Homocysteine, Vitamin B12, and Folic Acid Levels in Alzheimer's Disease, Mild Cognitive Impairment, and Healthy Elderly: Baseline Characteristics in Subjects of the Australian Imaging Biomarker Lifestyle Study

Article type: Research Article

Authors: Faux, Noel G.^a | Ellis, Kathryn A.^{a; b} | Porter, Lorine^c | Fowler, Chris J.^a | Laws, Simon M.^{d; e} | Martins, Ralph N.^{d; e} | Pertile, Kelly K.^a | Rembach, Alan^a | Rowe, Chris C.^f | Rumble, Rebecca L.^a | Szoeke, Cassandra^g | Taddei, Kevin^{d; f} | Taddei, Tania^{d; e} | Trounson, Brett O.^a | Villemagne, Victor L.^{a; f} | Ward, Vanessa^{d; e} | Ames, David^{b; h} | Masters, Colin L.^a | the AIBL research groupⁱ | Bush, Ashley I.^{a; *}

Affiliations: [a] The Mental Health Research Institute, The University of Melbourne, Parkville, VIC, Australia | [b] Department of Psychiatry, The University of Melbourne, Academic Unit for Psychiatry of Old Age, Kew, VIC, Australia | [c] Southern Health, Clayton, VIC, Australia | [d] Centre of Excellence for Alzheimer's Disease Research & Care, School of Exercise Biomedical and Health Sciences, Edith Cowan University, Joondalup. WA, Australia | [e] Sir James McCusker Alzheimer's Disease Research Unit (Hollywood Private Hospital), Perth, WA, Australia | [f] Department of Nuclear Medicine and Centre for PET, The University of Melbourne, Austin Health, Heidelberg, VIC, Australia | [g] CSIRO Molecular and Health Technologies, Parkville, VIC, Australia | [h] National Ageing Research Institute, Royal Melbourne Hospital, Parkville, VIC, Australia | [i] http://www.aibl.csiro.au/partners.html

Correspondence: [*] Correspondence to: Professor Ashley Bush, The Mental Health Research Institute, 155 Oak Street, Parkville, VIC 3052, Australia. Tel.: +6 13 9389 2914; Fax: +61 3 9387 5061; E-mail: [email protected].

Abstract: There is some debate regarding the differing levels of plasma homocysteine, vitamin B12 and serum folate between healthy controls (HC), mild cognitive impairment (MCI), and Alzheimer's disease (AD). As part of the Australian Imaging Biomarker Lifestyle (AIBL) study of aging cohort, consisting of 1,112 participants (768 HC, 133 MCI patients, and 211 AD patients), plasma homocysteine, vitamin B12, and serum and red cell folate were measured at baseline to investigate their levels, their inter-associations, and their relationships with cognition. The results of this cross-sectional study showed that homocysteine levels were increased in female AD patients compared to female HC subjects (+16%, p-value < 0.001), but not in males. Red cell folate, but not serum folate, was decreased in AD patients compared to HC (−10%, p-value = 0.004). Composite z-scores of short- and long-term episodic memory, total episodic memory, and global cognition all showed significant negative correlations with homocysteine, in all clinical categories. Increasing red cell folate had a U-shaped association with homocysteine, so that high red cell folate levels were associated with worse long-term episodic memory, total episodic memory, and global cognition. These findings underscore the association of plasma homocysteine with cognitive deterioration, although not unique to AD, and identified an unexpected abnormality of red cell folate.

Keywords: Alzheimer's disease, biomarker, folate, homocysteine, vitamin B12

DOI: 10.3233/JAD-2011-110752

Journal: Journal of Alzheimer's Disease, vol. 27, no. 4, pp. 909-922, 2011