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Epilepsy and subsequent dementia in adults with down syndrome: a propensity score-matched cohort study using federated electronic health records
Pereira da Silva AM, Tudella GCN, Lee AM, Santos DH, Cukiert CM, Perry G.. Seizure, 2026-08-28
Topic: Risk, prevention and care in population studies
Purpose Epilepsy and early-onset Alzheimer disease (AD) are both common in adults with Down syndrome (DS), and their temporal relationship remains unclear. We examined whether a recorded diagnosis of epilepsy was associated with higher subsequent recording of all-cause dementia, AD, non-Alzheimer dementia, and mortality among adults with DS aged 40 years or older. Methods Retrospective cohort study using deidentified electronic health records from the TriNetX Global Collaborative Network. Adults with DS (ICD-10-CM Q90; age ≥40 years; 2010-2025) were classified as having epilepsy (G40 recorded before any dementia code) or not; secondary seizures were excluded. Cohorts were balanced by 1:1 propensity score matching. Outcomes were assessed from 90 to 730 days after the index date using hazard ratios (HRs) and Kaplan-Meier analyses. Results After matching, 1812 patients per cohort were retained (mean [SD] age, 54.3 [7.0] vs 54.2 [7.4] years). Epilepsy was associated with higher subsequent recording of all-cause dementia (12.9%vs 6.5%; HR, 2.03 [95% CI, 1.59-2.60]), AD (6.1%vs 3.2%; HR, 1.97 [1.41-2.76]), non-Alzheimer dementia (12.9%vs 6.3%; HR, 2.08 [1.63-2.65]), and mortality (12.8%vs 5.1%; HR, 2.55 [2.00-3.24]). Estimates were similar by age and sex, and when exposure required an antiseizure medication prescription alongside the diagnostic code. Conclusion Epilepsy was associated with higher subsequent recording of dementia and mortality over 2 years. No biomarker, neuroimaging, or neuropathological measure was available; the estimates describe the order in which diagnoses were documented and do not establish that epilepsy marks the underlying neurodegenerative process. Differential ascertainment and residual confounding remain plausible contributors.
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APA 7th
Pereira da Silva, A. M., Tudella, G. C. N., Lee, A. M., Santos, D. H., Cukiert, C. M., & Perry, G. (2026). Epilepsy and subsequent dementia in adults with down syndrome: a propensity score-matched cohort study using federated electronic health records. Seizure. https://doi.org/10.1016/j.seizure.2026.08.023
Vancouver
Pereira da Silva AM, Tudella GCN, Lee AM, Santos DH, Cukiert CM, Perry G. Epilepsy and subsequent dementia in adults with down syndrome: a propensity score-matched cohort study using federated electronic health records. Seizure. 2026. doi:10.1016/j.seizure.2026.08.023. PMID: 42721539.
BibTeX
@article{pereiradasilva2026-42721539,
author = {Pereira da Silva, A. M. and Tudella, G. C. N. and Lee, A. M. and Santos, D. H. and Cukiert, C. M. and Perry, G.},
title = {{Epilepsy and subsequent dementia in adults with down syndrome: a propensity score-matched cohort study using federated electronic health records}},
journal = {Seizure},
year = {2026},
doi = {10.1016/j.seizure.2026.08.023},
pmid = {42721539},
url = {https://doi.org/10.1016/j.seizure.2026.08.023}
}
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Key findings
- We examined whether a recorded diagnosis of epilepsy was associated with higher subsequent recording of all-cause dementia, AD, non-Alzheimer dementia, and mortality among adults with DS aged 40 years or older.
- Results After matching, 1812 patients per cohort were retained (mean [SD] age, 54.3 [7.0] vs 54.2 [7.4] years).
- Epilepsy was associated with higher subsequent recording of all-cause dementia (12.9%vs 6.5%; HR, 2.03 [95% CI, 1.59-2.60]), AD (6.1%vs 3.2%; HR, 1.97 [1.41-2.76]), non-Alzheimer dementia (12.9%vs 6.3%; HR, 2.08 [1.63-2.65]), and mortality (12.8%vs 5.1%; HR, 2.55 [2.00-3.24]).
- Conclusion Epilepsy was associated with higher subsequent recording of dementia and mortality over 2 years.
Why it matters
In this matched cohort of adults with Down syndrome, a recorded epilepsy diagnosis was associated with higher later recording of all-cause dementia, Alzheimer's disease, non-Alzheimer dementia, and mortality. It is an observational association and does not show that treating epilepsy would prevent dementia.
Study details
- Study designcohort study
- Participants1,812
- Effect size12.9%; 6.5%; 6.1%
- Evidence strengthModerate
How this study scored 53/100
Published in a peer-reviewed journal, and it is a cohort study following people over time. Scored zero for randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Seizure) |
| Journal's citation record | 1 / 4 | Seizure: journal h-index 124 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A cohort study following people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 3 / 4 | 1,812 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 1 / 7 | Cited 1 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 3 / 6 | Cited 6.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 1 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author George L. Perry: h-index 154 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Universidade Federal de Minas Gerais: institution h-index 527 (OpenAlex) |
| Multicenter collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 42721539) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 53 / 100 | — |
What each of these 20 components measures, and what this score is not →
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