Association of Serum Antioxidant Vitamins and Carotenoids With Incident Alzheimer Disease and All-Cause Dementia Among US Adults.

BACKGROUND AND OBJECTIVES: Serum antioxidant vitamins and carotenoids may protect against neurodegeneration with age. We examined associations of these nutritional biomarkers with incident all-cause and Alzheimer disease (AD) dementia among US middle-aged and older adults. METHODS: Using data from the third National Health and Nutrition Examination Surveys (1988-1994), linked with Centers for Medicare & Medicaid follow-up data, we tested associations and interactions of serum vitamins A, C, and E and total and individual serum carotenoids and interactions with incident AD and all-cause dementia. Cox proportional hazards regression models were conducted. RESULTS: After ≤26 years follow-up (mean 16-17 years, 7,283 participants aged 45-90 years at baseline), serum lutein+zeaxanthin was associated with reduced risk of all-cause dementia (65+ age group), even in the lifestyle-adjusted model (per SD: hazard ratio [HR] 0.93, 95% CI 0.87-0.99; p = 0.037), but attenuated in comparison with a socioeconomic status (SES)-adjusted model (HR 0.92, 95% CI 0.86-0.93; p = 0.013). An inverse relationship was detected between serum ß-cryptoxanthin (per SD increase) and all-cause dementia (45+ and 65+) for age- and sex-adjusted models (HR 0.86, 95% CI 0.80-0.93; p < 0.001 for 45+; HR 0.86, 95% CI 0.80-0.93; p = 0.001 for 65+), a relationship remaining strong in SES-adjusted models (HR 0.89, 95% CI 0.82-0.96; p = 0.006 for 45+; HR 0.88, 95% CI 0.81-0.96; p = 0.007 for 65+), but attenuated in subsequent models. Antagonistic interactions indicate putative protective effects of 1 carotenoid may be observed at lower levels other carotenoids or antioxidant vitamin. DISCUSSION: Incident all-cause dementia was inversely associated with serum lutein+zeaxanthin and ß-cryptoxanthin levels. Further studies with time-dependent exposures and randomized trials are needed to test neuroprotective effects of supplementing the diet with select carotenoids. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that incident all-cause dementia was inversely associated with serum lutein+zeaxanthin and ß-cryptoxanthin levels.

Mixed carotenoid supplementation and dysmetabolic obesity: gaps in knowledge.

Dysmetabolic obesity during childhood and adolescence currently represents one of the greatest therapeutic challenge for healthcare systems worldwide. The global rates of obesity have more than doubled in the last 30 years. Recent meta-analysis from national surveys and food composition studies suggest an inverse association between lower carotenoid levels and the prevalence of Metabolic Syndrome in the general population, independent of serum retinol (vitamin A) levels. In children, two double-blind randomised placebo-controlled studies describing the effects of diet vs. mixed carotenoid supplementation on insulin resistance, adipokines and the rate of accrual of subcutaneous abdominal fat, implicate supplementation of these compounds to achieve targetable levels may be useful in the management of obesity accrual in this population. We will discuss the role of carotenoids and their conversion products (retinoids) in adipogenesis, lipolysis, insulin resistance and the pathophysiology of the metabolic syndrome and review the animal studies, which help support these findings.

Systemic Inflammation Is Associated With Longitudinal Changes in Cognitive Performance Among Urban Adults.

Objectives/Background: Systemic inflammation can affect cognitive performance over time. The current study examined associations between systemic inflammation and cognitive performance among African Americans and Whites urban adults, stratifying by sex, and age group and by race. Patients/Methods: Among 1,555-1,719 White and African-American urban adults [Agebase: 30-64y, 2004-2013, mean±SD follow-up time(y): 4.64 ± 0.93y], conducted linear mixed-effects regression models were conducted to test associations of inflammatory markers [C-reactive protein, Erythrocyte Sedimentation Rate (ESR), albumin, iron, and an inflammation composite score (ICS)] with longitudinal cognitive performance. Results: Among key findings, CRP was linked to poorer baseline mental status among younger women (≤50y, γ01 = -0.03 ± 0.01, p = 0.002) and poorer attention in older women (>50y, γ01 = -0.024 ± 0.007, p < 0.004) and African-Americans (γ01 = -0.029 ± 0.008, p < 0.001). ESR was related to faster decline on verbal memory among older men (>50y, γ11 = -0.008 ± 0.003, P = 0.009); with poorer performance on attention tests overall (γ01 = -0.010 ± 0.003, P = 0.003) and among African-Americans (γ01 = -0.013 ± 0.004, P = 0.002); on verbal fluency among older women (>50y,γ01 = -0.037 ± 0.013, P = 0.004) and on executive function: overall (γ01 = +0.62 ± 0.21, P = 0.004), older men (>50y, γ01 = +1.69 ± 0.53, P = 0.001) and African-Americans (γ01 = +0.84 ± 0.28, P = 0.002). Albumin was linked to slower attention decline among older men (>50y, γ11 = +0.329 ± 0.103, P = 0.009), over-time improvement in executive function overall (γ11 = -6.00 ± 2.26, P = 0.008), and better baseline psychomotor speed among African-Americans (γ01 = +0.56 ± 0.19, P = 0.003). Finally, ICS predicted faster decline on visual memory/visuo-constructive abilities among older men (>50y, γ11 = +0.17 ± 0.06, p = 0.003). Conclusion: In sum, strong associations between systemic inflammation and longitudinal cognitive performance were detected, largely among older individuals (>50y) and African-Americans. Randomized trials targeting inflammation are warranted.

