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White Matter Abnormalities and Cognitive Decline

Neurology; ePub 2018 Mar 23; Lindemer, et al

White matter signal abnormalities (WMSA) hold additional predictive power regarding cognitive progression in older individuals and are most effective as biomarkers in individuals who are cognitively impaired but do not fit the expected cerebrospinal fluid (CSF) biomarker profile of Alzheimer disease (AD), a recent study found. 236 individuals from the Alzheimer's Disease Neuroimaging Initiative database with clinical diagnoses of cognitively normal older adult (older controls [OCs]), mild cognitive impairment, and AD were studied. Researchers found:

  • CSF biomarkers alone classified individuals with AD vs OCs with 82% accuracy, and the addition of WMSA did not enhance this.
  • Both CSF biomarkers, as well as WMSA volume, significantly contributed to predicting cognitive decline in executive and memory domains when assessed across all individuals.
  • In individuals with pathologic levels of both CSF biomarkers, WMSA only significantly contributed to models of future executive function decline.
  • In individuals with subpathologic CSF biomarker levels (levels similar to those in OC individuals), WMSA significantly contributed to prediction of memory decline and were the sole significant predictor of executive function decline.


Lindemer ER, Greve DN, Fischl B, Salat DH, Gomez-Isla T. White matter abnormalities and cognition in patients with conflicting diagnoses and CSF profiles. [Published online ahead of print March 23, 2018]. Neurology. doi:10.1212/WNL.0000000000005353.

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