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Cognitive impairment risk

White matter hyperintensity progression matters

From the Department of Neurology (L.C.S., D.B.H., H.D., J.A.K.), Oregon Health & Science University, Portland; and Department of Neurology (L.C.S., J.A.K.), Veterans Affairs Medical Center, 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 Rd., Portland, OR 97239 silbertl{at}ohsu.edu

Objective: To determine whether white matter hyperintensity (WMH) progression rate is a better predictor of cognitive impairment risk than baseline WMH volume in healthy elderly individuals.

Method: Ninety-eight cognitively intact elderly subjects were followed in the Oregon Brain Aging Study. Forty-nine had at least 3 brain MRIs and annual cognitive and neurologic assessments until diagnosed with persistent cognitive impairment (PCI). Brain, ventricular CSF (vCSF), intracranial volume (ICV), hippocampus, total WMH, periventricular (PV) WMH, and subcortical WMH volumes were measured. Cox proportional hazards survival analyses were used to assess cognitive impairment risk.

Results: After adjusting for age, apolipoprotein E4 status, incident hypertension, ICV, entry Mini-Mental State Examination, baseline hippocampus, and both baseline vCSF volume and rate of vCSF volume change, increased progression of total WMH volume (hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.3–2.7, p = 0.0007) and PV WMH volume (HR 1.94, 95% CI 1.3–3.1, p = 0.001) conferred higher risk of PCI, whereas baseline WMH volumes did not. Every 1 mL/y increase in PV WMH volume was associated with a 94% increased risk of PCI.

Conclusion: Progression of total and periventricular (PV) white matter hyperintensity (WMH) volumes are better predictors of persistent cognitive impairment (PCI) than baseline WMH burden. Greater PV WMH burden progression is associated with the development of PCI, a potential precursor to Alzheimer or vascular dementia. Identification of factors that decrease WMH accumulation over time is needed to maintain cognitive health in our growing elderly population.

Abbreviations: AD = Alzheimer disease; CDR = Dementia Rating Scale; CI = confidence interval; HR = hazard ratio; HS = hippocampal sclerosis; HTN = hypertension; ICV = intracranial volume; MCI = mild cognitive impairment; MMSE = Mini-Mental State Examination; NA = not applicable; NS = not significant; PCI = persistent cognitive impairment; PV = periventricular; SES = socioeconomic status; TE = echo time; TR = repetition time; vCSF = ventricular CSF; vol = volume; WMH = white matter hyperintensity.

Supported in part by grants from the Department of Veterans Affairs and NIH (P30 AG 08017, M01 RR000334, and K23 AG 24826-01, K01AG023014), Paul B. Beeson Career Development Award in Aging, the Max Millis Fund for Neurological Research, and the Storms Family Fund at the Oregon Community Foundation.

Disclosure: Author disclosures are provided at the end of the article.

Received January 28, 2009. Accepted in final form April 2, 2009.