High homocysteine and epistasis between MTHFR and APOE: association with cognitive performance in the elderly

Experimental Gerontology
Letizia PolitoAntonio Guaita

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 memor...Continue Reading

References

Dec 1, 1995·Cortex; a Journal Devoted to the Study of the Nervous System and Behavior·G A CarlesimoC Caltagirone
Aug 1, 1996·Italian Journal of Neurological Sciences·A R GiovagnoliE Capitani
May 27, 1997·Proceedings of the National Academy of Sciences of the United States of America·S A LiptonJ S Stamler
Apr 27, 2002·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·P CaffarraA Venneri
Nov 13, 2002·Neurology·N D PrinsUNKNOWN Rotterdam Scan Study
Jan 11, 2003·Clinical Chemistry and Laboratory Medicine : CCLM·Werner KochAdnan Kastrati
Jan 31, 2003·Annals of Neurology·Carole DufouilChristophe Tzourio
Feb 20, 2003·Trends in Neurosciences·Mark P Mattson, Thomas B Shea
Apr 23, 2003·FEBS Letters·Sigfrido ScarpaRosaria A Cavallaro
Feb 6, 2004·Stroke; a Journal of Cerebral Circulation·Frank M Faraci, Steven R Lentz
Feb 9, 2005·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Angeles GarciaMorris Freedman
Mar 4, 2005·Journal of the American Geriatrics Society·Jyme H SchaferBrian S Schwartz
Jun 22, 2007·Lancet Neurology·Sarah E VermeerPeter J Koudstaal
Jul 11, 2007·Current Opinion in Neurology·Leonardo PantoniDomenico Inzitari
Nov 21, 2007·Neuroscience Letters·Merrill F EliasZsuzsanna Nagy
Jan 25, 2011·Genes, Brain, and Behavior·O J G SchiepersI J Deary
Jun 29, 2011·The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry·Rebecca K WestJeremy M Silverman
Sep 13, 2011·Neurobiology of Aging·Hadassa M JochemsenMirjam I Geerlings
Aug 7, 2012·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Hadassa M JochemsenUNKNOWN SMART Study Group
Apr 10, 2013·Dementia and Geriatric Cognitive Disorders Extra·A J Larner
Dec 25, 2013·Frontiers in Aging Neuroscience·Haoyang LuHong Qing
May 3, 2014·Alzheimer Disease and Associated Disorders·Natacha LoriusUNKNOWN Alzheimer’s Disease Neuroimaging Initiative
Nov 14, 2014·Neurology·Nikita L van der ZwaluwLisette C P G M de Groot
Dec 3, 2014·European Journal of Medical Genetics·Siaw-Cheok Liew, Esha Das Gupta
Feb 6, 2015·Expert Review of Clinical Pharmacology·Kilmer S McCully

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Citations

Jun 3, 2017·Biomolecular Concepts·Isabelle R MiousseIgor Koturbash
Aug 11, 2018·Jornal brasileiro de nefrologia : ʹorgão oficial de Sociedades Brasileira e Latino-Americana de Nefrologia·Álvaro de Oliveira FrancoMatheus Roriz-Cruz
Nov 25, 2017·International Journal of Immunopathology and Pharmacology·Jing-Wen ZhangJian-Zhong Zhang
Dec 9, 2020·The International Journal of Neuroscience·Mohit Kumar, Rajat Sandhir

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