Genetic Variants in KLOTHO Associate With Cognitive Function in the Oldest Old Group.
Jonas Mengel-From1, Mette Soerensen2, Marianne Nygaard2
1The Danish Aging Research Center and The Danish Twin Registry, Epidemiology, Biostatistics and Biodemography Unit, Department of Public Health, University of Southern Denmark, Odense, Denmark. Department of Clinical Genetics, Odense University Hospital, Odense, Denmark. jmengel-from@health.sdu.dk.
The KLOTHO (KL) gene influences cognitive function in aging individuals. Specific gene variants and haplotypes impact cognitive performance and decline, suggesting KL
Area of Science:
- Genetics
- Neuroscience
- Gerontology
Background:
- Cognitive decline is a significant concern in aging populations.
- The KLOTHO (KL) gene plays a role in central nervous system function and aging.
- KL gene expression in the brain suggests its involvement in cognitive processes.
Purpose of the Study:
- To investigate the association between KL gene variants and cognitive function in very old adults.
- To identify specific KL gene variants and haplotypes linked to cognitive performance and decline.
- To explore the potential age-dependent effects of KL gene variants on cognition.
Main Methods:
- Studied 19 tagging gene variants in the KL gene.
- Assessed cognitive function using a 5-item cognitive composite score and Mini Mental State Examination.
- Analyzed data from 1,480 Danish individuals aged 92-100 years.
Main Results:
- KL-VS heterozygotes showed poorer cognitive function compared to non-carriers.
- Variants rs398655 and rs562020 were associated with better cognitive function.
- Haplotype AG was linked to poorer cognition, with a stronger effect than KL-VS.
- Variants rs2283368 and rs9526984 were associated with cognitive decline over 7 years.
Conclusions:
- Multiple KL gene variants are associated with cognitive function in the oldest old.
- Specific KL variants and haplotypes may influence cognitive performance and long-term decline.
- The KL gene is a potential target for understanding and mitigating age-related cognitive changes.
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