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.

Metabolites and MRI-Derived Markers of AD/ADRD Risk in a Puerto Rican Cohort.

Objective: Several studies have examined metabolomic profiles in relation to Alzheimer's disease and related dementia (AD/ADRD) risk; however, few studies have focused on minorities, such as Latinos, or examined Magnetic-Resonance Imaging (MRI)-based outcomes. Methods: We used multiple linear regression, adjusted for covariates, to examine the association between metabolite concentration and MRI-derived brain age deviation. Metabolites were measured at baseline with untargeted metabolomic profiling (Metabolon, Inc). Brain age deviation (BAD) was calculated at wave 4 (~ 9 years from Boston Puerto Rican Health Study (BPRHS) baseline) as chronologic age, minus MRI-estimated brain age, representing the rate of biological brain aging relative to chronologic age. We also examined if metabolites associated with BAD were similarly associated with hippocampal volume and global cognitive function at wave 4 in the BPRHS. Results: Several metabolites, including isobutyrylcarnitine, propionylcarnitine, phenylacetylglutamine, phenylacetylcarnitine (acetylated peptides), p-cresol-glucuronide, phenylacetylglutamate, and trimethylamine N-oxide (TMAO) were inversely associated with brain age deviation. Taurocholate sulfate, a bile salt, was marginally associated with better brain aging. Most metabolites with negative associations with brain age deviation scores also were inversely associations with hippocampal volumes and wave 4 cognitive function. Conclusion: The metabolites identifiedin this study are generally consistent with prior literature and highlight the role of BCAA, TMAO and microbially derived metabolites in cognitive decline.

Longitudinal Associations Between Sleep and Cognitive Function in a Cohort of Older Puerto Rican Adults: Sex and Age Interactions.

BACKGROUND: Evidence on sleep duration or quality and cognitive function in diverse older adults is limited. We examined prospective associations between subjective sleep measures and cognitive function, with modifying effects of sex and age (<65 vs ≥65 years). METHODS: Data are from the longitudinal Boston Puerto Rican Health Study, Waves 2 (n = 943) and 4 (n = 444), with mean follow-up of 10.5 years (range 7.2-12.8). Subjective measures of sleep duration (short <7, ref. 7, or long ≥8 hours) and insomnia symptoms (sum of difficulty falling asleep, waking up at night, and early morning awakening), were assessed at Wave 2. Linear regression models were used to assess changes in global cognition, executive function, memory, and Mini-Mental State Examination, and tested for modifying roles of sex and age. RESULTS: Significant 3-way interaction (sex × age × cognition) in fully adjusted models showed greater decline in global cognitive function in older men with short (ß [95% confidence interval]: -0.67 [-1.24, -0.10]) or long sleep duration (-0.92 [-1.55, -0.30]), compared to women, younger men, and older men with 7 hours of sleep. Insomnia symptoms were associated with a greater decline in memory (-0.54, [-0.85, -0.22]) among older men, compared to women and younger men. CONCLUSION: Sleep duration showed a U-shaped association with cognitive decline, and insomnia symptoms were associated with memory decline in fully adjusted models. Older men, versus women and younger men, were at relatively greater risk for cognitive decline associated with sleep factors. These findings are important for personalizing sleep interventions to support cognitive health.

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.

Proton Pump Inhibitor Use and Cognitive Function in the Boston Puerto Rican Health Study.

BACKGROUND: There is a lack of consensus among studies on the association between proton pump inhibitor (PPI) use and cognitive impairment. This association is not well studied among minority populations, including among Puerto Ricans. Therefore, we sought to examine this association among Boston-area Puerto Ricans. METHODS: The Boston Puerto Rican Health Study is an ongoing longitudinal cohort that enrolled 1499 Boston-area Puerto Rican adults, aged 45-75 years at baseline. Complete outcome and exposure data was available for 1290 baseline participants. Covariate-adjusted linear regression and linear mixed effects models were used to examine the association between PPI use, and global cognition, executive function, and memory cross-sectionally and longitudinally over ~12.7 years of follow-up. Furthermore, we examined the cross-sectional association between long-term PPI use (continuous use of ~6.2 years) and global cognition, executive function, and memory. RESULTS: Among 1 290 participants at baseline, 313 (24.3%) self-reported PPI use. Baseline PPI use was not associated with baseline global cognition, executive function, or memory. Baseline PPI use also did not alter the trajectory of global cognition, executive function, or memory over ~12.7 years of follow-up. Long-term PPI use was not associated with global cognition, executive function, or memory over ~12.7 years of follow-up. CONCLUSION: In this study of Boston-area Puerto Ricans, we did not observe an association between PPI use and global cognition, executive function, or memory either cross-sectionally or over 12.7 years of follow-up.

