title: High homocysteine and epistasis between MTHFR and APOE: association with cognitive performance in the elderly.
abstract: High total homocysteine (tHcy) is associated with cognitive impairment in the elderly. The impact of high tHcy on different cognitive domains deserves further investigation, as does the role of the C677T polymorphism of the 5,10 methylenetetrahydrofolate reductase (MTHFR) gene. A cross-sectional analysis of 903 subjects from the population-based "InveCe.Ab" study was performed. The participants had no psychosis or active neurological disorders. They underwent a neuropsychological assessment. Principal component analysis allowed cognitive performance to be condensed into two components: executive functions and memory. Novel components were evaluated for association with tHcy, controlling for potential confounders. Regression models showed that high serum tHcy was associated with lower executive functions, but not with memory. MTHFR C677T TT was associated with higher tHcy but did not affect cognitive performance per se. However, when combined with the apolipoprotein E (APOE)-ε4 allele, it was a risk factor for lower executive performance, independently of tHcy levels. In summary, high tHcy per se, or MTHFR C677T TT in combination with the APOE-ε4 allele, might be associated primarily with executive dysfunctions rather than memory loss.
authors.affiliation: "Golgi Cenci" Foundation, Abbiategrasso 20081, Milan, Italy. Electronic address: l.polito@golgicenci.it.
authors.forename: Letizia
authors.initials: L
authors.lastname: Polito
authors.affiliation: "Golgi Cenci" Foundation, Abbiategrasso 20081, Milan, Italy; "C. Golgi" Geriatric Institute, Abbiategrasso 20081, Milan, Italy.
authors.forename: Tino Emanuele
authors.initials: TE
authors.lastname: Poloni
authors.affiliation: "Golgi Cenci" Foundation, Abbiategrasso 20081, Milan, Italy; "C. Golgi" Geriatric Institute, Abbiategrasso 20081, Milan, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Vaccaro
authors.affiliation: "Golgi Cenci" Foundation, Abbiategrasso 20081, Milan, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Abbondanza
authors.affiliation: "Golgi Cenci" Foundation, Abbiategrasso 20081, Milan, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Mangieri
authors.affiliation: "Golgi Cenci" Foundation, Abbiategrasso 20081, Milan, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Davin
authors.affiliation: Department of Public Health, Experimental and Forensic Medicine, Unit of Biostatistics and Clinical Epidemiology, University of Pavia, Pavia 27100, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Villani
authors.affiliation: "Golgi Cenci" Foundation, Abbiategrasso 20081, Milan, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Guaita
mesh_terms: D000367:Age Factors; D000368:Aged; D000375:Aging / Q000097:blood / Q000235:genetics* / Q000523:psychology; D001057:Apolipoproteins E / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D003071:Cognition; D003072:Cognition Disorders / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D003430:Cross-Sectional Studies; D004843:Epistasis, Genetic; D056344:Executive Function; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D015577:Geriatric Assessment; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D008297:Male; D008568:Memory; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D009483:Neuropsychological Tests; D010641:Phenotype; D011110:Polymorphism, Genetic; D025341:Principal Component Analysis; D012307:Risk Factors; D015854:Up-Regulation
chemical_list: D001057:Apolipoproteins E; D015415:Biomarkers; D006710:Homocysteine; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
keywords: Ageing; Alzheimer's disease; Apolipoprotein; Cognitive impairment; Genetics