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.

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.

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.

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.

A randomized controlled dosing study of Iyengar yoga and coherent breathing for the treatment of major depressive disorder: Impact on suicidal ideation and safety findings.

BACKGROUND: Yoga interventions offer promise for the treatment of major depressive disorder (MDD), yet their safety and potential impact on suicidal ideation (SI) have not been well documented. This study evaluated the safety of a randomized controlled dose-finding trial of Iyengar yoga plus coherent breathing for individuals with MDD, as well as the potential effects of the intervention on SI without intent. METHODS: Participants with Beck Depression Inventory-II (BDI-II) scores ≥14 and a diagnosis of MDD (using DSM-IV criteria) were randomized to either a low dose group (LDG) or high dose group (HDG) and received a 12-week manualized intervention. The LDG included two 90-min yoga classes plus three 30-min homework sessions weekly. The HDG offered three 90-min classes plus four 30-min homework sessions weekly. RESULTS: Thirty-two individuals with MDD were randomized, of which 30 completed the protocol. At screening, SI without intent was endorsed on the BDI-II by 9 participants; after completing the intervention, 8 out of 9 reported resolution of SI. There were 17 adverse events possibly-related and 15 definitely-related to the intervention. The most common protocol-related adverse event was musculoskeletal pain, which resolved over the course of the study. CONCLUSIONS: The Iyengar yoga plus coherent breathing intervention was associated with the resolution of SI in 8 out of 9 participants, with mild side effects that were primarily musculoskeletal in nature. This preliminary evidence suggests that this intervention may reduce SI without intent and be safe for use in those with MDD.

Metabolic fate of strawberry polyphenols after chronic intake in healthy older adults.

Strawberries contain a wide array of nutrients and phytochemicals including polyphenols such as anthocyanins, proanthocyanidins and ellagitannins. These polyphenols are absorbed and metabolized to various phenolic metabolites/conjugates in the body, which may play a role in disease risk reduction. In the present study, we investigated the metabolic fate of strawberry polyphenols after chronic (90 days) supplementation of freeze-dried strawberry (24 g d-1, equivalent to 2 cups of fresh strawberries) vs. control powder in 19 healthy older adults. Blood samples were collected at two time-points i.e., fasting (t = 0 h) and 2 h after the breakfast meal. On days 45 and 90 breakfast also included a control or strawberry drink consistent with their treatment randomization. A total of 21 polyphenolic metabolites were quantified in plasma consisting of 3 anthocyanins/metabolites, 3 urolithin metabolites and 15 phenolic acid metabolites. Among anthocyanins/metabolite, pelargonidin glucuronide (85.7 ± 9.0 nmol L-1, t = 2 h, day 90) was present in the highest concentration. Persistent concentrations of anthocyanins/metabolites, urolithins and some phenolic acids were observed in fasting (t = 0 h) plasma samples on day 45 and 90 after strawberry drink consumption suggesting a role of enteric, enterohepatic recycling or upregulation of gut microbial and/or human metabolism of these compounds. Our results suggest that strawberry polyphenols are absorbed and extensively metabolized, and can persist in the circulation.

Vitamin D and cognition in older adults: international consensus guidelines.

Hypovitaminosis D, a common condition in older adults, is associated with brain changes and dementia. Given the fast growing contribution of literature in this research field, clear guidance is needed for clinicians and researchers. International experts met at the invitational summit on "Vitamin D and cognition in older adults" in Boston, MA, July 2013. Based upon literature and expert opinion, the task force focused on key questions on the role of vitamin D in Alzheimer disease and related disorders. Each question was discussed and voted using a Delphi-like approach. Experts reached agreement that hypovitaminosis D increases the risk of cognitive decline and dementia in older adults, may alter the clinical presentation as a consequence of related comorbidities, but should not be used thus far as a diagnostic or prognostic biomarker of Alzheimer disease due to lack of specificity and insufficient evidence. Hypovitaminosis D should be screened in this population because of its high prevalence and supplemented, if necessary, but this advice was not specific to cognition. The task force agreed on 5 overarching principles related to vitamin D and cognition in older adults.

