Changes in brain 11C–nicotine binding sites in patients with mild Alzheimer’s disease following rivastigmine treatment as assessed by PET

Abstract

Marked reduction in the cortical nicotinic acetylcholine receptors is observed in the brain of patients suffering from Alzheimer's disease (AD). Although cholinesterase inhibitors are used for symptomatic treatment of mild to moderate AD patients, numerous long-term treatment studies indicate that they might stabilize or halt the progression of the disease by restoring the central cholinergic neurotransmission. Thus, we used positron emission tomography (PET) technique as a sensitive approach to assess longitudinal changes in the nicotine binding sites in the brains of patients with AD. To evaluate changes in brain nicotinic binding sites in relation to inhibition level of cholinesterases in cerebrospinal fluid (CSF) and plasma and changes in cognitive performance of the patients in different neuropsychological tests after rivastigmine treatment. Ten mild AD patients received rivastigmine for 12 months. A dual-tracer PET model with administration of (15)O-water and (S)(-)(11)C-nicotine was used to assess (11)C-nicotine binding sites in the brain at baseline and after 3 and 12 months of the treatment. Cholinesterase activities in CSF and plasma were assessed colorimetrically. The (11)C-nicotine binding sites were significantly increased 12-19% in several cortical brain regions after 3 months compared with baseline, while the increase was not significant after 12 months of the treatment. After 3 months treatment, low enzyme inhibition in CSF and plasma was correlated with higher cortical (11)C-nicotine binding. The (11)C-nicotine binding positively correlated with attentional task at the 12-month follow-up. Changes in the (11)C-nicotine binding during rivastigmine treatment might represent remodeling of the cholinergic and related neuronal network.