Peak Width of Skeletonized Mean Diffusivity as a Marker of Diffuse Cerebrovascular Damage

Low, Audrey; Mak, Elijah; Stefaniak, James D.; Malpetti, Maura; Nicastro, Nicolas; Savulich, George; Chouliaras, Leonidas; Markus, Hugh S.; Rowe, James B.

doi:10.3389/fnins.2020.00238

Cited by 26 publications

(70 citation statements)

References 31 publications

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“…PSMD was also more strongly associated with performance on select cognitive tasks compared to traditional diffusion metrics mean FA and mean MD. The relative superiority of PSMD observed here converges with recent evidence in healthy aging [33][34][35][36]58], preclinical Alzheimer's disease [59], and sporadic and inherited SVD [30,31,60] and highlights the clinical relevance of this marker in LLD.…”

Section: Agesupporting

confidence: 86%

“…By combining skeletonization and histogram analysis, PSMD captures the distribution of mean diffusivity (MD) values across the white matter compartment, providing a global estimate of diffuse white matter dysfunction [30]. In several recent studies, PSMD outperformed conventional MRI measures in detecting cognitive deficits in samples with sporadic and inherited SVD [30][31][32], and correlated more strongly with cognitive performance in healthy elderly community populations with imaging features of SVD (WMH) [33][34][35][36]. PSMD has not yet been evaluated in depressed older adults but may enable more precise characterization of the scope of cognitive deficits associated with vascular pathology in LLD.…”

Section: Introductionmentioning

confidence: 99%

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Late-life depression accentuates cognitive weaknesses in older adults with small vessel disease

Oberlin

Respino

Victoria

et al. 2021

Neuropsychopharmacol.

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Neuroimaging features of small vessel disease (SVD) are highly prevalent in older adulthood and associated with significant variability in clinical symptoms, yet the factors predicting these symptom disparities are poorly understood. We employed a novel metric of SVD, peak width of skeletonized mean diffusivity (PSMD), to elucidate the relationship of late-life depression (LLD) to the cognitive presentation of vascular pathology. A total of 109 older adults without a diagnosis of a neurocognitive disorder were enrolled in the study; 44 with major depressive disorder and 65 age-matched controls. Subjects completed neuropsychological testing and magnetic resonance imaging including FLAIR and diffusion tensor imaging sequences, from which white matter hyperintensity volume and diffusion metrics (fractional anisotropy, mean diffusivity, PSMD) were quantified. In hierarchical models, the relationship between vascular burden and cognitive performance varied as a function of diagnostic status, such that the negative association between PSMD and processing speed was significantly stronger in participants with LLD compared to controls. Greater PSMD also predicted poorer performance on delayed memory and executive function tasks specifically among those with LLD, while there were no associations between PSMD and task performance among controls. PSMD outperformed conventional SVD and diffusion markers in predicting cognitive performance and dysexecutive behaviors in participants with LLD. These data suggest that LLD may confer a vulnerability to the cognitive manifestations of white matter abnormalities in older adulthood. PSMD, a novel biomarker of diffuse microstructural changes in SVD, may be a more sensitive marker of subtle cognitive deficits stemming from vascular pathology in LLD.

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Section: Agesupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Late-life depression accentuates cognitive weaknesses in older adults with small vessel disease

Oberlin

Respino

Victoria

et al. 2021

Neuropsychopharmacol.

View full text Add to dashboard Cite

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“…In a recent study, we showed that diffusion tensor imaging can capture subtle microstructural WM changes due to increased vascular risk even in the absence of visible CVD. 8 Our study along with others 9 , 10 support the utility of dMRI as a marker of CVD.…”

Section: Introductionsupporting

confidence: 75%

“…Changes even in normal appearing WM associated with myelin damage, axonal loss and gliosis are expected and have been suggested to be captured using dMRI and these changes are predictive of cognitive performance. 9 , 10 The pathologic basis of the diffusion changes needs further confirmation. However, there is strong evidence that diffusion related changes in the tissue microstructure are reflective of progressive WM damage even before the appearance of WMH.…”

Section: Discussionmentioning

confidence: 99%

White matter abnormalities are key components of cerebrovascular disease impacting cognitive decline

Vemuri

Graff‐Radford

Lesnick

et al. 2021

Brain Communications

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While cerebrovascular disease can be observed in vivo using MRI, the multiplicity and heterogeneity in the mechanisms of cerebrovascular damage impedes accounting for these measures in aging and dementia studies. Our primary goal was to investigate the key sources of variability across MRI markers of cerebrovascular disease and evaluate their impact in comparison to amyloidosis on cognitive decline in a population-based sample. Our secondary goal was to evaluate the prognostic utility of a cerebrovascular summary measure from all markers. We included both visible lesions seen on MRI (white matter hyperintensities, cortical and subcortical infarctions, lobar and deep microbleeds) and early white matter damage due to systemic vascular health using diffusion changes in the genu of the corpus callosum from diffusion MRI.

