The Reduction of Baseline Serotonin 2A Receptors in Mild Cognitive Impairment is Stable at Two-year Follow-up

Abstract

We previously demonstrated a 20–30% reduction in cortical 5-HT_2A 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-HT_2A 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-HT_2A receptor binding was found as compared to baseline values. In MCI patients, the average BP_P 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 BP_P ranged from 1.85 to 3.10 at baseline and 1.81 to 2.98 at two-year follow-up. The BP_P 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-HT_2A 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-HT_2A receptor binding is an early feature in MCI whereas the clinical progression from MCI to AD is less associated with further decrease in binding.