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Clinical effects of Lewy body pathology in cognitively impaired individuals

Quadalti, Corinne ; Palmqvist, Sebastian LU orcid ; Hall, Sara LU ; Rossi, Marcello ; Mammana, Angela ; Janelidze, Shorena LU ; Dellavalle, Sofia ; Mattsson-Carlgren, Niklas LU orcid ; Baiardi, Simone and Stomrud, Erik LU orcid , et al. (2023) In Nature Medicine 29(8). p.1964-1970
Abstract

There is poor knowledge about the clinical effects of Lewy body (LB) pathology in patients with cognitive impairment, especially when coexisting with Alzheimer's disease (AD) pathology (amyloid-β and tau). Using a seed amplification assay, we analyzed cerebrospinal fluid for misfolded LB-associated α-synuclein in 883 memory clinic patients with mild cognitive impairment or dementia from the BioFINDER study. Twenty-three percent had LB pathology, of which only 21% fulfilled clinical criteria of Parkinson's disease or dementia with Lewy bodies at baseline. Among these LB-positive patients, 48% had AD pathology. Fifty-four percent had AD pathology in the whole sample (17% of mild cognitive impairment and 24% of patients with dementia were... (More)

There is poor knowledge about the clinical effects of Lewy body (LB) pathology in patients with cognitive impairment, especially when coexisting with Alzheimer's disease (AD) pathology (amyloid-β and tau). Using a seed amplification assay, we analyzed cerebrospinal fluid for misfolded LB-associated α-synuclein in 883 memory clinic patients with mild cognitive impairment or dementia from the BioFINDER study. Twenty-three percent had LB pathology, of which only 21% fulfilled clinical criteria of Parkinson's disease or dementia with Lewy bodies at baseline. Among these LB-positive patients, 48% had AD pathology. Fifty-four percent had AD pathology in the whole sample (17% of mild cognitive impairment and 24% of patients with dementia were also LB-positive). When examining independent cross-sectional effects, LB pathology but not amyloid-β or tau, was associated with hallucinations and worse attention/executive, visuospatial and motor function. LB pathology was also associated with faster longitudinal decline in all examined cognitive functions, independent of amyloid-β, tau, cognitive stage and a baseline diagnosis of dementia with Lewy bodies/Parkinson's disease. LB status provides a better precision-medicine approach to predict clinical trajectories independent of AD biomarkers and a clinical diagnosis, which could have implications for the clinical management of cognitive impairment and the design of AD and LB drug trials.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Medicine
volume
29
issue
8
pages
1964 - 1970
publisher
Nature Publishing Group
external identifiers
  • scopus:85165050829
  • pmid:37464058
ISSN
1546-170X
DOI
10.1038/s41591-023-02449-7
language
English
LU publication?
yes
additional info
© 2023. The Author(s).
id
9e87907f-e69a-4d26-9dad-a31726031702
date added to LUP
2023-07-25 13:34:56
date last changed
2024-04-20 00:59:22
@article{9e87907f-e69a-4d26-9dad-a31726031702,
  abstract     = {{<p>There is poor knowledge about the clinical effects of Lewy body (LB) pathology in patients with cognitive impairment, especially when coexisting with Alzheimer's disease (AD) pathology (amyloid-β and tau). Using a seed amplification assay, we analyzed cerebrospinal fluid for misfolded LB-associated α-synuclein in 883 memory clinic patients with mild cognitive impairment or dementia from the BioFINDER study. Twenty-three percent had LB pathology, of which only 21% fulfilled clinical criteria of Parkinson's disease or dementia with Lewy bodies at baseline. Among these LB-positive patients, 48% had AD pathology. Fifty-four percent had AD pathology in the whole sample (17% of mild cognitive impairment and 24% of patients with dementia were also LB-positive). When examining independent cross-sectional effects, LB pathology but not amyloid-β or tau, was associated with hallucinations and worse attention/executive, visuospatial and motor function. LB pathology was also associated with faster longitudinal decline in all examined cognitive functions, independent of amyloid-β, tau, cognitive stage and a baseline diagnosis of dementia with Lewy bodies/Parkinson's disease. LB status provides a better precision-medicine approach to predict clinical trajectories independent of AD biomarkers and a clinical diagnosis, which could have implications for the clinical management of cognitive impairment and the design of AD and LB drug trials.</p>}},
  author       = {{Quadalti, Corinne and Palmqvist, Sebastian and Hall, Sara and Rossi, Marcello and Mammana, Angela and Janelidze, Shorena and Dellavalle, Sofia and Mattsson-Carlgren, Niklas and Baiardi, Simone and Stomrud, Erik and Hansson, Oskar and Parchi, Piero}},
  issn         = {{1546-170X}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{8}},
  pages        = {{1964--1970}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Medicine}},
  title        = {{Clinical effects of Lewy body pathology in cognitively impaired individuals}},
  url          = {{http://dx.doi.org/10.1038/s41591-023-02449-7}},
  doi          = {{10.1038/s41591-023-02449-7}},
  volume       = {{29}},
  year         = {{2023}},
}