TY - JOUR
T1 - White matter hyperintensities
T2 - Relationship to amyloid and tau burden
AU - Graff-Radford, Jonathan
AU - Arenaza-Urquijo, Eider M.
AU - Knopman, David S.
AU - Schwarz, Christopher G.
AU - Brown, Robert D.
AU - Rabinstein, Alejandro A.
AU - Gunter, Jeffrey L.
AU - Senjem, Matthew L.
AU - Przybelski, Scott A.
AU - Lesnick, Timothy
AU - Ward, Chadwick
AU - Mielke, Michelle M.
AU - Lowe, Val J.
AU - Petersen, Ronald C.
AU - Kremers, Walter K.
AU - Kantarci, Kejal
AU - Jack, Clifford R.
AU - Vemuri, Prashanthi
N1 - Funding Information:
This work was funded by the National Institute on Aging R37 AG011378 (C.R.J.), K76 AG057015 (J.G-R.), R01 AG041851 (C.R.J. and D.S.K.), U01 AG006786 (R.C.P.), R01 AG034676 (Dr Rocca, PI of the REP study), and R01 AG56366 (P.V.); the National Institute of Neurologic Disorders and Stroke R01 NS097495 (P.V.), and a grant from the GHR Foundation. The sponsors had no role in the development of this study.
Publisher Copyright:
© 2019 The Author(s) (2019). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
PY - 2019/8/1
Y1 - 2019/8/1
N2 - Although white matter hyperintensities have traditionally been viewed as a marker of vascular disease, recent pathology studies have found an association between white matter hyperintensities and Alzheimer's disease pathologies. The objectives of this study were to investigate the topographic patterns of white matter hyperintensities associated with Alzheimer's disease biomarkers measured using PET. From the population-based Mayo Clinic Study of Aging, 434 participants without dementia (55% male) with FLAIR and gradient recall echo MRI, tau-PET (AV-1451) and amyloid-PET scans were identified. A subset had cerebral microbleeds detected on T2∗ gradient recall echo scans. White matter hyperintensities were semi-automatically segmented using FLAIR MRI in participant space and normalized to a custom template. We used statistical parametric mapping 12-based, voxel-wise, multiple-regression analyses to detect white matter hyperintense regions associated with Alzheimer's biomarkers (global amyloid from amyloid-PET and meta-regions of interest tau uptake from tau-PET) after adjusting for age, sex and hypertension. For amyloid associations, we additionally adjusted for tau and vice versa. Topographic patterns of amyloid-associated white matter hyperintensities included periventricular white matter hyperintensities (frontal and parietal lobes). White matter hyperintense volumes in the detected topographic pattern correlated strongly with lobar cerebral microbleeds (P < 0.001, age and sex adjusted Cohen's d = 0.703). In contrast, there were no white matter hyperintense regions significantly associated with increased tau burden using voxel-based analysis or region-specific analysis. Among non-demented elderly, amyloid load correlated with a topographic pattern of white matter hyperintensities. Further, the amyloid-associated, white matter hyperintense regions strongly correlated with lobar cerebral microbleeds suggesting that cerebral amyloid angiopathy contributes to the relationship between amyloid and white matter hyperintensities. The study did not support an association between increased tau burden and white matter hyperintense burden.
AB - Although white matter hyperintensities have traditionally been viewed as a marker of vascular disease, recent pathology studies have found an association between white matter hyperintensities and Alzheimer's disease pathologies. The objectives of this study were to investigate the topographic patterns of white matter hyperintensities associated with Alzheimer's disease biomarkers measured using PET. From the population-based Mayo Clinic Study of Aging, 434 participants without dementia (55% male) with FLAIR and gradient recall echo MRI, tau-PET (AV-1451) and amyloid-PET scans were identified. A subset had cerebral microbleeds detected on T2∗ gradient recall echo scans. White matter hyperintensities were semi-automatically segmented using FLAIR MRI in participant space and normalized to a custom template. We used statistical parametric mapping 12-based, voxel-wise, multiple-regression analyses to detect white matter hyperintense regions associated with Alzheimer's biomarkers (global amyloid from amyloid-PET and meta-regions of interest tau uptake from tau-PET) after adjusting for age, sex and hypertension. For amyloid associations, we additionally adjusted for tau and vice versa. Topographic patterns of amyloid-associated white matter hyperintensities included periventricular white matter hyperintensities (frontal and parietal lobes). White matter hyperintense volumes in the detected topographic pattern correlated strongly with lobar cerebral microbleeds (P < 0.001, age and sex adjusted Cohen's d = 0.703). In contrast, there were no white matter hyperintense regions significantly associated with increased tau burden using voxel-based analysis or region-specific analysis. Among non-demented elderly, amyloid load correlated with a topographic pattern of white matter hyperintensities. Further, the amyloid-associated, white matter hyperintense regions strongly correlated with lobar cerebral microbleeds suggesting that cerebral amyloid angiopathy contributes to the relationship between amyloid and white matter hyperintensities. The study did not support an association between increased tau burden and white matter hyperintense burden.
KW - cerebral amyloid angiopathy
KW - cerebral microbleeds
KW - tau burden
KW - white matter hyperintensities
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U2 - 10.1093/brain/awz162
DO - 10.1093/brain/awz162
M3 - Article
C2 - 31199475
AN - SCOPUS:85070659205
SN - 0006-8950
VL - 142
SP - 2483
EP - 2491
JO - Brain
JF - Brain
IS - 8
ER -