Apathy as a feature of prodromal Alzheimer’s disease: an FDG-PET ADNI study Julien Delrieu 1 , Thomas Desmidt 2 , Vincent Camus 2 , Sandrine Sourdet 1 , Claire Boutoleau-Bretonnière 3 , Emmanuel Mullin 4 , Bruno Vellas 1,5 , Pierre Payoux 6,7 , Thibaud Lebouvier 3 and Alzheimer’s Disease Neuroimaging Initiative † 1 Alzheimer’s Disease Clinical Research Centre, Gérontopôle, Toulouse University Hospital, Toulouse, France 2 CM2R, CHU de Tours, Tours, France 3 CM2R, CHU de Nantes, Nantes, France 4 CM2R, CHU de Nice, Nice, France 5 UMR1027 INSERM, Universite de Toulouse, Toulouse, France 6 Department of Nuclear Medicine, Toulouse University Hospital, Toulouse, France 7 UMR825 INSERM, Universite de Toulouse, Toulouse, France Correspondence to: J. Delrieu, E-mail: delrieu.j@chu-toulouse.fr † Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.ucla.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at http://adni.loni.ucla.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf. Objective: The goal of this study is to evaluate brain metabolism in mild cognitive impairment (MCI) patients with and without apathy (as determined by the Neuropsychiatric Inventory Questionnaire). Methods: Baseline data from 65 MCI participants (11 with apathy and 54 without) from the Alzheimer’s Disease (AD) Neuroimaging Initiative study were analyzed. All participants underwent a comprehensive cognitive and neuropsychiatric assessment, volumetric MRI and measures of cerebral glucose metabo- lism applying 18 F-fluorodeoxyglucose positron emission tomography at baseline. The presence of apathy at baseline was determined by the Neuropsychiatric Inventory Questionnaire. Results: There was no difference between apathy and apathy-free MCI patients regarding cognitive assessment and neuropsychiatric measures when apathy-specific items were removed. Cerebrovascular disease load and cerebral atrophy were equivalent in both groups. Compared with the apathy-free MCI pa- tients, MCI patients with apathy had significantly decreased metabolism in the posterior cingulate cortex. Conclusion: The presence of apathy in MCI patients is associated with AD-specific pattern of brain meta- bolic defect. These results could suggest that apathy belongs to the spectrum of prodromal AD symptoms. Copyright # 2014 John Wiley & Sons, Ltd. Key words: apathy; FDG-PET; biomarker; Alzheimer’s disease; mild cognitive impairment; Alzheimer’s disease neuroimaging initiative (ADNI) History: Received 18 April 2013; Accepted 28 May 2014; Published online in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/gps.4161 Introduction Apathy and depression are the most frequent neuro- psychiatric features in mild cognitive impairment (MCI) (Feldman et al., 2004; Gabryelewicz et al., 2004; Lopez et al., 2005). Differentiating apathy from depression can be challenging as lack of motivation is one of the clinical dimensions of major depression (Starkstein and Leentjens, 2008). However, in Alzheimer’s disease (AD), there are strong arguments to consider that depression and apathy are indepen- dent clinical dimensions (Aalten et al., 2007; Aalten et al., 2008). Depression is a well-characterized mental disorder with validated clinical diagnostic criteria and specific validated clinical rating scales (Gelenberg, 2010; Nutt, 2011), but there is still inconsistent evidence that depression increases the conversion rate to dementia in MCI (Panza et al., 2008; Caracciolo et al., 2011; Copyright # 2014 John Wiley & Sons, Ltd. Int J Geriatr Psychiatry (2014) RESEARCH ARTICLE