What are White Matter Hyperintensities Made of?

Wardlaw, Joanna M.; Hernández, Maria C. Valdés; Muñoz‐Maniega, Susana

doi:10.1161/jaha.114.001140

Cited by 664 publications

(439 citation statements)

References 173 publications

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“…25-27 35 WMH have important clinical and risk factor associations, underlining that they should not be ignored as inevitable 'silent' consequences of the physiological ageing of the brain. 36 In our study, 7.8% of the participants presented with relevant WMH (Fazekas score ≥2) and their prevalence significantly increased with advancing age. These results confirm previous findings where a 10-fold increase in the prevalence of WMH was found in participants older than 55, especially in those with risk factors for small vessel disease such as hypertension and diabetes.…”

Section: Discussionmentioning

confidence: 43%

Incidental findings on brain MRI of cognitively normal first-degree descendants of patients with Alzheimer's disease: a cross-sectional analysis from the ALFA (Alzheimer and Families) project

et al. 2017

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ObjectivesTo describe the prevalence of brain MRI incidental findings (IF) in a cohort of cognitively normal first-degree descendants of patients with Alzheimer's disease (AD).DesignCross-sectional observational study.SettingAll scans were obtained with a 3.0 T scanner. Scans were evaluated by a single neuroradiologist and IF recorded and categorised. The presence of white matter hyperintensities (WMH) was determined with the Fazekas scale and reported as relevant if ≥2.Participants575 participants (45–75 years) underwent high-resolution structural brain MRI. Participants were cognitively normal and scored over the respective cut-off values in all the following neuropsychological tests: Mini-Mental State Examination (≥26), Memory Impairment Screen (≥6), Time Orientation Subtest of the Barcelona Test II (≥68), verbal semantic fluency (naming animals ≥12). Clinical Dementia Rating (CDR) had to be 0.Results155 participants (27.0%) presented with at least one IF. Relevant WMH were present in 7.8% of the participants, and vascular abnormalities, cyst and brain volume loss in 10.7%, 3.1% and 6.9% of the study volunteers, respectively. Neoplastic brain findings were found in 2.4% of participants and within these, meningiomas were the most common (1.7%) and more frequently found in women. A positive correlation between increasing age and the presence of IF was found. Additionally, brain atrophy greater than that expected by age was significantly more prevalent in participants without a parental history of AD.ConclusionsBrain MRIs of healthy middle-aged participants show a relatively high prevalence of IF even when study participants have been screened for subtle cognitive alterations. Most of our participants are first-degree descendants of patients with AD, and therefore these results are of special relevance for novel imaging studies in the context of AD prevention in cognitively healthy middle-aged participants.Trial registration numberNCT02198586.

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Section: Discussionmentioning

confidence: 43%

Incidental findings on brain MRI of cognitively normal first-degree descendants of patients with Alzheimer's disease: a cross-sectional analysis from the ALFA (Alzheimer and Families) project

et al. 2017

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“…The result that information about white matter water diffusion from both NODDI and more conventional measures is more informative for age than white matter volume might indicate that these biomarkers are more sensitive to subtle age-related differences in white matter. However, it is important to note that a global white matter measure can be divided into normal-appearing and white-matter hyperintensity volume in older subjects45. The latter, a marker of white matter disease45, appears to progress independently of grey matter changes46, but was not derived in the current data set.…”

Section: Discussionmentioning

confidence: 86%

“…However, it is important to note that a global white matter measure can be divided into normal-appearing and white-matter hyperintensity volume in older subjects45. The latter, a marker of white matter disease45, appears to progress independently of grey matter changes46, but was not derived in the current data set. It may be that the insensitivity of total white matter volume to the important ratio of normal-appearing:white-matter hyperintensity volume may partly account for its lack of predictive value in our models.…”

Section: Discussionmentioning

confidence: 86%

Ageing and brain white matter structure in 3,513 UK Biobank participants

et al. 2016

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Quantifying the microstructural properties of the human brain's connections is necessary for understanding normal ageing and disease. Here we examine brain white matter magnetic resonance imaging (MRI) data in 3,513 generally healthy people aged 44.64-77.12 years from the UK Biobank. Using conventional water diffusion measures and newer, rarely studied indices from neurite orientation dispersion and density imaging, we document large age associations with white matter microstructure. Mean diffusivity is the most age-sensitive measure, with negative age associations strongest in the thalamic radiation and association fibres. White matter microstructure across brain tracts becomes increasingly correlated in older age. This may reflect an age-related aggregation of systemic detrimental effects. We report several other novel results, including age associations with hemisphere and sex, and comparative volumetric MRI analyses. Results from this unusually large, single-scanner sample provide one of the most extensive characterizations of age associations with major white matter tracts in the human brain.

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“…Imaging techniques, such as diffusion tensor imaging (DTI), can possibly provide additional information on these earlier stages by the assessment of the microstructural organization of the white matter (WM). [6][7][8][9] Previous longitudinal studies have shown changes in baseline DTI parameters, that is, decreased fractional anisotropy (FA) and increased mean diffusivity (MD), that predicted incident WMH at follow-up. over time.…”

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confidence: 99%

Progression of White Matter Hyperintensities Preceded by Heterogeneous Decline of Microstructural Integrity

Leijsen¹,

Bergkamp²,

Uden³

et al. 2018

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Background and Purpose-White matter hyperintensities (WMH) are frequently seen on neuroimaging of elderly and are associated with cognitive decline and the development of dementia. Yet, the temporal dynamics of conversion of normalappearing white matter (NAWM) into WMH remains unknown. We examined whether and when progression of WMH was preceded by changes in fluid-attenuated inversion recovery and diffusion tensor imaging values, thereby taking into account differences between participants with mild versus severe baseline WMH. Methods-From 266 participants of the RUN DMC study (Radboud University Nijmegen Diffusion Tensor and MagneticResonance Imaging Cohort), we semiautomatically segmented WMH at 3 time points for 9 years. Images were registered to standard space through a subject template. We analyzed differences in baseline fluid-attenuated inversion recovery, fractional anisotropy, and mean diffusivity (MD) values and changes in MD values over time between 4 regions: (1) remaining NAWM, (2) NAWM converting into WMH in the second follow-up period, (3) NAWM converting into WMH in the first follow-up period, and (4)

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What are White Matter Hyperintensities Made of?

Cited by 664 publications

References 173 publications

Incidental findings on brain MRI of cognitively normal first-degree descendants of patients with Alzheimer's disease: a cross-sectional analysis from the ALFA (Alzheimer and Families) project

Incidental findings on brain MRI of cognitively normal first-degree descendants of patients with Alzheimer's disease: a cross-sectional analysis from the ALFA (Alzheimer and Families) project

Ageing and brain white matter structure in 3,513 UK Biobank participants

Progression of White Matter Hyperintensities Preceded by Heterogeneous Decline of Microstructural Integrity

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