Abstract
BackgroundBlood-based markers of cognitive functioning might provide an accessible way to track neurodegeneration years prior to clinical manifestation of cognitive impairment and dementia.ResultsUsing blood-based epigenome-wide analyses of general cognitive function, we show that individual differences in DNA methylation (DNAm) explain 35.0% of the variance in general cognitive function (g). A DNAm predictor explains ~4% of the variance, independently of a polygenic score, in two external cohorts. It also associates with circulating levels of neurology- and inflammation-related proteins, global brain imaging metrics, and regional cortical volumes.ConclusionsAs sample sizes increase, the ability to assess cognitive function from DNAm data may be informative in settings where cognitive testing is unreliable or unavailable.
Highlights
Blood-based markers of cognitive functioning might provide an accessible way to track neurodegeneration years prior to clinical manifestation of cognitive impairment and dementia
The DNA methylation data were corrected for batch, age, sex and epigenetic smoking, which all have pervasive effects on DNAm levels
Estimating the proportion of variance in cognitive ability explained by all CpG sites We first explored if global patterns of DNA methylation associated with individual differences in cognitive ability
Summary
Blood-based markers of cognitive functioning might provide an accessible way to track neurodegeneration years prior to clinical manifestation of cognitive impairment and dementia. They might form an easy, objective, and less stressful way to assess neurodegeneration compared to pen-and-paper cognitive tests or in circumstances where biosamples alone are available. They could help to inform our understanding of the biological basis of brain health differences.
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