Ventilatory Response to Hypercapnia Predicts Dementia with Lewy Bodies in Late-Onset Major Depressive Disorder

Article type: Research Article

Authors: Takahashi, Sho^{a; b} | Mizukami, Katsuyoshi^c | Arai, Tetsuaki^a | Ogawa, Ryoko^d | Kikuchi, Norihiro^d | Hattori, Satoshi^e | Darby, David^f | Asada, Takashi^{g; *}

Affiliations: [a] Department of Psychiatry, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan | [b] Department of Disaster Psychiatry, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan | [c] Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan | [d] Department of Pulmonology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan | [e] Biostatistics Center, Kurume University, Kurume, Fukuoka, Japan | [f] The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville VIC, Australia | [g] Tokyo Medical and Dental University, Tokyo, Japan

Correspondence: [*] Correspondence to: Takashi Asada, MD, PhD, Tokyo Medicaland Dental University, Specially Appointed Professor, 1-5-45 Yushima, Bunkyo, Tokyo 113-0034, Japan. Tel.: +81 368018718; Fax: +81 368018718; E-mail: tasada@tmd.ac.jp.

Abstract: Background:Studies have shown that developing major depressive disorder (MDD) at 50 years of age or older can predict dementia. Depression is particularly common in dementia with Lewy bodies (DLB), and occasionally occurs before the onset of extrapyramidal symptoms. Moreover, systemic autonomic dysfunction, including an abnormal ventilatory response to hypercapnia (VRH), is common in patients with DLB. Objective:Here, we aimed to determine whether the VRH is useful for distinguishing depression that is predictive of DLB from other types of MDD. Methods:Participants were 35 consecutive patients with first onset MDD at 50 years or older with bradykinesia. After diagnosing the clinical subtype of MDD according to DSM-IV criteria, each subject underwent a battery of psychological tests, autonomic examinations including VRH, brain magnetic resonance imaging, and 123I-meta-iodobenzylguanidine scintigraphy. Results:Longitudinal follow-up showed that all 18 patients with abnormal VRH results developed DLB, whereas none of the 17 patients with normal VRH results converted to DLB within the study period (sensitivity: 100% , specificity: 100%). Additionally, over half of the DLB converters showed abnormalities on other autonomic examinations. For converters, the most common MDD subtype had psychotic and melancholic features simultaneously. The frequency of hypersensitivity to psychotropics was higher in converters than it was in non-converters. Conclusion:In the present study, patients with abnormal VRH results were very likely to develop DLB. Thus, for patients with late-onset MDD accompanied by bradykinesia, the VRH in combination with the clinical subtype of MDD or hypersensitivity to psychotropics may be useful for diagnosing prodromal DLB.

Keywords: Autonomic failure, conversion, dementia with Lewy bodies, depression, ventilatory response to hypercapnia

DOI: 10.3233/JAD-150507

Journal: Journal of Alzheimer's Disease, vol. 50, no. 3, pp. 751-758, 2016