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

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...

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Autores principales:	Atul Kumar, Maryam Shoai, Sebastian Palmqvist, Erik Stomrud, John Hardy, Niklas Mattsson-Carlgren, Oskar Hansson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/eca63dc7f9f04a0a98a3074419d85dc2
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spelling	oai:doaj.org-article:eca63dc7f9f04a0a98a3074419d85dc22021-12-02T18:37:08ZGenetic effects on longitudinal cognitive decline during the early stages of Alzheimer’s disease10.1038/s41598-021-99310-z2045-2322https://doaj.org/article/eca63dc7f9f04a0a98a3074419d85dc22021-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-99310-zhttps://doaj.org/toc/2045-2322Abstract 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.Atul KumarMaryam ShoaiSebastian PalmqvistErik StomrudJohn HardyNiklas Mattsson-CarlgrenOskar HanssonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Atul Kumar Maryam Shoai Sebastian Palmqvist Erik Stomrud John Hardy Niklas Mattsson-Carlgren Oskar Hansson Genetic effects on longitudinal cognitive decline during the early stages of Alzheimer’s disease
description	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 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.
format	article
author	Atul Kumar Maryam Shoai Sebastian Palmqvist Erik Stomrud John Hardy Niklas Mattsson-Carlgren Oskar Hansson
author_facet	Atul Kumar Maryam Shoai Sebastian Palmqvist Erik Stomrud John Hardy Niklas Mattsson-Carlgren Oskar Hansson
author_sort	Atul Kumar
title	Genetic effects on longitudinal cognitive decline during the early stages of Alzheimer’s disease
title_short	Genetic effects on longitudinal cognitive decline during the early stages of Alzheimer’s disease
title_full	Genetic effects on longitudinal cognitive decline during the early stages of Alzheimer’s disease
title_fullStr	Genetic effects on longitudinal cognitive decline during the early stages of Alzheimer’s disease
title_full_unstemmed	Genetic effects on longitudinal cognitive decline during the early stages of Alzheimer’s disease
title_sort	genetic effects on longitudinal cognitive decline during the early stages of alzheimer’s disease
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/eca63dc7f9f04a0a98a3074419d85dc2
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Genetic effects on longitudinal cognitive decline during the early stages of Alzheimer’s disease

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