Maternal diet quality during pregnancy and child cognition and behavior in a US cohort.

BACKGROUND: Maternal intake of several nutrients during pregnancy is linked to offspring cognition. The relation between maternal dietary patterns and offspring cognition is less established. OBJECTIVES: We aimed to examine associations of maternal diet quality during pregnancy with child cognition and behavior. METHODS: Among 1580 mother-child pairs in Project Viva, a prospective prebirth cohort, we assessed maternal diet during pregnancy using FFQs and evaluated diet quality using versions modified for pregnancy of the Mediterranean Diet Score (MDS-P) and Alternate Healthy Eating Index (AHEI-P). Child cognitive and behavioral outcomes were assessed using standardized tests and questionnaires at infancy and in early and mid-childhood. We conducted multivariable linear regression analyses. RESULTS: Mothers were predominantly white, college-educated, and nonsmokers. After adjustment for child age and sex and maternal sociodemographic and lifestyle characteristics, maternal high (6-9) compared with low (0-3) MDS-P during pregnancy was associated with higher child Kaufman Brief Intelligence Test (KBIT-II) nonverbal (mean difference for first trimester: 4.54; 95% CI: 1.53, 7.56) and verbal scores (3.78; 95% CI: 1.37, 6.19) and lower Behavioral Rating Inventory of Executive Function (BRIEF) Metacognition Index (-1.76; 95% CI: -3.25, -0.27), indicating better intelligence and fewer metacognition problems in mid-childhood. Maternal Q4 compared with Q1 AHEI-P during pregnancy was associated with higher Wide Range Assessment of Visual Motor Abilities matching scores in early childhood (mean difference for first trimester: 2.79; 95% CI: 0.55, 5.04) and higher KBIT-II verbal scores (2.59; 95% CI: 0.13, 5.04) and lower BRIEF Global Executive Composite scores in mid-childhood (-1.61; 95% CI: -3.20, -0.01), indicating better visual spatial skills, verbal intelligence, and executive function. CONCLUSIONS: Maternal intake of a better-quality diet during pregnancy was associated with better visual spatial skills in the offspring at early childhood and with better intelligence and executive function in the offspring at mid-childhood.

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.

MIND Diet and Cognitive Function in Puerto Rican Older Adults.

BACKGROUND: Healthy diets have been associated with better cognitive function. Socioeconomic factors including education, poverty, and job complexity may modify the relationship between diet and cognition. METHODS: We used adjusted linear mixed models to examine the association between long-term adherence to the Mediterranean-Dietary Approaches to Stop Hypertension - Intervention for Neurodegenerative Delay (MIND) diet and cognitive function over 8 years of follow-up in Puerto Rican adults residing in the Boston, MA area (aged 45-75 years at baseline). We also examined whether the MIND diet-cognition association was confounded or modified by socioeconomic measures. RESULTS: In both cross-sectional and longitudinal analyses the highest, versus lowest, MIND quintile was associated with better cognition function (ß = 0.093; 95% CI: 0.035, 0.152; p trend = .0019), but not with cognitive trajectory over 8 years. Education <=8th grade (ß = -0.339; 95% CI: 0.394, -0.286; p < .0001) and income-to-poverty ratio <120% (ß = -0.049; 95% CI: -0.092, -0.007; p = .024) were significantly associated with lower cognitive function, while higher job complexity (ß = 0.008; 95% CI: 0.006, 0.011; p < .0001) was associated with better cognition function. These variables acted as confounders, but not effect modifiers of the MIND-diet-cognitive function relationship. CONCLUSION: Adherence to the MIND diet was associated with better cognitive function at baseline and over 8 years of follow-up; however, MIND diet was not associated with 8-year cognitive trajectory. More studies are needed to better understand whether the MIND diet is protective against long-term cognitive decline.

