title: Dopamine transporter availability in clinically normal aging is associated with individual differences in white matter integrity.
abstract: Aging-related differences in white matter integrity, the presence of amyloid plaques, and density of biomarkers indicative of dopamine functions can be detected and quantified with in vivo human imaging. The primary aim of the present study was to investigate whether these imaging-based measures constitute independent imaging biomarkers in older adults, which would speak to the hypothesis that the aging brain is characterized by multiple independent neurobiological cascades. We assessed MRI-based markers of white matter integrity and PET-based marker of dopamine transporter density and amyloid deposition in the same set of 53 clinically normal individuals (age 65-87). A multiple regression analysis demonstrated that dopamine transporter availability is predicted by white matter integrity, which was detectable even after controlling for chronological age. Further post-hoc exploration revealed that dopamine transporter availability was further associated with systolic blood pressure, mirroring the established association between cardiovascular health and white matter integrity. Dopamine transporter availability was not associated with the presence of amyloid burden. Neurobiological correlates of dopamine transporter measures in aging are therefore likely unrelated to Alzheimer's disease but are aligned with white matter integrity and cardiovascular risk. More generally, these results suggest that two common imaging markers of the aging brain that are typically investigated separately do not reflect independent neurobiological processes. Hum Brain Mapp 37:621-631, 2016. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Department of Radiology, Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, Massachusetts.|Department of Radiation Sciences, Diagnostic Radiology, Umeå University, Umeå, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Rieckmann
authors.affiliation: Department of Radiology, Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, Massachusetts.|Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Trey
authors.initials: T
authors.lastname: Hedden
authors.affiliation: Department of Radiology, Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, Massachusetts.
authors.forename: Alayna P
authors.initials: AP
authors.lastname: Younger
authors.affiliation: Department of Radiology, Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, Massachusetts.|Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.|Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Center for Alzheimer Research and Treatment, Boston, Massachusetts.
authors.forename: Reisa A
authors.initials: RA
authors.lastname: Sperling
authors.affiliation: Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.|Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.|Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Johnson
authors.affiliation: Department of Radiology, Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, Massachusetts.|Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.|Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.|Department of Psychology and Center for Brain Science, Harvard University, Cambridge, Massachusetts.
authors.forename: Randy L
authors.initials: RL
authors.lastname: Buckner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism* / Q000473:pathology*; D000814:Aniline Compounds; D052160:Benzothiazoles; D001794:Blood Pressure / Q000502:physiology; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D003042:Cocaine / Q000031:analogs & derivatives; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D064847:Multimodal Imaging; D009929:Organ Size; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D012044:Regression Analysis; D013844:Thiazoles; D066127:White Matter / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000814:Aniline Compounds; D052160:Benzothiazoles; D050483:Dopamine Plasma Membrane Transport Proteins; C102282:N-iodoallyl-2-carbomethoxy-3-(4-fluorophenyl)tropane; D019275:Radiopharmaceuticals; D013844:Thiazoles; D003042:Cocaine
keywords: aging; amyloid; dopamine; magnetic resonance imaging; positron emission tomography; white matter