Association between Acid-Lowering Agents, Metformin, and Vitamin B12 among Boston-Area Puerto Ricans.

BACKGROUND: Vitamin B12 involves several physiological functions, and malabsorption is reported with medication use. OBJECTIVES: Studies have reported an inverse association between the use of metformin or acid-lowering agents (ALAs), such as proton pump inhibitors, histamine 2 receptor antagonists, and blood vitamin B12 concentration, because of malabsorption. The concomitant use of these medications is underreported. We sought to examine these associations in a cohort of Boston-area Puerto Rican adults. METHODS: This analysis was conducted within the Boston Puerto Rican Health Study (BPRHS), an ongoing longitudinal cohort that enrolled 1499 Puerto Rican adults aged 45-75 y at baseline. Our study comprised 1428, 1155, and 782 participants at baseline, wave2 (2.2 y from baseline), and wave3 (6.2 y from baseline), respectively. Covariate-adjusted linear and logistic regression was used to examine the association between baseline medication use and vitamin B12 concentration or deficiency (vitamin B12 <148 pmol/L or methylmalonic acid >271 nmol/L), and long-term medication use (continuous use for ∼6.2 y) and wave3 vitamin B12 concentration and deficiency. Sensitivity analyses were done to examine these associations in vitamin B12 supplement users. RESULTS: At baseline, we observed an association between metformin use (ß = -0.069; P = 0.03) and concomitant ALA and metformin use (ß = -0.112; P = 0.02) and vitamin B12 concentration, but not a deficiency. We did not observe associations between ALA, proton pump inhibitors, or histamine 2 receptor antagonists, individually, with vitamin B12 concentration or deficiency. CONCLUSIONS: These results suggest an inverse relationship between metformin, concomitant ALA, metformin use, and serum vitamin B12 concentration.

Early Childhood Lutein and Zeaxanthin Intake Is Positively Associated with Early Childhood Receptive Vocabulary and Mid-Childhood Executive Function But No Other Cognitive or Behavioral Outcomes in Project Viva.

BACKGROUND: Lutein and zeaxanthin are carotenoids associated with better cognition in older adults. Recent evidence suggests that their dietary intake may also have cognitive implications in childhood. OBJECTIVE: The aim was to examine associations of early childhood lutein and zeaxanthin (L/Z) intake with cognition in early and mid-childhood. METHODS: Among 1378 children in Project Viva, a prospective cohort, mothers reported their child's dietary intake in early childhood (median: 3.2 y) using a food-frequency questionnaire. Child cognition and behavior were assessed at the same time point using the Peabody Picture Vocabulary Test (PPVT-III) and the Wide Range Assessment of Visual Motor Abilities (WRAVMA) and at mid-childhood (median: 7.7 y) using the Kaufman Brief Intelligence Test, the WRAVMA drawing subtest, the Wide Range Assessment of Memory and Learning, the Behavior Rating Inventory of Executive Function (BRIEF), and the Strengths and Difficulties Questionnaire. RESULTS: Children consumed a daily mean (SD) of 1.0 (0.4) mg L/Z in early childhood. Children in the third-quartile category of L/Z intake had a mean PPVT-III score 2.40 (95% CI: 0.27, 4.53) points higher than children in the lowest quartile category in early childhood, suggesting better receptive vocabulary. Children in the highest quartile category of L/Z intake had a parent-reported mean BRIEF Global Executive Composite score 1.65 (95% CI: -3.27, -0.03) points lower than children in the lowest quartile category in mid-childhood, indicating better executive function. We did not observe associations between L/Z intake and any of the other cognitive or behavioral outcomes assessed. CONCLUSIONS: The overall findings do not provide strong evidence of an association between child L/Z intake and cognition and behavior. However, the positive associations found between early childhood L/Z intake and early childhood receptive vocabulary and mid-childhood executive function, in addition to previous evidence of neurodevelopmental benefit of L/Z intake, suggest that this relation deserves further investigation.

Effects of daily almond consumption for six months on cognitive measures in healthy middle-aged to older adults: a randomized control trial.

