Multimodal Magnetic Resonance Imaging Assessment of White Matter Aging Trajectories Over the Lifespan of Healthy Individuals

• Published in: Biological psychiatry (1969) Vol. 72; no. 12; pp. 1026 - 1034
• Main Authors: Bartzokis, George, Lu, Po H, Heydari, Panthea, Couvrette, Alexander, Lee, Grace J, Kalashyan, Greta, Freeman, Frank, Grinstead, John W, Villablanca, Pablo, Finn, J. Paul, Mintz, Jim, Alger, Jeffry R, Altshuler, Lori L
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 15.12.2012; Elsevier
• Subjects: Adolescent; Adult; Adult and adolescent clinical studies; Aged; Aged, 80 and over; Aging; Aging - physiology; Alzheimer; Anisotropy; axial diffusivity; Axons - ultrastructure; Biological and medical sciences; Biomarkers; Brain - anatomy & histology; Brain - growth & development; Cerebral Cortex - anatomy & histology; Cerebral Cortex - growth & development; cognition; degeneration; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; development; diffusion tensor imaging (DTI); Diffusion Tensor Imaging - methods; Echo-Planar Imaging; Female; fractional anisotropy; Humans; Image Processing, Computer-Assisted; magnetic resonance imaging (MRI); Male; Medical sciences; Middle Aged; myelin; Myelin Sheath - physiology; Nerve Degeneration - pathology; Nerve Fibers - ultrastructure; Neurology; oligodendrocytes; Oligodendroglia - physiology; Organic mental disorders. Neuropsychology; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; radial diffusivity; Reference Values; Regression Analysis; relaxation rate (R2); Relaxation. Biofeedback. Hypnosis. Selfregulation. Meditation; Sex Characteristics; Treatments; white matter (WM); Young Adult; myelin; development; cognition; radial diffusivity; oligodendrocytes; Alzheimer; degeneration; magnetic resonance imaging (MRI); Aging; fractional anisotropy; diffusion tensor imaging (DTI); axial diffusivity; white matter (WM); relaxation rate (R 2); relaxation rate (R2); Senescence; Alzheimer disease; Neuroglia; Multimodal imaging; Cognition; Relaxation; Oligodendrocyte; Development; Degenerative disease; Degeneration; Evaluation; Nervous system diseases; Healthy subject; Myelin; ); Nuclear magnetic resonance imaging; White matter; Cerebral disorder; Diffusion tensor imaging; Treatment; Anisotropy; Central nervous system disease; Medical imagery; relaxation rate (R
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2012.07.010

Background Postmortem and volumetric imaging data suggest that brain myelination is a dynamic lifelong process that, in vulnerable late-myelinating regions, peaks in middle age. We examined whether known regional differences in axon size and age at myelination influence the timing and rates of development and degeneration/repair trajectories of white matter (WM) microstructure biomarkers. Methods Healthy subjects ( n = 171) 14–93 years of age were examined with transverse relaxation rate (R2 ) and four diffusion tensor imaging measures (fractional anisotropy [FA] and radial, axial, and mean diffusivity [RD, AxD, MD, respectively]) of frontal lobe, genu, and splenium of the corpus callosum WM (FWM, GWM, and SWM, respectively). Results Only R2 reflected known levels of myelin content with high values in late-myelinating FWM and GWM regions and low ones in early-myelinating SWM. In FWM and GWM, all metrics except FA had significant quadratic components that peaked at different ages (R2 < RD < MD < AxD), with FWM peaking later than GWM. Factor analysis revealed that, although they defined different factors, R2 and RD were the metrics most closely associated with each other and differed from AxD, which entered into a third factor. Conclusions The R2 and RD trajectories were most dynamic in late-myelinating regions and reflect age-related differences in myelination, whereas AxD reflects axonal size and extra-axonal space. The FA and MD had limited specificity. The data suggest that the healthy adult brain undergoes continual change driven by development and repair processes devoted to creating and maintaining synchronous function among neural networks on which optimal cognition and behavior depend.