Among Vitamin B12 Deficient Older People, High Folate Levels are Associated with Worse Cognitive Function: Combined Data from Three Cohorts

Article type: Research Article

Authors: Moore, Eileen M.^{a; b; *} | Ames, David^{a; c} | Mander, Alastair G.^b | Carne, Ross P.^{b; d} | Brodaty, Henry^{e; f} | Woodward, Michael C.^g | Boundy, Karyn^h | Ellis, Kathryn A.^{a; c; i} | Bush, Ashley I.^{i; j} | Faux, Noel G.ⁱ | Martins, Ralph N.^{k; l} | Masters, Colin L.^{i; m} | Rowe, Christopher C.ⁿ | Szoeke, Cassandra^{c; o} | Watters, David A.^{b; d}

Affiliations: [a] Department of Psychiatry, The University of Melbourne, Parkville, VIC, Australia | [b] Barwon Health, Geelong, VIC, Australia | [c] National Ageing Research Institute, Parkville, VIC, Australia | [d] Deakin University, School of Medicine, Waurn Ponds, VIC, Australia | [e] The University of New South Wales, Centre for Healthy Brain Ageing and Dementia Collaborative Research Centre, Sydney, NSW, Australia | [f] Aged Care Psychiatry, Prince of Wales Hospital, Randwick, NSW, Australia | [g] Austin Health, Heidelberg Repatriation Hospital, Heidelberg, VIC, Australia | [h] The Queen Elizabeth Hospital, Woodville South, SA, Australia | [i] The University of Melbourne, Florey Institute of Neuroscience & Mental Health, Parkville, VIC, Australia | [j] Department of Pathology, The University of Melbourne, Parkville, VIC, Australia | [k] Edith Cowan University, Centre of Excellence for Alzheimer's Disease Research & Care, School of Exercise, Biomedical and Health Sciences, Joondalup, WA, Australia | [l] Sir James McCusker Alzheimer's Disease Research Unit (Hollywood Private Hospital), Neurosciences Unit, Health Department of Western Australia, Perth, WA, Australia | [m] The University of Melbourne, Centre for Neuroscience, Parkville, VIC, Australia | [n] Austin PET centre, Austin Hospital, Heidelberg, VIC, Australia | [o] Preventative Health Flagship, Commonwealth Science Industry Research Organization, Parkville, VIC, Australia

Correspondence: [*] Correspondence to: Dr. Eileen Moore, CNR Bellarine and Ryrie Street, PO Box 281, Level 4, Douglas Hocking Research Institute, The Geelong Hospital, Geelong, VIC 3220, Australia. Tel.: +61 420693726; Fax: +61 342152023; E-mails: [email protected]; [email protected].

Abstract: Background:Folate fortification of food aims to reduce the number of babies born with neural tube defects, but has been associated with cognitive impairment when vitamin B12 levels are deficient. Given the prevalence of low vitamin B12 levels among the elderly, and the global deployment of food fortification programs, investigation of the associations between cognitive impairment, vitamin B12, and folate are needed. Objective:To investigate the associations of serum vitamin B12, red cell folate, and cognitive impairment. Methods:Data were collected on 1,354 subjects in two studies investigating cognitive impairment, and from patients attending for assessment or management of memory problems in the Barwon region of south eastern Australia between 2001 and 2011. Eligible subjects who had blood measurements of vitamin B12 and red cell folate taken within six months of cognitive testing were included. Subjects with stroke or neurodegenerative diseases other than Alzheimer’s disease were excluded. A Mini-Mental State Examination score of <24 was used to define impaired cognitive function. Results:Participants with low serum vitamin B12 (<250 pmol/L) and high red cell folate (>1,594 nmol/L) levels were more likely to have impaired cognitive performance (adjusted odds ratio (AOR) 3.45, 95% confidence interval (CI): 1.60–7.43, p = 0.002) when compared to participants with biochemical measurements that were within the normal ranges. Participants with high folate levels, but normal serum vitamin B12, were also more likely to have impaired cognitive performance (AOR 1.74, 95% CI: 1.03–2.95, p = 0.04). Conclusions:High folate or folic acid supplements may be detrimental to cognition in older people with low vitamin B12 levels. This topic is of global significance due to the wide distribution of food fortification programs, so prospective studies should be a high priority.

Keywords: Aged, Alzheimer's disease, cognition, folic acid, vitamin B12

DOI: 10.3233/JAD-131265

Journal: Journal of Alzheimer's Disease, vol. 39, no. 3, pp. 661-668, 2014