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

Abstract

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.

Apathy and White Matter Integrity in Alzheimer’s Disease: A Whole Brain Analysis with Tract-Based Spatial Statistics

“…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].…”

Brain tissue modifications induced by cholinergic therapy in Alzheimer's disease

“…Finally, if our interpretation of sprouting of collateral fibers is correct, this phenomenon is expected to reduce rather than increase the FA locally. This might have mitigated the expected effect of Galantamine (FA preservation) in the study conducted by Likitjaroen et al [Likitjaroen et al, ].…”

Central effects of cholinesterase inhibitors in Alzheimer’s disease: insights from advanced neuroimaging

“…Negative findings were obtained in a DTI study in which 25 mild AD patients, 14 active and 11 with placebo, were treated with galantamine for 6 months with a further open-label extension of 6 months [61]. In this study, fractional anisotropy values were significantly maintained in the posterior part of the corpus callosum in the AD-treated subgroup at 6-months follow-up, but there was no difference between the treated and placebo groups at 12-months follow-up.…”