title: Multiple Brain Markers are Linked to Age-Related Variation in Cognition.
abstract: Age-related alterations in brain structure and function have been challenging to link to cognition due to potential overlapping influences of multiple neurobiological cascades. We examined multiple brain markers associated with age-related variation in cognition. Clinically normal older humans aged 65-90 from the Harvard Aging Brain Study (N = 186) were characterized on a priori magnetic resonance imaging markers of gray matter thickness and volume, white matter hyperintensities, fractional anisotropy (FA), resting-state functional connectivity, positron emission tomography markers of glucose metabolism and amyloid burden, and cognitive factors of processing speed, executive function, and episodic memory. Partial correlation and mediation analyses estimated age-related variance in cognition shared with individual brain markers and unique to each marker. The largest relationships linked FA and striatum volume to processing speed and executive function, and hippocampal volume to episodic memory. Of the age-related variance in cognition, 70-80% was accounted for by combining all brain markers (but only ∼20% of total variance). Age had significant indirect effects on cognition via brain markers, with significant markers varying across cognitive domains. These results suggest that most age-related variation in cognition is shared among multiple brain markers, but potential specificity between some brain markers and cognitive domains motivates additional study of age-related markers of neural health.
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Trey
authors.initials: T
authors.lastname: Hedden
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Schultz
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA Department of Radiation Sciences, Umeå University, Umeå SE-901 87, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Rieckmann
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Mormino
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Johnson
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Reisa A
authors.initials: RA
authors.lastname: Sperling
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Department of Psychology and Center for Brain Science, Harvard University, Cambridge, MA, USA.
authors.forename: Randy L
authors.initials: RL
authors.lastname: Buckner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000682:Amyloid / Q000378:metabolism; D016880:Anisotropy; D015415:Biomarkers; D001921:Brain / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000378:metabolism / Q000502:physiology*; D001931:Brain Mapping; D003071:Cognition / Q000502:physiology*; D056344:Executive Function / Q000502:physiology; D005260:Female; D066128:Gray Matter / Q000033:anatomy & histology / Q000000981:diagnostic imaging; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D061212:Memory, Episodic; D009434:Neural Pathways / Q000033:anatomy & histology / Q000502:physiology; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D066127:White Matter / Q000033:anatomy & histology / Q000000981:diagnostic imaging
chemical_list: D000682:Amyloid; D015415:Biomarkers
keywords: aging; amyloid; executive function; memory; white matter