s-adenosylhomocysteine and Dementia

We examined the association of serum s-adenosylmethionine (SAM), s-adenosylhomocysteine (SAH) (methionine metabolites), and their ratio on the risk of dementia and death in a community-dwelling population of older Japanese individuals. 1371 residents of Hisayama, Japan, aged 65 years or older and without dementia, were followed for a median of 10.2 years (2007-2017). We divided serum SAM, SAH, and SAM/SAH ratio into quartiles. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and their 95% confidence intervals (CIs) of serum SAM, SAH, and SAM/SAH ratio levels on the risk of a composite outcome of all-cause dementia or death, and each outcome. During the follow-up, 635 participants developed all-cause dementia and/or died, of which 379 participants developed dementia and 394 deaths occurred. The multivariable-adjusted HRs of the composite outcome decreased significantly with increasing serum SAM levels (P for trend = 0.01), while they increased significantly with higher serum SAH levels (P for trend = 0.03). Higher serum SAM/SAH ratio levels were significantly associated with a lower risk of the composite outcome (P for trend = 0.002), as well as with lower risk of each outcome. Our findings suggest that the balance of methionine metabolites may closely associate with the risk of dementia and death.

Topics: Dementia; Humans; Methionine; Proportional Hazards Models; S-Adenosylhomocysteine; S-Adenosylmethionine

Very recent findings confirmed that S-adenosylmethionine (SAM) can exert a direct effect on glutathione S-transferase (GST) activity. Alzheimer's disease (AD) is accompanied by reduced GST activity, diminished SAM, and increased S-adenosyl homocysteine (SAH), the downstream metabolic product resulting from SAM-mediated transmethylation reactions, when deprived of folate. Therefore, these findings underscored the critical role of SAM in maintenance of neuronal health, suggesting a possible role of SAM as a neuroprotective dietary supplement in AD. Given recent findings from clinical trials in which omega-3 polyunsturated fatty acids (PUFA) supplementation was effective only in very mild AD subgroups or mild cognitive impairment (MCI), we suggest intervention trials using measures of dietary supplementation (dietary omega-3 PUFA and SAM plus B vitamin supplementation) to determine if such supplements will reduce the risk for cognitive decline in very mild AD and MCI. Therefore, key supplements are not necessarily working in isolation, and the most profound impact, or in some cases the only impact, is noted very early in the course of AD, suggesting that nutriceutical supplements may bolster pharmacological approaches well past the window where supplements can work on their own.

Topics: Alzheimer Disease; Animals; Dementia; Fatty Acids, Unsaturated; Humans; S-Adenosylhomocysteine; S-Adenosylmethionine

Recent epidemiological evidence showed that dietary fatty acids, antioxidants, and micronutrients appear to have a role in cognitive decline, and may permit a beneficial effect on the risk of dementia and predementia syndromes. We discussed in the present paper the issue of the suggested protective role of polyunsaturated fatty acids (PUFA) on Alzheimer's disease, mild cognitive impairment, and other predementia syndromes, supported by the findings of the Italian Longitudinal Study on Aging (ILSA) and other population-based studies. In particular, we discussed the possible metabolic link of plasma S-adenosylhomocysteine concentrations with PUFA erythrocyte composition in explaining this suggested protective role of fatty acids against dementia and predementia syndromes.

Topics: Alzheimer Disease; Dementia; Early Diagnosis; Fatty Acids, Unsaturated; Humans; S-Adenosylhomocysteine