BACKGROUND: Age-related cognitive decline is a major public health issue. Almonds are rich in nutrients that benefit cognitive function. OBJECTIVE: To investigate the impact of almonds on cognition in elderly adults. DESIGN: In a six-month, single-blinded, randomized-controlled trial, the effects of an almond intervention on cognition in healthy, middle-aged/older adults (50-75 years) was tested. Subjects were assigned to one of three groups: 1.5 oz/d almond (n = 19), 3 oz/d almond (n = 24), or 3.5 oz/d snack (control, matched for macronutrients in 3.0 oz almonds, (n = 17). Serum analyses for tocopherols, oxidative status and inflammation, and cognition were assessed at baseline (M0), three (M3), and six (M6) months. RESULTS: At M6, serum alpha-tocopherol concentrations increased by 8% from M0 (p < 0.05) in the 3 oz almond group but did not increase in the other groups. Serum markers of inflammation and oxidative stress were not significantly different throughout the study among the groups. There was no difference in change over time in cognitive tests among the groups. However, there was a significant improvement in visuospatial working memory (p = 0.023), visual memory and learning (p = 0.017), and spatial planning and working memory (p < 0.001) in subjects receiving 3 oz/d almonds at M6, while the snack group showed no improvement. CONCLUSIONS: Almonds did not significantly improve cognitive function in cognitively intact middle-aged/older adults over six months. However, a significant improvement at M6 in cognitive measures was observed with 3 oz/d almonds. While these results are encouraging, a study of longer duration in subjects at risk for age-related cognitive decline is warranted.Trial registration: ClinicalTrials.gov identifier: NCT03093896.

Maternal Intake of Lutein and Zeaxanthin during Pregnancy Is Positively Associated with Offspring Verbal Intelligence and Behavior Regulation in Mid-Childhood in the Project Viva Cohort.

BACKGROUND: Lutein and zeaxanthin are carotenoids associated with better cognition at older age. To our knowledge, no previous study has evaluated their cognitive implications in the prenatal period, when the brain undergoes its most rapid development. OBJECTIVE: The objective of this study was to examine associations of maternal lutein and zeaxanthin (L/Z) intake during pregnancy with child cognition. DESIGN: Among 1580 mother-child pairs in Project Viva, a prospective cohort, we assessed maternal intake of L/Z during pregnancy using food frequency questionnaires and offspring cognition by the Visual Recognition Memory paradigm in infancy, the Peabody Picture Vocabulary Test and the Wide Range Assessment of Visual Motor Abilities (WRAVMA) in early childhood, and the Kaufman Brief Intelligence Test (KBIT-II), the WRAVMA drawing subtest, and the Wide Range Assessment of Memory and Learning in mid-childhood. Parents completed the Behavior Rating Inventory of Executive Function (BRIEF) and Strengths and Difficulties Questionnaire. RESULTS: Mothers consumed a daily mean (SD) of 2.6 (2.0) mg L/Z in the first and second trimesters of pregnancy. Mean mid-childhood KBIT-II verbal scores were higher with greater maternal L/Z intake [difference of Q4-Q1 means for first trimester: 2.67 (95% CI: 0.13, 5.20) and for second trimester: 3.55 (95% CI: 0.81, 6.28)], indicating better verbal intelligence. Secondary analyses on cognitive subtests showed that mean mid-childhood BRIEF Behavioral Regulation Index scores were lower with greater maternal L/Z intake [difference of Q4-Q1 means for first trimester: -1.63 (95% CI: -3.22, -0.04) and for second trimester: -1.89 (95% CI: -3.58, -0.21)], indicating better behavior regulation ability. CONCLUSIONS: Higher maternal L/Z intake during pregnancy was associated with better offspring verbal intelligence and behavior regulation ability in mid-childhood, suggesting a potential benefit during prenatal development. We did not find a benefit of higher maternal L/Z intake on other child cognitive or behavioral outcomes. Project Viva is registered at clinicaltrials.gov as NCT02820402.

Dietary strawberry improves cognition in a randomised, double-blind, placebo-controlled trial in older adults.

Functional changes in the brain during ageing can alter learning and memory, gait and balance - in some cases leading to early cognitive decline, disability or injurious falls among older adults. Dietary interventions with strawberry (SB) have been associated with improvements in neuronal, psychomotor and cognitive functions in rodent models of ageing. We hypothesised that dietary supplementation with SB would improve mobility and cognition among older adults. In this study, twenty-two men and fifteen women, between the ages of 60 and 75 years, were recruited into a randomised, double-blind, placebo-controlled trial in which they consumed either freeze-dried SB (24 g/d, equivalent to two cups of fresh SB) or a SB placebo for 90 d. Participants completed a battery of balance, gait and cognitive tests at baseline and again at 45 and 90 d of intervention. Significant supplement group by study visit interactions were observed on tests of learning and memory. Participants in the SB group showed significantly shorter latencies in a virtual spatial navigation task (P = 0·020, ηp2 = 0·106) and increased word recognition in the California Verbal Learning test (P = 0·014, ηp2 = 0·159) across study visits relative to controls. However, no improvement in gait or balance was observed. These findings show that the addition of SB to the diets of healthy, older adults can improve some aspects of cognition, but not gait or balance, although more studies with a larger sample size and longer follow-up are needed to confirm this finding.