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“…In contrast, PSMD was not associated with cognitive function in subjects with non-CAA-MCI. PSMD studies have, so far, focused mainly on community-dwelling 13,32,33 and cognitively impaired elderly subjects, 13,34 as well as those with inherited 13,35 and sporadic cSVD. 13,36 To our knowledge, only 1 previous study has investigated the performance of PSMD in sporadic CAA, including subjects with and without ICH recruited from both stroke-prevention and memory clinics.…”

Section: Discussionmentioning

confidence: 99%

Peak Width of Skeletonized Mean Diffusivity as Neuroimaging Biomarker in Cerebral Amyloid Angiopathy

Raposo

Zotin

Schoemaker

et al. 2021

AJNR Am J Neuroradiol

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BACKGROUND AND PURPOSE: Whole-brain network connectivity has been shown to be a useful biomarker of cerebral amyloid angiopathy and related cognitive impairment. We evaluated an automated DTI-based method, peak width of skeletonized mean diffusivity, in cerebral amyloid angiopathy, together with its association with conventional MRI markers and cognitive functions. MATERIALS AND METHODS: We included 24 subjects (mean age, 74.7 [SD, 6.0] years) with probable cerebral amyloid angiopathy and mild cognitive impairment and 62 patients with MCI not attributable to cerebral amyloid angiopathy (non-cerebral amyloid angiopathy-mild cognitive impairment). We compared peak width of skeletonized mean diffusivity between subjects with cerebral amyloid angiopathy-mild cognitive impairment and non-cerebral amyloid angiopathy-mild cognitive impairment and explored its associations with cognitive functions and conventional markers of cerebral small-vessel disease, using linear regression models. RESULTS: Subjects with Cerebral amyloid angiopathy-mild cognitive impairment showed increased peak width of skeletonized mean diffusivity in comparison to those with non-cerebral amyloid angiopathy-mild cognitive impairment (P , .001). Peak width of skeletonized mean diffusivity values were correlated with the volume of white matter hyperintensities in both groups. Higher peak width of skeletonized mean diffusivity was associated with worse performance in processing speed among patients with cerebral amyloid angiopathy, after adjusting for other MRI markers of cerebral small vessel disease. The peak width of skeletonized mean diffusivity did not correlate with cognitive functions among those with non-cerebral amyloid angiopathy-mild cognitive impairment. CONCLUSIONS: Peak width of skeletonized mean diffusivity is altered in cerebral amyloid angiopathy and is associated with performance in processing speed. This DTI-based method may reflect the degree of white matter structural disruption in cerebral amyloid angiopathy and could be a useful biomarker for cognition in this population. ABBREVIATIONS: CAA ¼ cerebral amyloid angiopathy; CMB ¼ cerebral microbleeds; CSO-PVS ¼ perivascular spaces in the centrum semiovale; cSS ¼ cortical superficial siderosis; cSVD ¼ cerebral small vessel disease; ICH ¼ intracerebral hemorrhage; IQR ¼ interquartile range; MCI ¼ mild cognitive impairment; MD ¼ mean diffusivity; MMSE ¼ Mini-Mental State Examination; PSMD ¼ peak width of skeletonized mean diffusivity; nTBV ¼ normalized total brain volume; nWMHV ¼ normalized white matter hyperintensity volume; WMH ¼ white matter hyperintensities S poradic cerebral amyloid angiopathy (CAA) is a highly prevalent cerebral small-vessel disease (cSVD) in the elderly. 1 CAA is a well-known cause of lobar intracerebral hemorrhage (ICH) and is also increasingly recognized as a major contributor to vascular cognitive impairment and dementia. 2,3 Although underlying

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Peak Width of Skeletonized Mean Diffusivity as a Marker of Diffuse Cerebrovascular Damage

Cited by 26 publications

References 31 publications

Late-life depression accentuates cognitive weaknesses in older adults with small vessel disease

Late-life depression accentuates cognitive weaknesses in older adults with small vessel disease

White matter abnormalities are key components of cerebrovascular disease impacting cognitive decline

Peak Width of Skeletonized Mean Diffusivity as Neuroimaging Biomarker in Cerebral Amyloid Angiopathy

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