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Better methylation status may lower dementia risk

The methionine to homocysteine status was linked to dementia development and structural brain changes, indicating that a higher methionine to homocysteine ratio may reduce the risk for dementia in older adults, data published in JAMA Psychiatry showed.

“Whereas several studies have reported an association between increased [serum total homocysteine] values and dementia or structural brain changes, only a few cross-sectional studies have investigated the associations between methylation status (ie, methionine to homocysteine ratio) and cognitive impairment or dementia with mixed results,” Babak Hooshmand, MD, PhD, MPH, from the Karolinska Institute Aging Research Center, and colleagues wrote.

In this population-based longitudinal study, Hooshmand and colleagues studied the correlation of serum markers of methylation status and sulfur amino acids with risk for incident dementia, Alzheimer’s disease and rate of total brain tissue volume loss over a 6 year period. Overall, 2,570 older adults aged 60 years and older from the Swedish Study on Aging and Care in Kungsholmen without dementia at baseline underwent comprehensive assessments and structural brain MRI two or three times in the 6 years.

Participants who took vitamin supplements had higher methionine to homocysteine ratios (median = 1.9; interquartile range [IQR] = 1.5-2.6) than those who did not (median = 1.8; IQR = 1.3-2.3; P < .001), and this rose per each quartile increase of vitamin B12 or folate, according to the results.

Analysis indicated that those with the highest quartile of homocysteine levels at baseline vs. those with the lowest quartile had a higher risk for dementia (HR = 1.6; 95% CI, 1.01-2.55) and for Alzheimer’s disease ( HR =2.33; 95% CI, 1.26-4.3). In addition, increased concentrations of methionine were linked to a lower dementia risk for the highest quartile compared with the lowest (HR = 0.54; 95% CI, 0.36-0.81).

The results showed that higher values of the methionine to homocysteine ratio were significantly tied to a lower dementia risk among older adults (fourth methionine-homocysteine quartile vs. the first for incident dementia [HR = 0.44; 95% CI, 0.27-0.71] and for Alzheimer’s disease [HR = 0.43; 95% CI, 0.23-0.8]). Based on the multiadjusted linear mixed models, the investigators also found that an elevated methionine to homocysteine ratio was linked to a lower rate of total brain tissue volume loss (P = .007).

“A better methylation status, reflected by a higher methionine to homocysteine ratio, may be beneficial for the structure and functioning of the brain,” Hooshmand and colleagues wrote “Because of the observational design of our study, a causal interpretation of our findings cannot be made. Future studies will need to investigate in more detail possible underlying mechanisms and identify the role of the optimal methionine to homocysteine ratio.” – by Savannah Demko

Disclosure: Hooshmand reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.