The Place of Neuroimaging in the Assessment of Cerebral Small Vessel Disease.

The burden of cerebrovascular disease is high: each year, approximately 795000 people in the United States experience a new or recurrent stroke, leading to death in 128824 individuals or being associated with death in 215864 cases.1 However, the number of silent infarcts and microhemorrhages is much higher, causing cognitive and behavioral impairment in 17% of the population older than65 years.2 These usually primarily asymptomatic events are often caused by cerebral small vessel disease (SVD) detected aswhitematter hyperintensities, lacunas,microbleeds, and cortical and subcortical atrophy in magnetic resonance imaging (MRI)of elderlypeople.TheseMRIchanges haveahighprevalence in thispopulation.3The long-termprognosisofSVDishighlyvariable,but functionaldeclineanddeath may be a consequence.4,5 Prediction of functional outcome andmortality is important for the planning and management of treatment in patients with cerebrovascular disease, andmorphologic as well as functional imaging might be used to improve the modest levels of predictive accuracy if based only on clinical data.6 In olderadults, gait speedandcognitionwereshown7,8 tobeclinical risk factors associatedwithmortality and theextentof SVD was associated with mortality,9,10 but, to my knowledge, a study on the value of imaging in addition to clinical data for prediction of outcome was missing. In the study by van der Holst et al,11 the cumulative mortality of older patients with SVD during 8 years of follow-up wasassessed inassociationwithbaseline risk factors and typical clinical and MRI variables. Significant differences between patients who survived and those who had died during the follow-upperiodwere found forage,diabetesmellitus, cardiovascularmorbidity, gait velocity,Mini-Mental StateExamination scores, and cognitive index, aswell as for theMRI findings (volume of white matter hyperintensities, presence of lacunas, whitematter volume, graymatter volume, presence of microbleeds, fractional anisotropy, and mean diffusitivity ofwhitematter). UsingCoxproportional hazardsmodelswith backward, stepwise selection, older age, lower gait speed, low gray matter volume, and higher diffusitivity of white matter were identified as risk factors associated with mortality, whereas cognitive index and other imaging markers did not contribute to predictive accuracy. This study is important becauseprecision inpredictionof mortality can be improved by imagingmodalities, suggesting that these diagnostic procedures should be included in the evaluation of patients with SVD. Two findings are especially remarkable: 1. The presence of SVDdoes not only increase the risk of vascular death, it is also significantly related to all-causemortality; this associationmight result fromthe relationshipbetweenSVDand the incidenceofpathologic changes inother organ systems.12 As a consequence, gait speed is a risk factor associatedwithanegativeoutcomebecause it isnotonly dependenton the functionof thebrain, but alsoon the state of the respiratory, circulatory,musculoskeletal, andperipheral nerve systems.7 In this context, it is of interest that the presence of territorial infarcts is not related to mortality. 2. Diffusion abnormalities in white matter have a higher predictivevaluethanconventionalMRImarkersbecausetheyreflect themicrostructural changesof thewhitematterpreceding the development of whitematter hyperintensities.13 For example, in theCerebral AutosomalDominantArteriopathy withSubcortical Infarcts andLeukoencephalopathystudy,14 themean diffusitivity value has been identified as themain factorassociatedwithclinicalprogressionamongotherdemographic, clinical, and conventional MRI markers for various clinical endpoints, includingdisability, cognition,andnewly occurring strokes. In addition, changes in diffusion tensor imaging of the pyramidal tract and alternative motor fibers arerelatedtomotordeficits15andmightaffectgaitspeed.This finding also stresses that the connectivity in networks as assessedbydiffusiontensor imaging ismore important foroutcome than the extent of primary structural lesions. The effect of SVD as detected in morphologic changes in routineMRI or asmicrostructural alterations in diffusion tensor imaging might be elucidated if morphologic MRI scanning is combined with functional and molecular imaging. A comparison with functional MRI could demonstrate the effect of lesions in thewhitematter or disturbanceof fiber tracts on the functional connectivity of networks. Additional magnetic resonance spectroscopy shows injury to axons by meaRelated article page 402 Opinion Editorial