White Matter Hyperintensities And Their Relationship To Cognition

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Abstract

White matter hyperintensities (WMHs) are brain white matter lesions that are hyperintense on fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) scans. Larger WMH volumes have been associated with Alzheimer's disease (AD) and with cognitive decline. However, the relationship between WMH volumes and cross-sectional cognitive measures has been inconsistent. We hypothesize that this inconsistency may arise from 1) the presence of AD-specific neuropathology that may obscure any WMH effects on cognition, and 2) varying criteria for creating a WMH segmentation. Manual and automated programs are typically used to determine segmentation boundaries, but criteria for those boundaries can differ. It remains unclear whether WMH volumes are associated with cognitive deficits, and which segmentation criteria influence the relationships between WMH volumes and clinical outcomes. In a sample of 260 non-demented participants (ages 55-90, 141 males, 119 females) from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we compared the performance of five WMH segmentation methods, by relating the WMH volumes derived using each method to both clinical diagnosis and composite measures of executive function and memory. To separate WMH effects on cognition from effects related to AD-specific processes, we performed analyses separately in people with and without abnormal cerebrospinal fluid amyloid levels. WMH volume estimates that excluded more diffuse, lower-intensity lesions were more strongly correlated with clinical diagnosis and cognitive performance, and only in those without abnormal amyloid levels. These findings may inform best practices for WMH segmentation, and suggest that AD neuropathology may mask WMH effects on clinical diagnosis and cognition.

Keywords: Aging; Amyloid; Cognitively normal; Executive function; MRI; Mild cognitive impairment.

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Conflict of interest statement

Financial interests or conflicts of interest:

The authors do not have financial interests or conflicts of interest related to the topic of the paper.

Figures

Figure 1.

Figure 1.

Flow diagram illustrating the workflow…

Figure 1.

Flow diagram illustrating the workflow of our method to segment WMH. The intensity…

Figure 1. Flow diagram illustrating the workflow of our method to segment WMH. The intensity ratio is defined as Minimum Intensity of WMHMean WM Intensity without WMH.
Figure 2.

Figure 2.

Image on the left depicts…

Figure 2.

Image on the left depicts the coronal view of the MNI lobe map…

Figure 2. Image on the left depicts the coronal view of the MNI lobe map atlas from FSL 5.0.7 (maxprobthr0-1mm). The image on the right depicts the lobe map after we manually extended the boundaries of the lobes into the white matter.
Figure 3.

Figure 3.

WMH boundary segmentation based on…

Figure 3.

WMH boundary segmentation based on varying intensity thresholds of the study-specific intensity ratio.…

Figure 3. WMH boundary segmentation based on varying intensity thresholds of the study-specific intensity ratio. The far-right image illustrates the 85%, 100%, and 105% threshold masks all overlaid on the base FLAIR image for comparison purposes.
Figure 4.

Figure 4.

Range of WMH severity and…

Figure 4.

Range of WMH severity and variation in white matter segmentation methods. The severity…

Figure 4. Range of WMH severity and variation in white matter segmentation methods. The severity was evaluated as WMH volume corrected for ICV. We defined mild WMH volume in a participant, when the individual’s total WMH volume was less than the mean total WMH volume across participants. Moderate WMH volume was defined as the individual’s total WMH volume being between the mean and two standard deviations above the mean across participants, and severe WMH volume when the individual’s total WMH volume was greater than two standard deviations above the mean across participants. For BIANCA, “masked” indicates that the same WM mask generated for our in-house algorithm was used as input for the analysis.
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References

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