Associations between dietary fatty acid patterns and cognitive function in the Hispanic Community Health Study/Study of Latinos.

Our objective was to quantify the cross-sectional associations between dietary fatty acid (DFA) patterns and cognitive function among Hispanic/Latino adults. This study included data from 8,942 participants of the Hispanic Community Health Study/Study of Latinos, a population-based cohort study (weighted age 56.2 y and proportion female 55.2%). The NCI (National Cancer Institute) method was used to estimate dietary intake from two 24-hr recalls. We derived DFA patterns using principal components analysis with 26 fatty acid and total plant and animal monounsaturated fatty acid (MUFA) input variables. Global cognitive function was calculated as the average z-score of 4 neurocognitive tests. Survey linear regression models included multiple potential confounders such as age, sex, education, depressive symptoms, physical activity, energy intake, and cardiovascular disease. DFA patterns were characterized by consumption of long-chain saturated fatty acids (SFA), animal-based MUFA, and trans fatty acids (Factor 1); short to medium-chain SFA (Factor 2); very-long-chain omega-3 polyunsaturated fatty acids (PUFA) (Factor 3); very-long-chain SFA and plant-based MUFA and PUFA (Factor 4). Factor 2 was associated with greater scores for global cognitive function (ß=0.037 ± 0.012) and the Digit Symbol Substitution (DSS) (ß=0.56±0.17), Brief Spanish English Verbal Learning-Sum (B-SEVLT) (ß=0.23 ± 0.11), and B-SEVLT-Recall (ß=0.11 ± 0.05) tests (P<0.05 for all). Factors 1 (ß=0.04 ± 0.01) and 4 (ß=0.70 ± 0.18) were associated with the DSS test (P<0.05 for all). Consumption of short to medium-chain SFA may be associated with higher cognitive function among U.S.-residing Hispanic/Latino adults. Prospective studies are necessary to confirm these findings.

Evaluation of Screening Tests for Cognitive Impairment in Patients Receiving Maintenance Hemodialysis.

BACKGROUND: Neurocognitive testing shows that cognitive impairment is common among patients receiving maintenance hemodialysis. Identification of a well performing screening test for cognitive impairment might allow for broader assessment in dialysis facilities and thus optimal delivery of education and medical management. METHODS: From 2015 to 2018, in a cohort of 150 patients on hemodialysis, we performed a set of comprehensive neurocognitive tests that included the cognitive domains of memory, attention, and executive function to classify whether participants had normal cognitive function versus mild, moderate, or severe cognitive impairment. Using area-under-the-curve (AUC) analysis, we then examined the predictive ability of the Mini Mental State Examination, the Modified Mini Mental State Examination, the Montreal Cognitive Assessment, the Trail Making Test Part B, the Mini-Cog test, and the Digit Symbol Substitution Test, determining each test's performance for identifying severe cognitive impairment. RESULTS: Mean age was 64 years; 61% were men, 39% were black, and 94% had at least a high-school education. Of the 150 participants, 21% had normal cognitive function, 17% had mild cognitive impairment, 33% had moderate impairment, and 29% had severe impairment. The Montreal Cognitive Assessment had the highest overall predictive ability for severe cognitive impairment (AUC, 0.81); a score of ≤21 had a sensitivity of 86% and specificity of 55% for severe impairment, with a negative predictive value of 91%. The Trails B and Digit Symbol tests also performed reasonably well (AUCs, 0.73 and 0.78, respectively). The other tests had lower predictive performances. CONCLUSIONS: The Montreal Cognitive Assessment, a widely available and brief cognitive screening tool, showed high sensitivity and moderate specificity in detecting severe cognitive impairment in patients on maintenance hemodialysis.

Serum Vitamin D and Depressive Symptomatology among Boston-Area Puerto Ricans.

