Corpus Callosum Structure is Topographically Correlated with the Early Course of Cognition and Depression in Alzheimer's Disease

Article type: Research Article

Authors: Di Paola, Margherita^{a; b; *} | Phillips, Owen^{a; c} | Orfei, Maria Donata^a | Piras, Fabrizio^a | Cacciari, Claudia^a | Caltagirone, Carlo^{a; c} | Spalletta, Gianfranco^{a; d; *}

Affiliations: [a] Department of Clinical and Behavioural Neurology, IRCCS Santa Lucia Foundation, Rome, Italy | [b] LUMSA University, Department of Human Studies, Piazza delle Vaschette, Rome, Italy | [c] Neuroscience Department, Tor Vergata University, Rome, Italy | [d] Beth K. and Stuart C. Yudofsky Division of Neuropsychiatry, Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA

Correspondence: [*] Correspondence to: Margherita Di Paola, Psy. S., PhD, IRCCS Santa Lucia Foundation, Via Ardeatina 306, 00179 Rome, Italy. Tel.: +39 06 51501121; Fax: +39 06 51501213; E-mail: m.dipaola@hsantalucia.it and Gianfranco Spalletta, MD, PhD, IRCCS Santa Lucia Foundation, Via Ardeatina 306, 00179 Rome, Italy. Tel.: +39 06 51501575; Fax: +39 06 51501575; E-mail: g.spalletta@hsantalucia.it.

Abstract: Corpus callosum (CC) abnormalities may cause cognitive and neuropsychiatric complications due to reduced hemispheric integration. Over a one-year period, we investigated whether the CC structure of 20 patients with mild Alzheimer's disease (AD) was linked to the evolution of cognitive and neuropsychiatric symptoms. We also investigated whether this anatomical-clinical relationship was localized topographically on the CC by combining voxel-based morphometry and diffusion tensor imaging approaches. We assessed patients' global cognitive deterioration and neuropsychiatric symptoms with the Mini-Mental State Examination and the Neuropsychiatric Inventory. Increased global cognitive deterioration during the early course of AD was significantly related to reduced white matter density (p = 0.004) and fractional anisotropy (FA) (p = 0.012) and increased mean diffusivity (MD) (p = 0.017) at the level of the CC isthmus/splenium. Further, increased depression severity was significantly related to reduced FA (p = 0.008) and increased MD (p = 0.018) at the level of the CC rostrum. These results indicate that changes in early myelinated CC fibers, which subserve the lateral temporal and parietal cortices and are less vulnerable to damage, may be related to cognitive impairment. Furthermore, changes in late myelinated CC fibers, which connect the orbitofrontal cortices and are more vulnerable to damage, may be related to the earliest neuropsychiatric symptoms of AD, such as depression.

Keywords: Cognitive domain, corpus callosum, depression, diffusion tensor imaging , diffusivity, drug-free, first diagnosed AD, fractional anisotropy, mean diffusivity, mild Alzheimer's disease, Mini-Mental State Examination, neuropsychiatric symptoms, structural MRI, volume, voxel-based morphometry

DOI: 10.3233/JAD-142895

Journal: Journal of Alzheimer's Disease, vol. 45, no. 4, pp. 1097-1108, 2015