title: Homocysteine, Alzheimer genes and proteins, and measures of cognition and depression in older men.
abstract: The epsilon4 allele of apolipoprotein E (APOE), and the plasma levels of APOE, amyloid beta-protein precursor, amyloid beta1-40 (Abeta40) and homocysteine (Hcy) have all been correlated with the presence of dementia. Mutations in the methylnetetrahydrofolate reductase enzyme (MTHFR) have been associated with elevated levels of Hcy. This study explored the association of these factors with cognition and depression in community dwelling older men. Two hundred and ninety-nine men, mean age 78.9 years (SD 2.8), were studied in this cross-sectional survey. Mean plasma Hcy was 13.5 (SD 5.3) micromol/L. The MTHFR genotype had no obvious impact on Hcy levels. Ln Hcy and Ln Abeta40 were both inversely correlated with calculated glomerular filtration rate (cGFR), r = -0.41 (p < 0.001) and r = -0.28 (p < 0.001), respectively. There was a positive correlation between Ln Hcy and Ln Abeta40, r = 0.19 (p < 0.001), which remained significant after adjusting for cGFR, with a doubling of Hcy associated with a 24% increase of Abeta40. The e4 allele was associated with increased depressive symptoms as measured by the Geriatric Depression Scale-15, Odds ratio (OR) = 2.59 (95%CI 1.06-6.34) and poorer performance on the Clock Drawing Test, OR = 2.32 (95% CI: 1.25-4.29). There was a positive association between Abeta40 and Hcy, even after adjustment for cGFR in this sample of well, community dwelling older men. This association may help elucidate the link between elevated levels of Hcy and Alzheimer's disease.
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia. leonflic@cyllene.uwa.edu.au
authors.forename: L
authors.initials: L
authors.lastname: Flicker
authors.forename: R N
authors.initials: RN
authors.lastname: Martins
authors.forename: J
authors.initials: J
authors.lastname: Thomas
authors.forename: J
authors.initials: J
authors.lastname: Acres
authors.forename: K
authors.initials: K
authors.lastname: Taddei
authors.forename: P
authors.initials: P
authors.lastname: Norman
authors.forename: K
authors.initials: K
authors.lastname: Jamrozik
authors.forename: O P
authors.initials: OP
authors.lastname: Almeida
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D001057:Apolipoproteins E / Q000378:metabolism; D003072:Cognition Disorders / Q000175:diagnosis / Q000453:epidemiology*; D003430:Cross-Sectional Studies; D003863:Depression / Q000175:diagnosis / Q000453:epidemiology*; D015870:Gene Expression / Q000235:genetics*; D006710:Homocysteine / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D017354:Point Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D013763:Tetrahydrofolates / Q000235:genetics* / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D013763:Tetrahydrofolates; D006710:Homocysteine; C013123:5,10-methylenetetrahydrofolic acid