BACKGROUND: Low vitamin D status, assessed using serum 25-hydroxyvitamin D [25(OH)D] concentration, has been associated with depression, but research among minority populations, such as Puerto Ricans is limited. We examined the association between serum 25(OH)D and self-reported depressive symptomatology across 3 waves of follow-up in a cohort of Puerto Rican adults residing in Massachusetts. OBJECTIVES: We evaluated the cross-sectional and longitudinal associations between serum 25(OH)D and self-reported depressive symptoms in the Boston Puerto Rican Health Study (BPRHS) cohort. METHODS: Participants of the BPRHS were evaluated for depressive symptoms using the Center for Epidemiologic Studies Depression Scale (CES-D). Serum 25(OH)D was measured at baseline (n = 1434), year 2 (n = 1218), and year 5 (n = 914). We categorized serum 25(OH)D concentration as sufficient (≥20 ng/mL), insufficient (12 to <20 ng/mL), and deficient (<12 ng/mL). Multivariable linear regression was used for cross-sectional analyses at baseline, and repeated measures mixed effects modeling was used over 3 waves of follow-up for longitudinal analyses. We conducted sensitivity analyses in vitamin D supplement nonusers and participants with complete data on baseline serum 25(OH)D and CES-D at all 3 visits. RESULTS: Serum 25(OH)D concentration was not associated with CES-D score in cross-sectional analysis [ß = -0.85; 95% CI: -2.80, 1.10 for deficient compared with sufficient 25(OH)D; P-trend = 0.59] or in longitudinal analyses over 5 y [ß = -0.41; 95% CI: -1.95, 1.13 for deficient compared with sufficient 25(OH)D; P-trend = 0.93]. Results were similar in sensitivity analyses restricted to vitamin D supplement nonusers (n = 1371) and in analyses conducted in participants with complete measures of baseline serum 25(OH)D and CES-D score at all 3 visits (n = 887) [ß = -0.12; 95% CI: -1.98, 1.74 for deficient compared with sufficient 25(OH)D; P-trend = 0.93]. CONCLUSIONS: We did not observe a significant association between serum 25(OH)D and depressive symptomatology in the BPRHS cohort.

Concentrations of Circulating Phylloquinone, but Not Cerebral Menaquinone-4, Are Positively Correlated with a Wide Range of Cognitive Measures: Exploratory Findings in Centenarians.

BACKGROUND: Vitamin K (VK) exists in the form of phylloquinone (PK) and menaquinones (MKs). Roles of VK on cognitive health in the elderly are emerging, but there is limited evidence on VK uptake and metabolism in human brain. OBJECTIVES: The primary objective of this study was to characterize VK distribution in brains of an elderly population with varied cognitive function. In addition, associations among circulating (a biomarker of VK intake) and cerebral VK concentrations and cognition were investigated. METHODS: Serum or plasma (n = 27) and brain samples from the frontal cortex (FC; n = 46) and the temporal cortex (TC; n = 33) were acquired from 48 decedents (aged 98-107 y; 25 demented and 23 nondemented) enrolled in the Georgia Centenarian Study. Both circulating and brain VK concentrations were measured using HPLC with fluorescence detection. Cognitive assessment was performed within 1 y prior to mortality. Partial correlations between serum/plasma or cerebral VK concentrations and cognitive function were performed, adjusting for covariates and separating by dementia and antithrombotic use. RESULTS: MK-4 was the predominant vitamer in both FC (mean ± SD = 4.92 ± 2.31 pmol/g, ≥89.15% ± 5.09% of total VK) and TC (4.60 ± 2.11 pmol/g, ≥89.71% ± 4.43% of total VK) regardless of cognitive status. Antithrombotic users had 34.0% and 53.9% lower MK-4 concentrations in FC (P < 0.05) and TC (P < 0.001), respectively. Circulating PK was not correlated with cerebral MK-4 or total VK concentrations. Circulating PK concentrations were significantly associated with a wide range of cognitive measures in nondemented centenarians (P < 0.05). In contrast, cerebral MK-4 concentrations were not associated with cognitive performance, either before or after exclusion of antithrombotic users. CONCLUSIONS: Circulating VK concentrations are not related to cerebral MK-4 concentrations in centenarians. Cerebral MK-4 concentrations are tightly regulated over a range of VK intakes and cognitive function. Circulating PK may reflect intake of VK-rich foods containing other dietary components beneficial to cognitive health. Further investigation of VK uptake and metabolism in the brain is warranted.

Serum vitamin D and cognition in a cohort of Boston-area Puerto Ricans.

