Inhibition of hippocampal function in mild cognitive impairment: targeting the cholinergic hypothesis.

Mild cognitive impairment (MCI) is a condition with an increased risk of developing Alzheimer's disease. Chief complaint and diagnostic criterion in subjects with mild cognitive impairment is memory failure. We hypothesized that cholinergic malfunction may underlie memory impairment in these subjects and applied a low dosage of an acetylcholinesterase inhibitor and modulator of nicotinic acetylcholine receptors, galantamine (4 mg bid), for 7 days. We used neuropsychological tests to investigate attention, cognitive flexibility, verbal and visual short-term and working memory, susceptibility to interference and episodic memory and functional magnetic resonance imaging to assess spatial navigation both prior to and after treatment. Late episodic learning and delayed recall improved on treatment as did recruitment of the hippocampal region during spatial navigation. Performance in all other neuropsychological measures remained unchanged. We show that an increase of cholinergic neurotransmission in subjects with MCI specifically improves hippocampal function and thus that a cholinergic deficit is functionally relevant in subjects with MCI. Malfunction of the cholinergic system may be tackled pharmacologically via the inhibition of acetylcholinesterase even when the impairment is slight.

Structural changes of Toxoplasma gondii bradyzoites and cysts following therapy with sulfamethoxypyrazine-pyrimethamine: studies by light and electron microscopy. Consequences for chemotherapy.

Mastomys natalensis chronically infected with Toxoplasma gondii strain ALT over two months were treated with sulfamethoxypyrazine-pyrimethamine for 10 and 25 days. 72 hours after discontinuation of therapy the animals were sacrificed. The brains were removed and, following corresponding preparation, studied for the presence of the parasite and structural changes of cysts by light and transmission electron microscopy. More or less pronounced structural changes could be found in cyst walls, bradyzoites, and in particular in the endodyogeny stages. The degree of damage proved to be proportional to the intensity of the bradyzoite metabolism. The combination of drugs used was capable of passing the cyst membrane as long as the bradyzoites maintained their metabolism irrespective of its intensity. In cysts with a largely dormant metabolism that had been subject to therapy, no micromorphological differences of the ultrastructure could be recognized when compared with untreated controls of identical age; these cysts could not be influenced by treatment.