title: Physiological phenotyping of dementias using emotional sounds.
abstract: BACKGROUND
  Emotional behavioral disturbances are hallmarks of many dementias but their pathophysiology is poorly understood. Here we addressed this issue using the paradigm of emotionally salient sounds.
  
  
  METHODS
  Pupil responses and affective valence ratings for nonverbal sounds of varying emotional salience were assessed in patients with behavioral variant frontotemporal dementia (bvFTD) (n = 14), semantic dementia (SD) (n = 10), progressive nonfluent aphasia (PNFA) (n = 12), and AD (n = 10) versus healthy age-matched individuals (n = 26).
  
  
  RESULTS
  Referenced to healthy individuals, overall autonomic reactivity to sound was normal in Alzheimer's disease (AD) but reduced in other syndromes. Patients with bvFTD, SD, and AD showed altered coupling between pupillary and affective behavioral responses to emotionally salient sounds.
  
  
  CONCLUSIONS
  Emotional sounds are a useful model system for analyzing how dementias affect the processing of salient environmental signals, with implications for defining pathophysiological mechanisms and novel biomarker development.
authors.affiliation: Dementia Research Centre, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Phillip D
authors.initials: PD
authors.lastname: Fletcher
authors.affiliation: Dementia Research Centre, UCL Institute of Neurology, University College London, London, UK ; London School of Hygiene and Tropical Medicine, University of London, London, UK.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Nicholas
authors.affiliation: Dementia Research Centre, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Shakespeare
authors.affiliation: Dementia Research Centre, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Downey
authors.affiliation: Dementia Research Centre, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Hannah L
authors.initials: HL
authors.lastname: Golden
authors.affiliation: Dementia Research Centre, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Agustus
authors.affiliation: Dementia Research Centre, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Camilla N
authors.initials: CN
authors.lastname: Clark
authors.affiliation: Dementia Research Centre, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Mummery
authors.affiliation: Dementia Research Centre, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Schott
authors.affiliation: Dementia Research Centre, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Sebastian J
authors.initials: SJ
authors.lastname: Crutch
authors.affiliation: Dementia Research Centre, UCL Institute of Neurology, University College London, London, UK.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Warren
keywords: Alzheimer's disease; Autonomic; Emotion; Frontotemporal dementia; Pupillometry; Sound