Dementia, Alzheimer Disease Risk Increased With Lower Branched-Chain Amino Acid Levels

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A total of 995 and 745 cases of incident dementia and AD were detected, respectively.
A total of 995 and 745 cases of incident dementia and AD were detected, respectively.

Lower branched-chain amino acid (BCAA) levels may be associated with an increased risk of incident dementia, independent of other conventional risk factors, according to a study published in Alzheimer's & Dementia.

Juho Tynkkynen, from the Department of Cardiology at Tays Heart Hospital, Tampere University Hospital and Faculty of Medicine and Life Sciences in Finland, and colleagues, examined 8 prospective cohort studies relating blood metabolites, lipids, and lipoprotein lipids quantified by nuclear magnetic resonance (NMR) or mass spectrometry (MS) metabolomics to risk of incident dementia and Alzheimer disease (AD). Altogether, 22,623 participants were included, and patients were excluded if they had a history of doctor-diagnosed prevalent dementia, including AD, stroke, or other neurologic disease affecting cognitive function.

Four cohorts were used for discovery with replication undertaken in the other 4 to avoid false positives. For metabolites that survived replication, combined association results are presented.

The study included 22,623 subjects with 246,698 person years of follow-up. A total of 995 and 745 cases of incident dementia and AD were detected, respectively. Three branched-chain amino acids (isoleucine, leucine, and valine), creatinine, and 2 very low-density lipoprotein (VLDL)-specific lipoprotein lipid subclasses were associated with lower dementia risk. One high-density lipoprotein (HDL; the concentration of cholesterol esters relative to total lipids in large HDL) and 1 VLDL (total cholesterol to total lipids ratio in very large VLDL) lipoprotein lipid subclass were associated with increased dementia risk. Branched-chain amino acids were also associated with decreased Alzheimer disease risk and the concentration of cholesterol esters relative to total lipids in large HDL with increased Alzheimer disease risk.

“In conclusion, our large prospective study identified lower BCAA levels to be associated with an increased risk of incident dementia, independent of other conventional risk factors, stated the authors. “Moreover, creatinine, one HDL, and three VLDL lipoprotein subclasses were also associated with dementia risk, but these associations disappeared when adjusted for BMI and cholesterol-lowering medication.”

Reference

Tynkkynen J, Chouraki V, van der Lee SJ, et al. Association of branched-chain amino acids and other circulating metabolites with risk of incident dementia and Alzheimer's disease: A prospective study in eight cohorts [published online March 6, 2018]. Alzheimers Dement. doi: 10.1016/j.jalz.2018.01.003

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