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Original Investigation
July 24, 2019

Association of Methionine to Homocysteine Status With Brain Magnetic Resonance Imaging Measures and Risk of Dementia

Author Affiliations
  • 1Aging Research Center, Karolinska Institute, Stockholm, Sweden
  • 2Department of Neurology, Ulm University Hospital, Ulm, Germany
  • 3Department of Pharmacology, University of Oxford, Oxford, United Kingdom
  • 4Institute of Nutrition, University of Oslo, Oslo, Norway
  • 5Division of Clinical Geriatrics, Center for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden
  • 6Theme Aging, Karolinska University Hospital, Stockholm, Sweden
  • 7Stockholms Sjukhem, Research & Development Unit, Stockholm, Sweden
  • 8Neuroepidemiology and Ageing Research Unit, School of Public Health, Imperial College London, London, United Kingdom
  • 9Department of Neurology, University of Eastern Finland, Kuopio, Finland
JAMA Psychiatry. 2019;76(11):1198-1205. doi:10.1001/jamapsychiatry.2019.1694
Key Points

Question  Is methylation status (ie, methionine to homocysteine ratio) associated with incident dementia and structural brain changes in older adults?

Findings  In this cohort study of longitudinal data from 2570 elderly individuals who were dementia free at baseline, a higher methionine to homocysteine ratio was observed in participants with better B12 or folate status and was associated with decreased risk of incident dementia and Alzheimer disease. A higher methionine to homocysteine ratio was associated with a decreased rate of total brain tissue volume loss during 6 years.

Meanings  Markers of methylation status were associated with dementia development and structural brain changes during 6 years, suggesting that a higher methionine to homocysteine ratio may be important in reducing the rate of brain atrophy and decreasing the risk of dementia in older adults.

Abstract

Importance  Impairment of methylation status (ie, methionine to homocysteine ratio) may be a modifiable risk factor for structural brain changes and incident dementia.

Objective  To investigate the association of serum markers of methylation status and sulfur amino acids with risk of incident dementia, Alzheimer disease (AD), and the rate of total brain tissue volume loss during 6 years.

Design, Setting, and Participants  This population-based longitudinal study was performed from March 21, 2001, to October 10, 2010, in a sample of 2570 individuals aged 60 to 102 years from the Swedish Study on Aging and Care in Kungsholmen who were dementia free at baseline and underwent comprehensive examinations and structural brain magnetic resonance imaging (MRI) on 2 to 3 occasions during 6 years. Data analysis was performed from March 1, 2018, to October 1, 2018.

Main Outcomes and Measures  Incident dementia, AD, and the rate of total brain volume loss.

Results  This study included 2570 individuals (mean [SD] age, 73.1 [10.4] years; 1331 [56.5%] female). The methionine to homocysteine ratio was higher in individuals who consumed vitamin supplements (median, 1.9; interquartile range [IQR], 1.5–2.6) compared with those who did not (median, 1.8; IQR, 1.3–2.3; P < .001) and increased per each quartile increase of vitamin B12 or folate. In the multiadjusted model, an elevated baseline serum total homocysteine level was associated with an increased risk of dementia and AD during 6 years: for the highest homocysteine quartile compared with the lowest, the hazard ratios (HRs) were 1.60 (95% CI, 1.01-2.55) for dementia and 2.33 (95% CI, 1.26-4.30) for AD. In contrast, elevated concentrations of methionine were associated with a decreased risk of dementia (HR, 0.54; 95% CI, 0.36-0.81) for the highest quartile compared with the lowest. Higher values of the methionine to homocysteine ratio were significantly associated with lower risk of dementia and AD: for the fourth methionine-homocysteine quartile compared with the first quartile, the HR was 0.44 (95% CI, 0.27-0.71) for incident dementia and 0.43 (95% CI, 0.23-0.80) for AD. In the multiadjusted linear mixed models, a higher methionine to homocysteine ratio was associated with a decreased rate of total brain tissue volume loss during the study period (β [SE] per 1-SD increase, 0.038 [0.014]; P = .007).

Conclusions and Relevance  The methionine to homocysteine status was associated with dementia development and structural brain changes during the 6-year study period, suggesting that a higher methionine to homocysteine ratio may be important in reducing the rate of brain atrophy and decreasing the risk of dementia in older adults.

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