title: Structural correlates of apathy in Alzheimer's disease: a multimodal MRI study.
abstract: Apathy is one of the most frequent symptoms of dementia, whose underlying neurobiology is not well understood. The objective was to analyze the correlations of apathy and its dimensions with gray and white matter damage in the brain of patients with advanced Alzheimer's disease (AD).
  
  
  
  The setting of the study was at the Alzheimer Center Reina Sofía Foundation Research Unit. Participants include 37 nursing home patients with moderate to severe AD, 78.4% were women, and mean Standard Deviation (SD) age is 82.7 (5.8). Several measurements were taken: severe mini-mental state examination and Global Deterioration Scale for cognitive and functional status, Neuropsychiatric Inventory for behavioral problems, and Apathy In Dementia-Nursing Home Version Scale for apathy, including total score and subscores of emotional blunting, deficit of thinking, and cognitive inertia. 3T magnetic resonance imaging measures (voxel-based morphometry, fluid-attenuated inversion recovery, and diffusion tensor imaging) were also conducted.
  
  
  
  Moderate levels of apathy (mean Apathy In Dementia-Nursing Home Version Scale: 31.1 ± 18.5) were found. Bilateral damage to the corpus callosum and internal capsule was associated with apathy severity (cluster size 2435, p < 0.0005, family-wise error [FWE]-corrected). A smaller and more anteriorly located region of the right internal capsule and corpus callosum was associated with higher emotional blunting (cluster size 334, p < 0.0005, FWE-corrected). Ischemic damage in the right periventricular frontal region was associated with higher deficit of thinking (cluster size 3805, p < 0.005, FWE-corrected).
  
  
  
  Brain damage related to apathy may have different features in the advanced stages of AD and differs between the three apathy dimensions. Besides atrophy, brain connectivity and vascular lesions are relevant in the study of apathy, especially in the more severe stages of dementia. Further magnetic resonance imaging studies should include multimodal techniques. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Alzheimer Disease Research Unit, CIEN Foundation, Carlos III Institute of Health, Alzheimer Center Reina Sofia Foundation, Madrid, Spain.|Centro de Investigación Biomédica en Red de Salud Mental. CIBERSAM, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Agüera-Ortiz
authors.affiliation: Medical Image and BIometry Laboratory, Rey Juan Carlos University, Madrid, Spain.|MR Physics Group, Radiology and Nuclear Medicine Department, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Hernandez-Tamames
authors.affiliation: National Center of Epidemiology and CIBERNED, Carlos III Institute of Health, Madrid, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Martinez-Martin
authors.affiliation: Alzheimer Disease Research Unit, CIEN Foundation, Carlos III Institute of Health, Alzheimer Center Reina Sofia Foundation, Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Cruz-Orduña
authors.affiliation: Medical Image and BIometry Laboratory, Rey Juan Carlos University, Madrid, Spain.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Pajares
authors.affiliation: Alzheimer Disease Research Unit, CIEN Foundation, Carlos III Institute of Health, Alzheimer Center Reina Sofia Foundation, Madrid, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: López-Alvarez
authors.affiliation: Department of Psychiatry, NYU Langone Medical Center, New York, USA.
authors.forename: Ricardo S
authors.initials: RS
authors.lastname: Osorio
authors.affiliation: Instituto Psiquiátrico José Germain, Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Sanz
authors.affiliation: Alzheimer Disease Research Unit, CIEN Foundation, Carlos III Institute of Health, Alzheimer Center Reina Sofia Foundation, Madrid, Spain.|Servicio de Neurología, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Olazarán
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000503:physiopathology*; D057565:Apathy / Q000502:physiology*; D001284:Atrophy / Q000473:pathology; D056324:Diffusion Tensor Imaging / Q000379:methods; D005260:Female; D005625:Frontal Lobe / Q000473:pathology; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D066127:White Matter / Q000000981:diagnostic imaging / Q000473:pathology*
keywords: 3T magnetic resonance imaging; Alzheimer's disease; apathy; apathy dimensions; brain morphometry; diffusion tensor imaging; vascular damage