title: Synergistic effects of the MTHFR C677T polymorphism and hypertension on spatial navigation.
abstract: Navigation skills deteriorate with age, but the mechanisms of the decline are poorly understood. Part of the decrement may be due to age-related vascular risk factors. The T allele in a C677T variant in methylenetetrahydrofolate reductase (MTHFR) gene is associated with elevated plasma homocysteine, which is detrimental to vascular integrity and has been linked to cognitive decline. We inquired if a combination of physiological (hypertension) and genetic (MTHFR 677T) vascular risks has a synergistic negative impact on cognitive performance in otherwise healthy adults. We tested 160 participants (18-80 years old) on a virtual water maze. Advanced age, female sex, and hypertension were associated with poorer performance. However, hypertensive carriers of the T allele performed significantly worse than the rest of the participants at all ages. These findings indicate that hypertension combined with a genetic vascular risk factor may significantly increase risk for cognitive impairment.
authors.affiliation: Institute of Gerontology, Wayne State University, Detroit, MI 48202, United States.
authors.forename: Awantika
authors.initials: A
authors.lastname: Deshmukh
authors.forename: Karen M
authors.initials: KM
authors.lastname: Rodrigue
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Kennedy
authors.forename: Susan
authors.initials: S
authors.lastname: Land
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Jacobs
authors.forename: Naftali
authors.initials: N
authors.lastname: Raz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000802:Angiotensin Amide / Q000235:genetics*; D001794:Blood Pressure / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D018782:Maze Learning / Q000502:physiology; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011597:Psychomotor Performance / Q000502:physiology; D012727:Sex Characteristics; D013037:Spatial Behavior / Q000502:physiology*; D014584:User-Computer Interface; D055815:Young Adult
chemical_list: D000802:Angiotensin Amide; D042965:Methylenetetrahydrofolate Reductase (NADPH2)