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Up-regulation of hippocampal serotonin metabolism in mild cognitive impairment

2007; Lippincott Williams & Wilkins; Volume: 69; Issue: 10 Linguagem: Inglês

10.1212/01.wnl.0000271377.52421.4a

1526-632X

L. Truchot, Nicolas Costes, Luc Zimmer, B. Laurent, Didier Le Bars, C. Thomas-Antérion, Bernard Croisile, Bernadette Mercier, M. Hermier, Alain Vighetto, Pierre Krolak‐Salmon,

Memory and Neural Mechanisms

Objective: Recent studies have suggested modifications of serotonin cerebral metabolism and of 5-HT 1A receptors density in Alzheimer disease (AD). This study aims at exploring hippocampus 5-HT 1A 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-HT 1A antagonist, 2′-methoxyphenyl-( N -2′-pyridinyl)- p -[ 18 F]fluoro-benzamidoethylpiperazine ([ 18 F]MPPF), the hippocampus 5-HT 1A 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 [ 18 F]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 BP c 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 BP c 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-HT 1A receptors with 2′-methoxyphenyl-( N -2′-pyridinyl)- p - 18 F-fluoro-benzamidoethylpiperazine PET seems to be of interest for better understanding pathophysiologic changes at early stages of AD.