Cognitive impairment risk: white matter hyperintensity progression matters.
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.


METHODS
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.


CONCLUSIONS
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.
Silbert
Lisa C
LC
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, USA. silbertl@ohsu.edu
Howieson
Diane B
DB
Dodge
Hiroko
H
Kaye
Jeffrey A
JA
D000367:Age Factors; D000369:Aged, 80 and over; D053327:Apolipoprotein E4 / Q000235:genetics; D001921:Brain / Q000473:pathology*; D002552:Cerebral Ventricles / Q000473:pathology; D003072:Cognition Disorders / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D009413:Nerve Fibers, Myelinated; D009929:Organ Size; D016016:Proportional Hazards Models; D012307:Risk Factors
D053327:Apolipoprotein E4