Dietary factors are associated with serum uric acid trajectory differentially by race among urban adults.

Serum uric acid (SUA), a causative agent for gout, is linked to dietary factors, perhaps differentially by race. Cross-sectional (SUAbase, i.e. baseline SUA) and longitudinal (SUArate; i.e. annual rate of change in SUA) associations of SUA with diet were evaluated across race and sex-race groups, in a large prospective cohort study of urban adults. Of 3720 African American (AA) and White urban adults participating in the Healthy Aging in Neighborhoods of Diversity across the Life Span study, longitudinal data (2004-2013, k=1·7 repeats, follow-up, 4·64 (sd 0·93) years) on n 2138 participants were used. The main outcome consisted of up to two repeated measures on SUA. Exposures included the dietary factors such as 'added sugar', 'alcoholic beverages', 'red meat', 'total fish', 'legumes', 'total dairy product', 'caffeine', 'vitamin C' and a composite measure termed 'dietary urate index'. Mixed-effects linear regression models were conducted, stratifying by race and by race×sex. A positive association between legume intake and SUArate was restricted to AA, whereas alcohol intake was positively associated with SUAbase overall without racial differences. Added sugars were directly related to SUAbase among White men (P<0·05 for race×sex interaction), whereas dairy product intake was linked with slower SUArate among AA women, unlike among White women. Nevertheless, dairy product intake was associated with a lower SUAbase among Whites. Finally, the dietary urate index was positively associated with both SUAbase and SUArate, particularly among AA. In sum, race and sex interactions with dietary intakes of added sugars, dairy products and legumes were detected in determining SUA. Similar studies are needed to replicate these findings.

Vitamin D Status and Intakes and Their Association With Cognitive Trajectory in a Longitudinal Study of Urban Adults.

Context: Serum 25-hydroxyvitamin D [25(OH)D], and dietary and supplemental vitamin D may influence cognitive outcomes. Objectives: Sex-, age-, and race-specific associations of vitamin D status and intake with longitudinal change in various cognitive domains were examined in a large sample of ethnically and socioeconomically diverse US urban adults. Design: Two prospective waves of data from the Healthy Aging in Neighborhoods of Diversity across the Life Span study were used. Participants: Adults in Baltimore, Maryland, aged 30 to 64 years at baseline (n = 1231 to 1803), were followed for a mean (± standard deviation) of 4.64 ± 0.93 years. Visit 1 occurred between 2004 and 2009; visit 2, between 2009 and 2013; there were 1.5 to 2.0 visits per participant. Main outcome and exposure measures: Cognitive performance was assessed using 11 test scores covering domains of global cognition, attention, learning/memory, executive function, visuospatial/visuoconstruction ability, psychomotor speed, and language/verbal. Serum 25(OH)D, vitamin D intake, and use of supplements containing vitamin D were the key exposures. Results: A consistent relationship was found between vitamin D status (overall) and supplemental intake (older women and black adults), with a slower rate of decline in the domain of verbal fluency. Higher dietary intake of vitamin D was linked to slower rate of decline in verbal memory among younger women, and a slower rate of decline in visual memory/visuoconstructive abilities among white adults. All other associations were inconsistent. Conclusions: Vitamin D status and intakes were inversely related to domain-specific cognitive decline in US urban adults.

Vitamin D Receptor and Megalin Gene Polymorphisms Are Associated with Longitudinal Cognitive Change among African-American Urban Adults.

