Methylation status and sulfur amino acids as risk factors for cognitive decline over 15 years: A longitudinal, population‐based study: Prevention (non‐pharmacological): Developing ADRD non‐pharmacological intervention targets. (7th December 2020) - Hooshmand, Babak
Abstract: Background: Impairment of methylation status and raised values of homocysteine and cysteine may be modifiable risk factors for cognitive decline. We aimed to investigate the association of vitamin B12, folate, and sulfur amino‐acids with cognitive decline in a large sample of community dwelling older adults. Method: From the Swedish National Study of Aging and Care in Kungsholmen (SNAC‐K), 2900 dementia‐free individuals at baseline aged 60‐102 years with comprehensive assessments and Mini‐mental state examination (MMSE) were recruited. A total of 2202 participants underwent repeated MMSE assessments up to 5 occasions over 15 years. The association of baseline vitamin B12, holotranscobalamin, folate, homocysteine, methionine, cystathionine, cysteine, glutathione, and methylation status (defined as serum methionine/homocysteine ratio) with rate of cognitive decline was examined using linear mixed models, adjusted for several potential confounders, including common vascular risk factors. Result: After adjusting for age, sex, education, creatinine, albumin, smoking status, systolic blood pressure, and APOE ε4 status, raised baseline serum total homocysteine and cysteine values were associated with faster rate of cognitive decline: for the highest quartile compared with the lowest, β coefficient and standard error (SE) were ‐0.0058 (0.002) for homocysteine (p=0.004) and ‐0.0051 (0.002) for cysteine (p=0.014) In contrast, a better methylation status was associated with less MMSE decline over 15 years: β (SE) was 0.0058 (0.002) for the highest quartile compared with the lowest (p=0.004). Furthermore, elevated methionine values tended to slow rate of cognitive decline (p=0.079). No relationships were found for other sulfur amino acids, vitamin B12 or folate. Conclusion: Markers of methylation status and raised cysteine values were related to more rapid cognitive decline over 15 years, suggesting that optimizing homocysteine, cysteine, and methionine values may be important in reducing the risk of cognitive decline in older adults.