Posterior Cingulum White Matter Disruption and Its Associations with Verbal Memory and Stroke Risk in Mild Cognitive Impairment

Article type: Research Article

Authors: Delano-Wood, Lisa^{a; c} | Stricker, Nikki H.^{d; e} | Sorg, Scott F.^a | Nation, Daniel A.^a | Jak, Amy J.^{a; c} | Woods, Steven P.^a | Libon, David J.^f | Delis, Dean C.^{a; c} | Frank, Lawrence R.^{b; d} | Bondi, Mark W.^{a; c; *}

Affiliations: [a] Department of Psychiatry, University of California San Diego School of Medicine, San Diego, CA, USA | [b] Department of Radiology, University of California San Diego School of Medicine, San Diego, CA, USA | [c] VA San Diego Healthcare System, San Diego, CA, USA | [d] Psychology Service, VA Boston Healthcare System, Boston, MA, USA | [e] Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA | [f] Department of Neurology, Drexel University College of Medicine, Philadelphia, PA, USA

Correspondence: [*] Correspondence to: Mark W. Bondi, Ph.D., Psychology Service (116B), VA San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161, USA. Tel.: +1 858 552 8585 (Ext. 2809); E-mail: mbondi@ucsd.edu.

Abstract: Medial temporal lobe and temporoparietal brain regions are among the earliest neocortical sites to undergo pathophysiologic alterations in Alzheimer's disease (AD), although the underlying white matter changes in these regions is less well known. We employed diffusion tensor imaging to evaluate early alterations in regional white matter integrity in participants diagnosed with mild cognitive impairment (MCI). The following regions of interests (ROIs) were examined: 1) anterior cingulum (AC); 2) posterior cingulum (PC); 3) genu of the corpus callosum; 4) splenium of the corpus callosum; and 5) as a control site for comparison, posterior limb of the internal capsule. Forty nondemented participants were divided into demographically-similar groups based on cognitive status (MCI: n = 20; normal control: n = 20), and fractional anisotropy (FA) estimates of each ROI were obtained. MCI participants showed greater posterior white matter (i.e., PC, splenium) but not anterior white matter (i.e., AC, genu) changes, after adjusting for age, stroke risk, and whole brain volume. FA differences of the posterior white matter were best accounted for by changes in radial but not axial diffusivity. PC FA was also significantly positively correlated with hippocampal volume as well as with performance on tests of verbal memory, whereas stroke risk was significantly correlated with genu FA and was unrelated to PC FA. When investigating subtypes of our MCI population, amnestic MCI participants showed lower PC white matter integrity relative to those with non-amnestic MCI. Findings implicate involvement of posterior microstructural white matter degeneration in the development of MCI-related cognitive changes and suggest that reduced FA of the PC may be a candidate neuroimaging marker of AD risk.

Keywords: Aging, diffusion tensor imaging, memory, mild cognitive impairment, posterior cingulum, white matter

DOI: 10.3233/JAD-2012-102103

Journal: Journal of Alzheimer's Disease, vol. 29, no. 3, pp. 589-603, 2012