White matter hyperintensities and their penumbra lie along a continuum of injury in the aging brain.
OBJECTIVE
Aging is accompanied by clinically silent cerebral white matter injury identified through white matter hyperintensities (WMHs) on fluid-attenuated inversion recovery (FLAIR)- and diffusion tensor imaging-based measures of white matter integrity. The temporal course of FLAIR and diffusion tensor imaging changes within WMHs and their less-injured periphery (ie, their penumbra), however, has not been fully studied. We used longitudinal diffusion tensor imaging and FLAIR to explore these changes.


METHODS
One hundred fifteen participants, aged 73.7±6.7 years, received clinical evaluations and MRIs on 2 dates. WMHs and fractional anisotropy (FA) maps were produced from FLAIR and diffusion tensor imaging and coregistered to a standardized space. Each distinct WMH was categorized as growing, stagnant, or noncontiguous incident. The penumbra of each WMH was similarly categorized as corresponding to a stagnant, growing, or noncontiguous incident WMH. Linear mixed-effect models were used to assess whether FA and FLAIR measurements changed between baseline and follow-up and differed between tissue categories.


RESULTS
Baseline FA differed significantly by tissue category, with the following ordering of categories from highest to lowest FA: penumbra of noncontiguous incident, then stagnant, then growing WMHs; noncontiguous incident, then stagnant, then growing WMHs. Despite differences in baseline values, all tissue categories experienced declines in FA over time. Only noncontiguous incident WMHs showed significant FLAIR signal increases over time, and FLAIR signal significantly decreased in stagnant WMHs.


CONCLUSIONS
WMHs and their penumbra vary in severity and together span a continuous spectrum of white matter injury that worsens with time. FLAIR fails to capture this continuous injury process fully but does identify a subclass of lesions that seem to improve over time.
From the Imaging of Dementia and Aging Laboratory (P.M., E.F., S.N.L., A.E.R., B.R., D.M., C.D., O.T.C.), Department of Neurology (P.M., E.F., B.R., D.M., C.D., O.T.C.), and Center for Neuroscience (S.N.L., A.E.R., C.D.), University of California, Davis.
Pauline
P
Maillard
From the Imaging of Dementia and Aging Laboratory (P.M., E.F., S.N.L., A.E.R., B.R., D.M., C.D., O.T.C.), Department of Neurology (P.M., E.F., B.R., D.M., C.D., O.T.C.), and Center for Neuroscience (S.N.L., A.E.R., C.D.), University of California, Davis.
Evan
E
Fletcher
From the Imaging of Dementia and Aging Laboratory (P.M., E.F., S.N.L., A.E.R., B.R., D.M., C.D., O.T.C.), Department of Neurology (P.M., E.F., B.R., D.M., C.D., O.T.C.), and Center for Neuroscience (S.N.L., A.E.R., C.D.), University of California, Davis.
Samuel N
SN
Lockhart
From the Imaging of Dementia and Aging Laboratory (P.M., E.F., S.N.L., A.E.R., B.R., D.M., C.D., O.T.C.), Department of Neurology (P.M., E.F., B.R., D.M., C.D., O.T.C.), and Center for Neuroscience (S.N.L., A.E.R., C.D.), University of California, Davis.
Alexandra E
AE
Roach
From the Imaging of Dementia and Aging Laboratory (P.M., E.F., S.N.L., A.E.R., B.R., D.M., C.D., O.T.C.), Department of Neurology (P.M., E.F., B.R., D.M., C.D., O.T.C.), and Center for Neuroscience (S.N.L., A.E.R., C.D.), University of California, Davis.
Bruce
B
Reed
From the Imaging of Dementia and Aging Laboratory (P.M., E.F., S.N.L., A.E.R., B.R., D.M., C.D., O.T.C.), Department of Neurology (P.M., E.F., B.R., D.M., C.D., O.T.C.), and Center for Neuroscience (S.N.L., A.E.R., C.D.), University of California, Davis.
Dan
D
Mungas
From the Imaging of Dementia and Aging Laboratory (P.M., E.F., S.N.L., A.E.R., B.R., D.M., C.D., O.T.C.), Department of Neurology (P.M., E.F., B.R., D.M., C.D., O.T.C.), and Center for Neuroscience (S.N.L., A.E.R., C.D.), University of California, Davis.
Charles
C
DeCarli
From the Imaging of Dementia and Aging Laboratory (P.M., E.F., S.N.L., A.E.R., B.R., D.M., C.D., O.T.C.), Department of Neurology (P.M., E.F., B.R., D.M., C.D., O.T.C.), and Center for Neuroscience (S.N.L., A.E.R., C.D.), University of California, Davis. ocarmichael@ucdavis.edu.
Owen T
OT
Carmichael
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D056324:Diffusion Tensor Imaging; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D011859:Radiography; D013997:Time Factors
aging; diffusion tensor imaging; magnetic resonance imaging; neuroimaging