Background: The link between longitudinal cognitive change and polymorphisms in the vitamin D receptor (VDR) and MEGALIN [or LDL receptor-related protein 2 (LRP2)] genes remains unclear, particularly among African-American (AA) adults.Objectives: We aimed to evaluate associations of single nucleotide polymorphisms (SNPs) for VDR [rs11568820 (Cdx-2:T/C), rs1544410 (BsmI:G/A), rs7975232 (ApaI:A/C), rs731236 (TaqI:G/A)] and LRP2 [rs3755166:G/A,rs2075252:C/T, rs2228171:C/T] genes with longitudinal cognitive performance change in various domains of cognition.Methods: Data from 1024 AA urban adult participants in the Healthy Aging in Neighborhoods of Diversity Across the Life Span (Baltimore, Maryland) with complete genetic data were used, of whom 660-797 had complete data on 9 cognitive test scores at baseline and/or the first follow-up examination and complete covariate data (∼52% female; mean age: ∼52 y; mean years of education: 12.6 y). Time between examination visits 1 (2004-2009) and 2 (2009-2013) ranged from <1 y to ∼8 y, with a mean ± SD of 4.64 ± 0.93 y. Latent class and haplotype analyses were conducted by creating gene polymorphism groups that were related to longitudinal annual rate of cognitive change predicted from mixed-effects regression models.Results: Among key findings, the rs3755166:G/A MEGALIN SNP was associated with faster decline on the Mini-Mental State Examination overall (ß = -0.002, P = 0.018) and among women. VDR2 (BsmI/ApaI/TaqI: G-/A-/A-) SNP latent class [SNPLC; compared with VDR1 (ApaI: "AA")] was linked to faster decline on the Verbal Fluency Test, Categorical, in women, among whom the MEGALIN2 (rs2228171: "TT") SNPLC (compared with MEGALIN1:rs2228171: "CC") was also associated with a faster decline on the Trailmaking Test, Part B (Trails B), but with a slower decline on the Digit Span Backward (DS-B). Moreover, among men, the VDR1 SNP haplotype (SNPHAP; GCA:baT) was associated with a slower decline on the Trails B, whereas the MEGALIN1 SNPHAP (GCC) was associated with a faster decline on the DS-B, reflected as a faster decline on cognitive domain 2 ("visual/working memory").Conclusion:VDR and MEGALIN gene variations can alter age-related cognitive trajectories differentially between men and women among AA urban adults, specifically in global mental status and domains of verbal fluency, visual/working memory, and executive function.

Genetic risk scores, sex and dietary factors interact to alter serum uric acid trajectory among African-American urban adults.

Serum uric acid (SUA), a causative agent for gout among others, is affected by both genetic and dietary factors, perhaps differentially by sex. We evaluated cross-sectional (SUAbase) and longitudinal (SUArate) associations of SUA with a genetic risk score (GRS), diet and sex. We then tested the interactive effect of GRS, diet and sex on SUA. Longitudinal data on 766 African-American urban adults participating in the Healthy Aging in Neighborhood of Diversity across the Lifespan study were used. In all, three GRS for SUA were created from known SUA-associated SNP (GRSbase (n 12 SNP), GRSrate (n 3 SNP) and GRStotal (n 15 SNP)). Dietary factors included added sugar, total alcohol, red meat, total fish, legumes, dairy products, caffeine and vitamin C. Mixed-effects linear regression models were conducted. SUAbase was higher among men compared with that among women, and increased with GRStotal tertiles. SUArate was positively associated with legume intake in women (γ=+0·14; 95 % CI +0·06, +0·22, P=0·001) and inversely related to dairy product intake in both sexes combined (γ=-0·042; 95 % CI -0·075, -0·009), P=0·010). SUAbase was directly linked to alcohol consumption among women (γ=+0·154; 95 % CI +0·046, +0·262, P=0·005). GRSrate was linearly related to SUArate only among men. Legume consumption was also positively associated with SUArate within the GRStotal's lowest tertile. Among women, a synergistic interaction was observed between GRSrate and red meat intake in association with SUArate. Among men, a synergistic interaction between low vitamin C and genetic risk was found. In sum, sex-diet, sex-gene and gene-diet interactions were detected in determining SUA. Further similar studies are needed to replicate our findings.

Serum Uric Acid and Its Association with Longitudinal Cognitive Change Among Urban Adults.

Uric acid, a waste metabolite among humans, was linked to various cognitive outcomes. We describe sex and age-group specific associations of baseline serum uric acid (SUAbase) and significant change in SUA (ΔSUA: 1 versus 0 = decrease versus no change; 2 versus 0 = increase versus no change) with longitudinal annual rate of cognitive change among a large sample of urban adults. Data from the Healthy Aging in Neighborhoods of Diversity across the Life Span study, 2004-2009 (visit 1) and 2009-2013 (visit 2) were used. Of 3,720 adults selected at baseline (age range: 30-64 y), complete data were available for N = 1,487-1,602 with a mean repeat of 1.5-1.7 visits/participant. Cognitive test domains spanned attention, processing speed, learning/memory, executive function, visuo-spatial/visuo-construction ability, language/verbal, and global cognitive function. SUA was measured at both visits. Multiple mixed-effects regression analyses were conducted. In the total population, a higher SUAbase was associated with a faster annual rate of decline on a measure of visual memory/visuo-construction ability (the Benton Visual Retention Test) by γ= 0.07 with a standard error of 0.02, p < 0.001. Among older men, a significant increase in SUA was associated with slower decline on a test of attention/processing speed, namely Trailmaking test, Part A, measured in seconds to completion (γ= -6.91 ± 1.73, p < 0.001). In sum, a higher SUAbase was associated with faster cognitive decline over-time in a visual memory/visuo-construction ability test. ΔSUA had particular beneficial effects of an increasing ΔSUA on the domain of attention/processing speed among older men. More longitudinal studies are needed to examine cognitive domain-specific effects of over-time change in SUA within sex and age groups.