title: A methodological study of locus coeruleus degeneration in dementing disorders.
abstract: BACKGROUND
  Degeneration of the locus coeruleus (LC) of the brain stem is a recognized phenomenon in Alzheimer's disease (AD), in dementia with Lewy bodies (DLB), and in Parkinson's disease with dementia (PDD). Prior studies have suggested that LC degeneration can be used to differentiate various dementing disorders histologically, but the paucity of methodological data may hamper systematic research on this nucleus.
  
  
  OBJECTIVE
  The purpose of this study was to evaluate various approaches to quantifying LC degeneration in dementing disorders, and to inform future decisions regarding the most appropriate method for diagnostics and research.
  
  
  METHODS
  105 LCs from brains of demented individuals with AD, DLB/PDD, vascular dementia (VaD), mixed dementia (AD+VaD), or frontotemporal lobar degeneration (FTLD) were examined, and the extent of LC degeneration was assessed using macroscopic evaluation, cell counting, and two degeneration scales. Scores were compared across diagnostic categories; diagnostic utility and intra- and interobserver reliability were assessed.
  
  
  RESULTS
  AD and DLB/PDD were associated with greater LC damage using either assessment method, significantly different from VaD and FTLD. Macroscopic appearance was informative, but cell counting was more sensitive and specific. The degeneration scales did not add significant diagnostic value over cell counting and were associated with greater observer variability.
  
  
  CONCLUSIONS
  The LC degenerates in certain dementia subtypes, especially in AD and DLB/PDD. Macroscopic assessment of the LC postmortem can be used to differentiate between disorders associated with degeneration (AD, DLB/PDD) or sparing (VaD) of the LC, but counting LC cells in a representative pontine section is the most appropriate method by which to assess LC degeneration.
authors.forename: Mattias
authors.initials: M
authors.lastname: Haglund
authors.forename: Niklas
authors.initials: N
authors.lastname: Friberg
authors.forename: Erik J D
authors.initials: EJ
authors.lastname: Danielsson
authors.forename: Jakob
authors.initials: J
authors.lastname: Norrman
authors.forename: Elisabet
authors.initials: E
authors.lastname: Englund
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000473:pathology; D019540:Area Under Curve; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D020961:Lewy Body Disease / Q000175:diagnosis* / Q000473:pathology; D008125:Locus Coeruleus / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000175:diagnosis* / Q000473:pathology; D012372:ROC Curve; D012680:Sensitivity and Specificity