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Abstract
Objective To determine whether free water (FW) content, initially developed to correct metrics derived from diffusion tensor imaging and recently found to be strongly associated with vascular risk factors, may constitute a sensitive biomarker of white matter (WM) microstructural differences associated with cognitive performance but remains unknown.
Methods Five hundred thirty-six cognitively diverse individuals, aged 77 ± 8 years, received yearly comprehensive clinical evaluations and a baseline MRI examination of whom 224 underwent follow-up MRI. WM microstructural measures, including FW, fractional anisotropy, and mean diffusivity corrected for FW and WM hyperintensity burden were computed within WM voxels of each individual. Baseline and change in MRI metrics were then used as independent variables to explain baseline and change in episodic memory (EM), executive function (EF), and Clinical Dementia Rating (CDR) scores using linear, logistic, and Cox proportional-hazards regressions.
Results Higher baseline FW and WM hyperintensity were associated with lower baseline EM and EF, higher baseline CDR, accelerated EF and EM decline, and higher probability to transition to a more severe CDR stage (p values <0.01). Annual change in FW was also found to be associated with concomitant change in cognitive and functional performance (p values <0.01).
Conclusions This study finds cross-sectional and longitudinal associations between FW content and trajectory of cognitive and functional performance in a large sample of cognitively diverse individuals. It supports the need to investigate the pathophysiologic process that manifests increased FW, potentially leading to more severe WM territory injury and promoting cognitive and functional decline.
Glossary
- AD=
- Alzheimer disease;
- CDR=
- Clinical Dementia Rating;
- CeVD=
- cerebrovascular disease;
- EF=
- executive function;
- EM=
- episodic memory;
- FA=
- fractional anisotropy;
- FACOR=
- corrected fractional anisotropy;
- FLAIR=
- fluid-attenuated inversion recovery;
- FOV=
- field of view;
- FSL=
- FMRIB's Software Library;
- FW=
- free water;
- MCI=
- mild cognitive impairment;
- MD=
- mean diffusivity;
- MDCOR=
- corrected mean diffusivity;
- NAWM=
- normal-appearing white matter;
- OR=
- odds ratio;
- TCV=
- total cranial volume;
- TE=
- echo time;
- VaD=
- vascular dementia;
- WM=
- white matter;
- WMH=
- white matter hyperintensity
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
- Received July 10, 2018.
- Accepted in final form January 8, 2019.
- © 2019 American Academy of Neurology
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