White matter hyperintensities

Background: White matter hyperintensities are an important marker of cerebral small vessel disease.

Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. White matter hyperintensities WMHs are commonly seen on brain MRI in older people, and result from chronic ischaemia associated with cerebral small vessel disease. The histopathology of WMHs is heterogeneous, with tissue damage ranging from slight disentanglement of the matrix to varying degrees of myelin and axonal loss. This heterogeneity might partly explain the weak clinicoradiological associations found in patients with WMHs.

White matter hyperintensities

As such, white matter hyperintensities have been targeted as a surrogate biomarker in intervention trials with older adults. However, it is unclear at what stage of aging white matter hyperintensities begin to relate to cognition and if they may be a viable target for early prevention. In the Dunedin Study, a population-representative cohort followed since birth, we measured white matter hyperintensities in year-old participants using T 2 -weighted magnetic resonance imaging and we assessed cognitive decline from childhood to midlife. Our results demonstrate that a link between white matter hyperintensities and early signs of cognitive decline is detectable decades before clinical symptoms of dementia emerge. Thus, white matter hyperintensities may be a useful surrogate biomarker for identifying individuals in midlife at risk for future accelerated cognitive decline and selecting participants for dementia prevention trials. However, the success of this investment hinges on developing surrogate biomarkers—biological measures that are part of the putative disease pathway and are measurable before the onset of clinical symptoms—so that prevention can target at-risk individuals before cerebral decline has taken hold. Successful surrogate biomarkers would allow clinicians to assess risk, monitor sub-clinical disease progression and intervene before clinically significant dementia symptoms manifest. Research shows that white matter hyperintensities WMHs are one such surrogate biomarker of cognitive decline and ADRD that can be measured in the brains of older adults Cees De Groot et al. While WMHs are uncommon in adults before age 30 Habes et al. In older adults, WMHs are associated with multiple dementia risk factors, including increasing age, hypertension, stroke, brain atrophy and cognitive ability Prins and Scheltens, Longitudinal studies in older adults have reported that the spread of WMHs contributes to elevated risk for ADRD and coincides with age-related cognitive decline Debette and Markus, Consequently, WMHs have been targeted as a surrogate biomarker for dementia prevention trials Debette and Markus, However, these trials have produced mixed results Prins and Scheltens, A limitation of existing trials is that they have targeted older adults in their 60s, 70s and 80s. Older brains are characterized by age-related deterioration and may be less responsive to intervention Sperling et al.

Studies have demonstrated associations with various cognitive impairments, neurological diseases, and neuropathologies, as well as clinical and risk factors, such as age, sex, and hypertension.

White matter hyperintensities WMHs are lesions in the brain that show up as areas of increased brightness when visualised by T2-weighted magnetic resonance imaging MRI. The prevailing view is that these intensities are a marker of small-vessel vascular disease and in clinical practice, are indicative of cognitive and emotional dysfunction, particularly in the ageing population. This is clearly not true. Although WMH do become more common with advancing age, their prevalence is highly variable. There is strong evidence that WMH are clinically important markers of increased risk of stroke, dementia, death, depression, impaired gait, and mobility, in cross-sectional and in longitudinal studies. They associate with brain damage such as global atrophy and other features of small vessel brain damage, with focal progressive visible brain damage, are markers of underlying subvisible diffuse brain damage, and predict infarct growth and worse outcome after large artery stroke.

