No further decrease of 5-HT2A receptors in patients with mild cognitive impairment: A two-year follow up study

Abstract

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Objectives: In patients with mild cognitive impairment of the amnestic type (MCI), we have previously demonstrated a 20-30% reduction in cortical 5-HT2A-receptor binding as compared to healthy subjects using [18F]-Altanserin positron emission tomography (PET). Here we present a two-year follow-up of both patients and healthy subjects. Methods: At baseline (n=16 patients, 17 healthy subjects) and at two-year follow-up (n=14 patients, 12 healthy subjects), all individuals were investigated with magnetic resonance imaging and [18F]-Altanserin PET using a bolus-infusion approach and partial volume correction. The binding potential of specific binding (BP1) was calculated using cerebellum as a reference region and metabolite corrected plasma values. As the temporal and parietal cortical regions often show hypometabolism in early AD and at the same time have a high 5-HT2A-receptor density, they were chosen for the present analysis. Results: In the two-year follow-up period, 9 out of 14 patients with MCI had progressed to fulfill AD criteria. In both patients and healthy subjects, no significant change in binding was found as compared to the investigation carried out two years earlier. In patients, the average BP1 was 2.16 at baseline and 2.09 at two-year follow-up (95% C.I. for difference: [-0.48 0.19]) and in healthy subjects BP1 was 2.62 and 2.54 (95% C.I. for difference: [-0.35 0.20]). The patients that converted to AD during the follow-up period did not differ significantly from the patients that did not convert. Conclusions: We conclude that the reduced levels of 5-HT2A-receptor binding in MCI patients are relatively stable, even in patients that convert to AD. Our finding suggests that the lower cortical 5-HT2A-receptor binding in MCI patients is due to brain changes that take place in the very early stages of AD before symptoms are present or perhaps even constitute a permanent trait marker for the risk of developing AD.