Levels of Circulating Cell-Free DNA Predict Risk of Developing Dementia

and frailty.

Altered cellular equilibrium, seen in cognitive decline and frailty, leads to cell death and turnover, releasing circulating cell-free DNA (ccf-DNA). In a recently published study, investigators at Johns Hopkins University (Baltimore, MD, USA) determined whether serum genomic cell-free DNA (ccf-gDNA) was associated with physical and cognitive decline in older adults.

For this study, the investigators used digital PCR to analyze blood samples from 631 individuals with an average age of 79 years who showed no cognitive impairment when the study began. An array of cognitive and physical traits, risk of dementia, global cognition, and frailty at or nearest the time of blood draw were compared to ccf-DNA levels, with adjustment for age, sex, race, and education. The data gathering period lasted for eight years.

Results across the group showed that higher ccf-gDNA levels were associated with lower global cognition score and slower gait speed at the evaluation nearest to blood draw. Furthermore, higher ccf-gDNA levels were associated with increased odds of incident dementia. Individually, higher levels of ccf-gDNA were associated with steeper general cognitive decline and worsening frailty over the eight years of follow up.

“These ccf-gDNA fragments may trigger long-term chronic inflammatory reactions that have previously been linked to the premature destruction and aging of tissues and organs, including the brain,” said senior author Dr. Peter Abadir, associate professor of geriatric medicine and gerontology at Johns Hopkins University. “The body sees these ccf-gDNA fragments as something that needs to be removed, therefore the body’s immune system is running at a higher rate than it should. Such immune system overdrive may be a factor in identifying the onset of dementia.”

Results of the study were published in the October 11, 2022, issue of the Journal of Alzheimer’s Disease.

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