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Educational attainment and sex modulate clinical outcomes in genetic frontotemporal dementia
Enrico Premi, Damiano Archetti, Alberto Redolfi, Valeria Bracca, Valentina Cantoni, Armin Iraji, Vince D Calhoun, Sonia Bellini et al.. Brain communications, 2026-08-04
Topic: Brain imaging, connectivity and assessment
Individuals with autosomal dominant frontotemporal dementia (FTD) exhibit considerable variability in disease onset and progression. Both modifiable and non-modifiable factors-such as sex, educational attainment or geographic region of residence-may contribute to this heterogeneity, potentially through their influence on cognitive reserve. The aim of the present study was to investigate the role of cognitive reserve modulators within the Genetic Frontotemporal dementia Initiative (GENFI) cohort. To this end, we used functional MRI (i.e. spatial chronnectome measures) and neurodegenerative markers (i.e. plasma neurofilament light chains levels) to determine disease stage using a Discriminative Event-Based Model (DEBM). We then examined how potential modulators influence the relationship between disease stage and cognitive performance. We analysed a total of 711 participants, including 106 patients with genetic FTD, 325 presymptomatic mutation carriers and 280 non-carriers healthy controls. Female participants showed a weaker association between disease stage and cognitive performance compared to males (P < 0.001), with difference becoming progressively more pronounced across symptomatic stages. Educational attainment exhibited a similar effect: individuals with higher education demonstrated an attenuated association compared to those with secondary or primary schooling (P < 0.001), with differences already detectable at prodromal disease stages. The effect of geographical region of residence was associated with education levels, but appeared to have an indirect and less strong influence. In summary, sex and educational attainment significantly affect the development and maintenance of cognitive reserve in individuals with genetic FTD. These findings underscore the importance of identifying disease-modifying interventions since the presymptomatic stages of the disease.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Premi, E., Archetti, D., Redolfi, A., Bracca, V., Cantoni, V., Iraji, A., et al. (2026). Educational attainment and sex modulate clinical outcomes in genetic frontotemporal dementia. Brain communications. https://doi.org/10.1093/braincomms/fcag262
Vancouver
Premi E, Archetti D, Redolfi A, Bracca V, Cantoni V, Iraji A, et al. Educational attainment and sex modulate clinical outcomes in genetic frontotemporal dementia. Brain communications. 2026. doi:10.1093/braincomms/fcag262. PMID: 42553777.
BibTeX
@article{premi2026-42553777,
author = {Premi, Enrico and Archetti, Damiano and Redolfi, Alberto and Bracca, Valeria and Cantoni, Valentina and Iraji, Armin and Calhoun, Vince D and Bellini, Sonia and others},
title = {{Educational attainment and sex modulate clinical outcomes in genetic frontotemporal dementia}},
journal = {Brain communications},
year = {2026},
doi = {10.1093/braincomms/fcag262},
pmid = {42553777},
url = {https://doi.org/10.1093/braincomms/fcag262}
}
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Key findings
- Female participants showed a weaker association between disease stage and cognitive performance compared to males (P < 0.001), with difference becoming progressively more pronounced across symptomatic stages.
- Educational attainment exhibited a similar effect: individuals with higher education demonstrated an attenuated association compared to those with secondary or primary schooling (P < 0.001), with differences already detectable at prodromal disease stages.
- The effect of geographical region of residence was associated with education levels, but appeared to have an indirect and less strong influence.
- In summary, sex and educational attainment significantly affect the development and maintenance of cognitive reserve in individuals with genetic FTD.
- These findings underscore the importance of identifying disease-modifying interventions since the presymptomatic stages of the disease.
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Study details
- Participants711
- Evidence strengthModerate
How this study scored 61/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomized / blinded because the record does not state it. We have no data on journal's citation record, 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, multicenter collaboration and free to read, so those were left out: it earned 34 of the 56 points we could judge it on, which is 61 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain communications) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| 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 | 2 / 4 | 711 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| 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 | — / 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 |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 42553777) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 34 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 34 of the 56 points we could judge it on is 61 out of 100. |
| Total | 61 / 100 | — |
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