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.

Carotenoid-Rich Brain Nutrient Pattern Is Positively Correlated With Higher Cognition and Lower Depression in the Oldest Old With No Dementia.

Background: Healthy dietary patterns are related to better cognitive health in aging populations. While levels of individual nutrients in neural tissues are individually associated with cognitive function, the investigation of nutrient patterns in human brain tissue has not been conducted. Methods: Brain tissues were acquired from frontal and temporal cortices of 47 centenarians from the Georgia Centenarian Study. Fat-soluble nutrients (carotenoids, vitamins A, E, K, and fatty acids [FA]) were measured and averaged from the two brain regions. Nutrient patterns were constructed using principal component analysis. Cognitive composite scores were constructed from cognitive assessment from the time point closest to death. Dementia status was rated by Global Deterioration Scale (GDS). Pearson's correlation coefficients between NP scores and cognitive composite scores were calculated controlling for sex, education, hypertension, diabetes, and APOE ε4 allele. Result: Among non-demented subjects (GDS = 1-3, n = 23), a nutrient pattern higher in carotenoids was consistently associated with better performance on global cognition (r = 0.38, p = 0.070), memory (r = 0.38, p = 0.073), language (r = 0.42, p = 0.046), and lower depression (r = -0.40, p = 0.090). The findings were confirmed with univariate analysis. Conclusion: Both multivariate and univariate analyses demonstrate that brain nutrient pattern explained mainly by carotenoid concentrations is correlated with cognitive function among subjects who had no dementia. Investigation of their synergistic roles on the prevention of age-related cognitive impairment remains to be performed.

Walnut intake, cognitive outcomes and risk factors: a systematic review and meta-analysis.

BACKGROUND: Walnuts contain nutrients that are associated with improved cognitive health. To our knowledge, no review has systematically examined the effects of walnuts on cognitive function and risk for cognitive decline. OBJECTIVE: To conduct a systematic review and meta-analysis evaluating the effects of walnut intake on cognition-related outcomes and risk-factors for cognitive decline in adults. METHODS: Medline®, Commonwealth Agricultural Bureau, and Cochrane Central Register of Controlled Trials were searched for randomized controlled trials (RCTs) and observational studies published until April 2020 on walnut intake, cognition (e.g. cognitive function, stroke, and mood), and selected risk factors for cognitive decline (e.g. glucose homeostasis and inflammation). Risk-of-bias and strength-of-evidence assessments were conducted using standard validated tools. Random-effects meta-analyses were conducted when ≥3 studies reported quantitative data for each outcome. RESULTS: 32 RCT and 7 observational study publications were included. Meta-analysis of cognition-related outcomes could not be conducted due to heterogeneity of tests. None of the 5 cognition RCTs found significant effects of walnuts on overall cognition, although 3 studies found improvements on subdomains and/or subgroups. All 7 observational studies found significant associations and a dose-response relationship between walnut intake and cognition-related outcomes. Meta-analyses of 27 RCTs reporting glucose homeostasis and inflammation outcomes, selected risk factors for cognitive decline, did not show significant effects of walnut intake. CONCLUSIONS: Due to the non-uniformity of tests for cognition-related outcomes, definitive conclusions regarding the effect of walnut consumption on cognition could not be reached. Additionally, evidence does not show associations between walnut intake and glucose homeostasis or inflammation, cognitive decline risk-factors. High-quality studies with standardized measures are needed to clarify the role of walnuts in cognitive health.KEY MESSAGESThis is a systematic review and meta-analysis of 5 randomized clinical trials and 7 observational study articles of the impact of walnut intake on cognition decline and 27 randomized clinical trials of the effect of walnut intake on risk factors for cognitive decline including glucose homeostasis and inflammation.The non-uniformity of tests performed to measure cognitive function in the various studies did not allow for a meta-analysis of these studies. A definitive conclusion could therefore not be reached regarding the effect of walnut intake on cognitive decline.The evidence available does not show an association between walnut intake and glucose homeostasis or inflammation.

