Relationship of Cognitive Function with B Vitamin Status, Homocysteine, and Tissue Factor Pathway Inhibitor in Cognitively Impaired Elderly: A Cross-Sectional Survey

Article type: Research Article

Authors: Kim, Ggotpin^{a; 1} | Kim, Hyesook^{a; 1} | Kim, Ki Nam^b | Son, Jung In^c | Kim, Seong Yoon^{c; **} | Tamura, Tsunenobu^{a; 2} | Chang, Namsoo^{a; *}

Affiliations: [a] Department of Nutritional Science and Food Management, Ewha Womans University, Seoul, Republic of Korea | [b] Department of Food and Nutrition, Daejeon University, Daejeon, Republic of Korea | [c] Department of Psychiatry, Asan Medical Center, University of Ulsan, Medical College, Seoul, Republic of Korea

Correspondence: [*] Correspondence to: Professor Namsoo Chang, Department of Nutritional Science and Food Management, Ewha Womans University, Seoul, 120-750, Republic of Korea. Tel.: +82 2 3277 3468; Fax: +82 2 3277 2862; E-mail: [email protected].

Correspondence: [**] Co-correspondence to: Seong Yoon Kim, MD., Ph.D., Chairperson, Department of Psychiatry, Asan Medical Center, University of Ulsan, Medical College, Seoul, 138-736, Republic of Korea. Tel.: +82 2 3010 3417; Fax: +82 2 485 8381; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Note: [2] Current address: Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, USA.

Abstract: Elevated homocysteine (Hcy) levels have been associated with an increased risk of cognitive impairment and Alzheimer's disease (AD). Tissue factor pathway inhibitor (TFPI) has recently emerged as a candidate marker of endothelial damage in AD. We investigated the relationship between plasma levels of folate, vitamin B12, Hcy, and TFPI, as well as cognitive function in 321 [100 each with mild cognitive impairment (MCI) and AD, 121 normal subjects] Korean elderly (mean age 74.8 ± 7.2 years). Plasma folate and vitamin B12 concentrations were analyzed by radioimmunoassay, Hcy by the HPLC-fluorescence method, and TFPI by enzyme-linked immunosorbent assay. Plasma Hcy levels were higher in patients with AD and MCI than those in normal subjects (p < 0.001). The AD group had higher proportions of hyperhomocysteinemic (>15 μM) and folate deficient (<3.0 ng/mL) (p = 0.026) subjects. A multiple regression analysis after adjusting for covariates revealed positive relationships between plasma folate and the MMSE-KC and Boston Naming Test, and between plasma vitamin B12 and the Word List Memory Test in the AD group, but negative associations between plasma Hcy and the Word List Memory and Constructional Recall Tests and between plasma TFPI and the Boston Naming, Word List Recall, and Constructional Recall Tests. In contrast, only plasma folate level was positively associated with the MMSE-KC and Boston Naming Test in the MCI group. No associations were observed in the normal group. These results suggest that plasma folate, vitamin B12, Hcy, and TFPI are associated with cognitive function in cognitively impaired (AD and MCI) elderly and that the association was stronger in patients with AD.

Keywords: Alzheimer's disease, cognitive function, folate, homocysteine, mild cognitive impairment, tissue factor pathway inhibitor, vitamin B12

DOI: 10.3233/JAD-2012-121345

Journal: Journal of Alzheimer's Disease, vol. 33, no. 3, pp. 853-862, 2013