Polygenic risk scores for Alzheimer's disease in relation to cognitive change: A representative sample from the general population followed over 16 years.

Jenna Najar; Valgeir Thorvaldsson; Silke Kern; Johan Skoog; Margda Waern; Henrik Zetterberg; Kaj Blennow; Ingmar Skoog; Anna Zettergren

Neurobiology of Disease (Dec 2023)

Polygenic risk scores for Alzheimer's disease in relation to cognitive change: A representative sample from the general population followed over 16 years.

Jenna Najar,
Valgeir Thorvaldsson,
Silke Kern,
Johan Skoog,
Margda Waern,
Henrik Zetterberg,
Kaj Blennow,
Ingmar Skoog,
Anna Zettergren

Affiliations

Jenna Najar: Neuropsychiatric Epidemiology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, Centre for Ageing and Health (AGECAP) at the University of Gothenburg, Sweden; Region Västra Götaland, Sahlgrenska University Hospital, Psychiatry, Cognition and Old Age Psychiatry Clinic, Gothenburg, Sweden; Department of Human Genetics, Genomics of Neurodegenerative Diseases and Aging at the Amsterdam University Medical Center, Amsterdam, the Netherlands; Corresponding author at: Neuropsychiatric Epidemiology unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, Centre for Ageing and Health (AGECAP) at the University of Gothenburg, Wallinsgatan 6, 431 41 Mölndal, Sweden.
Valgeir Thorvaldsson: Department of Psychology, and Centre for Ageing and Health (AGECAP), at the University of Gothenburg, Sweden
Silke Kern: Neuropsychiatric Epidemiology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, Centre for Ageing and Health (AGECAP) at the University of Gothenburg, Sweden; Region Västra Götaland, Sahlgrenska University Hospital, Psychiatry, Cognition and Old Age Psychiatry Clinic, Gothenburg, Sweden
Johan Skoog: Neuropsychiatric Epidemiology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, Centre for Ageing and Health (AGECAP) at the University of Gothenburg, Sweden
Margda Waern: Neuropsychiatric Epidemiology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, Centre for Ageing and Health (AGECAP) at the University of Gothenburg, Sweden; Region Västra Götaland, Sahlgrenska University Hospital, Psychosis Clinic, Gothenburg, Sweden
Henrik Zetterberg: Department of Neurodegenerative Disease, UCL Institute of Neurology, London, United Kingdom; Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Hong Kong Center for Neurodegenerative Diseases, Clear Water Bay, Hong Kong, China; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA
Kaj Blennow: Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
Ingmar Skoog: Neuropsychiatric Epidemiology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, Centre for Ageing and Health (AGECAP) at the University of Gothenburg, Sweden; Region Västra Götaland, Sahlgrenska University Hospital, Psychiatry, Cognition and Old Age Psychiatry Clinic, Gothenburg, Sweden
Anna Zettergren: Neuropsychiatric Epidemiology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, Centre for Ageing and Health (AGECAP) at the University of Gothenburg, Sweden

Journal volume & issue: Vol. 189
p. 106357

Abstract

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Background: Polygenic risk scores for Alzheimer's disease (AD-PRSs) have been associated with cognition. However, few studies have examined the effect of AD-PRS beyond the APOE gene, and the influence of genetic variants related to level of cognitive ability (COG-PRS) on cognitive performance over time in the general older population. Method: A population-based sample of 965 individuals born in 1930, with genetic and standardized cognitive data on six psychometric tests (Thurstone's picture memory, immediate recall of 10 words, Block design, word fluency, figure identification, delayed recall of 12 items), were examined at age 70, 75, 79, and 85 years. Non-APOE AD-PRSs and COG-PRSs (P < 5e−8, P < 1e−5, P < 1e−3, P < 1e−1) were generated from recent genome-wide association studies. Linear mixed effect models with random intercepts and slope were used to analyze the effect of APOE ε4 allele, AD-PRSs, and COG-PRSs, on cognitive performance and rate of change. Analyses were repeated in samples excluding dementia. Results: APOE ε4 and AD-PRS predicted change in cognitive performance (APOE ε4*age: β = −0.03, P < 0.0001 and AD-PRS *age: β = −0.01, P = 0.02). The results remained similar in the sample excluding those with dementia. COG-PRS predicted level of cognitive performance, while APOE ε4 and AD-PRS did not. COG-PRSs did not predict change in cognitive performance. Conclusion: We found that genetic predisposition of AD predicted cognitive decline among 70-year-olds followed over 16 years, regardless of dementia status, while polygenic risk for general cognitive performance did not.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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