Longitudinal Changes in Fiber Tract Integrity in Healthy Aging and Mild Cognitive Impairment: A DTI Follow-Up Study

Article type: Research Article

Authors: Teipel, Stefan J.^{a; b; *} | Meindl, Thomas^c | Wagner, Maximilian^d | Stieltjes, Bram^e | Reuter, Sigrid^{a; b} | Hauenstein, Karl-Heinz^f | Filippi, Massimo^g | Ernemann, Ulrike^h | Reiser, Maximilian F.^c | Hampel, Harald^{d; i; j}

Affiliations: [a] Department of Psychiatry, University Rostock, Rostock, Germany | [b] DZNE, German Center for Neurodegenerative Diseases, Rostock, Germany | [c] Institute for Clinical Radiology, Ludwig-Maximilian University, Munich, Germany | [d] Department of Psychiatry, Ludwig-Maximilian University, Munich, Germany | [e] Division of Radiology, German Cancer Research Center, Heidelberg, Germany | [f] Department of Radiology, University Rostock, Rostock, Germany | [g] Institute of Experimental Neurology, Scientific Institute and University Hospital San Raffaele, Milan, Italy | [h] Department of Diagnostic and Interventional Neuroradiology, University Hospital T\"{u}bingen, Germany | [i] Discipline of Psychiatry and Trinity College Institute of Neuroscience (TCIN), Trinity College Dublin, The Adelaide and Meath Hospital incorporating the National Children's Hospital (AMiNCH), Dublin, Ireland | [j] Department of Psychiatry, University of Frankfurt, Frankfurt/Main, Germany

Correspondence: [*] Correspondence to: Stefan J. Teipel, M.D., Department of Psychiatry and Psychotherapy, University Rostock, Gehlsheimer Str. 20, 18147 Rostock, Germany. Tel.: +49 01149 381 494 9610; Fax: + 49 01149 381 494 9682; E-mail: stefan.teipel@med.uni-rostock.de.

Note: [] Handling Associate Editor: Uwe Friese

Abstract: Cross-sectional studies using diffusion tensor imaging (DTI) suggest decline of the integrity of intracortically projecting fiber tracts with aging and in neurodegenerative diseases, such as Alzheimer's disease (AD). Longitudinal studies on the change of fiber tract integrity in normal and pathological aging are still rare. Here, we prospectively studied 11 healthy elderly subjects and 14 subjects with amnestic mild cognitive impairment (MCI), a clinical risk group for AD, using high-resolution DTI and MRI at baseline and after 13 to 16 months follow-up. Fractional anisotropy (FA), a DTI measure of fiber tract integrity, was compared across time points and groups using a repeated measures linear model and tract based spatial statistics. Additionally, we determined rates of grey matter and white matter atrophy using automated deformation based morphometry. Healthy elderly subjects showed decline of FA in intracortical projecting fiber tracts, such as corpus callosum, superior longitudinal fasciculus, uncinate fasciculus, inferior fronto-occipital fasciculus, and cingulate bundle (p < 0.05, corrected for multiple comparisons). MCI subjects showed significant FA decline predominantly in the anterior corpus callosum (p < 0.05, corrected for multiple comparisons). Grey and white matter atrophy involved prefrontal, parietal, and temporal lobe areas in controls and prefrontal, cingulate, and parietal lobe areas in MCI subjects and agreed with the pattern of fiber tract changes. Our findings indicate that DTI allows detection of microstructural changes in subcortical fiber tracts over time that are related to aging as well as to early stages of AD type neurodegeneration. The underlying mechanisms for these changes are unknown.

Keywords: Cortical connectivity, fractional anisotropy, longitudinal study

DOI: 10.3233/JAD-2010-100234

Journal: Journal of Alzheimer's Disease, vol. 22, no. 2, pp. 507-522, 2010