Title | Metabolomics and cognition in African American adults in midlife: the atherosclerosis risk in communities study. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Bressler, J, Yu, B, Mosley, TH, Knopman, DS, Gottesman, RF, Alonso, A, Sharrett, AR, Wruck, LM, Boerwinkle, E |
Journal | Transl Psychiatry |
Volume | 7 |
Issue | 7 |
Pagination | e1173 |
Date Published | 2017 Jul 18 |
ISSN | 2158-3188 |
Keywords | Atherosclerosis, Black or African American, Black People, Cognition, Female, Humans, Longitudinal Studies, Male, Metabolomics, Middle Aged, Neuropsychological Tests, Prospective Studies, Risk Factors, White People |
Abstract | Clinical studies have shown alterations in metabolic profiles when patients with mild cognitive impairment and Alzheimer's disease dementia were compared to cognitively normal subjects. Associations between 204 serum metabolites measured at baseline (1987-1989) and cognitive change were investigated in 1035 middle-aged community-dwelling African American participants in the biracial Atherosclerosis Risk in Communities (ARIC) Study. Cognition was evaluated using the Delayed Word Recall Test (DWRT; verbal memory), the Digit Symbol Substitution Test (DSST; processing speed) and the Word Fluency Test (WFT; verbal fluency) at visits 2 (1990-1992) and 4 (1996-1998). In addition, Cox regression was used to analyze the metabolites as predictors of incident hospitalized dementia between baseline and 2011. There were 141 cases among 1534 participants over a median 17.1-year follow-up period. After adjustment for established risk factors, one standard deviation increase in N-acetyl-1-methylhistidine was significantly associated with greater 6-year change in DWRT scores (β=-0.66 words; P=3.65 × 10). Two metabolites (one unnamed and a long-chain omega-6 polyunsaturated fatty acid found in vegetable oils (docosapentaenoate (DPA, 22:5 n-6)) were significantly associated with less decline on the DSST (DPA: β=1.25 digit-symbol pairs, P=9.47 × 10). Two unnamed compounds and three sex steroid hormones were associated with an increased risk of dementia (all P<3.9 × 10). The association of 4-androstene-3beta, 17beta-diol disulfate 1 with dementia was replicated in European Americans. These results demonstrate that screening the metabolome in midlife can detect biologically plausible biomarkers that may improve risk stratification for cognitive impairment at older ages. |
DOI | 10.1038/tp.2017.118 |
Alternate Journal | Transl Psychiatry |
PubMed ID | 28934192 |
PubMed Central ID | PMC5538110 |
Grant List | HHSN268201100008C / HL / NHLBI NIH HHS / United States U01 HL096812 / HL / NHLBI NIH HHS / United States HHSN268201100007C / HL / NHLBI NIH HHS / United States U01 HL096917 / HL / NHLBI NIH HHS / United States HHSN268201100011C / HL / NHLBI NIH HHS / United States U01 HL096902 / HL / NHLBI NIH HHS / United States U01 HG004402 / HG / NHGRI NIH HHS / United States HHSN268201100012C / HL / NHLBI NIH HHS / United States U01 HL096814 / HL / NHLBI NIH HHS / United States HHSN268201100005C / HL / NHLBI NIH HHS / United States HHSN268201100009C / HL / NHLBI NIH HHS / United States U01 HL096899 / HL / NHLBI NIH HHS / United States HHSN268201100006C / HL / NHLBI NIH HHS / United States HHSN268201100010C / HL / NHLBI NIH HHS / United States |
Metabolomics and cognition in African American adults in midlife: the atherosclerosis risk in communities study.
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