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.

Folate, vitamin B-12, and cognitive function in the Boston Puerto Rican Health Study.

BACKGROUND: There is evidence that low plasma vitamin B-12 and folate individually, as well as an imbalance of high folic acid and low vitamin B-12 status, may be associated with lower cognitive function. OBJECTIVES: We examined dietary and plasma folate and vitamin B-12 status, and their interaction, in relation to cognitive function in a cohort of older Puerto Rican adults. METHODS: The design is cross-sectional, with 1408 participants from the Boston Puerto Rican Health Study (mean ± SD age: 57.1 ± 7.9 y). Cognitive function was assessed with a comprehensive test battery and a global composite score was derived. Plasma folate, vitamin B-12, and methylmalonic acid (MMA) were assessed in fasting blood samples. RESULTS: After adjusting for covariates, high plasma folate and high plasma vitamin B-12 were each positively associated with global cognitive score (ß: 0.063; 95% CI: -0.0008, 0.127; P = 0.053 and ß: 0.062; 95% CI: 0.009, 0.12; P = 0.023, respectively, for logged values, and ß: 0.002; 95% CI: 0.00005, 0.004; P-trend = 0.044 and ß: 0.00018; 95% CI: 0.00001, 0.0003; P-trend = 0.036, respectively, across tertiles). Nine percent of participants had vitamin B-12 deficiency (plasma vitamin B-12 < 148 pmol/L or MMA > 271 nmol/L), but none were folate deficient (plasma folate < 4.53 nmol/L). Deficient compared with higher vitamin B-12 was significantly associated with lower cognitive score (ß: -0.119; 95% CI: -0.208, -0.029; P = 0.009). We could not examine the interaction for vitamin B-12 deficiency and high plasma folate, because there were too few individuals (<1% of the cohort) in this category to draw conclusions. CONCLUSIONS: Low plasma vitamin B-12 and low plasma folate were each associated with worse cognitive function in this population. Vitamin B-12 deficiency was prevalent and clearly associated with poorer cognitive function. More attention should be given to identification and treatment of vitamin B-12 deficiency in this population. Additional, larger studies are needed to examine the effect of vitamin B-12 deficiency in the presence of high exposure to folic acid.

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.

Thalamic Gamma Aminobutyric Acid Level Changes in Major Depressive Disorder After a 12-Week Iyengar Yoga and Coherent Breathing Intervention.

Objective: To determine if a 12-week yoga intervention (YI) was associated with increased gamma aminobutyric acid (GABA) levels and decreased depressive symptoms in participants with major depressive disorder (MDD). Methods: Subjects were randomized to a high-dose group (HDG) of three YIs a week and a low-dose group (LDG) of two YIs a week. Thalamic GABA levels were obtained using magnetic resonance spectroscopy at Scan-1 before randomization. After the assigned 12-week intervention, Scan-2 was obtained, immediately followed by a YI and Scan-3. Beck Depression Inventory II (BDI-II) scores were obtained before Scan-1 and Scan-3. Settings/Location: Screenings and interventions occurred at the Boston University Medical Center. Imaging occurred at McLean Hospital. Subjects: Subjects met criteria for MDD. Intervention: Ninety minutes of Iyengar yoga and coherent breathing at five breaths per minute plus homework. Outcome measures: GABA levels and the BDI-II. Results: BDI-II scores improved significantly in both groups. GABA levels from Scan-1 to Scan-3 and from Scan-2 to Scan-3 were significantly increased in the LDG (n = 15) and showed a trend in the total cohort. Post hoc, participants were divided into two groups based on having an increase in GABA levels at Scan-2. Increases in Scan-2 GABA levels were observed in participants whose mean time between their last YI and Scan-2 was 3.93 ± 2.92 standard deviation (SD) days, but not in those whose mean time between their last YI and Scan-2 was 7.83 ± 6.88 SD. Conclusions: This study tentatively supports the hypothesis that one of the mechanisms through which yoga improves mood is by increasing the activity of the GABA system. The observed increase in GABA levels following a YI that was no longer observed 8 days after a YI suggests that the associated increase in GABA after a YI is time limited such that at least one YI a week may be necessary to maintain the elevated GABA levels.

