Abstract
Objective
To compare all-cause mortality rates across the severity range of white matter hyperintensities
(WMH).
Patients and Methods
Between October 26, 2010, and October 5, 2017, the ongoing Mayo Clinic Florida Familial
Cerebrovascular Diseases Registry prospectively enrolled 1011 diverse participants
with and without cerebrovascular disease. T2-weighted magnetic resonance imaging of
the brain was used to evaluate WMH in 455 participants using the Fazekas scale. Fazekas
deep WMH (FD) and periventricular WMH (FPV) scores (0-3 points) were assigned on the
basis of WMH severity. Kaplan-Meier survival analyses, Cox proportional hazards models,
and estimated hazard ratios compared survival rates across FD and FPV categories.
The Fisher exact and χ2 tests evaluated the relationship of categorical variables, and the Kruskal-Wallis
test measured the relationship of continuous variables across FD and FPV categories.
All tests were performed at a P<.05 significance level.
Results
Over a median follow-up of 3.06 years (range, 0.00-6.96 years), 96 deaths occurred.
Higher FD scores corresponded to a higher likelihood of mortality (P<.001). Participants with an FD score of 3 were 4.69 (95% CI, 2.60-8.46) times more
likely to die compared with those with an FD score of 0. Participants with higher
FPV scores had a higher likelihood of mortality (P<.001). Participants with an FPV score of 3 were 7.04 (95% CI, 3.39-14.62) times more
likely to die compared with those with an FPV score of 0. Once adjusted, age and baseline
functional status explained most of the survival differences among the FD scores.
Conclusion
Associations between all-cause mortality rates across the severity range of WMH were
observed in the Registry. Further studies are warranted to understand the clinical
importance of WMH in other clinical populations.
Abbreviations and Acronyms:
CVD (cerebrovascular disease), FD (Fazekas deep white matter hyperintensity), FLAIR (fluid-attenuated inversion recovery), FPV (Fazekas periventricular white matter hyperintensity), GFR (glomerular filtration rate), MRI (magnetic resonance imaging), mRS (modified Rankin Scale), SBP (systolic blood pressure), WMH (white matter hyperintensities)To read this article in full you will need to make a payment
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References
- Prevalence of cerebral white matter lesions in elderly people: a population based magnetic resonance imaging study; the Rotterdam Scan Study.J Neurol Neurosurg Psychiatry. 2001; 70: 9-14
- Cerebral white matter changes and geriatric syndromes: is there a link?.J Gerontol A Biol Sci Med Sci. 2004; 59: 818-826
- Severity of leukoaraiosis correlates with clinical outcome after ischemic stroke.Neurology. 2009; 72: 1403-1410
- White matter hyperintensities and functional outcomes at 2 weeks and 1 year after stroke.Cerebrovasc Dis. 2013; 35: 138-145
- White matter hyperintensity volume and outcome of mechanical thrombectomy with stentriever in acute ischemic stroke.Stroke. 2017; 48: 2892-2894
- The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: systematic review and meta-analysis.BMJ. 2010; 341: c3666
- Acute ischemic cerebrovascular syndrome: diagnostic criteria.Stroke. 2003; 34: 2995-2998
- Verifying the stroke-free phenotype by structured telephone interview.Stroke. 2000; 31: 1076-1080
- MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging.AJR Am J Roentgenol. 1987; 149: 351-356
- Rationale, design and methodology of the image analysis protocol for studies of patients with cerebral small vessel disease and mild stroke.Brain Behav. 2015; 5: e00415
- Silent brain infarction and subcortical white matter lesions increase the risk of stroke and mortality: a prospective cohort study.J Stroke Cerebrovasc Dis. 2006; 15: 57-63
- Association of MRI markers of vascular brain injury with incident stroke, mild cognitive impairment, dementia, and mortality: the Framingham Offspring Study.Stroke. 2010; 41: 600-606
- Increased risk of death in community-dwelling older people with white matter hyperintensities on MRI.J Neurol Sci. 2006; 250: 33-38
