ORIGINAL INVESTIGATION Changes in brain 11 C–nicotine binding sites in patients with mild Alzheimer’ s disease following rivastigmine treatment as assessed by PET Ahmadul Kadir & Taher Darreh-Shori & Ove Almkvist & Anders Wall & Bengt Långström & Agneta Nordberg Received: 13 October 2006 / Accepted: 24 January 2007 / Published online: 20 February 2007 # Springer-Verlag 2007 Abstract Rationale Marked reduction in the cortical nicotinic ace- tylcholine receptors is observed in the brain of patients suffering from Alzheimer ’ s disease (AD). Although cho- linesterase inhibitors are used for symptomatic treatment of mild to moderate AD patients, numerous long-term treat- ment studies indicate that they might stabilize or halt the progression of the disease by restoring the central cholin- ergic 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. Objective 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 neuro- psychological tests after rivastigmine treatment. Materials and methods 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. Results 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. Conclusion Changes in the 11 C–nicotine binding during rivastigmine treatment might represent remodeling of the cholinergic and related neuronal network. Keywords Alzheimer’ s disease (AD) . Rivastigmine . Positron emission tomography (PET) . 11 C–nicotine binding . Acetylcholinesterase (AChE) . Butyrylcholinesterase (BuChE) . Cognitive function . Attention Introduction Alzheimer’ s disease (AD) is the most common neurode- generative disorder. Cholinesterase inhibitors (ChEIs) are so far the most extensively studied and developed agents used in the symptomatic treatment of mild to moderate AD. Rivastigmine is a pseudo-irreversible (slowly reversible) ChEI with an intermediate duration of action. Whereas the primary target of this agent is acetylcholinesterase (AChE), Psychopharmacology (2007) 191:1005–1014 DOI 10.1007/s00213-007-0725-z A. Kadir : T. Darreh-Shori : O. Almkvist : A. Nordberg (*) Karolinska Institute, Department of Neurobiology, Care Sciences and Society, Division of Molecular Neuropharmacology, Karolinska University Hospital Huddinge, Novum Floor-5, 141 86 Stockholm, Sweden e-mail: Agneta.K.Nordberg@ki.se O. Almkvist : A. Nordberg Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden O. Almkvist Department of Psychology, Stockholm University, Stockholm, Sweden A. Wall : B. Långström Uppsala PET Centre/Imanet, Uppsala, Sweden