Premium
P2‐248: Continuous and cyclic progesterone differentially affect estrogen regulation of Alzheimer‐like pathology in female 3xTg‐AD mice
Author(s) -
Carroll Jenna C.,
Rosario Emily R.,
Villamagna Angela,
Gentzschein Elisabet,
Stanczyk Frank Z.,
Pike Christian J.
Publication year - 2009
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2009.04.561
Subject(s) - estrogen , ovariectomized rat , medicine , endocrinology , hormone , progestin , menopause , neuropathology , hippocampal formation , disease
particularly in deep cortical and subcortical structures that map to the distribution of white matter. Attenuation of progression of cortical atrophy in patients treated with dual inhibitory agents might, therefore, be due to reduced white matter damage. To test this hypothesis, this exploratory study investigated the effect of different ChEI treatment agents on white matter volumes in patients with minimal to mild AD. Methods: Using the database from a previous study in 26 minimal to mild AD patients (Venneri et al, 2005), this retrospective analysis evaluated the effects of cholinesterase inhibition on white matter in the AD brain. White matter volume changes were quantified using voxel-based morphometry in patients receiving a dual inhibitor (rivastigmine) or an AChE-selective inhibitor (donepezil or galantamine) for 20 weeks. Results: The rivastigmine group (n 1⁄4 9) was titrated to 9 mg/day for all subjects except one, who tolerated 12 mg/day. Final dose was 10 mg/day for all subjects in the donepezil group (n1⁄4 9) except one, who tolerated only 5 mg/day. All patients in the galantamine group (n 1⁄4 8) tolerated a final dose of 32 mg/day. Donepezil and galantamine were associated with reduced white matter volume, while white matter was preserved in subjects receiving rivastigmine. Conclusions: Dual cholinesterase inhibition may influence white matter volume specifically. The enzymatic functions of BChE include the hydrolysis of extracellular acetylcholine (ACh). Extracellular ACh acts as a local ‘‘anti-inflammatory’’ signalling molecule that blocks proinflammatory responses in regions distal from synaptic sites. White matter changes in old age and in neurodegenerative diseases have been traditionally attributed to Wallerian degeneration of axonal fibres caused by neuronal loss, but white matter changes may be a primary pathophysiological event, with secondary grey matter degeneration.