Background: Vitamin D has been suggested as a protective factor for cognitive health, however results of prior studies have been mixed. To examine whether serum 25(OH)D concentration is related to cognition and cognitive decline in a study of Boston Area Puerto Ricans. Methods: We examined the association between serum 25(OH)D, cognitive function and cognitive decline in a longitudinal study of 967 Boston Area Puerto Rican adults. Results: In analyses adjusted for potential confounders, participants in the bottom quintile of 25(OH)D had similar cognitive function at baseline, as measured by a global cognitive score (mean difference: 0.09 (95% CI: -0.02, 0.19); p-trend: 0.18), and similar 2-year rates of cognitive decline (mean difference: -0.01 (95% CI: -0.09, 0.07), p-trend: 0.61) as those in the top 25(OH)D quintile. No significant associations were observed between baseline serum 25(OH)D concentration and 2-year change in individual cognitive test scores or change in executive function or memory domains. Conclusions: We observed no significant association between serum 25(OH)D and cognition in this cohort of Boston Area Puerto Ricans.

Lower Plasma Vitamin B-6 is Associated with 2-Year Cognitive Decline in the Boston Puerto Rican Health Study.

BACKGROUND: Despite its important role in cognitive development and regulation of nervous system function, vitamin B-6 has been under-studied in relation to cognitive aging. OBJECTIVE: We investigated whether plasma pyridoxal-5'-phosphate (PLP, vitamin B-6) concentrations were associated with cognitive function and subsequent cognitive decline. METHODS: In a longitudinal study of 949 participants (aged 45-75 y at baseline; 70% women) from the Boston Puerto Rican Health Study cohort, we examined the association between baseline plasma PLP and baseline cognitive function and 2-y cognitive decline. Cognitive function was assessed with an in-person 7-test cognitive battery, at baseline and 2-y follow-up. We also used logistic regression to estimate the odds of major 2-y decline in global cognitive function (defined as decline ≥1 SD below the mean), as well as decline in executive function and memory. We also used multivariable linear regression to calculate adjusted mean differences in cognitive scores, and 95% CIs, across tertiles of plasma PLP at baseline, as well as cross-sectional and longitudinal associations with individual test scores. RESULTS: In analyses adjusted for potential confounders, the OR of having a major 2-y decline in global cognitive function was 2.46 (95% CI: 1.49, 4.05; P-trend: 0.001) among participants in the lowest tertile of PLP compared with those in the top tertile of PLP. The association of PLP with cognition was stronger in participants older than 55 y at baseline (OR for bottom to top tertile: 4.58; 95% CI: 2.02, 10.35; P-interaction: 0.01) compared with those 55 y old or younger, as well as in ever smokers (OR for bottom to top tertile: 2.99; 95% CI: 1.45, 6.19; P-interaction: 0.02) compared with never smokers. CONCLUSIONS: Lower baseline plasma PLP was associated with increased odds of 2-y cognitive decline in a cohort of Boston area Puerto Ricans. The association was stronger among older participants and among ever smokers.

Blood Pressure and Cognitive Decline in Prevalent Hemodialysis Patients.

BACKGROUND: Hypertension is associated with cognitive decline in the general population. It is unclear what impact blood pressure (BP) has on cognitive decline in patients receiving maintenance hemodialysis (HD). METHODS: Using a longitudinal cohort of 314 prevalent HD patients without dementia at baseline, we examined the association of predialysis systolic BP (SBP) and diastolic BP (DBP), pulse pressure, and intradialytic SBP change (pre minus post), averaged for a month, with cognitive decline. Cognitive function was determined by a neurocognitive battery, administered yearly. Individual cognitive test results were reduced into 2 domain scores using principal components analysis (by definition mean of 0 and SD of 1), representing memory and executive function. Joint models, allowing for characterization of cognitive score slopes and including adjustment for potential confounders, were utilized to account for competing risks from death, dropout, or kidney transplantation. RESULTS: Mean age was 62 years; 54% were men, 23% were black, and 90% had at least a high school education. During median follow-up of 2.1 years (25th-75th: 1.0-4.5), 191 had at least one follow-up test, 148 died, and 43 received kidney transplants. Low predialysis DBP and high pulse pressure were both associated with steeper executive function decline (each 10 mm Hg lower DBP = -0.03 SD [-0.01 to -0.05] per year steeper decline) in executive function (each 10 mm Hg higher pulse pressure = -0.03 SD [-0.06 to -0.01] steeper decline) but not for memory function. SBP and intradialytic change were not associated with steeper decline for either memory or executive function. CONCLUSIONS: No relationship was seen between SBP or intradialytic change in BP with cognitive decline. In prevalent HD patients, lower predialysis DBP and wider predialysis pulse pressure are associated with steeper cognitive decline in executive function but not memory.

