Serotonin receptor binding in mild cognitive impairment studied by PET and |[lsqb]|18F|[rsqb]|-altanserin

In post mortem studies of patients with Alzheimer's disease (AD) reduced serotonin (5-HT) receptor density has been described. Using positron emission tomography (PET) in patients with AD with and without depression, reduced binding to the 5-HT2A receptor subtype in cortical areas was found in two studies 1, 2. These reductions may reflect early and specific changes in the serotonergic transmitter system in AD. To evaluate possible changes in 5-HT2A receptor densities in cortical and mesial temporal lobe structures in patients with mild cognitive impairment (MCI). Fifteen patients with MCI of the amnestic type (considered to be prodromal AD) (8 females, 7 males, mean age 72, range 63-82, mean MMSE 26. 3, range 23-30) and 15 age and sex matched control subjects were studied with PET and MRI. The distribution volumes of specific tracer binding (BP1) were calculated for 17 brain regions using cerebellum as a reference region and individual plasma-curves corrected for radiolabelled metabolites. Volumes of interest were applied by an automated MRI-based template approach 3. PET data was corrected for partial volume effects due to atrophy 2, 4. Significant reductions in BP1 were found bilaterally in orbitofrontal cortex (p<0. 03, t-test) and in right entorhinal cortex (p<0.05, t-test). Reductions in 5-HT2A receptor binding were found in areas known to be affected early in the course of AD. It is likely that this reduction reflects a specific dysfunction of the serotonergic system in prodromal AD because atrophy could not explain the reduced tracer activity. Further, in a previous study of AD, applying atrophy correction did not change the finding of a reduction in 5-HT2A receptor binding in cortical areas, suggesting that a specific dysfunction of the serotonergic system can be demonstrated in vivo in AD 2.