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

ABSTRACT 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 (β: 0.063; 95% CI: −0.0008, 0.127; P = 0.053 and β: 0.062; 95% CI: 0.009, 0.12; P = 0.023, respectively, for logged values, and β: 0.002; 95% CI: 0.00005, 0.004; P-trend = 0.044 and β: 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 (β: −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.

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Interactions between plasma concentrations of folate and markers of vitamin B12status with cognitive performance in elderly people not exposed to folic acid fortification: the Hordaland Health Study

British Journal Of Nutrition ◽

10.1017/s000711451300336x ◽

2013 ◽

Vol 111 (6) ◽

pp. 1085-1095 ◽

Cited By ~ 23

Author(s):

Esmée L. Doets ◽

Per M. Ueland ◽

Grethe S. Tell ◽

Stein Emil Vollset ◽

Ottar K. Nygård ◽

...

Keyword(s):

Cognitive Impairment ◽

Folic Acid ◽

Cognitive Performance ◽

Sex Education ◽

Plasma Concentrations ◽

Health Study ◽

Vitamin B ◽

Plasma Vitamin ◽

Folic Acid Fortification ◽

Plasma Folate

A combination of high folate with low vitamin B12plasma status has been associated with cognitive impairment in a population exposed to mandatory folic acid fortification. The objective of the present study was to examine the interactions between plasma concentrations of folate and vitamin B12markers in relation to cognitive performance in Norwegian elderly who were unexposed to mandatory or voluntary folic acid fortification. Cognitive performance was assessed by six cognitive tests in 2203 individuals aged 72–74 years. A combined score was calculated using principal component analysis. The associations of folate concentrations, vitamin B12markers (total vitamin B12, holotranscobalamin (holoTC) and methylmalonic acid (MMA)) and their interactions in relation to cognitive performance were evaluated by quantile regression and least-squares regression, adjusted for sex, education, apo-ɛ4 genotype, history of CVD/hypertension and creatinine. Cross-sectional analyses revealed an interaction (P= 0·009) between plasma concentrations of folate and vitamin B12in relation to cognitive performance. Plasma vitamin B12concentrations in the lowest quartile ( < 274 pmol/l) combined with plasma folate concentrations in the highest quartile (>18·5 nmol/l) were associated with a reduced risk of cognitive impairment compared with plasma concentrations in the middle quartiles of both vitamins (OR 0·22, 95 % CI 0·05, 0·92). The interaction between folate and holoTC or MMA in relation to cognitive performance was not significant. In conclusion, this large study population unexposed to mandatory folic acid fortification showed that plasma folate, but not plasma vitamin B12, was associated with cognitive performance. Among the elderly participants with vitamin B12concentrations in the lower range, the association between plasma folate and cognitive performance was strongest.

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

Journal of Nutrition ◽

10.1093/jn/nxy268 ◽

2019 ◽

Vol 149 (4) ◽

pp. 635-641 ◽

Cited By ~ 7

Author(s):

Natalia Palacios ◽

Tammy Scott ◽

Neha Sahasrabudhe ◽

Xiang Gao ◽

Katherine L Tucker

Keyword(s):

Cognitive Function ◽

Cognitive Decline ◽

Puerto Rican ◽

Cognitive Aging ◽

Health Study ◽

Vitamin B ◽

Study Cohort ◽

Plasma Vitamin ◽

Global Cognitive Function ◽

Bottom To Top

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

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Effect of oral vitamin B-12 with or without folic acid on cognitive function in older people with mild vitamin B-12 deficiency: a randomized, placebo-controlled trial

American Journal of Clinical Nutrition ◽

10.1093/ajcn/84.2.361 ◽

2006 ◽

Vol 84 (2) ◽

pp. 361-370 ◽

Cited By ~ 123

Author(s):

Simone J Eussen ◽

Lisette C de Groot ◽

Liesbeth W Joosten ◽

Rubia J Bloo ◽

Robert Clarke ◽

...

Keyword(s):

Folic Acid ◽

Cognitive Function ◽

Older People ◽

Controlled Trial ◽

Vitamin B ◽

Oral Vitamin ◽

Vitamin B 12

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Effect of oral vitamin B-12 with or without folic acid on cognitive function in older people with mild vitamin B-12 deficiency: a randomized, placebo-controlled trial1–3

American Journal of Clinical Nutrition ◽

10.1093/ajcn/84.1.361 ◽

2006 ◽

Vol 84 (2) ◽

pp. 361-370 ◽

Cited By ~ 7

Author(s):

Simone J Eussen ◽

Lisette C de Groot ◽

Liesbeth W Joosten ◽

Rubia J Bloo ◽

Robert Clarke ◽

...