Vitamin B-6 and depressive symptomatology, over time, in older Latino adults.

Background: Low vitamin B-6 status has been linked to depressive symptomatology. We examined the longitudinal association of vitamin B-6 status with depressive symptomatology across 3-time points over ∼5-7 years in a cohort of older Hispanic adults. Methods: We used two-level hierarchical linear regression models for continuous outcomes. Vitamin B-6 status was associated with depressive symptomatology across these time points. Results: Plasma pyridoxyl-5-phosphate (PLP) concentration, a time-varying predictor, was significantly associated with depressive symptomatology. Study participants with PLP deficiency, vs. optimal PLP, had higher baseline depressive symptoms (Center for Epidemiologic Studies-Depression Scale (CES-D) score of 22 ± 14, vs. 20 ± 13); this differential remained constant over time and persisted after controlling for age, sex, education, body mass index, smoking and alcohol use, other relevant nutritional factors, perceived stress, stressful life events, allostatic load, and use of antidepressant medication. However, PLP concentration was not associated with the rate of change in depressive symptomatology over time. Conclusions: Suboptimal plasma PLP is associated with higher depressive symptomatology in older Hispanic of Puerto Rican descent and this appears to persist over time. Our data suggest that identification and treatment of vitamin B-6 deficiency may be a useful preventive approach in this population.

Cognitive Decline and Its Risk Factors in Prevalent Hemodialysis Patients.

BACKGROUND: Cognitive impairment is common in patients treated with hemodialysis. The trajectory of cognitive function and risk factors for cognitive decline remain uncertain in this population. STUDY DESIGN: Longitudinal cohort. SETTING & PARTICIPANTS: 314 prevalent hemodialysis patients. PREDICTORS: Age, sex, race, education level, hemodialysis vintage, cause of end-stage renal disease, and baseline history of cardiovascular disease. OUTCOMES: Cognitive function as determined by a comprehensive neurocognitive battery, administered at baseline and yearly when possible. Individual cognitive test results were reduced into 2 domain scores using principal components analysis, representing memory and executive function, which were used as our coprimary outcomes and by definition have a mean of zero and SD of 1. RESULTS: Mean age was 63 years; 54% were men, 22% were black, and 90% had at least a high school education. During a median follow-up of 2.1 (IQR, 0.9-4.2) years, 196 had at least 1 follow-up test, 156 died, and 43 received a kidney transplant. Linear mixed models and joint models, which accounted for competing risks from death, dropout, or kidney transplantation, showed nearly identical results. The joint model demonstrated a decline in executive function (-0.09 [95% CI, -0.13 to -0.05] SD per year), whereas memory improved slightly (0.05 [95% CI, 0.02 to 0.08] SD per year). A significant yearly decline was also seen in the Mini-Mental State Examination score (median change, -0.41; 95% CI, -0.57 to -0.25). Older age was the only significant risk factor for steeper executive function decline (-0.04 [95% CI, -0.06 to -0.02] SD steeper annual decline for each 10 years of age). LIMITATIONS: Prevalent hemodialysis patients only, limited follow-up testing due to high mortality rate, and exclusion of participants with severe cognitive deficits or dementia. CONCLUSIONS: Prevalent hemodialysis patients demonstrate significant cognitive decline, particularly within tests of executive function. Older age was the only statistically significant risk factor for steeper cognitive decline, which may have important clinical consequences for patient management and education. Future studies should evaluate strategies to maintain or improve cognitive function.

White matter damage in maintenance hemodialysis patients: a diffusion tensor imaging study.

BACKGROUND: Patients treated with dialysis have high rates of brain infarcts, brain atrophy, and white matter disease. There are limited data regarding the presence of more subtle damage to brain white matter. METHODS: In the Cognition and Dialysis Study, we compared brain structure using diffusion tensor imaging in hemodialysis (HD) patients to individuals without known kidney disease, using tract based spatial statistics (TBSS) to compare Fractional Anisotropy (FA) and Mean Diffusivity (MD). Statistical comparison of each overlaid voxel was age controlled using a permutation based corrected p value of <0.05. RESULTS: Thirty-four HD patients and twenty six controls (52 vs 51 years for HD vs control) had adequate magnetic resonance imaging for analysis. The HD group had fewer women (38% vs 23%) and a higher prevalence of diabetes (29% vs 8%), heart failure (29% vs 0%) and clinical stroke (15% vs 0%). Hemodialysis patients had significantly lower FA across multiple white matter fiber tracts, with fronto-temporal connections, the genu of the corpus callosum and the fornix more significantly affected than posterior regions of the brain. Similarly, HD patients had significantly higher mean diffusivity in multiple anterior brain regions. Results remained similar when those with a prior history of stroke were excluded. CONCLUSIONS: In HD patients, there is more white matter disease in the anterior than posterior parts of the brain compared to controls without kidney disease. This pattern of injury is most similar to that seen in aging, suggesting that developing chronic kidney disease and ultimately kidney failure may result in a phenotype consistent with accelerated aging.

