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Extensive white matter dysfunction in cognitively impaired patients with secondary-progressive multiple sclerosis

P L Francis1, T L Chia2, R Jakubovic2

  • 1Medical Imaging (P.L.F., T.L.C., R.J., R.I.A.), Sunnybrook Health Sciences Centre philip.francis@utoronto.ca.

AJNR. American Journal of Neuroradiology
|May 17, 2014
PubMed
Abstract

Insights

Cognitive impairment in multiple sclerosis is linked to widespread white matter (WM) damage. White matter fractional anisotropy, a measure of WM integrity, is a key predictor of cognitive status in patients.

Area of Science:

  • Neuroscience
  • Radiology
  • Neurology

Background:

  • Cognitive impairment is a significant disabling symptom in multiple sclerosis (MS).
  • White matter (WM) dysfunction is implicated in cognitive decline in MS.
  • Diffusion Tensor Imaging (DTI) allows for the investigation of WM integrity.

Purpose of the Study:

  • To investigate the association between cognitive impairment and WM dysfunction in secondary-progressive multiple sclerosis (SPMS).
  • To identify specific WM tracts affected in cognitively impaired SPMS patients using DTI.

Main Methods:

  • Cognitive performance was assessed using the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS).
  • Cognitive impairment was defined as scoring >1.5 standard deviations below healthy controls on ≥2 subtests.
  • Tract-based spatial statistics with threshold-free cluster enhancement was used to compare fractional anisotropy maps against cognitive status.

Main Results:

  • Cognitively impaired SPMS patients (25/45) showed reduced global gray matter (GM) and WM volumes, increased WM lesion volumes, and lower WM skeleton fractional anisotropy compared to non-impaired patients.
  • Impaired patients exhibited significantly lower fractional anisotropy in over 50% of voxels within all major WM tracts, notably the corpus callosum.
  • Multivariate logistic regression indicated that only WM skeleton fractional anisotropy remained a significant predictor of cognitive status after accounting for confounders.

Conclusions:

  • Patients with SPMS and cognitive impairment demonstrate extensive WM dysfunction.
  • Specific WM tracts crucial for cognition, such as the corpus callosum, are preferentially affected.
  • WM skeleton fractional anisotropy is a significant predictor of cognitive status in SPMS.

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