title: Hypertension-related alterations in white matter microstructure detectable in middle age.
abstract: Most studies examining associations between hypertension and brain white matter microstructure have focused on older adults or on cohorts with a large age range. Because hypertension effects on the brain may vary with age, it is important to focus on middle age, when hypertension becomes more prevalent. We used linear mixed-effect models to examine differences in white matter diffusion metrics as a function of hypertension in a well-characterized cohort of middle-aged men (n=316; mean, 61.8 years; range, 56.7-65.6). Diffusion metrics were examined in 9 tracts reported to be sensitive to hypertension in older adults. Relative to normotensive individuals, individuals with long-standing hypertension (>5.6 years) showed reduced fractional anisotropy or increased diffusivity in most tracts. Effects were stronger among carriers than among noncarriers of the apolipoprotein E ε4 allele for 2 tracts connecting frontal regions with other brain areas. Significant differences were observed even after adjustment for potentially related lifestyle and cardiovascular risk factors. Shorter duration of hypertension or better blood pressure control among hypertensive individuals did not lessen the adverse effects. These findings suggest that microstructural white matter alterations appear early in the course of hypertension and may persist despite adequate treatment. Although longitudinal studies are needed to confirm these findings, the results suggest that prevention-rather than management-of hypertension may be vital to preserving brain health in aging.
authors.affiliation: From the Departments of Radiology (L.K.M., C.F.-N., D.J.H., A.M.D.), Psychiatry (C.F.-N., L.T.E., C.E.F., M.S.P., W.S.K.), and Neurosciences (A.M.D.), University of California, San Diego; Mental Illness Research, Education, and Clinical Center (L.T.E.) and Center of Excellence for Stress and Mental Health (W.S.K.), VA San Diego Healthcare System; Department of Psychiatry and Brain Sciences, Boston University, Boston, MA (M.J.L.); and Imaging Genetics Center, Institute for Neuroimaging and Informatics, University of Southern California, Los Angeles (D.A.R.). lkmcevoy@ucsd.edu.
authors.forename: Linda K
authors.initials: LK
authors.lastname: McEvoy
authors.affiliation: From the Departments of Radiology (L.K.M., C.F.-N., D.J.H., A.M.D.), Psychiatry (C.F.-N., L.T.E., C.E.F., M.S.P., W.S.K.), and Neurosciences (A.M.D.), University of California, San Diego; Mental Illness Research, Education, and Clinical Center (L.T.E.) and Center of Excellence for Stress and Mental Health (W.S.K.), VA San Diego Healthcare System; Department of Psychiatry and Brain Sciences, Boston University, Boston, MA (M.J.L.); and Imaging Genetics Center, Institute for Neuroimaging and Informatics, University of Southern California, Los Angeles (D.A.R.).
authors.forename: Christine
authors.initials: C
authors.lastname: Fennema-Notestine
authors.affiliation: From the Departments of Radiology (L.K.M., C.F.-N., D.J.H., A.M.D.), Psychiatry (C.F.-N., L.T.E., C.E.F., M.S.P., W.S.K.), and Neurosciences (A.M.D.), University of California, San Diego; Mental Illness Research, Education, and Clinical Center (L.T.E.) and Center of Excellence for Stress and Mental Health (W.S.K.), VA San Diego Healthcare System; Department of Psychiatry and Brain Sciences, Boston University, Boston, MA (M.J.L.); and Imaging Genetics Center, Institute for Neuroimaging and Informatics, University of Southern California, Los Angeles (D.A.R.).
authors.forename: Lisa T
authors.initials: LT
authors.lastname: Eyler
authors.affiliation: From the Departments of Radiology (L.K.M., C.F.-N., D.J.H., A.M.D.), Psychiatry (C.F.-N., L.T.E., C.E.F., M.S.P., W.S.K.), and Neurosciences (A.M.D.), University of California, San Diego; Mental Illness Research, Education, and Clinical Center (L.T.E.) and Center of Excellence for Stress and Mental Health (W.S.K.), VA San Diego Healthcare System; Department of Psychiatry and Brain Sciences, Boston University, Boston, MA (M.J.L.); and Imaging Genetics Center, Institute for Neuroimaging and Informatics, University of Southern California, Los Angeles (D.A.R.).
authors.forename: Carol E
authors.initials: CE
authors.lastname: Franz
authors.affiliation: From the Departments of Radiology (L.K.M., C.F.-N., D.J.H., A.M.D.), Psychiatry (C.F.-N., L.T.E., C.E.F., M.S.P., W.S.K.), and Neurosciences (A.M.D.), University of California, San Diego; Mental Illness Research, Education, and Clinical Center (L.T.E.) and Center of Excellence for Stress and Mental Health (W.S.K.), VA San Diego Healthcare System; Department of Psychiatry and Brain Sciences, Boston University, Boston, MA (M.J.L.); and Imaging Genetics Center, Institute for Neuroimaging and Informatics, University of Southern California, Los Angeles (D.A.R.).
