Reduced 5-HT2A receptor binding in patients with mild cognitive impairment

Previous studies of patients with Alzheimerʹs disease (AD) have described reduced brain serotonin 2A (5-HT2A) receptor density. It is unclear whether this abnormality sets in early in the course of the disease and whether it is related to early cognitive and neuropsychiatric symptoms. We assessed cerebral 5-HT2A receptor binding in patients with mild cognitive impairment (MCI) and related 5-HT2A receptor binding to clinical symptoms. Sixteen patients with MCI of the amnestic type (mean age 73, mean MMSE 26.1) and 17 age and sex matched control subjects were studied with MRI and [18F]altanserin PET in a bolus–infusion approach. A significant global reduction of 20–30% in 5-HT2A binding (atrophy corrected) was found in most neocortical areas. Reduced 5-HT2A binding in the striatum correlated significantly with Neuropsychiatric Inventory depression and anxiety scores. We conclude that widespread reductions in 5-HT2A receptor binding were found in amnestic MCI, pointing at the presence of serotonergic dysfunction in prodromal AD. This may provide some of the pathophysiological background for the neuropsychiatric symptoms found in early AD.