Dihydrofolate reductase 19-bp deletion polymorphism modifies the association of folate status with memory in a cross-sectional multi-ethnic study of adults.

BACKGROUND: Folate status has been positively associated with cognitive function in many studies; however, some studies have observed associations of poor cognitive outcomes with high folate. In search of an explanation, we hypothesized that the association of folate with cognition would be modified by the interaction of high-folate status with a common 19-bp deletion polymorphism in the dihydrofolate reductase (DHFR) gene. To our knowledge, the cognitive effects of this gene have not been studied previously. OBJECTIVE: We examined the association between cognitive outcomes with the 19-bp deletion DHFR polymorphism, folate status, and their interaction with high or normal plasma folate. DESIGN: This was a pooled cross-sectional study of the following 2 Boston-based cohorts of community living adults: the Boston Puerto Rican Health Study and the Nutrition, Aging, and Memory in Elders study. Individuals were genotyped for the DHFR 19-bp deletion genotype, and plasma folate status was determined. Cognitive outcomes included the Mini-Mental State Examination, Center for Epidemiologic Studies Depression Scale, and factor scores for the domains of memory, executive function, and attention from a set of cognitive tests. RESULTS: The prevalence of the homozygous deletion (del/del) genotype was 23%. In a multivariable analysis, high folate status (>17.8 ng/mL) was associated with better memory scores than was normal-folate status (fourth-fifth quintiles compared with first-third quintiles: ß ± SE = -0.22 ± 0.06, P < 0.01). Carriers of the DHFR del/del genotype had worse memory scores (ß ± SE = -0.24 ± 0.10, P < 0.05) and worse executive scores (ß = -0.19, P < 0.05) than did those with the del/ins and ins/ins genotypes. Finally, we observed an interaction such that carriers of the del/del genotype with high folate had significantly worse memory scores than those of both noncarriers with high-folate and del/del carriers with normal-folate (ß-interaction = 0.26 ± 0.13, P < 0.05). CONCLUSIONS: This study identifies a putative gene-nutrient interaction that, if confirmed, would predict that a sizable minority carrying the del/del genotype might not benefit from high-folate status and could see a worsening of memory. An understanding of how genetic variation affects responses to high-folate exposure will help weigh risks and benefits of folate supplementation for individuals and public health.

A novel comparative effectiveness study of Tai Chi versus aerobic exercise for fibromyalgia: study protocol for a randomized controlled trial.

BACKGROUND: Fibromyalgia is a chronic musculoskeletal pain syndrome that causes substantial physical and psychological impairment and costs the US healthcare system over $25 billion annually. Current pharmacological therapies may cause serious adverse effects, are expensive, and fail to effectively improve pain and function. Finding new and effective non-pharmacological treatments for fibromyalgia patients is urgently needed. We are currently conducting the first comparative effectiveness randomized trial of Tai Chi versus aerobic exercise (a recommended component of the current standard of care) in a large fibromyalgia population. This article describes the design and conduct of this trial. METHODS/DESIGN: A single-center, 52-week, randomized controlled trial of Tai Chi versus aerobic exercise is being conducted at an urban tertiary medical center in Boston, Massachusetts. We plan to recruit 216 patients with fibromyalgia. The study population consists of adults ≥21 years of age with fibromyalgia who meet American College of Rheumatology 1990 and 2010 diagnostic criteria. Participants are randomized to one of four Tai Chi intervention groups: 12 or 24 weeks of supervised Tai Chi held once or twice per week, or a supervised aerobic exercise control held twice per week for 24 weeks. The primary outcome is the change in Revised Fibromyalgia Impact Questionnaire total score from baseline to 24 weeks. Secondary outcomes include measures of widespread pain, symptom severity, functional performance, balance, muscle strength and power, psychological functioning, sleep quality, self-efficacy, durability effects, and health-related quality of life at 12, 24, and 52 week follow-up. DISCUSSION: This study is the first comparative effectiveness randomized trial of Tai Chi versus aerobic exercise in a large fibromyalgia population with long-term follow up. We present here a robust and well-designed trial to determine the optimal frequency and duration of a supervised Tai Chi intervention with regard to short- and long-term effectiveness. The trial also explores multiple outcomes to elucidate the potential mechanisms of Tai Chi and aerobic exercise and the generalizability of these interventions across instructors. Results of this study are expected to have important public health implications for patients with a major disabling disease that incurs substantial health burdens and economic costs. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01420640 , registered 18 August 2011.