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Hagler
authors.affiliation: From the Departments of Radiology (L.K.M., C.F.-N., D.J.H., A.M.D.), Psychiatry (C.F.-N., L.T.E., C.E.F., M.S.P., W.S.K.), and Neurosciences (A.M.D.), University of California, San Diego; Mental Illness Research, Education, and Clinical Center (L.T.E.) and Center of Excellence for Stress and Mental Health (W.S.K.), VA San Diego Healthcare System; Department of Psychiatry and Brain Sciences, Boston University, Boston, MA (M.J.L.); and Imaging Genetics Center, Institute for Neuroimaging and Informatics, University of Southern California, Los Angeles (D.A.R.).
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lyons
authors.affiliation: From the Departments of Radiology (L.K.M., C.F.-N., D.J.H., A.M.D.), Psychiatry (C.F.-N., L.T.E., C.E.F., M.S.P., W.S.K.), and Neurosciences (A.M.D.), University of California, San Diego; Mental Illness Research, Education, and Clinical Center (L.T.E.) and Center of Excellence for Stress and Mental Health (W.S.K.), VA San Diego Healthcare System; Department of Psychiatry and Brain Sciences, Boston University, Boston, MA (M.J.L.); and Imaging Genetics Center, Institute for Neuroimaging and Informatics, University of Southern California, Los Angeles (D.A.R.).
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Panizzon
authors.affiliation: From the Departments of Radiology (L.K.M., C.F.-N., D.J.H., A.M.D.), Psychiatry (C.F.-N., L.T.E., C.E.F., M.S.P., W.S.K.), and Neurosciences (A.M.D.), University of California, San Diego; Mental Illness Research, Education, and Clinical Center (L.T.E.) and Center of Excellence for Stress and Mental Health (W.S.K.), VA San Diego Healthcare System; Department of Psychiatry and Brain Sciences, Boston University, Boston, MA (M.J.L.); and Imaging Genetics Center, Institute for Neuroimaging and Informatics, University of Southern California, Los Angeles (D.A.R.).
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Rinker
authors.affiliation: From the Departments of Radiology (L.K.M., C.F.-N., D.J.H., A.M.D.), Psychiatry (C.F.-N., L.T.E., C.E.F., M.S.P., W.S.K.), and Neurosciences (A.M.D.), University of California, San Diego; Mental Illness Research, Education, and Clinical Center (L.T.E.) and Center of Excellence for Stress and Mental Health (W.S.K.), VA San Diego Healthcare System; Department of Psychiatry and Brain Sciences, Boston University, Boston, MA (M.J.L.); and Imaging Genetics Center, Institute for Neuroimaging and Informatics, University of Southern California, Los Angeles (D.A.R.).
authors.forename: Anders M
authors.initials: AM
authors.lastname: Dale
authors.affiliation: From the Departments of Radiology (L.K.M., C.F.-N., D.J.H., A.M.D.), Psychiatry (C.F.-N., L.T.E., C.E.F., M.S.P., W.S.K.), and Neurosciences (A.M.D.), University of California, San Diego; Mental Illness Research, Education, and Clinical Center (L.T.E.) and Center of Excellence for Stress and Mental Health (W.S.K.), VA San Diego Healthcare System; Department of Psychiatry and Brain Sciences, Boston University, Boston, MA (M.J.L.); and Imaging Genetics Center, Institute for Neuroimaging and Informatics, University of Southern California, Los Angeles (D.A.R.).
authors.forename: William S
authors.initials: WS
authors.lastname: Kremen
mesh_terms: D000368:Aged; D000375:Aging / Q000473:pathology*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D053327:Apolipoprotein E4 / Q000235:genetics; D015331:Cohort Studies; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D059906:Neuroimaging; D013997:Time Factors; D016896:Treatment Outcome; D066127:White Matter / Q000473:pathology*
chemical_list: D000959:Antihypertensive Agents; D053327:Apolipoprotein E4
keywords: aging; apolipoproteins E; blood pressure; brain ischemia; neuroimaging