- Extent of white matter lesions is related to acute subcortical infarcts and predicts further stroke risk in patients with first ever ischaemic stroke.J Neurol Neurosurg Psychiatry. 2005; 76: 793-796
- Age related white matter changes predict stroke death in long term follow-up.J Neurol Neurosurg Psychiatry. 2009; 80: 762-766
- Lacunar infarcts: functional and cognitive outcomes at five years in relation to MRI findings.Cerebrovasc Dis. 2005; 20: 34-40
- Visual rating of age-related white matter changes on magnetic resonance imaging: scale comparison, interrater agreement, and correlations with quantitative measurements.Stroke. 2003; 34: 441-445
- Total small vessel disease score and risk of recurrent stroke: validation in 2 large cohorts.Neurology. 2017; 88: 2260-2267
- White matter hyperintensities and cognitive dysfunction in patients with infratentorial stroke.Ann Rehabil Med. 2014; 38: 620-627
- Stroke subtype, vascular risk factors, and total MRI brain small-vessel disease burden.Neurology. 2014; 83: 1228-1234
- Age-related changes in normal-appearing brain tissue and white matter hyperintensities: more of the same or something else?.AJNR Am J Neuroradiol. 2005; 26: 725-729
- Neuroprotection for ischemic stroke: past, present and future.Neuropharmacology. 2008; 55: 363-389
- Multiple sclerosis.Lancet. 2008; 372: 1502-1517
- Higher blood-brain barrier permeability is associated with higher white matter hyperintensities burden.J Neurol. 2017; 264: 1474-1481
- Update on cerebral small vessel disease: a dynamic whole-brain disease.Stroke Vasc Neurol. 2016; 1: 83-92
- Morphologic, distributional, volumetric, and intensity characterization of periventricular hyperintensities.AJNR Am J Neuroradiol. 2014; 35: 55-62
- Incidental periventricular white matter hyperintensities revisited: what detailed morphologic image analyses can tell us.AJNR Am J Neuroradiol. 2014; 35: 63-64
- Classification of white matter lesions on magnetic resonance imaging in elderly persons.Biol Psychiatry. 2008; 64: 273-280
- Cerebral white matter lesions and depressive symptoms in elderly adults.Arch Gen Psychiatry. 2000; 57: 1071-1076
- Periventricular lesions in the white matter on magnetic resonance imaging in the elderly: a morphometric correlation with arteriolosclerosis and dilated perivascular spaces.Brain. 1991; 114: 761-774
- Heterogeneity in age-related white matter changes.Acta Neuropathol. 2011; 122: 171-185
- What are white matter hyperintensities made of? relevance to vascular cognitive impairment.J Am Heart Assoc. 2015; 4 ([published correction appears in J Am Heart Assoc. 2016;5(1):e002006]): 001140
- Pathologic correlates of incidental MRI white matter signal hyperintensities.Neurology. 1993; 43: 1683-1689
- White matter lesions in an unselected cohort of the elderly: molecular pathology suggests origin from chronic hypoperfusion injury.Stroke. 2006; 37: 1391-1398
- Impact of white matter hyperintensities scoring method on correlations with clinical data: the LADIS study.Stroke. 2006; 37: 836-840
- Measuring progression of cerebral white matter lesions on MRI: visual rating and volumetrics.Neurology. 2004; 62: 1533-1539
- Variable agreement between visual rating scales for white matter hyperintensities on MRI: comparison of 13 rating scales in a poststroke cohort.Stroke. 1997; 28: 1614-1623
- Measuring longitudinal white matter changes: comparison of a visual rating scale with a volumetric measurement.AJNR Am J Neuroradiol. 2006; 27: 875-878
- Complexity of MRI white matter hyperintensity assessments in relation to cognition in aging and dementia from the Sunnybrook Dementia Study.J Alzheimers Dis. 2011; 26: 379-388
Article Info
Footnotes
For editorial comment, see page 380
Grant Support: The Mayo Clinic Florida Familial Cerebrovascular Diseases Registry receives funding from the Harley N. and Rebecca N. Hotchkiss Endowed Fund in Neuroscience Research and the Earl and Nyda Swanson Neurosciences Research Fund .
Potential Competing Interests: The authors report no competing interests.
Identification
Copyright
© 2018 Mayo Foundation for Medical Education and Research
