Association of vitamin k with cognitive decline and neuropathology in community-dwelling older persons

Authors: BOOTH, SARAH - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; SHEA, KYLA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; BARGER, KATHRYN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; LEURGANS, SUE - Rush University; JAMES, BRYAN - Rush University; HOLLAND, THOMAS - Rush University; AGARWAL, PUJA - Rush University; FU, XUEYAN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; WANG, JIFAN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; MATUSZEK, GREGORY - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; SCHNEIDER, JULIE - Rush University

Submitted to: Alzheimer's & Dementia
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/21/2021
Publication Date: 1/28/2022
Citation: Booth, S., Shea, K., Barger, K., Leurgans, S.E., James, B.D., Holland, T.M., Agarwal, P., Fu, X., Wang, J., Matuszek, G., Schneider, J. 2022. Association of vitamin k with cognitive decline and neuropathology in community-dwelling older persons. Alzheimer's & Dementia. https://doi.org/10.1002/trc2.12255.
DOI: https://doi.org/10.1002/trc2.12255

Interpretive Summary: Accumulating evidence implicates dietary and nutritional factors in reducing cognitive decline and dementia risk, including vitamin K. The purpose of this study was to analyze postmortem brain concentrations of vitamin K and related metabolites in 325 decedents of the well-characterized, community-based Rush Memory and Aging Project, and determine the association of these different forms with ante-mortem measures of cognitive function. To further obtain mechanistic insight, we also evaluated the association of brain vitamin K concentrations with Alzheimer's disease and other dementia-related neuropathologies. The vitamin K metabolite, menaquinone-4 (MK4), was the main form of vitamin K in all brain regions evaluated. The odds of having dementia or mild cognitive impairment at the last visit prior to death were up to 20% lower per doubling of MK4 in the brain. Further investigation of neuropathologically-defined outcomes revealed that higher brain MK4 concentrations were associated with lower global AD pathology, including fewer neurofibrillary tangles.

Technical Abstract: Higher vitamin K intakes have been associated with better cognitive function, suggestive of a vitamin K mechanistic effect or simply reflective of a healthy diet. To test the hypothesis that brain vitamin K is linked to cognitive decline and dementia, vitamin K concentrations were measured in four brain regions, and their associations with cognitive and neuropathological outcomes were estimated in 325 decedents of the Rush Memory and Aging Project. Menaquinone-4 (MK4) was the main vitamin K form in the brain regions evaluated. Higher brain MK4 concentrations were associated with a 17% to 20% lower odds of dementia or mild cognitive impairment (MCI) (P-value < .014), with a 14% to 16% lower odds of Braak stage equal IV (P-value < 0.045), with lower Alzheimer's disease global pathology scores and fewer neuronal neurofibrillary tangles (P-value < 0.012). These findings provide new and compelling evidence implicating vitamin K in neuropathology underlying cognitive decline and dementia.