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Vitamin B₁₂ status and rate of brain volume loss in community-dwelling elderly

From OPTIMA (A.V., H.R., C.J., K.M.B., C.d.J., M.M.B., A.D.S.), Department of Physiology, Anatomy and Genetics, University of Oxford, UK; Institute of Basic Medical Sciences (A.V., H.R.), Department of Nutrition, University of Oslo, Norway; Oxford University Centre for Functional MRI of the Brain (S.M.S.), UK; and Department of Geriatric Medicine (M.M.B.), The Canberra Hospital and Australian National University Medical School, Australia.

Address correspondence and reprint requests to Anna Vogiatzoglou, Department of Physiology, Anatomy and Genetics, University of Oxford, Le Gros Clark Building, South Parks Rd., Oxford OX1 3QX, UK anna.vogiatzoglou{at}dpag.ox.ac.uk

Objectives: To investigate the relationship between markers of vitamin B₁₂ status and brain volume loss per year over a 5-year period in an elderly population.

Methods: A prospective study of 107 community-dwelling volunteers aged 61 to 87 years without cognitive impairment at enrollment. Volunteers were assessed yearly by clinical examination, MRI scans, and cognitive tests. Blood was collected at baseline for measurement of plasma vitamin B₁₂, transcobalamin (TC), holotranscobalamin (holoTC), methylmalonic acid (MMA), total homocysteine (tHcy), and serum folate.

Results: The decrease in brain volume was greater among those with lower vitamin B₁₂ and holoTC levels and higher plasma tHcy and MMA levels at baseline. Linear regression analysis showed that associations with vitamin B₁₂ and holoTC remained significant after adjustment for age, sex, creatinine, education, initial brain volume, cognitive test scores, systolic blood pressure, ApoE 4 status, tHcy, and folate. Using the upper (for the vitamins) or lower tertile (for the metabolites) as reference in logistic regression analysis and adjusting for the above covariates, vitamin B₁₂ in the bottom tertile (<308 pmol/L) was associated with increased rate of brain volume loss (odds ratio 6.17, 95% CI 1.25–30.47). The association was similar for low levels of holoTC (<54 pmol/L) (odds ratio 5.99, 95% CI 1.21–29.81) and for low TC saturation. High levels of MMA or tHcy or low levels of folate were not associated with brain volume loss.

Conclusion: Low vitamin B₁₂ status should be further investigated as a modifiable cause of brain atrophy and of likely subsequent cognitive impairment in the elderly.

Abbreviations: AD = Alzheimer disease; CAMCOG = Cambridge Mental Disorders of the Elderly Examination; CV = coefficient of variation; holoTC = holotranscobalamin; MMA = methylmalonic acid; NS = not significant; OPTIMA = Oxford Project to Investigate Memory and Aging; OR = odds ratio; PBVL = percentage of brain volume loss; SIENA = structural image evaluation using normalization of atrophy; TC = transcobalamin; tHcy = total homocysteine.

Supplemental data at www.neurology.org

Supported by Alzheimer’s Research Trust (UK), the Medical Research Council, the Charles Wolfson Charitable Trust, the Norwegian Foundation for Health and Rehabilitation through the Norwegian Health Association, Axis-Shield plc, and the Johan Throne Holst Foundation for Nutrition Research.

Disclosure: The authors report no disclosures.

Received December 12, 2007. Accepted in final form June 4, 2008.