Are acute infarcts the cause of leukoaraiosis? Brain mapping for 16 consecutive weeks

Conklin, John; Silver, Frank L.; Mikulis, David J.; Mandell, Daniel M.

doi:10.1002/ana.24285

Cited by 73 publications

(62 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5,6 Recent findings link WMHs to an accumulation of tiny infarctions, 34 which could cause such tissue damage. However, WMHs primarily develop in regions with low perfusion, suggesting that low perfusion is involved in WMH conception.…”

Section: Discussionmentioning

confidence: 99%

White Matter Hyperintensity Volume and Cerebral Perfusion in Older Individuals with Hypertension Using Arterial Spin-Labeling

Dalen¹,

Mutsaerts

Nederveen

et al. 2016

AJNR Am J Neuroradiol

View full text Add to dashboard Cite

BACKGROUND AND PURPOSE:White matter hyperintensities of presumed vascular origin in elderly patients with hypertension may be part of a general cerebral perfusion deficit, involving not only the white matter hyperintensities but also the surrounding normal-appearing white matter and gray matter. We aimed to study the relation between white matter hyperintensity volume and CBF and assess whether white matter hyperintensities are related to a general perfusion deficit.

show abstract

Section: Discussionmentioning

confidence: 99%

White Matter Hyperintensity Volume and Cerebral Perfusion in Older Individuals with Hypertension Using Arterial Spin-Labeling

Dalen¹,

Mutsaerts

Nederveen

et al. 2016

AJNR Am J Neuroradiol

View full text Add to dashboard Cite

show abstract

“…However, recent evidence has shown that accumulation of microinfarcts may lead to the development of WMHs. 36 Recent research using transcranial Doppler ultrasound found that arterial stiffening reduces damping of the arterial waveform and increases cerebral pulsatility, which may damage small vessels, increase shear stress, and exacerbate impaired CVR. 37 Another factor influencing arterial pulsations, venous collagenosis, is a mechanical consequence of increased cerebral pulsatility and mechanical fatigue of vascular smooth muscles.…”

Section: Methods Participant Recruitment and Assessmentmentioning

confidence: 99%

Cerebrovascular reactivity and white matter integrity

et al. 2016

Self Cite

View full text Add to dashboard Cite

Objective: To compare the diffusion and perfusion MRI metrics of normal-appearing white matter (NAWM) with and without impaired cerebrovascular reactivity (CVR).Methods: Seventy-five participants with moderate to severe leukoaraiosis underwent blood oxygen level-dependent CVR mapping using a 3T MRI system with precise carbon dioxide stimulus manipulation. Several MRI metrics were statistically compared between areas of NAWM with positive and negative CVR using one-way analysis of variance with Bonferroni correction for multiple comparisons.Results: Areas of NAWM with negative CVR showed a significant reduction in fractional anisotropy by a mean (SD) of 3.7% (2.4), cerebral blood flow by 22.1% (8.2), regional cerebral blood volume by 22.2% (7.0), and a significant increase in mean diffusivity by 3.9% (3.1) and time to maximum by 10.9% (13.2) (p , 0.01), compared to areas with positive CVR.Conclusions: Impaired CVR is associated with subtle changes in the tissue integrity of NAWM, as evaluated using several quantitative diffusion and perfusion MRI metrics. These findings suggest that impaired CVR may contribute to the progression of white matter disease. Changes in the periventricular and subcortical white matter are observed on both CT and MRI scans of elderly individuals.1 The affected areas appear hyperintense on T2-weighted MRI, and are labeled as white matter hyperintensities (WMHs) if they are of presumed vascular origin. 2They are associated with an increased risk of dementia, 3 stroke, 4 and cognitive disability, 5 and correlated with age; as many as 95% of individuals over age 50 have WMHs.6,7 Therefore, preventing or slowing the progression of WMHs has the potential to lower the disease burden. Although several modifiable risk factors have been associated with WMH progression, such as smoking and high blood pressure, 8 the detailed pathogenesis of WMHs remains controversial. Nevertheless, the prevailing view is that a chronic low-grade ischemic injury is the final common pathway for these lesions, 9,10 and this view was the motivation for our study. Accordingly, this study characterized vascular pathophysiology in normal-appearing white matter (NAWM) before progression to overt leukoaraiosis by measuring cerebrovascular reactivity (CVR); the change in cerebral blood flow in response to a vasodilatory stimulus. Negative CVR values represent steal physiology, in which blood flow is redistributed from regions of exhausted cerebral vasodilatory reserve to areas with preserved vasodilatory capacity. 11 WeFrom the Department of Physiology

