White matter imaging changes in subjective and mild cognitive impairment Per Selnes a,b, *, Anders M. Fjell c,d , Leif Gjerstad e , Atle Bjørnerud f,g , Anders Wallin h , Paulina Due-Tønnessen f , Ramune Grambaite a , Vidar Stenset a,b , Tormod Fladby a,b a Department of Neurology, Faculty Division, Akershus University Hospital, University of Oslo, Lørenskog, Norway b Department of Neurology, Akershus University Hospital, Lørenskog, Norway c Department of Psychology, Center for the Study of Human Cognition, University of Oslo, Oslo, Norway d Department of Neuropsychology, Oslo University Hospital, Ullevaal, Oslo, Norway e Department of Neurology, Oslo University Hospital, Rikshospitalet, Oslo, Norway f Department of Radiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway g Department of Physics, University of Oslo, Oslo, Norway h Department of Neurochemistry and Psychiatry, Institute of Neuroscience and Physiology, Sahlgrenska Academy at G€ oteborg University, SU/Sahlgrenska, Gothenburg, Sweden Abstract Background: To determine whether white matter (WM) memory network changes accompany early cognitive impairment and whether these changes represent early, pathologically independent axonal affection, we combined WM diffusion tensor imaging and cortical morphometric measurements of normal control subjects, patients with only subjective cognitive impairment (SCI), or mild cognitive impairment (MCI). Methods: We included 66 patients with SCI or MCI and 21 control subjects from a university- hospital-based memory clinic in a cross-sectional study. Morphometric analysis was performed in FreeSurfer, and Tract-Based Spatial Statistics was used for analysis of diffusion tensor imaging- derived WM fractional anisotropy, radial diffusivity (DR), and mean diffusivity (MD). Relationships between WM measures and stage were assessed with whole-brain voxelwise statistics and on a re- gion-of-interest basis, with subsequent correction for cortical atrophy. Results: In SCI patients, as compared with control subjects, there were widespread changes in DR and MD. No significant differences in thickness could be demonstrated. In MCI patients, as compared with control subjects, there were widespread changes in DR, MD, and fractional anisotropy; the pre- cuneal and inferior parietal cortices were thinner; and the hippocampus was smaller. Multiple logistic regression analysis eliminated morphometry as an explanatory variable in favor of DR/MD for all regions of interest, except in the precuneus, where both thickness and DR/MD were significant explanatory variables. Conclusions: WM tract degeneration is prominent in SCI and MCI patients, and is at least in part independent of overlying gray matter atrophy. Ó 2012 The Alzheimer’s Association. All rights reserved. Keywords: Alzheimer’s disease; Subjective cognitive impairment; Mild cognitive impairment; Diffusion tensor imaging; Vol- umetric MRI; White matter 1. Background Characterization of predementia stages is necessary to understand early mechanisms for dementia development. Mild cognitive impairment (MCI) is a clinical condition as- sociated with an increased risk of dementia [1,2]. From clinical normalcy to dementia, there is a broad range of pathological affection, but the majority of MCI cases have The authors have no conflicts of interest to report. V.S. is currently at the Department of Neurosurgery, Oslo University Hospital, Ullevaal, 0450 Oslo, Norway. *Corresponding author. Tel.: 147 02900; Fax: 147 67968132. E-mail address: per.selnes@medisin.uio.no 1552-5260/$ - see front matter Ó 2012 The Alzheimer’s Association. All rights reserved. doi:10.1016/j.jalz.2011.07.001 Alzheimer’s & Dementia 8 (2012) S112–S121