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Updated: Mar 12, 2026
High-resolution Functional Magnetic Resonance Imaging Methods for Human Midbrain
Published on: May 10, 2012
Mental speed is associated with the shape irregularity of white matter MRI hyperintensity load
Catharina Lange1,2, Per Suppa1,3, Anja Mäurer4
1Department of Nuclear Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Abstract:
Brain MRI white matter hyperintensities (WMHs) are common in elderly subjects. Their impact on cognition, however, appears highly variable. Complementing conventional scoring of WMH load (volume and location) by quantitative characterization of the shape irregularity of WMHs might improve the understanding of the relationship between WMH load and cognitive performance. Here we propose the "confluency sum score" (COSU) as a marker of the total shape irregularity of WMHs in the brain. The study included two independent patient samples: 87 cognitively impaired geriatric inpatients from a prospective neuroimaging study (iDSS) and 198 subjects from the National Alzheimer's Coordinating Center (NACC) database (132 with, 66 w/o cognitive impairment). After automatic segmentation and clustering of the WMHs on FLAIR (LST toolbox, SPM8), the confluency of the i-th contiguous WMH cluster was computed as confluencyi = [1/(36π)∙surfacei3/volumei2]1/3-1. The COSU was obtained by summing the confluency over all WMH clusters. COSU was tested for correlation with CERAD-plus subscores. Correlation analysis was restricted to subjects with at least moderate WMH load (≥ 13.5 ml; iDSS / NACC: n = 52 / 80). In the iDSS sample, among the 12 CERAD-plus subtests the trail making test A (TMT-A) was most strongly correlated with the COSU (Spearman rho = -0.345, p = 0.027). TMT-A performance was not associated with total WMH volume (rho = 0.147, p = 0.358). This finding was confirmed in the NACC sample (rho = -0.261, p = 0.023 versus rho = -0.040, p = 0.732). Cognitive performance in specific domains including mental speed and fluid abilities seems to be more strongly associated with the shape irregularity of white matter MRI hyperintensities than with their volume.
Insights
White matter hyperintensities (WMHs) on brain MRI impact cognition variably. A new "confluency sum score" (COSU) measuring WMH shape irregularity, not just volume, better predicts cognitive performance, particularly in mental speed.
Area of Science:
- Neuroimaging
- Geriatric Medicine
- Cognitive Neurology
Background:
- White matter hyperintensities (WMHs) are prevalent in elderly individuals.
- The relationship between WMH load and cognitive decline is variable.
- Conventional WMH assessment (volume, location) may not fully capture their impact on cognition.
Purpose of the Study:
- To introduce a novel quantitative marker, the "confluency sum score" (COSU), for assessing WMH shape irregularity.
- To investigate the association between WMH shape irregularity and cognitive performance.
- To compare the predictive value of WMH shape irregularity versus WMH volume on cognition.
Main Methods:
- Automatic segmentation and clustering of WMHs from brain MRI FLAIR sequences.
- Calculation of WMH cluster confluency using the formula: confluencyi = [1/(36π)∙surfacei3/volumei2]1/3-1.
- Summation of confluency values to derive the COSU, followed by correlation analysis with cognitive subscores (CERAD-plus) in two independent cohorts (iDSS and NACC).
Main Results:
- The COSU, reflecting WMH shape irregularity, showed a significant correlation with Trail Making Test A (TMT-A) performance in both iDSS (rho = -0.345, p = 0.027) and NACC (rho = -0.261, p = 0.023) cohorts.
- WMH volume did not significantly correlate with TMT-A performance in either cohort (iDSS: rho = 0.147, p = 0.358; NACC: rho = -0.040, p = 0.732).
- These findings suggest WMH shape irregularity is more strongly associated with specific cognitive domains like mental speed than WMH volume.
Conclusions:
- WMH shape irregularity, quantified by COSU, offers a more sensitive marker for cognitive impairment than WMH volume.
- Assessing WMH confluency may enhance our understanding of the neurobiological underpinnings of cognitive decline in aging.
- Future research should explore the clinical utility of COSU in predicting cognitive trajectories and guiding interventions.
