What this means
Parental history of dementia is a risk factor for Alzheimer's disease, although the mechanisms underlying this association remain poorly understood. We hypothesize that differences in epigenetic aging may contribute to this increased risk.
A plain-English summary is on its way. Until then, this is the start of the authors' own summary.
- Who it was tested in
- Not stated
- Kind of research
- Early results, not yet checked by other scientists
The science
- Original title
- Parental Dementia History is Associated with Peripheral Immune Aging Rather than Generalized Biological and Brain Age Acceleration in Midlife
- Authors
- Winford, E. D., Huber, B. D., Avila-Rieger, J. F. et al.
- Journal
- medRxiv (preprint, not yet peer reviewed)
- Published
- Oct 24, 2026
- Study type
- Preprint
Abstract
Parental history of dementia is a risk factor for Alzheimer's disease, although the mechanisms underlying this association remain poorly understood. We hypothesize that differences in epigenetic aging may contribute to this increased risk. We examined DNA methylation (DNAm)-based measures of epigenetic aging, telomere length, immune cell composition, and MRI-based measures of brain aging in 1,204 middle-aged adults. Parental dementia history was not associated with accelerated epigenetic or brain aging. However, it was associated with CD8 memory T cell expansion, with nominal differences in CD4 memory T cells, memory B cells, and telomere length. The association with shorter telomere length was attenuated after accounting for CD8 memory T cells, supporting a CD8-specific relationship. Earlier parental dementia onset was associated with faster pace of biological aging, while poorer parental cognitive performance was associated with lower naive and higher memory immune cell proportions, accelerated epigenetic aging, and a larger brain age gap. These findings suggest that midlife adults with parental dementia history exhibit a peripheral immune aging signature characterized by a naive-to-memory T cell shift. Parental cognitive performance was also associated with accelerated epigenetic aging and brain age gap, suggesting that familial dementia risk is reflected across multiple aging dimensions in midlife offspring.
Winford, E. D., Huber, B. D., Avila-Rieger, J. F. et al. Parental Dementia History is Associated with Peripheral Immune Aging Rather than Generalized Biological and Brain Age Acceleration in Midlife. medRxiv. 2026. doi:10.64898/2026.10.22.26366051. https://doi.org/10.64898/2026.10.22.26366051