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

• Rationale  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. 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 neuropsychological tests after rivastigmine treatment. Materials and methods  Ten mild AD patients received rivastigmine for 12 months. A dual-tracer PET model with administration of 15O–water and (S)(–)11C–nicotine was used to assess 11C–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 11C–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 11C–nicotine binding. The 11C–nicotine binding positively correlated with attentional task at the 12-month follow-up. Conclusion  Changes in the 11C–nicotine binding during rivastigmine treatment might represent remodeling of the cholinergic and related neuronal network.

Ämnesord

NATURVETENSKAP  -- Kemi (hsv//swe)

NATURAL SCIENCES  -- Chemical Sciences (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)

Nyckelord

Alzheimer’s disease (AD)

Rivastigmine

Positron emission tomography (PET)

11C–nicotine binding

Acetylcholinesterase (AChE)

Butyrylcholinesterase (BuChE)

Cognitive function

Attention

Chemistry

Kemi

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