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.

Psychological Function, Iyengar Yoga, and Coherent Breathing: A Randomized Controlled Dosing Study.

BACKGROUND: Evidence suggests that yoga may be an effective treatment for major depressive disorder (MDD). Studies evaluating the "dosing" of yoga treatment and efficacy for MDD are needed. The goal of this study was to assess the effects of an intervention combining Iyengar yoga and coherent breathing in participants with MDD and determine the optimal intervention dose. METHODS: Thirty-two participants (18 to 65 y of age) diagnosed with MDD were randomized to a high-dose group (HDG) or a low-dose group (LDG) of yoga and coherent breathing for 12 weeks. The HDG (n=15) involved three 90-minute yoga classes and four 30-minute homework sessions per week. The LDG (n=15) involved two 90-minute yoga classes and three 30-minute homework sessions per week. Participants were evaluated at baseline, week 4, week 8, and week 12 with the following instruments: Positivity Self-Test, Spielberger State Anxiety Inventory, Patient Health Questionnaire-9, Pittsburgh Sleep Quality Index, and Exercise-induced Feeling Inventory. Data were analyzed using intent-to-treat methods. RESULTS: Significant improvements in all outcome measures were found for both groups, with acute and cumulative benefits. Although the HDG showed greater improvements on all scales, between-group differences did not reach significance, possibly due to lack of power because of the small sample size. Cumulative yoga minutes were correlated with improvement in outcome measures. LIMITATION: This dosing study did not include a non-yoga control. CONCLUSIONS: Improvement in psychological symptoms correlated with cumulative yoga practice. Both interventions reduced symptoms of depression and anxiety and increased feelings of positivity. The time commitment for yoga practice needs to be weighed against benefits when designing yoga interventions.

Clinico-Neuropathological Findings in the Oldest Old from the Georgia Centenarian Study.

BACKGROUND: Centenarian studies are important sources for understanding of factors that contribute to longevity and healthy aging. Clinico-neuropathological finding is a key in identifying pathology and factors contributing to age-related cognitive decline and dementia in the oldest old. OBJECTIVE: To characterize the cross-sectional relationship between neuropathologies and measures of premortem cognitive performance in centenarians. METHODS: Data were acquired from 49 centenarians (≥98 years) from the Georgia Centenarian Study. Cognitive assessment from the time point closest to mortality was used (<1 year for all subjects) and scores for cognitive domains were established. Neuropathologies [cerebral atrophy, ventricular dilation, atherosclerosis, cerebral amyloid angiopathy (CAA), Lewy bodies, hippocampal sclerosis (HS), hippocampal TDP-43 proteinopathy, neuritic plaque (NP) and neurofibrillary tangle (NFT) counts, Braak staging, and National Institute on Aging-Reagan Institute (NIARI) criteria for the neuropathological diagnosis of Alzheimer's disease (AD)] were compared among subjects with different ratings of dementia. Linear regression was applied to evaluate the association between cognitive domain scores and neuropathologies. RESULTS: Wide ranges of AD-type neuropathological changes were observed in both non-demented and demented subjects. Neocortical NFT and Braak staging were related to clinical dementia rating. Neocortical NFT and NP, Braak and NIARI staging, cerebral and ventricular atrophy, HS, CAA, and TDP-43 proteinopathy were differentially associated with poor performance in multiple cognitive domains and activities of daily living. CONCLUSION: AD-type pathology was associated with severe dementia and poor cognition but was not the only variable that explained cognitive impairment, indicating the complexity and heterogeneity of pathophysiology of dementia in the oldest old.

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.