Food Insecurity Is Associated with Subsequent Cognitive Decline in the Boston Puerto Rican Health Study.

BACKGROUND: Living with hunger and fear of not having enough food is a growing worldwide concern. In our previous cross-sectional study, we found that food insecurity was associated with poor cognitive function, but the direction of this relation remains unclear. OBJECTIVE: We investigated whether food insecurity is associated with subsequent cognitive decline. METHODS: This was a longitudinal study of 597 participants aged 40-75 y from the Boston Puerto Rican Health Study cohort, with a Mini-Mental State Examination score of ≥24 at baseline. Food security was assessed at baseline with the US Household Food Security Scale. Participants completed cognitive batteries, which included 7 cognitive tests, twice-at baseline and again at a 2-y follow-up. The primary outcome was the change in global cognitive function over 2 y. Multiple linear regression was used to obtain adjusted mean differences and 95% CIs in cognitive decline across baseline food security status. RESULTS: Food insecurity at baseline was associated with a 2-y decline in global cognitive function (P-trend = 0.03) after adjusting for relevant potential confounders, including age, sex, baseline cognitive score, body mass index, education, poverty, acculturation score, depression score, smoking status, use of alcohol, physical activity score, presence of diabetes and hypertension, apolipoprotein E status, plasma homocysteine, healthy eating index, and time between baseline and follow-up measures. Compared with the food-secure group, the decline in the very low food security group was greater [mean difference: -0.26 (95% CI: -0.41, -0.10)]. Baseline food insecurity was significantly associated with a faster decline in executive function (P-trend = 0.02) but not memory function (P-trend = 0.66). CONCLUSIONS: Food insecurity was associated with faster cognitive decline in this cohort of Puerto Rican adults. Our study emphasizes the importance of developing interventions for food insecurity that take into account the impact of food insecurity on cognition.

Cognitive function and all-cause mortality in maintenance hemodialysis patients.

BACKGROUND: Cognitive impairment is common in hemodialysis patients and is associated with significant morbidity. Limited information exists about whether cognitive impairment is associated with survival and whether the type of cognitive impairment is important. STUDY DESIGN: Longitudinal cohort. SETTING & PARTICIPANTS: Cognitive function was assessed at baseline and yearly using a comprehensive battery of cognitive tests in 292 prevalent hemodialysis patients. PREDICTOR: Using principal component analysis, individual test results were reduced into 2 domain scores, representing memory and executive function. By definition, each score carried a mean of 0 and SD of 1. OUTCOMES: Association of each score with all-cause mortality was assessed using Cox proportional hazards models adjusted for demographics and dialysis and cardiovascular (CV) risk factors. RESULTS: Mean age of participants was 63 years, 53% were men, 23% were African American, and 90% had at least a high school education. During a median follow-up of 2.1 (IQR, 1.1-3.7) years, 145 deaths occurred. Each 1-SD better executive function score was associated with a 35% lower hazard of mortality (HR, 0.65; 95% CI, 0.55-0.76). In models adjusting for demographics and dialysis-related factors, this relationship was partially attenuated but remained significant (HR, 0.81; 95% CI, 0.67-0.98), whereas adjustment for CV disease and heart failure resulted in further attenuation (HR, 0.87; 95% CI, 0.72-1.06). Use of time-dependent models showed a similar unadjusted association (HR, 0.62; 95% CI, 0.54-0.72), with the relationship remaining significant after adjustment for demographics and dialysis and CV risk factors (HR, 0.79; 95% CI, 0.66-0.94). Better memory was associated with lower mortality in univariate analysis (HR per 1 SD, 0.82; 95% CI, 0.69-0.96), but not when adjusting for demographics (HR, 1.00; 95% CI, 0.83-1.19). LIMITATIONS: Patients with dementia were excluded from the full battery, perhaps underestimating the strength of the association. CONCLUSIONS: Worse executive function and memory are associated with increased risk of mortality. For memory, this association is explained by patient demographics, whereas for executive function, this relationship may be explained in part by CV disease burden.

