J Psychiatry Neurosci 2013; 39(2):135-43
Shantel L. Duffy, MDR (Hons); Matt Paradise, FRANZCP; Ian B. Hickie, FRANZCP; Simon J.G. Lewis, FRACP; Sharon L. Naismith, DPsych; Jim Lagopoulos, PhD
Duffy, Paradise, Hickie, Lewis, Naismith — Ageing Brain Centre, Brain & Mind Research Institute, University of Sydney, Camperdown, Australia; Duffy, Paradise, Hickie, Lewis, Naismith, Lagopoulos — Clinical Research Unit, Brain & Mind Research Institute, University of Sydney, Camperdown, Australia
Background: Mild cognitive impairment (MCI) and late-life depression are clinical syndromes that often co-occur and may represent an early manifestation of neurodegenerative disease. The present study examined white matter microstructure in patients with MCI with and without a history of major depression compared with healthy controls.
Methods: Older adults with MCI and no history of major depression (MCI), adults with MCI and euthymic major depression (MCI-MD) and healthy controls underwent comprehensive medical, psychiatric and neuropsychological assessments. Participants also underwent diffusion tensor imaging, which was analyzed using tract-based spatial statistics. White matter hyperintensity (WMH) burden and medical burden were also quantified.
Results: We enrolled 30 participants in the MCI group, 36 in the MCI-MD group and 22 in the control group. Compared with controls, participants in the MCI group had significantly reduced fractional anisotropy (FA) in the corpus callosum, superior longitudinal fasciculus (SLF), corona radiata and posterior thalamic radiation. Participants in the MCI-MD group had significantly reduced FA in the corpus callosum, internal capsule, external capsule, corona radiata, posterior thalamic radiation, sagittal striatum, fornix, SLF, uncinate fasciculus and right cingulum compared with controls. No significant differences in FA were observed between the MCI and MCI-MD groups. Participants in the MCI-MD group had greater medical burden (p = 0.020) and WMH burden than controls (p = 0.013).
Limitations: Study limitations include the crosssectional design and antidepressant medication use.
Conclusion: To our knowledge, this study is the first to compare white matter microstructure in patients with MCI with and without a history of major depression and suggests that a common underlying structural white matter change may underpin cognitive impairment in both MCI groups. Further research is needed to delineate the pathophysiological mechanisms underlying these microstructural changes.
Submitted Apr. 30, 2013; Revised Sept. 6, Sept. 25, 2013; Accepted Oct. 1, 2013.
Acknowledgments: We gratefully acknowledge the generosity of the patients and control participants who undertook this research. We also thank old age psychiatrist Dr. Louisa Norrie and the clinical neuropsychologists, including Dr. Zoe Terpening, for their assistance with assessments and clinical consensus ratings.
Funding: S. Duffy is supported by an Australian Rotary Health/ Rotary Club of Parkes Funding Partners scholarship. I. Hickie and M. Paradise are supported by a National Health and Medical Research Council (NHMRC) Australian Fellowship awarded to I. Hickie. S. Lewis is supported by an NHMRC Practitioner Fellowship. S. Naismith is supported by an NHMRC Career Development Award. J. Lagopoulos is supported by Dreikurs bequest supporting Alzheimer’s research.
Competing interests: None declared.
Contributors: S. Duffy, I. Hickie, S. Lewis, S. Naismith and J. Lagopoulos designed the study. S. Duffy, M. Paradise, S. Naismith and J. Lagopoulos acquired the data, which S. Duffy, I. Hickie, S. Lewis, S. Naismith and J. Lagopoulos analyzed. S. Duffy, S. Naismith and J. Lagopoulos wrote the article, which all authors reviewed and approved for publication.
Correspondence to: S.L. Naismith, Ageing Brain Centre, 94 Mallett St., Camperdown NSW 2050 Australia; firstname.lastname@example.org