Keyword(s):

Folic Acid ◽

Cognitive Function ◽

Older People ◽

Vitamin B ◽

Oral Vitamin ◽

Vitamin B 12

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High folic acid or folate combined with low vitamin B-12 status: potential but inconsistent association with cognitive function in a nationally representative cross-sectional sample of US older adults participating in the NHANES

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqaa239 ◽

2020 ◽

Vol 112 (6) ◽

pp. 1547-1557 ◽

Cited By ~ 2

Author(s):

Regan L Bailey ◽

Shinyoung Jun ◽

Lisa Murphy ◽

Ralph Green ◽

Jaime J Gahche ◽

...

Keyword(s):

Older Adults ◽

Folic Acid ◽

Cognitive Function ◽

Serum Folate ◽

Vitamin B ◽

Digit Symbol Substitution Test ◽

Cross Sectional ◽

Folate Status ◽

Normal Vitamin ◽

Vitamin B 12

ABSTRACT Background Potential safety concerns relative to impaired cognitive function may exist when high folic acid exposures are combined with low vitamin B-12 status. Objectives We aimed to examine the relation of the coexistence of high folate and low vitamin B-12 status with cognitive function, utilizing various definitions of “high” folate status. Methods Cross-sectional data from older adults (≥60 y; n = 2420) from the 2011–2014 NHANES were analyzed. High folate status was defined as unmetabolized serum folic acid (UMFA) > 1 nmol/L or serum total folate > 74.1 nmol/L, and low vitamin B-12 status as methylmalonic acid > 271 nmol/L or serum vitamin B-12 < 150 pmol/L. Logistic regression models estimated ORs of scoring low on 1 of 4 cognitive tests: the Digit Symbol Substitution Test (DSST), the Consortium to Establish a Registry for Alzheimer's Disease Delayed Recall (CERAD-DR) and Word Learning tests, and the Animal Fluency test (AF). Results A significant interaction was observed relative to scoring low on the DSST (<34; UMFA; P-interaction = 0.0071) and AF (serum folate; P-interaction = 0.0078) for low vitamin B-12 and high folate status. Among those with low vitamin B-12, high UMFA or high serum total folate was associated with higher risk of scoring low on the DSST (OR: 2.16; 95% CI: 1.05, 4.47) and the AF (OR: 1.93; 95% CI: 1.08, 3.45). Among those with “normal” vitamin B-12, higher UMFA or serum total folate was protective on the CERAD-DR. In noninteraction models, when high folate and normal vitamin B-12 status was the reference group, low vitamin B-12 combined with high UMFA was associated with greater risk based on the DSST (<34, OR: 2.87; 95% CI: 1.85, 4.45; <40, OR: 2.22; 95% CI: 1.31, 3.75) and AF (OR: 1.97; 95% CI: 1.30, 2.97); but low vitamin B-12 and lower UMFA (OR: 1.69; 95% CI: 1.16, 2.47) was also significantly associated for DSST < 40 risk. Conclusions Low vitamin B-12 was associated with cognitive impairment both independently and in an interactive manner with high folate for certain cognitive performance tests among older adults.

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Defining the plasma folate concentration associated with the red blood cell folate concentration threshold for optimal neural tube defects prevention: a population-based, randomized trial of folic acid supplementation

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqz027 ◽

2019 ◽

Vol 109 (5) ◽

pp. 1452-1461 ◽

Cited By ~ 10

Author(s):

Meng-Yu Chen ◽

Charles E Rose ◽

Yan Ping Qi ◽

Jennifer L Williams ◽

Lorraine F Yeung ◽

...

