Affiliations: [a] Neurobiology Research Unit, The Neuroscience Center, University Hospital Rigshospitalet, Copenhagen, Denmark | [b] Memory Disorders Research Unit, The Neuroscience Center, University Hospital Rigshospitalet, Copenhagen, Denmark | [c] Center for Integrated Molecular Imaging, The Neuroscience Center, University Hospital Rigshospitalet, Copenhagen, Denmark | [d] PET and Cyclotron Unit, Department of Clinical Physiology and Nuclear Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark | [e] Danish Research Center for Magnetic Resonance, University Hospital Hvidovre, Copenhagen, Denmark
Correspondence:
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Correspondence to: Lisbeth Marner, MD, Ph.D., Neurobiology Research Unit N9201, University Hospital Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. Tel.: +45 3545 6711; Fax: +45 3545 6713; Email: [email protected].
Abstract: 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.
