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A methodological study of locus coeruleus degeneration in dementing disorders

Haglund, Mattias LU ; Friberg, Niklas LU orcid ; Danielsson, Erik J.D. LU ; Norrman, Jakob and Englund, Elisabet LU orcid (2016) In Clinical Neuropathology 35(5). p.287-294
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. Purpose: 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... (More)

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. Purpose: 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.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer's disease, Cell loss, Lewy body dementia, Noradrenaline
in
Clinical Neuropathology
volume
35
issue
5
pages
287 - 294
publisher
Dustri-Verlag
external identifiers
  • pmid:27191912
  • scopus:84994476457
ISSN
0722-5091
DOI
10.5414/NP300930
language
English
LU publication?
yes
id
9ead5ddd-fac7-4a40-a365-ea0bc938c82a
date added to LUP
2019-06-29 23:00:56
date last changed
2024-06-11 20:19:12
@article{9ead5ddd-fac7-4a40-a365-ea0bc938c82a,
  abstract     = {{<p>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. Purpose: 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.</p>}},
  author       = {{Haglund, Mattias and Friberg, Niklas and Danielsson, Erik J.D. and Norrman, Jakob and Englund, Elisabet}},
  issn         = {{0722-5091}},
  keywords     = {{Alzheimer's disease; Cell loss; Lewy body dementia; Noradrenaline}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{5}},
  pages        = {{287--294}},
  publisher    = {{Dustri-Verlag}},
  series       = {{Clinical Neuropathology}},
  title        = {{A methodological study of locus coeruleus degeneration in dementing disorders}},
  url          = {{http://dx.doi.org/10.5414/NP300930}},
  doi          = {{10.5414/NP300930}},
  volume       = {{35}},
  year         = {{2016}},
}