show abstract

“…6 PVWMH have recently been shown to develop by acute infarction adjacent to older lesions with extension occurring proximally towards the cortical surface favoring cortical arterial disease and hypoperfusion as an important cause. 7,8 We hypothesized that measuring PVWMH burden would provide a quantitative measure of cortical arterial disease and facilitate exploration of associations with cerebral amyloid deposition. Therefore, in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort, we investigated the association between CSF and PET markers of elevated Ab and PVWMH.…”

mentioning

confidence: 99%

Periventricular hyperintensities are associated with elevated cerebral amyloid

Marnane¹,

Aljawadi²,

Mortazavi³

et al. 2016

Neurology

View full text Add to dashboard Cite

Objective: To investigate the association between periventricular white mater hyperintensities (PVWMH) and biomarkers of elevated cerebral b-amyloid (Ab) in the Alzheimer's Disease Neuroimaging Initiative, a large prospective multicenter observational study. Methods:The burden of frontal, parietal, and occipital PVWMH on 3T fluid-attenuated inversion recovery MRI was evaluated in 698 cognitively normal participants and participants with mild cognitive impairment (MCI) using a novel semiquantitative visual rating scale. Results were correlated with CSF-Ab, florbetapir-PET, and fluorodeoxyglucose (FDG)-PET.Results: Increased burden of parietal, occipital, and frontal PVWMH was associated with elevated cerebral amyloid evidenced by high florbetapir-PET signal (p , 0.01) and low CSF-Ab (p , 0.01).In logistic regression models, including PVWMH, age, sex, APOE status, vascular risk factors, pulse pressure, vascular secondary prevention medications, education, ethnicity, and race, parietal, occipital, and frontal PVWMH burden was independently associated with high florbetapir-PET uptake (p , 0.05). In a similar logistic regression model, parietal and occipital (p , 0.05) but not frontal (p 5 0.05) PVWMH were independently associated with CSF-Ab. Weaker associations were found between parieto-occipital PVWMH and elevated CSF-tau (p , 0.05) and occipital PVWMH and elevated CSF-phospho-tau (p , 0.05). PVWMH were associated with cerebral hypometabolism on FDG-PET independent of CSF-Ab levels (p , 0.05). Absolute and consistency of agreement intraclass correlation coefficients were, respectively, 0.83 and 0.83 for frontal, 0.78 and 0.8 for parietal, and 0.45 and 0.75 for occipital PVWMH measurements.Conclusions: Increased PVWMH were associated with elevated cerebral amyloid independent of potential confounders such as age, APOE genotype, and vascular risk factors. The mechanisms underlying the association between PVWMH and cerebral amyloid remain to be clarified. Pathologic and imaging studies have shown that in Alzheimer disease (AD), cerebral small vessel disease (SVD) is coexistent in up to 80% and hastens cognitive deterioration.1 Whether this reflects parallel neuronal injury or synergistic worsening of AD pathogenic mechanisms remains unclear. 2There has been recent interest in the putative role of SVD in disruption of physiologic interstitial fluid bulk flow and paravascular mechanisms of b-amyloid (Ab) clearance.3 If SVD is an

show abstract

Are acute infarcts the cause of leukoaraiosis? Brain mapping for 16 consecutive weeks

Cited by 73 publications

References 34 publications

White Matter Hyperintensity Volume and Cerebral Perfusion in Older Individuals with Hypertension Using Arterial Spin-Labeling

White Matter Hyperintensity Volume and Cerebral Perfusion in Older Individuals with Hypertension Using Arterial Spin-Labeling

Cerebrovascular reactivity and white matter integrity

Periventricular hyperintensities are associated with elevated cerebral amyloid

Contact Info

Product

Resources

About