Plasma free choline, betaine and cognitive performance: the Hordaland Health Study.
Choline and betaine are nutrients involved in one-carbon metabolism. Choline is essential for neurodevelopment and brain function. We studied the associations between cognitive function and plasma concentrations of free choline and betaine. In a cross-sectional study, 2195 subjects (55 % women), aged 70-74 years, underwent extensive cognitive testing including the Kendrick Object Learning Test (KOLT), Trail Making Test (part A, TMT-A), modified versions of the Digit Symbol Test (m-DST), Block Design (m-BD), Mini-Mental State Examination (m-MMSE) and Controlled Oral Word Association Test (COWAT). Compared with low concentrations, high choline (>8·4 μmol/l) was associated with better test scores in the TMT-A (56·0 v. 61·5, P=0·004), m-DST (10·5 v. 9·8, P=0·005) and m-MMSE (11·5 v. 11·4, P=0·01). A generalised additive regression model showed a positive dose-response relationship between the m-MMSE and choline (P=0·012 from a corresponding linear regression model). Betaine was associated with the KOLT, TMT-A and COWAT, but after adjustments for potential confounders, the associations lost significance. Risk ratios (RR) for poor test performance roughly tripled when low choline was combined with either low plasma vitamin B₁₂ (≤257 pmol/l) concentrations (RR(KOLT)=2·6, 95 % CI 1·1, 6·1; RR(m-MMSE)=2·7, 95 % CI 1·1, 6·6; RR(COWAT)=3·1, 95 % CI 1·4, 7·2) or high methylmalonic acid (MMA) (≥3·95 μmol/l) concentrations (RR(m-BD)=2·8, 95 % CI 1·3, 6·1). Low betaine (≤31·1 μmol/l) combined with high MMA was associated with elevated RR on KOLT (RR(KOLT)=2·5, 95 % CI 1·0, 6·2). Low plasma free choline concentrations are associated with poor cognitive performance. There were significant interactions between low choline or betaine and low vitamin B₁₂ or high MMA on cognitive performance.
Department of Nutrition, Faculty of Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
Eha
E
Nurk
Department of Nutrition, Faculty of Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
Helga
H
Refsum
Department of Child and Adolescent Psychiatry, Haukeland University Hospital, Bergen, Norway.
Ingvar
I
Bjelland
Department of Nutrition, Faculty of Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
Christian A
CA
Drevon
Department of Public Health and Primary Health Care, University of Bergen, Bergen, Norway.
Grethe S
GS
Tell
Section for Pharmacology, Institute of Medicine, Haukeland University Hospital, University of Bergen, Bergen, Norway.
Per M
PM
Ueland
Department of Public Health and Primary Health Care, University of Bergen, Bergen, Norway.
Stein E
SE
Vollset
Department of Geriatric Medicine, Norwegian Centre for Dementia Research, Oslo University Hospital, Oslo, Norway.
Knut
K
Engedal
Department of Public Health and Primary Health Care, University of Bergen, Bergen, Norway.
Harald A
HA
Nygaard
Department of Pharmacology, Oxford Project to Investigate Memory and Ageing (OPTIMA), University of Oxford, Oxford, UK.
David A
DA
Smith
D000368:Aged; D000375:Aging; D001622:Betaine / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002794:Choline / Q000097:blood*; D002796:Choline Deficiency / Q000209:etiology / Q000503:physiopathology*; D060825:Cognitive Dysfunction / Q000097:blood / Q000453:epidemiology / Q000209:etiology*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004032:Diet / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D015577:Geriatric Assessment; D006801:Humans; D008297:Male; D008764:Methylmalonic Acid / Q000097:blood; D009664:Norway / Q000453:epidemiology; D012307:Risk Factors; D013223:Statistics as Topic; D014805:Vitamin B 12 / Q000097:blood; D014806:Vitamin B 12 Deficiency / Q000209:etiology / Q000503:physiopathology
D015415:Biomarkers; D001622:Betaine; D008764:Methylmalonic Acid; D002794:Choline; D014805:Vitamin B 12