Keyword(s):

Folic Acid ◽

Intervention Group ◽

Population Based ◽

Folic Acid Supplementation ◽

Reproductive Age ◽

Vitamin B ◽

Acid Supplementation ◽

Folate Concentration ◽

Plasma Folate ◽

Vitamin B 12

ABSTRACT Background For women of reproductive age, a population-level red blood cell (RBC) folate concentration below the threshold 906 nmol/L or 400 ng/mL indicates folate insufficiency and suboptimal neural tube defect (NTD) prevention. A corresponding population plasma/serum folate concentration threshold for optimal NTD prevention has not been established. Objective The aim of this study was to examine the association between plasma and RBC folate concentrations and estimated a population plasma folate insufficiency threshold (pf-IT) corresponding to the RBC folate insufficiency threshold (RBCf-IT) of 906 nmol/L. Methods We analyzed data on women of reproductive age (n = 1673) who participated in a population-based, randomized folic acid supplementation trial in northern China. Of these women, 565 women with anemia and/or vitamin B-12 deficiency were ineligible for folic acid intervention (nonintervention group); the other 1108 received folic acid supplementation for 6 mo (intervention group). We developed a Bayesian linear model to estimate the pf-IT corresponding to RBCf-IT by time from supplementation initiation, folic acid dosage, methyltetrahydrofolate reductase (MTHFR) genotype, body mass index (BMI), vitamin B-12 status, or anemia status. Results Using plasma and RBC folate concentrations of the intervention group, the estimated median pf-IT was 25.5 nmol/L (95% credible interval: 24.6, 26.4). The median pf-ITs were similar between the baseline and postsupplementation samples (25.7 compared with 25.2 nmol/L) but differed moderately (±3–4 nmol/L) by MTHFR genotype and BMI. Using the full population-based baseline sample (intervention and nonintervention), the median pf-IT was higher for women with vitamin B-12 deficiency (34.6 nmol/L) and marginal deficiency (29.8 nmol/L) compared with the sufficient group (25.6 nmol/L). Conclusions The relation between RBC and plasma folate concentrations was modified by BMI and genotype and substantially by low plasma vitamin B-12. This suggests that the threshold of 25.5 nmol/L for optimal NTD prevention may be appropriate in populations with similar characteristics, but it should not be used in vitamin B-12 insufficient populations. This trial was registered at clinicaltrials.gov as NCT00207558.

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Plasma concentrations of vitamin B12 and folate and global cognitive function in an older population: cross-sectional findings from The Irish Longitudinal Study on Ageing (TILDA)

British Journal Of Nutrition ◽

10.1017/s0007114520001427 ◽

2020 ◽

Vol 124 (6) ◽

pp. 602-610 ◽

Cited By ~ 3

Author(s):

Deirdre M. A. O’Connor ◽

Eamon J. Laird ◽

Daniel Carey ◽

Aisling M. O’Halloran ◽

Robert Clarke ◽

...

Keyword(s):

Older Adults ◽

Folic Acid ◽

Longitudinal Study ◽

Cognitive Function ◽

Cognitive Performance ◽

Vitamin B ◽

Plasma Vitamin ◽

Cross Sectional ◽

Folate Status ◽

Global Cognitive Function

AbstractThe uncertainty surrounding high intakes of folic acid and associations with cognitive decline in older adults with low vitamin B12 status has been an obstacle to mandatory folic acid fortification for many years. We estimated the prevalence of combinations of low/normal/high vitamin B12 and folate status and compared associations with global cognitive function using two approaches, of individuals in a population-based study of those aged ≥50 years in the Republic of Ireland. Cross-sectional data from 3781 men and women from Wave 1 of The Irish Longitudinal Study on Ageing were analysed. Global cognitive function was assessed by the Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Prevalence estimates for combinations of vitamin B12 (plasma vitamin B12 < or ≥258 pmol/l) and folate (plasma folate ≤ or >45·3 nmol/l) concentrations were generated. Negative binomial regression models were used to investigate the associations of vitamin B12 and folate status with global cognitive function. Of the participants, 1·5 % (n 51) had low vitamin B12 (<258 pmol/l) and high folate (>45·3 nmol/l) status. Global cognitive performance was not significantly reduced in these individuals when compared with those with normal status for both B-vitamins (n 2433). Those with normal vitamin B12/high folate status (7·6 %) had better cognitive performance (MMSE: incidence rate ratio (IRR) 0·82, 95 % CI 0·68, 0·99; P = 0·043, MoCA: IRR 0·89, 95 % CI 0·80, 0·99; P = 0·025). We demonstrated that high folate status was not associated with lower cognitive scores in older adults with low vitamin B12 status. These findings provide important safety information that could guide fortification policy recommendations in Europe.

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