Up-regulation of hippocampal serotonin metabolism in mild cognitive impairment

Objective: Recent studies have suggested modifications of serotonin cerebral metabolism and of 5-HT1A receptors density in Alzheimer disease ( AD). This study aims at exploring hippocampus 5-HT1A receptor density in patients at the amnesic mild cognitive impairment (aMCI) and mild AD dementia stages. Methods: With use of PET with a selective 5-HT1A antagonist, 2'-methoxyphenyl-( N-2'-pyridinyl)p-[F-18] fluoro-benzamidoethylpiperazine ([F-18] MPPF), the hippocampus 5-HT1A binding potential ( BP) was quantified in 10 patients with mild AD, in 11 patients with aMCI, and in 21 aged paired control subjects. To take into account hippocampal atrophy, a partial volume correction was applied to the [F-18] MPPF data, leading to the calculation of a corrected BP ( BP c). Comparison of hippocampus BP over populations was performed using Kruskal-Wallis rank analysis. Results: Hippocampus serotonergic receptor binding distinguishes patients from controls and patients with aMCI from patients with AD. In aMCI patients, the mean hippocampus BPc was 59% higher than the controls' ( p < 0.005), and it was conversely 35% lower in patients with mild AD ( p < 0.01). The difference in BPc values between patients with aMCI and mild AD was large, resulting in a p value of < 0.0005. These differences were not related to hippocampus atrophy. Conclusion: A compensatory mechanism illustrated by an up-regulation of serotonergic metabolism has been shown at the stage of amnesic mild cognitive impairment ( aMCI) in contrast with a dramatic decrease at later stages of Alzheimer disease ( AD). This difference of hippocampus serotonergic receptor labeling allows distinguishing of patients with aMCI from those with mild AD. Exploring 5-HT1A receptors with 2'-methoxyphenyl-( N-2'-pyridinyl)-p-F-18-fluoro-benzamidoethylpiperazine PET seems to be of interest for better understanding pathophysiologic changes at early stages of AD.