtained 2.4 (standard deviation [SD], 1.9) years before incidence was the main predictor of mortality in Cox models and of cognitive decline in generalized estimating equation models that were adjusted for age, gender, ethnicity, education, comorbidities, and duration between PA evaluation and dementia onset. RESULTS One hundred fifty incident AD cases (54%) died during the course of 5.2 (SD, 4.4) years of follow-up. When compared with incident AD cases who were physically inactive, those with some PA had lower mortality risk, whereas incident AD participants with much PA had an even lower risk. Additional adjustments for apolipoprotein genotype, smoking, comorbidity index, and cognitive performance did not change the associations. PA did not affect rates of cognitive or functional decline. CONCLUSION Exercise may affect not only risk for AD but also subsequent disease duration: more PA is associated with prolonged survival in AD.

Nutrient intake and plasma β-amyloid

Objective: The widely reported associations between various nutrients and cognition may occur through many biologic pathways including those of β-amyloid (Aβ). However, little is known about the possible associations of dietary factors with plasma Aβ40 or Aβ42. The aim of the current study was to evaluate the association between nutrient intake and plasma Aβ levels. Methods: In this cross-sectional study, plasma Aβ40 and Aβ42 and dietary data were obtained from 1,219 cognitively healthy elderly (age >65 years), who were participants in a community-based multiethnic cohort. Information on dietary intake was obtained 1.2 years, on average, before Aβ assay. The associations of plasma Aβ40 and Aβ42 levels and dietary intake of 10 nutrients were examined using linear regression models, adjusted for age, gender, ethnicity, education, caloric intake, apolipoprotein E genotype, and recruitment wave. Nutrients examined included saturated fatty acid, monounsaturated fatty acid, ω-3 polyunsaturated fatty acid (PUFA), ω-6 PUFA, vitamin E, vitamin C, β-carotene, vitamin B12, folate, and vitamin D. Results: In unadjusted models that simultaneously included all nutrients, higher intake of ω-3 PUFA was associated with lower levels of Aβ40 (β = −24.7, p < 0.001) and lower levels of Aβ42 (β = −12.3, p < 0.001). In adjusted models, ω-3 PUFA remained a strong predictor of Aβ42 (β = −7.31, p = 0.02), whereas its association with Aβ40 was attenuated (β = −11.96, p = 0.06). Other nutrients were not associated with plasma Aβ levels. Conclusions: Our data suggest that higher dietary intake of ω-3 PUFA is associated with lower plasma levels of Aβ42, a profile linked with reduced risk of incident AD and slower cognitive decline in our cohort.

High adiposity: risk factor for dementia and Alzheimer’s disease?

Higher levels of total and central adiposity, measured as higher body mass index (BMI) (in kilograms per square meter), waist circumference, or waist-to-hip ratio, have been associated with late-onset Alzheimer’s disease (AD). However, some epidemiologic studies do not support this association, and potential underlying biological mechanisms that provide biological plausibility are not clear in terms of providing direct links to adipose tissue. Studies linking adiposity to AD have considered adiposity measures from mid-life and late-life. Given an evolving background trajectory of BMI that exists over the life course and the influence of dementia processes on BMI, results have been conflicting depending on when BMI is measured in relationship to clinical AD onset. This has made interpretation of the BMI-AD literature difficult. This debate will briefly review the epidemiologic evidence for and against an association between higher adiposity and AD, issues of timing of the adiposity measure in relation to AD onset, potential biological mechanisms for observed associations, and explanations for conflicting evidence.

Candidate genes for Alzheimer's disease are associated with individual differences in plasma levels of beta amyloid peptides in adults with Down syndrome

We examined the contribution of candidates genes for Alzheimers disease (AD) to individual differences in levels of beta amyloid peptides in adults with Down syndrom, a population at high risk for AD. Participants were 254 non-demented adults with Down syndrome, 30-78 years of age. Genomic deoxyribonucleic acid was genotyped using an Illumina GoldenGate custom array. We used linear regression to examine differences in levels of Aβ peptides associated with the number of risk alleles, adjusting for age, sex, level of intellectual disability, race and/or ethnicity, and the presence of the APOE ε4 allele. For Aβ42 levels, the strongest gene-wise association was found for a single nucleotide polymorphism (SNP) on CAHLM1; for Aβ40 levels, the strongest gene-wise associations were found for SNPs in IDE and SOD1, while the strongest gene-wise associations with levels of the Aβ42/Aβ40 ratio were found for SNPs in SORCS1. Broadly classified, variants in these genes may influence amyloid precursor protein processing (CALHM1, IDE), vesicular trafficking (SORCS1), and response to oxidative stress (SOD1).

Association of long-term dietary fat intake, exercise, and weight with later cognitive function in the Finnish Diabetes Prevention Study

ObjectivesTo investigate associations of long-term nutrient intake, physical activity and obesity with later cognitive function among the participants in the Finnish Diabetes Prevention Study, in which a lifestyle intervention was successful in diabetes prevention.DesignAn active lifestyle intervention phase during middle age (mean duration 4 years) and extended follow-up (additional 9 years) with annual lifestyle measurements, followed by an ancillary cognition assessment.Setting5 research centers in Finland.ParticipantsOf the 522 middle-aged, overweight participants with impaired glucose tolerance recruited to the study, 364 (70%) participated in the cognition assessment (mean age 68 years).MeasurementsA cognitive assessment was executed with the CERAD test battery and the Trail Making Test A on average 13 years after baseline. Lifestyle measurements included annual clinical measurements, food records, and exercise questionnaires during both the intervention and follow-up phase.ResultsLower intake of total fat (p=0.021) and saturated fatty acids (p=0.010), and frequent physical activity (p=0.040) during the whole study period were associated with better cognitive performance. Higher BMI (p=0.012) and waist circumference (p=0.012) were also associated with worse performance, but weight reduction prior to the cognition assessment predicted worse performance as well (decrease vs. increase, p=0.008 for BMI and p=0.002 for waist).ConclusionsLong-term dietary fat intake, BMI, and waist circumference have an inverse association with cognitive function in later life among people with IGT. However, decreases in BMI and waist prior to cognitive assessment are associated with worse cognitive performance, which could be explained by reverse causality.

Cognition in the Finnish Diabetes Prevention Study

We studied cognition in the Finnish Diabetes Prevention Study (DPS), a trial of lifestyle intervention that prevented diabetes in persons with impaired glucose tolerance. Cognition was similar in the randomization arms 9 years after the intervention in 364 participants, suggesting that the intervention did not benefit cognition.

Effect of a Long-Term Intensive Lifestyle Intervention on Cognitive Function: Action for Health in Diabetes Study

To assess whether randomization to 10 years of lifestyle intervention to induce and maintain weight loss improves cognitive function.