Dietary modulators of statin efficacy in cardiovascular disease and cognition.

Cardiovascular disease remains the leading cause of morbidity and mortality in the United States and other developed countries, and is fast growing in developing countries, particularly as life expectancy in all parts of the world increases. Current recommendations for the prevention of cardiovascular disease issued jointly from the American Academy of Cardiology and American Heart Association emphasize that lifestyle modification should be incorporated into any treatment plan, including those on statin drugs. However, there is a dearth of data on the interaction between diet and statins with respect to additive, complementary or antagonistic effects. This review collates the available data on the interaction of statins and dietary patterns, cognition, genetics and individual nutrients, including vitamin D, niacin, omega-3 fatty acids, fiber, phytochemicals (polyphenols and stanols) and alcohol. Of note, although the available data is summarized, the scope is limited, conflicting and disparate. In some cases it is likely there is unrecognized synergism. Virtually no data are available describing the interactions of statins with dietary components or dietary pattern in subgroups of the population, particularly those who may benefit most were positive effects identified. Hence, it is virtually impossible to draw any firm conclusions at this time. Nevertheless, this area is important because were the effects of statins and diet additive or synergistic harnessing the effect could potentially lead to the use of a lower intensity statin or dose.

Cognitive dysfunction and depression in adult kidney transplant recipients: baseline findings from the FAVORIT Ancillary Cognitive Trial (FACT).

OBJECTIVE: Hyperhomocysteinemia and B-vitamin deficiency may be treatable risk factors for cognitive impairment and decline. Hyperhomocysteinemia, cognitive impairment, and depression are all common in individuals with kidney disease, including kidney transplant recipients. Accordingly, we assessed the prevalence of cognitive impairment and depressive symptoms in transplant recipients and their association with kidney function, plasma total homocysteine, and B-vitamin concentrations. SETTING: Cross-sectional analysis of baseline data from the Folic Acid for Vascular Outcome Reduction In Transplantation (FAVORIT) Ancillary Cognitive Trial (FACT), which included 183 participants in FAVORIT who underwent detailed neuropsychological assessment before the study intervention. RESULTS: The mean age was 54.0 ± 9.5 years (range: 7 to 386 months). Men comprised 55.2% of the cohort, and the mean time between the current transplant and cognitive testing was 7.0 ± 5.8 years. Twenty-four percent of participants reported neurological or psychiatric complaints, and 30% exhibited symptoms of mild to severe depression. Testing revealed evidence of significant and selective deficits in this population: 33% performed more than 1 standard deviation (SD) below normed means on a memory test, 58% fell lower than 1 SD below the norms on a test of attention and mental processing speed, and 33% to 42% fell lower than 1 SD below the norms on several tests of executive function. Lower estimated glomerular filtration rate and lower folate were associated with poorer performance on tests of memory and executive function. CONCLUSIONS: These observations confirm previous reports of mood and cognitive impairments in adult kidney transplant recipients. Further research is needed to determine the benefit of B-vitamin supplementation and other interventions in this patient population.

Tai Chi on psychological well-being: systematic review and meta-analysis.

