Brain tissue modifications induced by cholinergic therapy in Alzheimer's disease.
A previous preliminary investigation based on a novel MRI approach to map anatomical connectivity revealed areas of increased connectivity in Alzheimer's disease (AD) but not in mild cognitive impairment patients. This prompted the hypothesis tested here, that these areas might reflect phenomena of brain plasticity driven by acetylcholinesterase inhibitors (AChEIs). Thirty-eight patients with probable AD (19 under medication with AChEIs and 19 drug-naïve) were recruited together with 11 healthy controls. All subjects had MRI scanning at 3T, including volumetric and diffusion-weighted scans. Probabilistic tractography was used to initiate streamlines from all parenchymal voxels, and anatomical connectivity maps (ACMs) were obtained by counting, among the total number of streamlines initiated, the fraction passing through each brain voxel. After normalization into standard space, ACMs were used to test for between-group comparisons, and for interactions between the exposure to AChEIs and global level of cognition. Patients with AD had reduced ACM values in the fornix, cingulum, and supramarginal gyri. The ACM value was strongly associated with the AChEI dosage-x-duration product in the anterior limb (non-motor pathway) of the internal capsule. Tractography from this region identified the anterior thalamic radiation as the main white matter (WM) tract passing through it. The reduced connectivity in WM bundles connecting the hippocampi with the rest of the brain (fornix/cingulum) suggests a possible mechanism for the spread of AD pathology. An intriguing explanation for the interaction between AChEIs and ACM is related to the mechanisms of brain plasticity, partially driven by neurotrophic properties of acetylcholine replacement.
['Bozzali|Marco|M|', 'Parker|Geoff J M|GJ|', 'Spanò|Barbara|B|', 'Serra|Laura|L|', 'Giulietti|Giovanni|G|', 'Perri|Roberta|R|', 'Magnani|Giuseppe|G|', 'Marra|Camillo|C|', 'G Vita|Maria|M|', 'Caltagirone|Carlo|C|', 'Cercignani|Mara|M|']
D000368:Aged D000369:Aged, 80 and over D000544:Alzheimer Disease D014150:Antipsychotic Agents D001921:Brain D001931:Brain Mapping D002800:Cholinesterase Inhibitors D003072:Cognition Disorders D038524:Diffusion Magnetic Resonance Imaging D005260:Female D006801:Humans D021621:Imaging, Three-Dimensional D008297:Male D008875:Middle Aged D009483:Neuropsychological Tests D011569:Psychiatric Status Rating Scales D013223:Statistics as Topic
brain plasticity anatomical connectivity mapping AChE inhibitor Alzheimer disease diffusion MRI