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.

Corrigendum: APOE4 allele-specific associations between diet, multimodal biomarkers, and cognition among Puerto Rican adults in Massachusetts.

[This corrects the article DOI: 10.3389/fnagi.2023.1285333.].

APOE4 allele-specific associations between diet, multimodal biomarkers, and cognition among Puerto Rican adults in Massachusetts.

Background: Apolipoprotein E (APOE) is the strongest genetic risk factor for sporadic Alzheimer's Disease (AD), and the ε4 allele (APOE4) may interact with lifestyle factors that relate to brain structural changes, underlying the increased risk of AD. However, the exact role of APOE4 in mediating interactions between the peripheral circulatory system and the central nervous system, and how it may link to brain and cognitive aging requires further elucidation. In this analysis, we investigated the association between APOE4 carrier status and multimodal biomarkers (diet, blood markers, clinical diagnosis, brain structure, and cognition) in the context of gene-environment interactions. Methods: Participants were older adults from a longitudinal observational study, the Boston Puerto Rican Health Study (BPRHS), who self-identified as of Puerto Rican descent. Demographics, APOE genotype, diet, blood, and clinical data were collected at baseline and at approximately 12th year, with the addition of multimodal brain magnetic resonance imaging (MRI) (T1-weighted and diffusion) and cognitive testing acquired at 12-year. Measures were compared between APOE4 carriers and non-carriers, and associations between multimodal variables were examined using correlation and multivariate network analyses within each group. Results: A total of 156 BPRHS participants (mean age at imaging = 68 years, 77% female, mean follow-up 12.7 years) with complete multimodal data were included in the current analysis. APOE4 carriers (n = 43) showed reduced medial temporal lobe (MTL) white matter (WM) microstructural integrity and lower mini-mental state examination (MMSE) score than non-carriers (n = 113). This pattern was consistent with an independent sample from the Alzheimer's Disease Neuroimaging Initiative (ADNI) of n = 283 non-Hispanic White adults without dementia (mean age = 75, 40% female). Within BPRHS, carriers showed distinct connectivity patterns between multimodal biomarkers, characterized by stronger direct network connections between baseline diet/blood markers with 12-year blood/clinical measures, and between blood markers (especially lipids and cytokines) and WM. Cardiovascular burden (i.e., hypertension and diabetes status) was associated with WM integrity for both carriers and non-carriers. Conclusion: APOE4 carrier status affects interactions between dietary factors, multimodal blood biomarkers, and MTL WM integrity across ~12 years of follow-up, which may reflect increased peripheral-central systems crosstalk following blood-brain barrier breakdown in carriers.

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.

Adherence to Mediterranean Diet and Depressive Symptomatology Among Boston Area Puerto Ricans.

BACKGROUND: Higher Mediterranean diet (MeD) adherence has been linked with lower depressive symptomatology, but research examining this association is limited, especially among Latinos, including mainland U.S. Puerto Ricans. Hence, we examined cross-sectional and longitudinal associations between MeD adherence and self-reported depressive symptomatology in Boston area Puerto Rican adults. METHODS: The Center for Epidemiologic Studies Depression Scale (CES-D) was used to evaluate depressive symptoms. Adherence to MeD was assessed at all 3 visits. We used multivariable linear regression for baseline cross-sectional analysis, and linear mixed effects modeling over 3 waves of follow-up for longitudinal analysis. We also assessed whether baseline MeD adherence affected 5y CES-D trajectory. We conducted sensitivity analyses among participants without diabetes, and among participants with complete MeD and CES-D measures at all visits. RESULTS: MeD adherence was significantly associated with CES-D score at baseline (ß = -2.0, 95% confidence interval [CI] -4.0, -0.04 for highest vs lowest tertile, p trend = .04) and across 3 waves (ß = -1.9, 95% CI = -3.0, -0.8 for highest vs lowest tertile, p trend = .0005). Results were similar in analyses restricted to participants without diabetes, as well as among participants with complete CES-D and MeD scores at all visits. CONCLUSIONS: While CES-D score was consistently lower in those with higher MeD adherence over 5 years of follow up, no relationship between baseline MeD adherence and 5y CES-D trajectory was observed.

