title: Covariant perfusion patterns provide clues to the origin of cognitive fluctuations and attentional dysfunction in dementia with Lewy bodies.
abstract: BACKGROUND
  Fluctuating cognition (FC), particularly in attention, is a core and defining symptom in dementia with Lewy bodies (DLB) but is seen much less frequently in Alzheimer's dementia (AD). However, its neurobiological origin is poorly understood. The aim of our study was therefore to characterize perfusion patterns in DLB patients that are associated with the severity and frequency of FC as measured both clinically and using objective neuropsychological assessments.
  
  
  METHODS
  Spatial covariance analyses were applied to data derived from single photon emission computed tomography (SPECT) HMPAO brain imaging in 19 DLB and 23 AD patients. Patients underwent clinical assessment of their FC and cognitive function as well as objective testing of their attention.
  
  
  RESULTS
  Covariant perfusion principal components (PCs) were not associated with either FC or cognitive or attentional measures in AD. However, in DLB patients, the second PC (defined as DLB-cognitive motor pattern, DLB-PCI2) which was characterized by bilateral relative increases in cerebellum, basal ganglia, and supplementary motor areas and widespread bilateral decreases in parietal regions, positively correlated with poorer cognitive function, increased FC and worse attentional function measured both clinically and neurophysiologically (p < 0.05) as well as with the severity of bradykinesia (p = 0.04).
  
  
  CONCLUSIONS
  FC in DLB appears distinct from those seen in AD, and likely to be driven by internal neurobiological perturbations in brain circuitry as evidenced using spatial covariance analyses of cerebral perfusion. FC and certain aspects of attentional dysfunction in DLB may, in part, depend upon both distributed motor and non-motor networks.
authors.affiliation: Institute for Ageing and Health, Campus for Aging and Vitality, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: John-Paul
authors.initials: JP
authors.lastname: Taylor
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Colloby
authors.forename: Ian G
authors.initials: IG
authors.lastname: McKeith
authors.forename: John T
authors.initials: JT
authors.lastname: O'Brien
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000503:physiopathology; D001288:Attention / Q000502:physiology*; D001921:Brain / Q000503:physiopathology; D003071:Cognition / Q000502:physiology; D003072:Cognition Disorders / Q000209:etiology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D020961:Lewy Body Disease / Q000150:complications / Q000503:physiopathology*; D008297:Male; D059906:Neuroimaging; D009483:Neuropsychological Tests; D015899:Tomography, Emission-Computed, Single-Photon