title: Neurobiological correlates of apathy in Alzheimer's disease and mild cognitive impairment: a critical review.
abstract: BACKGROUND
  In Alzheimer's disease (AD) and mild cognitive impairment (MCI), apathy was associated with faster clinical deterioration. Studies involving neurobiological correlates such as neuroimaging and biomarkers have presented distinct results.
  
  
  OBJECTIVE
  This work aimed to analyze neurobiological correlates of apathy in AD and MCI based on evidence from the literature involving brain neuroimaging and classical AD biomarkers.
  
  
  METHODS
  This review comprised studies published from 1996 to June 2013 from the Pubmed database. The studies were divided into Part I (neuroimaging) and Part II (chemical biomarkers). The analysis included the identification of brain regions involved and assessments of apathy and cognition. We found 68 publications: 33 fulfilled the inclusion criteria; 35 were case reports or were not clear about the measurements of apathy and were excluded. From the 33 eligible studies, 26 were classified into part I, and 7 studies were included in part II. We created specific criteria to appropriately classify the quality level of each publication.
  
  
  RESULTS
  Prefrontal regions and the anterior cingulate were the leading brain areas associated with apathy in AD and MCI. Other regions, including cortical and subcortical structures, have also been implicated in this syndrome.
  
  
  CONCLUSIONS
  Abnormalities in frontal regions (associated with impairments in planning and decision making) and anterior cingulate (related to emotional blunting and loss of motivation) were the crucial structures associated with apathy in AD and MCI.
authors.affiliation: UNESP - Universidade Estadual Paulista, Institute of Biosciences, Campus of Rio Claro-SP, Brazil Laboratory of Neurosciences (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Florindo
authors.initials: F
authors.lastname: Stella
authors.affiliation: Laboratory of Neurosciences (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Márcia
authors.initials: M
authors.lastname: Radanovic
authors.affiliation: Laboratory of Neurosciences (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Ivan
authors.initials: I
authors.lastname: Aprahamian
authors.affiliation: Laboratory of Neurosciences (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, SP, Brazil Pontifícia Universidade Católica de São Paulo, Gerontoly Program, São Paulo, Brazil.
authors.forename: Paulo Renato
authors.initials: PR
authors.lastname: Canineu
authors.affiliation: UNESP - Universidade Estadual Paulista, Biosciences Institute, Aging and Physical Activity Laboratory, Campus of Rio Claro-SP, Brazil.
authors.forename: Larissa Pires
authors.initials: LP
authors.lastname: de Andrade
authors.affiliation: Laboratory of Neurosciences (LIM-27), Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Orestes Vicente
authors.initials: OV
authors.lastname: Forlenza
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology*; D057565:Apathy; D001921:Brain / Q000473:pathology*; D060825:Cognitive Dysfunction / Q000503:physiopathology*; D006801:Humans; D009446:Neurobiology; D039781:PubMed / Q000706:statistics & numerical data; D013223:Statistics as Topic
keywords: Alzheimer's disease; Apathy; mild cognitive impairment; neurobiological correlates; neuroimaging; review