ArticleProceedings of the National Academy of Sciences of the United States of America2013
Genetic basis of neurocognitive decline and reduced white-matter integrity in normal human brain aging.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 3 of them syntheses that pooled it.
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Who cites it
56 citing papers in PubMed, 3 syntheses or guidelines pooled it, 78 citations in OpenAlex.
- Meta-analysis of age-related cognitive decline reveals a novel locus for the attention domain and implicates a COVID-19-related gene for global cognitive function.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Pooled it
- Cerebral small vessel disease genomics and its implications across the lifespan.Nature communications · 2020Pooled it
- Heterochronicity of white matter development and aging explains regional patient control differences in schizophrenia.Human brain mapping · 2016Pooled it
- Gene × sex interactions on cognition in the Philadelphia neurodevelopmental cohort.Biology of sex differences · 2026Article
- Lost in Thought or Just Lonely? Everyday Cognitive Competence in Middle Adulthood.European journal of investigation in health, psychology and education · 2025Article
- The Neural Association Between Symptom and Cognition in Major Depressive Disorder: A Network Control Theory Study.Human brain mapping · 2025Article
- Genetic Associations Among Inflammation, White Matter Architecture, and Extracellular Free Water.Human brain mapping · 2025Article
- Parietal alpha and theta power predict cognitive training gains in middle-aged adults.Frontiers in aging neuroscience · 2025Article
- Accelerating Heritability, Genetic Correlation, and Genome-Wide Association Imaging Genetic Analyses in Complex Pedigrees.Human brain mapping · 2024Article
- Population clustering of structural brain aging and its association with brain development.eLife · 2024Article
- Population clustering of structural brain aging and its association with brain development.medRxiv : the preprint server for health sciences · 2024Article
- Review
- Multi-omics and pathway analyses of genome-wide associations implicate regulation and immunity in verbal declarative memory performance.Alzheimer's research & therapy · 2024Article
- Structural Fingerprinting of the Frontal Aslant Tract: Predicting Cognitive Control Capacity and Obsessive-Compulsive Symptoms.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Article
- Neurodevelopmental model of schizophrenia revisited: similarity in individual deviation and idiosyncrasy from the normative model of whole-brain white matter tracts and shared brain-cognition covariation with ADHD and ASD.Molecular psychiatry · 2022Article
- Genomic Studies Across the Lifespan Point to Early Mechanisms Determining Subcortical Volumes.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2022Article
- The Role of OXT, OXTR, AVP, and AVPR1a Gene Expression in the Course of Schizophrenia.Current issues in molecular biology · 2022Article
- Comparing empirical kinship derived heritability for imaging genetics traits in the UK biobank and human connectome project.NeuroImage · 2021Article
- Genetic influences on externalizing psychopathology overlap with cognitive functioning and show developmental variation.European psychiatry : the journal of the Association of European Psychiatrists · 2021Article
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 2 countries.
Funding
Abstract
Identification of genes associated with brain aging should markedly improve our understanding of the biological processes that govern normal age-related decline. However, challenges to identifying genes that facilitate successful brain aging are considerable, including a lack of established phenotypes and difficulties in modeling the effects of aging per se, rather than genes that influence the underlying trait. In a large cohort of randomly selected pedigrees (n = 1,129 subjects), we documented profound aging effects from young adulthood to old age (18-83 y) on neurocognitive ability and diffusion-based white-matter measures. Despite significant phenotypic correlation between white-matter integrity and tests of processing speed, working memory, declarative memory, and intelligence, no evidence for pleiotropy between these classes of phenotypes was observed. Applying an advanced quantitative gene-by-environment interaction analysis where age is treated as an environmental factor, we demonstrate a heritable basis for neurocognitive deterioration as a function of age. Furthermore, by decomposing gene-by-aging (G × A) interactions, we infer that different genes influence some neurocognitive traits as a function of age, whereas other neurocognitive traits are influenced by the same genes, but to differential levels, from young adulthood to old age. In contrast, increasing white-matter incoherence with age appears to be nongenetic. These results clearly demonstrate that traits sensitive to the genetic influences on brain aging can be identified, a critical first step in delineating the biological mechanisms of successful aging.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.