The reduction of baseline serotonin 2A receptors in mild cognitive impairment is stable at two-year follow-up.

We previously demonstrated a 20-30% reduction in cortical 5-HT2A receptor binding in patients with mild cognitive impairment (MCI) as compared to healthy subjects. Here we present a two-year follow-up of 14 patients and 12 healthy age-matched subjects. Baseline and follow-up partial volume corrected levels of 5-HT2A in four neocortical lobes and the posterior cingulate gyrus were investigated using [18F]altanserin positron emission tomography with a bolus-infusion approach. In the two-year follow-up period, 8 of 14 patients with MCI had progressed to fulfill diagnostic criteria for probable Alzheimer's disease (AD). In both patients and healthy subjects, no significant change in 5-HT2A receptor binding was found as compared to baseline values. In MCI patients, the average BPP in neocortex ranged from 1.49 to 2.45 at baseline and 1.38 to 2.29 at two-year follow-up; and in healthy subjects BPP ranged from 1.85 to 3.10 at baseline and 1.81 to 2.98 at two-year follow-up. The BPP of the patients that converted to AD during the follow-up period did not differ significantly from the patients that had not (yet) converted, neither at baseline, nor at follow-up. We conclude that the reduced levels of 5-HT2A receptor binding in MCI patients decrease only slowly and non-significantly, even in patients who convert to AD. Our finding suggests that profoundly reduced cortical 5-HT2A receptor binding is an early feature in MCI whereas the clinical progression from MCI to AD is less associated with further decrease in binding.