Depression and all-cause mortality in hemodialysis patients.

BACKGROUND: There are limited data regarding the relationship between depression and mortality in hemodialysis (HD) patients. METHODS: Among 323 patients receiving maintenance HD, depression symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale, with a score of ≥16 consistent with depression. Adjusted Cox proportional-hazards models with additional analyses incorporating antidepressant medication use were used to evaluate the association between depression and mortality. Baseline CES-D scores were used for the primary analyses, while secondary time-dependent analyses incorporated subsequent CES-D results. RESULTS: The mean age was 62.9 ± 16.5 years, 46% of the subjects were women and 22% were African-American. The mean baseline CES-D score was 10.7± 8.3, and 83 (26%) participants had CES-D scores ≥16. During a median (25th, 75th) follow-up of 25 (13, 43) months, 154 participants died. After adjusting for age, sex, race, primary cause of kidney failure, dialysis vintage and access, baseline depression was associated with an increased risk of all-cause mortality (HR 1.51 and 95% CI 1.06-2.17). This attenuated with further adjustment for cardiovascular disease, smoking, Kt/V, serum albumin, log C-reactive protein and use of antidepressants (HR 1.21 and 95% CI 0.82-1.80). When evaluating time-dependent CES-D, depression remained associated with increased mortality risk in the fully adjusted model (HR 1.44 and 95% CI 1.00-2.06). CONCLUSIONS: Greater symptoms of depression are associated with an increased risk of mortality in HD patients, particularly when accounting for the most proximate assessment. This relationship was attenuated with adjustment for comorbid conditions, suggesting a complex relationship between clinical characteristics and depression symptoms. Future studies should evaluate whether treatment for depression impacts mortality among HD patients.

Macular pigment optical density is related to cognitive function in older people.

BACKGROUND: the xanthophylls lutein (L) and zeaxanthin (Z) exist in relatively high concentration in multiple central nervous tissues (e.g. cortex and neural retina). L + Z in macula (i.e. macular pigment, MP) are thought to serve multiple functions, including protection and improvement of visual performance. Also, L + Z in the macula are related to L + Z in the cortex. OBJECTIVE: to determine whether macular pigment optical density (MPOD, L + Z in the macula) is related to cognitive function in older adults. METHODS: participants were older adults (n = 108, 77.6 ± 2.7 years) sampled from the age-related maculopathy ancillary study of the Health Aging and Body Composition Study (Memphis, TN, USA). Serum carotenoids were measured using high performance liquid chromatography. MPOD was assessed using heterochromatic flicker photometry. Eight cognitive tests designed to evaluate several cognitive domains including memory and processing speed were administered. Partial correlation coefficients were computed to determine whether cognitive measures were related to serum L + Z and MPOD. RESULTS: MPOD levels were significantly associated with better global cognition, verbal learning and fluency, recall, processing speed and perceptual speed, whereas serum L + Z was significantly related to only verbal fluency. CONCLUSION: MPOD is related to cognitive function in older people. Its role as a potential biomarker of cognitive function deserves further study.

Metabolites and Cognitive Decline in a Puerto Rican Cohort.

Background: Recent studies have identified plasma metabolites associated with cognitive decline and Alzheimer's disease; however, little research on this topic has been conducted in Latinos, especially Puerto Ricans. Objective: This study aims to add to the growing body of metabolomics research in Latinos to better understand and improve the health of this population. Methods: We assessed the association between plasma metabolites and global cognition over 12 years of follow-up in 736 participants of the Boston Puerto Rican Health Study (BPRHS). Metabolites were measured with untargeted metabolomic profiling (Metabolon, Inc) at baseline. We used covariable adjusted linear mixed models (LMM) with a metabolite * time interaction term to identify metabolites (of 621 measured) associated with ∼12 years cognitive trajectory. Results: We observed strong inverse associations between medium-chain fatty acids, caproic acid, and the dicarboxylic acids, azelaic and sebacic acid, and global cognition. N-formylphenylalanine, a tyrosine pathway metabolite, was associated with improvement in cognitive trajectory. Conclusions: The metabolites identified in this study are generally consistent with prior literature and highlight a role medium chain fatty acid and tyrosine metabolism in cognitive decline.