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Impact of white matter hyperintensity volume progression on rate of cognitive and motor decline

From the Department of Neurology (L.C.S., C.N., D.B.H., M.M.M., J.A.K.), Oregon Health & Science University, and the Portland Veterans Affairs Medical Center (L.C.S., J.A.K.), Portland, OR.

Address correspondence and reprint requests to Dr. Lisa Silbert, Layton Aging and Alzheimer’s Disease Center, Department of Neurology, CR-131, Oregon Health & Science University, 3181 S.W. Sam Jackson Park Road, Portland, OR 97201 silbertl{at}ohsu.edu

Background: White matter hyperintensity (WMH) change on brain MRI is observed with increased frequency in the elderly and has been independently associated with neurologic decline. The degree to which the location and rate of volume increase in WMH affects other structural brain changes along with cognitive and motor performance over time may determine subsequent degrees of risk for dementia and other syndromes of aging.

Methods: One hundred four cognitively intact men and women followed longitudinally for up to 13 years underwent at least three MRIs with corresponding annual cognitive and neurologic assessments. Brain volume, ventricular CSF (vCSF), and total periventricular (PV) and subcortical WMH volumes were measured. Progression of MRI volumes was examined in relation to rates of cognitive, motor, and cerebral volume change based on slopes of outcomes.

Results: Higher initial total and PV WMH volume was associated with total WMH, PV WMH, and vCSF progression, and with increased time and number of steps to walk 30 feet. Progression of PV WMH volume was associated with increased time to walk 30 feet. Progression of subcortical WMH volume was associated with decreased performance on logical memory testing and increased rate of vCSF volume change.

Conclusion: Increased total and periventricular (PV) white matter hyperintensity (WMH) burden and progression of PV WMH burden are associated with decreased gait performance over time, while progression of subcortical WMH volume is associated with memory decline in cognitively intact elderly. Greater progression of WMH burden is associated with an increased risk of memory and gait dysfunction, and thus should not be considered a benign process.

Abbreviations: CDR = Clinical Dementia Rating Scale; ICV = intracranial volume; MMSE = Mini-Mental State Examination; PCI = persistent cognitive impairment; PV = periventricular; TE = echo time; TR = repetition time; vCSF = ventricular CSF; WMH = white matter hyperintensity.

Supported in part by grants from the Department of Veterans Affairs and National Institutes of Health (P30 AG 08017, M01 RR000334, and K23 AG 24826-01), Paul B. Beeson Career Development Award in Aging, and American Academy of Neurology Foundation Clinical Research Training Fellowship.

Disclosure: The authors report no disclosures.

Received November 9, 2007. Accepted in final form March 17, 2008.