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Cognitive effects of Lewy body pathology in clinically unimpaired individuals

Palmqvist, Sebastian LU orcid ; Rossi, Marcello ; Hall, Sara LU ; Quadalti, Corinne ; Mattsson-Carlgren, Niklas LU orcid ; Dellavalle, Sofia ; Tideman, Pontus LU ; Pereira, Joana B LU ; Nilsson, Maria H LU orcid and Mammana, Angela , et al. (2023) In Nature Medicine 29(8). p.1971-1978
Abstract

α-Synuclein aggregates constitute the pathology of Lewy body (LB) disease. Little is known about the effects of LB pathology in preclinical (presymptomatic) individuals, either as isolated pathology or coexisting with Alzheimer's disease (AD) pathology (β-amyloid (Aβ) and tau). We examined the effects of LB pathology using a cerebrospinal fluid α-synuclein-seed amplification assay in 1,182 cognitively and neurologically unimpaired participants from the BioFINDER study: 8% were LB positive, 26% Aβ positive (13% of those were LB positive) and 16% tau positive. LB positivity occurred more often in the presence of Aβ positivity but not tau positivity. LB pathology had independently negative effects on cross-sectional and longitudinal global... (More)

α-Synuclein aggregates constitute the pathology of Lewy body (LB) disease. Little is known about the effects of LB pathology in preclinical (presymptomatic) individuals, either as isolated pathology or coexisting with Alzheimer's disease (AD) pathology (β-amyloid (Aβ) and tau). We examined the effects of LB pathology using a cerebrospinal fluid α-synuclein-seed amplification assay in 1,182 cognitively and neurologically unimpaired participants from the BioFINDER study: 8% were LB positive, 26% Aβ positive (13% of those were LB positive) and 16% tau positive. LB positivity occurred more often in the presence of Aβ positivity but not tau positivity. LB pathology had independently negative effects on cross-sectional and longitudinal global cognition and memory and on longitudinal attention/executive function. Tau had cognitive effects of a similar magnitude, but these were less pronounced for Aβ. Participants with both LB and AD (Aβ and tau) pathology exhibited faster cognitive decline than those with only LB or AD pathology. LB, but not AD, pathology was associated with reduced sense of smell. Only LB-positive participants progressed to clinical LB disease over 10 years. These results are important for individualized prognosis, recruitment and choice of outcome measures in preclinical LB disease trials, but also for the design of early AD trials because >10% of individuals with preclinical AD have coexisting LB pathology.

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publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Medicine
volume
29
issue
8
pages
1971 - 1978
publisher
Nature Publishing Group
external identifiers
  • pmid:37464059
  • scopus:85165043720
ISSN
1546-170X
DOI
10.1038/s41591-023-02450-0
language
English
LU publication?
yes
additional info
© 2023. The Author(s).
id
74fadafd-5ae1-4ddd-a58d-76e7cc0b5d9f
date added to LUP
2023-07-25 12:00:02
date last changed
2025-04-07 13:44:18
@article{74fadafd-5ae1-4ddd-a58d-76e7cc0b5d9f,
  abstract     = {{<p>α-Synuclein aggregates constitute the pathology of Lewy body (LB) disease. Little is known about the effects of LB pathology in preclinical (presymptomatic) individuals, either as isolated pathology or coexisting with Alzheimer's disease (AD) pathology (β-amyloid (Aβ) and tau). We examined the effects of LB pathology using a cerebrospinal fluid α-synuclein-seed amplification assay in 1,182 cognitively and neurologically unimpaired participants from the BioFINDER study: 8% were LB positive, 26% Aβ positive (13% of those were LB positive) and 16% tau positive. LB positivity occurred more often in the presence of Aβ positivity but not tau positivity. LB pathology had independently negative effects on cross-sectional and longitudinal global cognition and memory and on longitudinal attention/executive function. Tau had cognitive effects of a similar magnitude, but these were less pronounced for Aβ. Participants with both LB and AD (Aβ and tau) pathology exhibited faster cognitive decline than those with only LB or AD pathology. LB, but not AD, pathology was associated with reduced sense of smell. Only LB-positive participants progressed to clinical LB disease over 10 years. These results are important for individualized prognosis, recruitment and choice of outcome measures in preclinical LB disease trials, but also for the design of early AD trials because &gt;10% of individuals with preclinical AD have coexisting LB pathology.</p>}},
  author       = {{Palmqvist, Sebastian and Rossi, Marcello and Hall, Sara and Quadalti, Corinne and Mattsson-Carlgren, Niklas and Dellavalle, Sofia and Tideman, Pontus and Pereira, Joana B and Nilsson, Maria H and Mammana, Angela and Janelidze, Shorena and Baiardi, Simone and Stomrud, Erik and Parchi, Piero and Hansson, Oskar}},
  issn         = {{1546-170X}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{8}},
  pages        = {{1971--1978}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Medicine}},
  title        = {{Cognitive effects of Lewy body pathology in clinically unimpaired individuals}},
  url          = {{http://dx.doi.org/10.1038/s41591-023-02450-0}},
  doi          = {{10.1038/s41591-023-02450-0}},
  volume       = {{29}},
  year         = {{2023}},
}