Dynamics of cognitive variability with age and its genetic underpinning in NIHR BioResource Genes and Cognition cohort participants.
Nat Med
; 30(6): 1739-1748, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38745010
ABSTRACT
A leading explanation for translational failure in neurodegenerative disease is that new drugs are evaluated late in the disease course when clinical features have become irreversible. Here, to address this gap, we cognitively profiled 21,051 people aged 17-85 years as part of the Genes and Cognition cohort within the National Institute for Health and Care Research BioResource across England. We describe the cohort, present cognitive trajectories and show the potential utility. Surprisingly, when studied at scale, the APOE genotype had negligible impact on cognitive performance. Different cognitive domains had distinct genetic architectures, with one indicating brain region-specific activation of microglia and another with glycogen metabolism. Thus, the molecular and cellular mechanisms underpinning cognition are distinct from dementia risk loci, presenting different targets to slow down age-related cognitive decline. Participants can now be recalled stratified by genotype and cognitive phenotype for natural history and interventional studies of neurodegenerative and other disorders.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cognição
/
Genótipo
Limite:
Adolescent
/
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
País/Região como assunto:
Europa
Idioma:
En
Revista:
Nat Med
Assunto da revista:
BIOLOGIA MOLECULAR
/
MEDICINA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Reino Unido