title: Thermolabile methylenetetrahydrofolate reductase gene and the risk of cognitive impairment in those over 85.
abstract: OBJECTIVE
  Previous reports have shown raised plasma concentrations of homocysteine in older persons with cognitive impairment. This may be caused by environmental and genetic factors. The relation between cognitive function and a common ala/val mutation in the methylenetetrahydrofolate reductase (MTHFR) gene was studied in those over 85. Homozygous carriers of this mutation are characterised by a lifelong exposure to moderately raised plasma concentrations of homocysteine.
  
  
  METHODS
  In the Leiden 85-plus Study, a population based study of persons aged 85 years and over, the score on the mini mental state examination (MMSE) and the presence of dementia dependent on the MTHFR genotypes were compared in 641 participants (456 women, 185 men) at baseline. In addition, the association between the MTHFR genotype and cognitive decline was studied by re-examining cognitive function of 172 participants without dementia at baseline after a median follow up of 4.0 years.
  
  
  RESULTS
  At baseline, carriers of the ala/ala genotype had a median MMSE score of 27 points (interquartile range (IQR) 21.5-29), for the ala/val genotype it was 26 points (IQR 20-29), and for the val/val genotype it was 27 points (IQR 20-28.3) (p=0.3). The prevalence of dementia was also not significantly different for the various genotypes (ala/ala 22%, ala/val 28%, val/val 27%; p=0.4). None of the carriers of the val/val genotype without cognitive impairment at baseline developed dementia during the follow up.
  
  
  CONCLUSIONS
  Although previous studies have shown that older persons with cognitive impairment have raised plasma concentrations of homocysteine, homozygosity for the ala to val mutation in the MTHFR gene is not a genetic risk factor for cognitive impairment in persons aged 85 years and over.
authors.affiliation: Section of Gerontology and Geriatrics, Department of General Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands. Leiden85plus@aig.ozl.nl
authors.forename: J
authors.initials: J
authors.lastname: Gussekloo
authors.forename: B T
authors.initials: BT
authors.lastname: Heijmans
authors.forename: P E
authors.initials: PE
authors.lastname: Slagboom
authors.forename: A M
authors.initials: AM
authors.lastname: Lagaay
authors.forename: D L
authors.initials: DL
authors.lastname: Knook
authors.forename: R G
authors.initials: RG
authors.lastname: Westendorp
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003072:Cognition Disorders / Q000097:blood / Q000209:etiology* / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012307:Risk Factors; D013696:Temperature
chemical_list: D006710:Homocysteine; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)