Parental Dementia History is Associated with Peripheral Immune Aging Rather than Generalized Biological and Brain Age Acceleration in Midlife
Winford ED, Huber BD, Avila-Rieger JF, Ryan CP, Alshiko MJ, Turney IC, Pyne J, Belsky DW et al.. medRxiv, 2026-10-24
Topic: Genetics and APOE
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 naïve-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.
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APA 7th
Winford, E. D., Huber, B. D., Avila-Rieger, J. F., Ryan, C. P., Alshiko, M. J., Turney, I. C., et al. (2026). Parental Dementia History is Associated with Peripheral Immune Aging Rather than Generalized Biological and Brain Age Acceleration in Midlife. medRxiv. https://doi.org/10.64898/2026.10.22.26366051
Vancouver
Winford ED, Huber BD, Avila-Rieger JF, Ryan CP, Alshiko MJ, Turney IC, 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.
BibTeX
@article{winford2026-7596643f,
author = {Winford, E. D. and Huber, B. D. and Avila-Rieger, J. F. and Ryan, C. P. and Alshiko, M. J. and Turney, I. C. and Pyne, J. and Belsky, D. W. and others},
title = {{Parental Dementia History is Associated with Peripheral Immune Aging Rather than Generalized Biological and Brain Age Acceleration in Midlife}},
journal = {medRxiv},
year = {2026},
doi = {10.64898/2026.10.22.26366051},
url = {https://doi.org/10.64898/2026.10.22.26366051}
}
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Key findings
- We hypothesize that differences in epigenetic aging may contribute to this increased risk.
- 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.
- 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 naïve-to-memory T cell shift.
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Study details
- Evidence strengthLow
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 21 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 13 of the 62 points we could judge it on, which is 21 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (medRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 13 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 13 of the 62 points we could judge it on is 21 out of 100. |
| Total | 21 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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