A hyperintensity or T2 hyperintensity is an area of high intensity on types of magnetic resonance imaging MRI scans of the brain of a human or of another mammal that reflect lesions produced largely by demyelination and axonal loss. The volume and frequency is strongly associated with increasing age. For example, deep white matter hyperintensities are 2. Hyperintensities are commonly divided into 3 types depending on the region of the brain where they are found. Deep white matter hyperintensities occur deep within white matter, periventricular white matter hyperintensities occur adjacent to the lateral ventricles and subcortical hyperintensities occur in the basal ganglia. Hyperintensities are often seen in auto immune diseases that have effects on the brain. Postmortem studies combined with MRI suggest that hyperintensities are dilated perivascular spaces , or demyelination caused by reduced local blood flow. White matter hyperintensities can be caused by a variety of factors including ischemia , micro- hemorrhages , gliosis , damage to small blood vessel walls, breaches of the barrier between the cerebrospinal fluid and the brain, or loss and deformation of the myelin sheath. In most elderly people, presence of severe WMH and medial temporal lobe atrophy MTA was linked with an increase in frequency of mild cognitive deficits. Studies suggest that a combination of MTA and severe WMH showed more than a fourfold increase in the frequency of mild cognitive deficits.

White matter hyperintensities

Leukoaraiosis is a particular abnormal change in appearance of white matter near the lateral ventricles. It is often seen in aged individuals, but sometimes in young adults. These white matter changes are also commonly referred to as periventricular white matter disease, or white matter hyperintensities WMH , due to their bright white appearance on T2 MRI scans. Many patients can have leukoaraiosis without any associated clinical abnormality. However, underlying vascular mechanisms are suspected to be the cause of the imaging findings. Hypertension , smoking, diabetes , [3] hyperhomocysteinemia , and heart diseases are all risk factors for leukoaraiosis. Leukoaraiosis has been reported to be an initial stage of Binswanger's disease but this evolution does not always happen. White matter hyperintensities can be caused by a variety of factors, including ischemia , micro- hemorrhages , gliosis , damage to small blood vessel walls, breaches of the barrier between the cerebrospinal fluid and the brain, or loss and deformation of the myelin sheath. Patients may develop cognitive impairment and dementia.

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A systematic review. Neuroepidemiology 24 , 51—62 The appearance of a new white matter lesion adjacent to the old infarct in first-ever lacunar stroke patients: a two-year follow-up study with MRI. The clinical importance of white matter hyperintensities Debette et al. White matter hyperintensities are a predictor for vascular disease for which age and high blood pressure are the main risk factors. Image processing methods that correct for magnetic field inhomogeneities have been used in some studies. Brickman, A. Article Navigation. Correspondence to: Dr. They associate with brain damage such as global atrophy and other features of small vessel brain damage, with focal progressive visible brain damage, are markers of underlying subvisible diffuse brain damage, and predict infarct growth and worse outcome after large artery stroke. Assessment of blood—brain barrier disruption using dynamic contrast-enhanced MRI. Although WMH do become more common with advancing age, 17 their prevalence is highly variable. Others have not identified direct evidence of blood-brain barrier BBB impairment despite identifying proteins associated with endothelial activation 83 and that had extravasated into the perivascular tissues. Kim, J. Data were extracted using a standardized form that captured 1 disease type s , 2 the number of patients of each disease type, 3 age, 4 sex, 5 the quantification method, and 6 spatial pattern analysis.

White matter provides connections between the different parts of the brain. The brain is made up of a mixture of grey matter and white matter. White matter is found in the deeper tissues known as the subcortical area.

Given that prevention of damage is often more efficacious than reversal of damage Sperling et al. Cigarette smoking is associated with reduced microstructural integrity of cerebral white matter. White matter hyperintensities and cognition: testing the reserve hypothesis. Mouse models to study the effect of cardiovascular risk factors on brain structure and cognition. It is commonly characterized using semi-quantitative visual rating scales, such as Fazekas, Fazekas et al. DeCarli, C. Image processing methods that correct for magnetic field inhomogeneities have been used in some studies. White matter hyperintensity progression and late-life depression outcomes Taylor, W. White matter hyperintensities WMH of presumed vascular origin, also referred to as leukoaraiosis, are a very common finding on brain magnetic resonance imaging MRI or computed tomography CT in older subjects and in patients with stroke and dementia. Search ADS. Viswanathan, A.