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Limbic-predominant age-related TDP-43 encephalopathy in the oldest old: a population-based study
Mikhailenko E, Colangelo K, Tuimala J, Kero M, Savola S, Raunio A, Kok EH, Tanskanen M, Mäkelä M, Puttonen H, Mäyränpää MI, Kumar D, et al.. Brain, 2025-01-07
Topic: Brain proteins, microglia and lab models
Previous studies have shown that limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) increases with age, but there have been only a few studies, which have investigated this entity in a population-based setting. Stages 1a (P < 0.01), 2 (P < 0.001) and 3 (P < 0.001) were significantly associated with dementia and lower MMSE scores. LATE-NC was associated with ADNC (P < 0.001), HS (P < 0.001), diffuse neocortical LRP (P < 0.002), and arteriolosclerosis in amygdala (P < 0.02). When LATE-NC and ADNC were assessed in a multivariate model without other dementia-associated pathologies, the attributable risk was higher for LATE-NC than ADNC (24.2% versus 18.6%). This population-based study provides evidence that LATE-NC is very common and one of the most significant determinants of dementia in the general late-life aged population.
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APA 7th
Mikhailenko, E., Colangelo, K., Tuimala, J., Kero, M., Savola, S., Raunio, A., et al. (2025). Limbic-predominant age-related TDP-43 encephalopathy in the oldest old: a population-based study. Brain. https://doi.org/10.1093/brain/awae212
Vancouver
Mikhailenko E, Colangelo K, Tuimala J, Kero M, Savola S, Raunio A, et al. Limbic-predominant age-related TDP-43 encephalopathy in the oldest old: a population-based study. Brain. 2025. doi:10.1093/brain/awae212. PMID: 38938199.
BibTeX
@article{mikhailenko2025-38938199,
author = {Mikhailenko, E. and Colangelo, K. and Tuimala, J. and Kero, M. and Savola, S. and Raunio, A. and Kok, E. H. and Tanskanen, M. and Mäkelä, M. and Puttonen, H. and Mäyränpää, M. I. and Kumar, D. and others},
title = {{Limbic-predominant age-related TDP-43 encephalopathy in the oldest old: a population-based study}},
journal = {Brain},
year = {2025},
doi = {10.1093/brain/awae212},
pmid = {38938199},
url = {https://doi.org/10.1093/brain/awae212}
}
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Key findings
- Previous studies have shown that limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) increases with age, but there have been only a few studies, which have investigated this entity in a population-based setting.
- Stages 1a (P < 0.01), 2 (P < 0.001) and 3 (P < 0.001) were significantly associated with dementia and lower MMSE scores.
- LATE-NC was associated with ADNC (P < 0.001), HS (P < 0.001), diffuse neocortical LRP (P < 0.002), and arteriolosclerosis in amygdala (P < 0.02).
- When LATE-NC and ADNC were assessed in a multivariate model without other dementia-associated pathologies, the attributable risk was higher for LATE-NC than ADNC (24.2% versus 18.6%).
- This population-based study provides evidence that LATE-NC is very common and one of the most significant determinants of dementia in the general late-life aged population.
Why it matters
In this population-based study, limbic-predominant age-related TDP-43 encephalopathy neuropathologic change stages were significantly associated with dementia and lower MMSE scores, and its attributable risk was higher than that of Alzheimer's disease neuropathologic change (24.2% versus 18.6%). The study shows this pathology is very common and a major determinant of dementia in the general late-life population, but it examines brain tissue after death and tests no treatment.
Study details
- Study designcohort
- Participants295
- Effect sizeAttributable risk of dementia 24.2% (LATE-NC) vs 18.6% (ADNC)
- Evidence strengthModerate
Limitations
Participants were genetically homogeneous Finns born 1887-1906 who reached very old age, with few highly educated, so results may not apply to other populations or younger ages; LATE-NC frequency was at the high end of published ranges; and technical limitations of TDP-43 immunohistochemistry mean frequencies could be underestimates.
How this study scored 65/100
Published in a leading specialty journal, and it is a cohort study following people over time. Scored zero for randomized / blinded because the record does not state it. We have no data on free to read, so that was left out: it earned 64 of the 98 points we could judge it on, which is 65 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain) |
| Journal's citation record | 4 / 4 | Brain: journal h-index 503 (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 | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 2 / 4 | 295 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 | 3 / 7 | Cited 28 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 9.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 7.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 4 other studies in this library |
| Still being cited | 2 / 4 | Cited 27 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Liisa Myllykangas: h-index 40 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Helsinki: institution h-index 1,201 (OpenAlex) |
| Multicenter collaboration | 2 / 3 | OpenAlex lists 7 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 38938199) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 64 / 98 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 64 of the 98 points we could judge it on is 65 out of 100. |
| Total | 65 / 100 | — |
What each of these 20 components measures, and what this score is not →
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