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.

Association of Diabetes and Hypertension With Brain Structural Integrity and Cognition in the Boston Puerto Rican Health Study Cohort.

BACKGROUND AND OBJECTIVES: The Boston Puerto Rican Health Study (BPRHS) is a longitudinal study following self-identified Puerto Rican older adults living in the Greater Boston area. Studies have shown higher prevalence of hypertension (HTN) and type 2 diabetes (T2D) within this ethnic group compared to age-matched non-Hispanic White adults. In this study, we investigated the associations of HTN and T2D comorbidity on brain structural integrity and cognitive capacity in community-dwelling Puerto Rican adults and compared these measures with older adult participants (non-Hispanic White and Hispanic) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and National Alzheimer's Coordinating Center (NACC) databases. METHODS: BPRHS participants who underwent brain MRI and cognitive testing were divided into 4 groups based on their HTN and T2D status: HTN-/T2D-, HTN+/T2D-, HTN-/T2D+, and HTN+/T2D+. We assessed microstructural integrity of white matter (WM) pathways using diffusion MRI, brain macrostructural integrity using hippocampal volumes, and brain age using T1-weighted MRI and cognitive test scores. BPRHS results were then compared with results from non-Hispanic White and Hispanic participants from the ADNI and NACC databases. RESULTS: The prevalence of HTN was almost 2 times (66.7% vs 38.7%) and of T2D was 5 times (31.8% vs 6.6.%) higher in BPRHS than in ADNI non-Hispanic White participants. Diffusion MRI showed clear deterioration patterns in major WM tracts in the HTN+/T2D+ group and, to a lesser extent, in the HTN+/T2D- group compared to the HTN-/T2D- group. HTN+/T2D+ participants also had the smallest hippocampal volume and larger brain aging deviations. Trends toward lower executive function and global cognitive scores were observed in HTN+/T2D+ relative to HTN-/T2D- individuals. MRI measures and the Mini-Mental State Examination (MMSE) scores from the HTN+/T2D+ BPRHS group resembled those of ADNI White participants with progressive mild cognitive impairment (MCI), while the BPRHS HTN-/T2D- participants resembled participants with stable MCI. The BPRHS was not significantly different from the ADNI + NACC Hispanic cohort on imaging or MMSE measures. DISCUSSION: The effects of T2D and HTN comorbidity led to greater brain structural disruptions than HTN alone. The high prevalence of HTN and T2D in the Puerto Rican population may be a key factor contributing to health disparities in cognitive impairment in this group compared to non-Hispanic White adults in the same age range. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov identifier: NCT01231958.

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.

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 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.

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.

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.

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.

Association of physical activity on memory interference: Boston Puerto Rican Health Study.

Background : The objective of this study was to evaluate the association between habitual physical activity engagement on memory interference. The present analysis used cross-sectional data from the Boston Puerto Rican Health Study (n=1,241; mean age= 57.2; 72.1% female). Methods : Physical activity was evaluated via self-report. Memory interference was evaluated using a word-list paradigm. The memory task included learning a list of 16 words (List A; 5 trials), followed by a distractor list (List B), and then an immediate recall of List A. Proactive interference occurs when preceding stimuli (e.g., Trial 1 and Trial 5 of List A) interferes with performance on a subsequent stimuli (List B). Retroactive interference occurs when subsequent stimuli (List B) interferes with the recall of previously encoded stimuli (Trial 5). Results : For proactive interference, there was no association between physical activity and the difference between performance on List B and Trial 1 of List A (ß=0.00001; P =0.96). Similarly, for retroactive interference, there was no association between physical activity and the difference between the short delay recall and Trial 5 of List A (ß=0.0002; P=0.50). Conclusion : The present study did not observe an association between habitual physical activity on attenuating memory interference.

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.

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.

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.

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.