Regional cortical acetylcholine esterase activity in healthy controls, mild cognitive impairment and Alzheimer's disease

Objectives [11C]N-methyl-4-piperidyl acetate (MP4A) is a positron emission tomography (PET) tracer for cerebral acetylcholine esterase (AChE) activity as a marker of the integrity of the cerebral cholinergic system. Previous preliminary studies indicate a general reduction of AChE activity in Alzheimer dementia (AD) and Mild Cognitive Impairment (MCI).

Methods MP4A PET was performed in 21 healthy controls (HC, age 64.6±8.7 y), 20 patients with MCI (age 67.1±7.9 y, MMSE 27.2±1.6) and 15 patients with AD (age 66.1±7.9 y, MMSE 21.1±2.7). Subjects were free of cholinesterase inhibitors. A neuropsychological battery was administered. Parametric images of hydrolysis rate constant k3 with putamen as reference region were generated by non-linear least squares fits and analysed using standard atlas regions.

Results The mean cortical k3 of HC (0.084±0.008 min-1) was significantly higher than in MCI (0.076±0.011 min-1, p<0.05, reduction 9.58%) and in AD patients (0.066±0.009 min-1, p<0.01, reduction 20.71%). The reduction of k3 in AD compared to MCI (12.32%) was also significant (p<0.05). Reduction in temporal regions was most pronounced. Hippocampus, amygdala and entorhinal also showed large k3 reductions in patients, but also high variance of values.

Conclusions Data confirm the reduction of AChE activity in MCI and AD. Since [11C]-MP4A PET allows a clear differentiation between groups it might be a valuable tool for early diagnosis of degenerative dementia.

Research Support This study was funded by the Marga and Walter Boll Foundation and the WDH Foundation.