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Structural neuroimaging in Altheimer's disease: do white matter hyperintensities matter?

Brickman AM, Muraskin J, Zimmerman ME - Dialogues Clin Neurosci (2009)

Bottom Line: The targeted brain dysfunction that accompanies aging can have a devastating effect on cognitive and intellectual abilities.Studies suggest that WMH distributed in anterior brain regions are related to decline in executive abilities that is typical of normal aging, whereas WMH distributed in more posterior brain regions are common in AD.Although epidemiological, observational, and pathological studies suggest that WMH may be ischemic in origin and caused by consistent or variable hypoperfusion, there is emerging evidence that they may also reflect vascular deposition of beta-amyloid, particularly when they are distributed in posterior areas and are present in patients with AD.

View Article: PubMed Central - PubMed

Affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. amb2139@columbia.edu

ABSTRACT
The targeted brain dysfunction that accompanies aging can have a devastating effect on cognitive and intellectual abilities. A significant proportion of older adults experience precipitous cognitive decline that negatively impacts functional activities. Such individuals meet clinical diagnostic criteria for dementia, which is commonly attributed to Alzheimer's disease (AD). Structural neuroimaging, including magnetic resonance imaging (MRI), has contributed significantly to our understanding of the morphological and pathology-related changes that may underlie normal and disease-associated cognitive change in aging. White matter hyperintensities (WMH), which are distributed patches of increased hyperintense signal on T2-weighted MRI, are among the most common structural neuroimaging findings in older adults. In recent years, WMH have emerged as robust radiological correlates of cognitive decline. Studies suggest that WMH distributed in anterior brain regions are related to decline in executive abilities that is typical of normal aging, whereas WMH distributed in more posterior brain regions are common in AD. Although epidemiological, observational, and pathological studies suggest that WMH may be ischemic in origin and caused by consistent or variable hypoperfusion, there is emerging evidence that they may also reflect vascular deposition of beta-amyloid, particularly when they are distributed in posterior areas and are present in patients with AD. Findings from the literature highlight the potential contribution of small-vessel cerebrovascular disease to the pathogenesis of AD, and suggest a mechanistic interaction, but future longitudinal studies using multiple imaging modalities are required to fully understand the complex role of WMH in AD.

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Three-dimensional reconstruction of white matter hyperintensities (WMH) superimposed on a T1 -weighted high resolution anatomical image. Patient on the left has relatively mild distribution of periventricular WMH; patient on the right has more severe distribution with WMH extending into deep cortical areas.
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DialoguesClinNeurosci-11-181-g002.tif: Three-dimensional reconstruction of white matter hyperintensities (WMH) superimposed on a T1 -weighted high resolution anatomical image. Patient on the left has relatively mild distribution of periventricular WMH; patient on the right has more severe distribution with WMH extending into deep cortical areas.

Mentions: White matter hyperintensities, sometimes referred to as leukoaraiosis or leukoencephalopathy, are areas of increased lucency visualized on T2-weighted images. They have enjoyed a rich, albeit capricious, history in clinical practice and in the aging literature, at points considered incidental with little clinical significance and at points considered a central source of cognitive, motoric, and emotional dysfunction. Initially, WMH were described as “unidentifiable bright objects,” confounding radiologists as either artifact ual or adventitious companions of aging. Indeed, chronological age is the strongest correlate of WMH severity14-16 and most older adults have some degree of WMH burden. (Figure 1) displays a typical example of distributed WMH and (Figure 2) shows examples of two elderly individuals, one with mild WMH and one with more severe WMH reconstructed in three dimensions. White matter hyperintensities usually appear in the white matter confluent to the lateral ventricles (ie, “periventricular” WMH), often projecting deep into cortical white matter and grey matter nuclei (ie, “deep” WMH), or as circumscribed punctate spheres in deep cortical tissue. Of note, punctate WMH often appear as isolated lesions on two-dimensional MRI axial slices, but with three-dimensional reconstruction it often becomes evident that they are contained within the same process stemming off the lateral ventricles.


