title: Age differences in arterial and venous extra-cerebral blood flow in healthy adults: contributions of vascular risk factors and genetic variants.
abstract: Sufficient cerebral blood flow (CBF) and venous drainage are critical for normal brain function, and their alterations can affect brain aging. However, to date, most studies focused on arterial CBF (inflow) with little attention paid to the age differences in venous outflow. We measured extra-cerebral arterial and venous blood flow rates with phase-contrast MRI and assessed the influence of vascular risk factors and genetic polymorphisms (ACE insertion/deletion, COMT val158met, and APOEε4) in 73 adults (age 18-74 years). Advanced age, elevated vascular risk, ACE Deletion, and COMT met alleles were linked to lower in- and outflow, with no effects of APOE ε4 noted. Lower age-related CBF rate was unrelated to brain volume and was observed only in val homozygotes of COMTval158met. Thus, in a disease-free population, age differences in CBF may be notable only in persons with high vascular risk and carriers of genetic variants associated with vasoconstriction and lower dopamine availability. It remains to be established if treatments targeting alleviation of the mutable factors can improve the course of cerebrovascular aging in spite of the immutable genetic influence.
authors.affiliation: Institute of Gerontology, Wayne State University, 87 E Ferry St. 226 Knapp Bldg., Detroit, MI, 48202, USA. nraz@wayne.edu.|Department of Psychology, Wayne State University, 5057 Woodward Ave., Detroit, MI, 48202, USA. nraz@wayne.edu.
authors.forename: Naftali
authors.initials: N
authors.lastname: Raz
authors.affiliation: Institute of Gerontology, Wayne State University, 87 E Ferry St. 226 Knapp Bldg., Detroit, MI, 48202, USA.|Beckman Institute for Advanced Science and Technology, University of Illinois Urbana-Champaign, 405 N Matthews Ave., Urbana, IL, 61801, USA.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Daugherty
authors.affiliation: The MRI Institute of Biomedical Research, 440 E Ferry St., Detroit, MI, 48202, USA.
authors.forename: Sean K
authors.initials: SK
authors.lastname: Sethi
authors.affiliation: Institute of Gerontology, Wayne State University, 87 E Ferry St. 226 Knapp Bldg., Detroit, MI, 48202, USA.|Department of Psychiatry and Behavioral Sciences, Wayne State University, 3990 John R, Detroit, MI, 48201, USA.
authors.forename: Muzamil
authors.initials: M
authors.lastname: Arshad
authors.affiliation: The MRI Institute of Biomedical Research, 440 E Ferry St., Detroit, MI, 48202, USA.|Department of Radiology, Wayne State University, 3990 John R, Detroit, MI, 48201, USA.
authors.forename: E Mark
authors.initials: EM
authors.lastname: Haacke
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics; D001158:Arteries / Q000502:physiology*; D001783:Blood Flow Velocity; D002394:Catechol O-Methyltransferase / Q000235:genetics; D002560:Cerebrovascular Circulation; D003430:Cross-Sectional Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D010641:Phenotype; D012039:Regional Blood Flow; D018570:Risk Assessment; D012307:Risk Factors; D014652:Vascular Diseases / Q000235:genetics* / Q000503:physiopathology; D014680:Veins / Q000502:physiology*; D055815:Young Adult
chemical_list: D053327:Apolipoprotein E4; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A
keywords: ACE; COMT; Internal carotid artery; Jugular vein; Phase-contrast MRI; Vertebral artery