BACKGROUND: Physical activity and exercise appear to improve psychological health. However, the quantitative effects of Tai Chi on psychological well-being have rarely been examined. We systematically reviewed the effects of Tai Chi on stress, anxiety, depression and mood disturbance in eastern and western populations. METHODS: Eight English and 3 Chinese databases were searched through March 2009. Randomized controlled trials, non-randomized controlled studies and observational studies reporting at least 1 psychological health outcome were examined. Data were extracted and verified by 2 reviewers. The randomized trials in each subcategory of health outcomes were meta-analyzed using a random-effects model. The quality of each study was assessed. RESULTS: Forty studies totaling 3817 subjects were identified. Approximately 29 psychological measurements were assessed. Twenty-one of 33 randomized and nonrandomized trials reported that 1 hour to 1 year of regular Tai Chi significantly increased psychological well-being including reduction of stress (effect size [ES], 0.66; 95% confidence interval [CI], 0.23 to 1.09), anxiety (ES, 0.66; 95% CI, 0.29 to 1.03), and depression (ES, 0.56; 95% CI, 0.31 to 0.80), and enhanced mood (ES, 0.45; 95% CI, 0.20 to 0.69) in community-dwelling healthy participants and in patients with chronic conditions. Seven observational studies with relatively large sample sizes reinforced the beneficial association between Tai Chi practice and psychological health. CONCLUSIONS: Tai Chi appears to be associated with improvements in psychological well-being including reduced stress, anxiety, depression and mood disturbance, and increased self-esteem. Definitive conclusions were limited due to variation in designs, comparisons, heterogeneous outcomes and inadequate controls. High-quality, well-controlled, longer randomized trials are needed to better inform clinical decisions.

Validity of estimated dietary eicosapentaenoic acid and docosahexaenoic acid intakes determined by interviewer-administered food frequency questionnaire among older adults with mild-to-moderate cognitive impairment or dementia.

Epidemiologic research is increasingly being focused on elderly persons, many of whom exhibit mild-to-moderate cognitive impairment. This presents a challenge for collection and interpretation of self-reported dietary data. There are few reports on the impact of cognitive function and dementia on the validity of self-reported dietary intakes. Using plasma phospholipid fatty acid profiles as a biomarker of intake, the authors assessed the validity of an interviewer-administered food frequency questionnaire (FFQ) to estimate intakes of 2 marine-based omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), among 273 community-dwelling adults aged > or =60 years participating in the Nutrition, Aging, and Memory in Elders Study (Boston, Massachusetts, 2002-2008). Age- and energy-adjusted Pearson correlation coefficients for correlations between dietary intakes and plasma phospholipids were consistent across categories of high and low cognitive function (r = 0.48), based on Mini-Mental State Examination score, and were similar across clinically diagnosed categories of normal functioning (r = 0.49), mild cognitive impairment (r = 0.45), and dementia (r = 0.52). The FFQ ranked 78% of subjects to within 1 quartile of their plasma phospholipid EPA + DHA quartile. This frequency was consistently high across all cognitive categories. With interviewer administration, this FFQ seems to be a valid method of assessing dietary EPA + DHA intake in older adults with mild-to-moderate cognitive impairment.

The Nutrition, Aging, and Memory in Elders (NAME) study: design and methods for a study of micronutrients and cognitive function in a homebound elderly population.

BACKGROUND: Micronutrient status can affect cognitive function in the elderly; however, there is much to learn about the precise effects. Understanding mediating factors by which micronutrient status affects cognitive function would contribute to elders' quality of life and their ability to remain in the home. OBJECTIVES: The Nutrition, Aging, and Memory in Elders (NAME) Study is designed to advance the current level of knowledge by investigating potential mediating factors by which micronutrient status contributes to cognitive impairment and central nervous system abnormalities in the elderly. NAME targets homebound elders because they are understudied and particularly at risk for poor nutritional status. METHODS: Subjects are community-based elders aged 60 and older, recruited through area Aging Services Access Points. The NAME core data include demographics; neuropsychological testing and activities of daily living measures; food frequency, health and behavioral questionnaires; anthropometrics; gene status; plasma micronutrients, homocysteine, and other blood determinants. A neurological examination, psychiatric examination, and brain MRI and volumetric measurements are obtained from a sub-sample. RESULTS: Preliminary data from first 300 subjects are reported. These data show that the NAME protocol is feasible and that the enrolled subjects are racially diverse, at-risk, and had similar basic demographics to the population from which they were drawn. CONCLUSION: The goal of the NAME study is to evaluate novel relationships between nutritional factors and cognitive impairment. These data may provide important information on potential new therapeutic strategies and supplementation standards for the elderly to maintain cognitive function and potentially reduce the public health costs of dementia.