Longitudinal changes of fractional anisotropy in Alzheimer's disease patients treated with galantamine: A 12-month randomized, placebo-controlled, double-blinded study

Department of Aging Science and Humanities, Interdisciplinary Faculty, University of Rostock, Rostock, Germany.
European Archives of Psychiatry and Clinical Neuroscience (Impact Factor: 3.53). 08/2011; 262(4):341-50. DOI: 10.1007/s00406-011-0234-2
Source: PubMed


Diffusion tensor imaging (DTI) demonstrates decline of fractional anisotropy (FA) as a marker of fiber tract integrity in Alzheimer's disease (AD). We aimed to assess the longitudinal course of white matter microstructural changes in AD and healthy elderly control (HC) subjects and to evaluate the effects of treatment with the cholinesterase inhibitor galantamine on white matter microstructure in AD patients. We enrolled 28 AD patients and 11 healthy elderly control subjects (HC). AD patients were randomly assigned to 6-month double-blind galantamine treatment or placebo, with a 6-month open-label extension phase. DTI was performed at baseline, as well as at 6 and 12-month follow-up in AD patients. The HC subjects underwent DTI at baseline and 12-month follow-up without treatment. We measured FA in regions of interest covering the posterior cingulate and corpus callosum. At 6-month follow-up, the AD group showed significant FA decline in the left posterior cingulate. FA decline was significantly preserved in the posterior body of the corpus callosum in AD group with treatment compared to placebo. At 12-month follow-up, the AD patients showed no differences in FA decline between initial treatment and placebo groups after the 6-month open-label extension phase. A significant FA decline occurred in the left posterior cingulate across the AD and HC groups without between-group differences. DTI demonstrated FA decline in intracortically projecting fiber tracts in aging and AD over 1 year. Galantamine had limited impact on regional FA decline, which was not preserved after additional 6-month open-label treatment.

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Available from: Harald J Hampel, Feb 14, 2015
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    • "This functional hub is known to exhibit connectivity alterations in AD patients (Greicius et al., 2004), especially early in the disease (Damoiseaux et al., 2012), emphasizing its role for this disease. The findings presented in the current work regarding increases of functional connectivity in the posterior DMN sub-component may be linked to those previously presented by Likitjaroen and colleagues who demonstrated an impact of Galantamine on the posterior body of the corpus callosum in AD patients using diffusion tensor imaging (Likitjaroen et al., 2012). As this area is known to contain fibers projecting into parietal regions (Hofer and Frahm, 2006), it can be assumed that changes in fiber tract integrity may have contributed to the observed increases of functional connectivity within the posterior cingulate cortex and the Precuneus. "
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    • "In addition, the effects of medication on WM structure changes were not investigated because all participants were drug-naive. In fact, a previous DTI study showed that FA decline was preserved in the posterior body of the corpus callosum in the AD group with galantamine treatment compared to the placebo group [36]. "
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