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Genetic effects on longitudinal cognitive decline during the early stages of Alzheimer’s disease

Kumar, Atul LU orcid ; Shoai, Maryam ; Palmqvist, Sebastian LU orcid ; Stomrud, Erik LU orcid ; Hardy, John ; Mattsson-Carlgren, Niklas LU orcid and Hansson, Oskar LU orcid (2021) In Scientific Reports 11(1).
Abstract

Cognitive decline in early-stage Alzheimer’s disease (AD) may depend on genetic variability. In the Swedish BioFINDER study, we used polygenic scores (PGS) (for AD, intelligence, and educational attainment) to predict longitudinal cognitive change (measured by mini-mental state examination (MMSE) [primary outcome] and other cognitive tests) over a mean of 4.2 years. We included 260 β-amyloid (Aβ) negative cognitively unimpaired (CU) individuals, 121 Aβ-positive CU (preclinical AD), 50 Aβ-negative mild cognitive impairment (MCI) patients, and 127 Aβ-positive MCI patients (prodromal AD). Statistical significance was determined at Bonferroni corrected p value < 0.05. The PGS for intelligence (beta = 0.1, p = 2.9e−02) was protective... (More)

Cognitive decline in early-stage Alzheimer’s disease (AD) may depend on genetic variability. In the Swedish BioFINDER study, we used polygenic scores (PGS) (for AD, intelligence, and educational attainment) to predict longitudinal cognitive change (measured by mini-mental state examination (MMSE) [primary outcome] and other cognitive tests) over a mean of 4.2 years. We included 260 β-amyloid (Aβ) negative cognitively unimpaired (CU) individuals, 121 Aβ-positive CU (preclinical AD), 50 Aβ-negative mild cognitive impairment (MCI) patients, and 127 Aβ-positive MCI patients (prodromal AD). Statistical significance was determined at Bonferroni corrected p value < 0.05. The PGS for intelligence (beta = 0.1, p = 2.9e−02) was protective against decline in MMSE in CU and MCI participants regardless of Aβ status. The polygenic risk score for AD (beta = − 0.12, p = 9.4e−03) was correlated with the rate of change in MMSE and was partially mediated by Aβ-pathology (mediation effect 20%). There was no effect of education PGS on cognitive measures. Genetic variants associated with intelligence mitigate cognitive decline independent of Aβ-pathology, while effects of genetic variants associated with AD are partly mediated by Aβ-pathology.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
11
issue
1
article number
19853
publisher
Nature Publishing Group
external identifiers
  • scopus:85116419331
  • pmid:34615922
ISSN
2045-2322
DOI
10.1038/s41598-021-99310-z
language
English
LU publication?
yes
additional info
Funding Information: The study was supported by the Swedish Research Council (2016-00906), the Knut and Alice Wallenberg foundation (2017-0383, and Wallenberg Center for Molecular Medicine Fellowship for NMC), the Medical Faculty at Lund University (Wallenberg Center for Molecular Medicine Fellowship for NMC), Region Skåne (Wallen-berg Center for Molecular Medicine Fellowship for NMC), the Marianne and Marcus Wallenberg foundation (2015.0125), the Strategic Research Area MultiPark (Multidisciplinary Research in Parkinson’s disease) at Lund University, the Swedish Alzheimer Foundation (AF-939932 and AF-930655), the Swedish Brain Foundation (FO2019-0326 and FO2019-0029), The Parkinson Foundation of Sweden (1280/20), the Skåne University Hospital Foundation (2020-O000028), Regionalt Forskningsstöd (2020-0314), Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse, Bundy Academy, and the Swedish federal government under the ALF agreement (2018-Projekt0279). Publisher Copyright: © 2021, The Author(s).
id
24dec15f-a93f-47f1-9a8f-fe7483db0dc5
date added to LUP
2021-10-21 10:22:56
date last changed
2024-09-22 03:35:17
@article{24dec15f-a93f-47f1-9a8f-fe7483db0dc5,
  abstract     = {{<p>Cognitive decline in early-stage Alzheimer’s disease (AD) may depend on genetic variability. In the Swedish BioFINDER study, we used polygenic scores (PGS) (for AD, intelligence, and educational attainment) to predict longitudinal cognitive change (measured by mini-mental state examination (MMSE) [primary outcome] and other cognitive tests) over a mean of 4.2 years. We included 260 β-amyloid (Aβ) negative cognitively unimpaired (CU) individuals, 121 Aβ-positive CU (preclinical AD), 50 Aβ-negative mild cognitive impairment (MCI) patients, and 127 Aβ-positive MCI patients (prodromal AD). Statistical significance was determined at Bonferroni corrected p value &lt; 0.05. The PGS for intelligence (beta = 0.1, p = 2.9e−02) was protective against decline in MMSE in CU and MCI participants regardless of Aβ status. The polygenic risk score for AD (beta = − 0.12, p = 9.4e−03) was correlated with the rate of change in MMSE and was partially mediated by Aβ-pathology (mediation effect 20%). There was no effect of education PGS on cognitive measures. Genetic variants associated with intelligence mitigate cognitive decline independent of Aβ-pathology, while effects of genetic variants associated with AD are partly mediated by Aβ-pathology.</p>}},
  author       = {{Kumar, Atul and Shoai, Maryam and Palmqvist, Sebastian and Stomrud, Erik and Hardy, John and Mattsson-Carlgren, Niklas and Hansson, Oskar}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Genetic effects on longitudinal cognitive decline during the early stages of Alzheimer’s disease}},
  url          = {{http://dx.doi.org/10.1038/s41598-021-99310-z}},
  doi          = {{10.1038/s41598-021-99310-z}},
  volume       = {{11}},
  year         = {{2021}},
}