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Components of the choline oxidation pathway modify the association between the apolipoprotein ε4 gene variant and cognitive decline in patients with dementia.

Abstract：

BACKGROUND:Metabolites involved in one-carbon metabolism (OCM) may predict cognitive prognosis in dementia. The link between OCM, apolipoprotein E (APOE), and DNA methylation creates a biologically plausible mechanism of interaction. AIM:To assess OCM metabolites as predictors of 5-year cognitive prognosis in patients with mild dementia, and in subgroups defined by the APOEε4 allele variant. METHODS:We followed one-hundred and fifty-two patients with mild dementia (86 with Alzheimer's disease, 66 with Lewy body dementia, including 90 with at least one APOEε4 allele) for 5 years with annual Mini-Mental State Examinations (MMSE). Total homocysteine, methionine, choline, betaine, dimethylglycine, sarcosine, folate, cobalamin and pyridoxal 5'-phoshate were measured in serum at baseline. We used linear mixed models to assess metabolite-MMSE associations, including 3-way interactions between metabolites, time, and APOEε4. False-discovery rate adjusted p-values (Q-values) are reported. RESULTS:Metabolite concentrations were not different in patients with dementia according to the presence of APOEε4. Overall, serum concentration of total homocysteine was inversely associated with MMSE performance, while betaine was positively associated with MMSE (Q < 0.05), but neither was associated with MMSE decline. Serum concentrations of betaine, dimethylglycine and sarcosine, however, were associated with slower MMSE decline in patients with APOEε4, but with faster MMSE decline in patients without the allele (all 3-way interactions: Q < 0.05). CONCLUSION:Components of the choline oxidation pathway are associated with a better cognitive prognosis in APOEε4 carriers and a worse cognitive prognosis in non-carriers. Further research investigating targeted metabolic interventions according to APOE allele status is warranted.

journal_name

Brain Res

journal_title

Brain research

authors

Hildre AS,Solvang SH,Aarsland D,Midtun Ø,McCann A,Ervik AO,Nygård O,Ueland PM,Nordrehaug JE,Giil LM

doi

10.1016/j.brainres.2019.146519

subject

Has Abstract

pub_date

2020-01-01 00:00:00

pages

146519

eissn

0006-8993

issn

1872-6240

pii

S0006-8993(19)30573-6

journal_volume

1726

pub_type

杂志文章

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Components of the choline oxidation pathway modify the association between the apolipoprotein ε4 gene variant and cognitive decline in patients with dementia.