Smith, Charles D.
https://orcid.org/0000-0001-8292-9857
Mayo Clinic
Alzheimer’s Disease Neuroimaging Initiative
Citations 2
Etiology of White Matter Hyperintensities in Autosomal Dominant and Sporadic Alzheimer Disease
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Murali , Petrella, Jeffrey R. , James, Olga, Borges‐Neto, Salvador , Karlawish, Jason , Vaishnavi, Sanjeev , Clark, Christopher M. , Arnold, Steven E. , Smith, Charles D. , Khouli, Riham El , Raslau, Flavius D., Oakley, MaryAnn, Simpson, Donna M., Martin, Kim, Kowalski, Nancy, Keltz, Melanie, Goldstein, Bonnie S., Makino, Kelly M., Ismail, M. 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JAMA Neurology | October 16, 2023 | Volume: 80 | Issue: 12 | Pages: 1353
ImportanceIncreased white matter hyperintensity (WMH) volume is a common magnetic resonance imaging (MRI) finding in both autosomal dominant Alzheimer disease (ADAD) and late-onset Alzheimer disease (LOAD), but it remains unclear whether increased WMH along the AD continuum is reflective of AD-intrinsic processes or secondary to elevated systemic vascular risk factors.ObjectiveTo estimate the associations of neurodegeneration and parenchymal and vessel amyloidosis with WMH accumulation and investigate whether systemic vascular risk is associated with WMH beyond these AD-intrinsic processes.Design, Setting, and ParticipantsThis cohort study used data from 3 longitudinal cohort studies conducted in tertiary and community-based medical centers—the Dominantly Inherited Alzheimer Network (DIAN; February 2010 to March 2020), the Alzheimer’s Disease Neuroimaging Initiative (ADNI; July 2007 to September 2021), and the Harvard Aging Brain Study (HABS; September 2010 to December 2019).Main Outcome and MeasuresThe main outcomes were the independent associations of neurodegeneration (decreases in gray matter volume), parenchymal amyloidosis (assessed by amyloid positron emission tomography), and vessel amyloidosis (evidenced by cerebral microbleeds [CMBs]) with cross-sectional and longitudinal WMH.ResultsData from 3960 MRI sessions among 1141 participants were included: 252 pathogenic variant carriers from DIAN (mean [SD] age, 38.4 [11.2] years; 137 [54%] female), 571 older adults from ADNI (mean [SD] age, 72.8 [7.3] years; 274 [48%] female), and 318 older adults from HABS (mean [SD] age, 72.4 [7.6] years; 194 [61%] female). Longitudinal increases in WMH volume were greater in individuals with CMBs compared with those without (DIAN: t = 3.2 [P = .001]; ADNI: t = 2.7 [P = .008]), associated with longitudinal decreases in gray matter volume (DIAN: t = −3.1 [P = .002]; ADNI: t = −5.6 [P < .001]; HABS: t = −2.2 [P = .03]), greater in older individuals (DIAN: t = 6.8 [P < .001]; ADNI: t = 9.1 [P < .001]; HABS: t = 5.4 [P < .001]), and not associated with systemic vascular risk (DIAN: t = 0.7 [P = .40]; ADNI: t = 0.6 [P = .50]; HABS: t = 1.8 [P = .06]) in individuals with ADAD and LOAD after accounting for age, gray matter volume, CMB presence, and amyloid burden. In older adults without CMBs at baseline, greater WMH volume was associated with CMB development during longitudinal follow-up (Cox proportional hazards regression model hazard ratio, 2.63; 95% CI, 1.72-4.03; P < .001).Conclusions and RelevanceThe findings suggest that increased WMH volume in AD is associated with neurodegeneration and parenchymal and vessel amyloidosis but not with elevated systemic vascular risk. Additionally, increased WMH volume may represent an early sign of vessel amyloidosis preceding the emergence of CMBs.
Peripheral (deep) but not periventricular MRI white matter hyperintensities are increased in clinical vascular dementia compared to Alzheimer's disease
Smith, Charles D. , Johnson, Eleanor S. , Jicha, Gregory A. , Schmitt, Frederick A. , Nelson, Peter T. , Kryscio, Richard J. , Murphy, Ronan, Wellnitz, Clinton V., Eldik, Linda J. Van , Jicha, Gregory A
Brain and Behavior | February 16, 2016 | Volume: 6 | Issue: 3 | Pages: No page available
AbstractBackground and purposeVascular dementia (VAD) is a complex diagnosis at times difficult to distinguish from Alzheimer's disease (AD). MRI scans often show white matter hyperintensities (WMH) in both conditions. WMH increase with age, and both VAD and AD are associated with aging, thus presenting an attribution conundrum. In this study, we sought to show whether the amount of WMH in deep white matter (dWMH), versus periventricular white matter (PVH), would aid in the distinction between VAD and AD, independent of age.MethodsBlinded semiquantitative ratings of WMH validated by objective quantitation of WMH volume from standardized MRI image acquisitions. PVH and dWMH were rated separately and independently by two different examiners using the Scheltens scale. Receiver operator characteristic (ROC) curves were generated using logistic regression to assess classification of VAD (13 patients) versus AD (129 patients). Clinical diagnoses were made in a specialty memory disorders clinic.ResultsUsing PVH rating alone, overall classification (area under the ROC curve, AUC) was 75%, due only to the difference in age between VAD and AD patients in our study and not PVH. In contrast, dWMH rating produced 86% classification accuracy with no independent contribution from age. A global Longstreth rating that combines dWMH and PVH gave an 88% AUC.ConclusionsIncreased dWMH indicate a higher likelihood of VAD versus AD. Assessment of dWMH on MRI scans using Scheltens and Longstreth scales may aid the clinician in distinguishing the two conditions.