Reduced Regional Cortical Thickness Rate of Change in Donepezil-Treated Subjects With Suspected Prodromal Alzheimer’s Disease
Year: 2016
Type: article
Abstract: OBJECTIVE: Cortical thinning, previously identified during prodromal stages of Alzheimer's disease (AD), is a "candidate" biomarker implemented in AD clinical therapy trials. We investigated the effect of donepezil treatment on cortical thickness in mild cognitively impaired subjects with the amnestic syndrome of the hippocampal type, a prodromal at-risk group for progression to AD dementia. METHODS: Data were from a longitudinal analysis of a community-based multicenter suspected prodromal AD cohort diagnosed by the Free and Cued Selective Reminding Test (81 donepezil vs 92 placebo) enrolled in a double-blind, randomized, placebo-controlled parallel group design using donepezil (10 mg/day). The study started in November 2006 and concluded in August 2010. All subjects underwent 2 brain structural magnetic resonance imaging (MRI) scans, at baseline and at the end of the trial. Structural MRI images had been processed using the automated pipeline for longitudinal segmentation and surface reconstruction implemented in FreeSurfer. The primary outcome measure of this post hoc study was the annualized percentage change (APC) of cortical thickness. RESULTS: The donepezil group exhibited reduced APC cortical thinning compared to placebo in the rostral anterior cingulate (right: P = .048; left: P = .032), the orbitofrontal (right: P = .012; left: P < .048), and the right inferior frontal (P = .022) cortices and in the right insula (P = .010). These results were not statistically significant after Bonferroni correction likely due to insufficient power for cortical thickness measurements in the study group powered for the predefined hippocampus outcome. CONCLUSIONS: Our findings support the hypothesis that cortical thickness is a reliable candidate surrogate outcome in early predementia AD trials. In addition, donepezil treatment may have an impact on cortical structure/morphology in areas innervated by the medial and lateral cholinergic pathways. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00403520.
DOI: 10.4088/jcp.15m10413
Authors: Enrica Cavedo, for the Hippocampus Study Group, Bruno Dubois, Olivier Colliot, Simone Lista, Bernard Croisile, Guy Louis Tisserand, Jacques Touchon, Alain Bonafe, Pierre J. Ousset, Olivier Rouaud, Fréderic Ricolfi, Alain Vighetto, Florence Pasquier, Samantha Galluzzi, Christine Delmaire, Mathieu Ceccaldi, Nadine Girard, Stéphane Lehericy, Françoise Duveau, Marie Chupin, Marie Sarazin, Didier Dormont, Harald Hampel
Institutions: Inserm, Sorbonne Université, Assistance Publique – Hôpitaux de Paris, Centro San Giovanni di Dio Fatebenefratelli, Pitié-Salpêtrière Hospital, Institut du Cerveau, Centre d'Acquisition et de Traitement des Images, Université Pierre-et-Marie-Curie, Centre National de la Recherche Scientifique, Institut national de recherche en sciences et technologies du numérique, ARAMIS: Algorithmes, modèles et méthodes pour les images et les signaux du cerveau humain sain et pathologique, AXA Research Fund, Hôpital Pierre Wertheimer, Hôpital Gui de Chauliac, CHU Dijon Bourgogne, Lyon 1 Université, Hospices Civils de Lyon, Université de Lille, Centre Hospitalier Universitaire de Lille, Hôpital Roger Salengro, Hôpital de la Timone, Sorbonne Paris Cité, Centre Hospitalier Sainte-Anne, Université Paris Descartes
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2532989070