Structural neuroimaging in Altheimer's disease: do white matter hyperintensities matter?

Brickman AM, Muraskin J, Zimmerman ME - Dialogues Clin Neurosci (2009)

Three-dimensional reconstruction of white matter hyperintensities (WMH) superimposed on a T1 -weighted high resolution anatomical image. Patient on the left has relatively mild distribution of periventricular WMH; patient on the right has more severe distribution with WMH extending into deep cortical areas.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2864151&req=5

DialoguesClinNeurosci-11-181-g002.tif: Three-dimensional reconstruction of white matter hyperintensities (WMH) superimposed on a T1 -weighted high resolution anatomical image. Patient on the left has relatively mild distribution of periventricular WMH; patient on the right has more severe distribution with WMH extending into deep cortical areas.
Mentions: White matter hyperintensities, sometimes referred to as leukoaraiosis or leukoencephalopathy, are areas of increased lucency visualized on T2-weighted images. They have enjoyed a rich, albeit capricious, history in clinical practice and in the aging literature, at points considered incidental with little clinical significance and at points considered a central source of cognitive, motoric, and emotional dysfunction. Initially, WMH were described as “unidentifiable bright objects,” confounding radiologists as either artifact ual or adventitious companions of aging. Indeed, chronological age is the strongest correlate of WMH severity14-16 and most older adults have some degree of WMH burden. (Figure 1) displays a typical example of distributed WMH and (Figure 2) shows examples of two elderly individuals, one with mild WMH and one with more severe WMH reconstructed in three dimensions. White matter hyperintensities usually appear in the white matter confluent to the lateral ventricles (ie, “periventricular” WMH), often projecting deep into cortical white matter and grey matter nuclei (ie, “deep” WMH), or as circumscribed punctate spheres in deep cortical tissue. Of note, punctate WMH often appear as isolated lesions on two-dimensional MRI axial slices, but with three-dimensional reconstruction it often becomes evident that they are contained within the same process stemming off the lateral ventricles.

Bottom Line: The targeted brain dysfunction that accompanies aging can have a devastating effect on cognitive and intellectual abilities.Studies suggest that WMH distributed in anterior brain regions are related to decline in executive abilities that is typical of normal aging, whereas WMH distributed in more posterior brain regions are common in AD.Although epidemiological, observational, and pathological studies suggest that WMH may be ischemic in origin and caused by consistent or variable hypoperfusion, there is emerging evidence that they may also reflect vascular deposition of beta-amyloid, particularly when they are distributed in posterior areas and are present in patients with AD.

View Article: PubMed Central - PubMed

Affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. amb2139@columbia.edu

ABSTRACT
The targeted brain dysfunction that accompanies aging can have a devastating effect on cognitive and intellectual abilities. A significant proportion of older adults experience precipitous cognitive decline that negatively impacts functional activities. Such individuals meet clinical diagnostic criteria for dementia, which is commonly attributed to Alzheimer's disease (AD). Structural neuroimaging, including magnetic resonance imaging (MRI), has contributed significantly to our understanding of the morphological and pathology-related changes that may underlie normal and disease-associated cognitive change in aging. White matter hyperintensities (WMH), which are distributed patches of increased hyperintense signal on T2-weighted MRI, are among the most common structural neuroimaging findings in older adults. In recent years, WMH have emerged as robust radiological correlates of cognitive decline. Studies suggest that WMH distributed in anterior brain regions are related to decline in executive abilities that is typical of normal aging, whereas WMH distributed in more posterior brain regions are common in AD. Although epidemiological, observational, and pathological studies suggest that WMH may be ischemic in origin and caused by consistent or variable hypoperfusion, there is emerging evidence that they may also reflect vascular deposition of beta-amyloid, particularly when they are distributed in posterior areas and are present in patients with AD. Findings from the literature highlight the potential contribution of small-vessel cerebrovascular disease to the pathogenesis of AD, and suggest a mechanistic interaction, but future longitudinal studies using multiple imaging modalities are required to fully understand the complex role of WMH in AD.

Show MeSH
Related in: MedlinePlus