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Comorbid neuropathologies but not Braak stage influence cognitive impairment in primary age-related tauopathy
Shrishtee Kandoi, Satomi Hiya, Carolina Maldonado‐Díaz, Susan Karijn Rohde, Catarina Bernardes, Francisco C Almeida, Jorge Samanamud, Kevin Clare et al.. Journal of Neuropathology & Experimental Neurology, 2026-05-02
Topic: Amyloid, tau and blood-test diagnosis
Primary age-related tauopathy (PART) is a β-amyloid-independent tauopathy, thought by some to be a distinct process from Alzheimer disease neuropathologic change (ADNC). Two categories of PART have been defined: definite PART (those with complete absence of β-amyloid deposition) and possible PART (those with minimal and restricted β-amyloid distribution). It is unclear whether there is any significant cognitive effect of "isolated" or "pure" PART, as opposed to ADNC, in which cognitive decline mirrors pathologic progression. We evaluated the effects of neurodegenerative pathologies on longitudinal cognitive decline using a combination of univariate analysis, multivariable logistic regression analysis, and variance decomposition in patient cohorts with neuropathologically confirmed definite PART (n = 174) and possible PART (n = 182). ADNC-related pathologies did not significantly contribute to cognitive impairment in either cohort. Cognitive decline in definite PART was instead dependent on the presence and severity of TDP-43 pathology/limbic-predominant age-related TDP-43 encephalopathy (LATE) stage, Lewy body pathology, and arteriolosclerosis, while cognitive impairment in possible PART was primarily affected by hippocampal sclerosis and infarcts. Additionally, 67.8%-75.7% of variance in cognitive decline was unaccounted for by these neurodegenerative pathologies. These results indicate that PART pathology in isolation does not significantly impair cognition, which is instead primarily influenced by comorbid neuropathologic features.
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APA 7th
Kandoi, S., Hiya, S., Maldonado‐Díaz, C., Rohde, S. K., Bernardes, C., Almeida, F. C., et al. (2026). Comorbid neuropathologies but not Braak stage influence cognitive impairment in primary age-related tauopathy. Journal of Neuropathology & Experimental Neurology. https://doi.org/10.1093/jnen/nlag053
Vancouver
Kandoi S, Hiya S, Maldonado‐Díaz C, Rohde SK, Bernardes C, Almeida FC, et al. Comorbid neuropathologies but not Braak stage influence cognitive impairment in primary age-related tauopathy. Journal of Neuropathology & Experimental Neurology. 2026. doi:10.1093/jnen/nlag053. PMID: 42215016.
BibTeX
@article{kandoi2026-42215016,
author = {Kandoi, Shrishtee and Hiya, Satomi and Maldonado‐Díaz, Carolina and Rohde, Susan Karijn and Bernardes, Catarina and Almeida, Francisco C and Samanamud, Jorge and Clare, Kevin and others},
title = {{Comorbid neuropathologies but not Braak stage influence cognitive impairment in primary age-related tauopathy}},
journal = {Journal of Neuropathology \& Experimental Neurology},
year = {2026},
doi = {10.1093/jnen/nlag053},
pmid = {42215016},
url = {https://doi.org/10.1093/jnen/nlag053}
}
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Key findings
- It is unclear whether there is any significant cognitive effect of "isolated" or "pure" PART, as opposed to ADNC, in which cognitive decline mirrors pathologic progression.
- ADNC-related pathologies did not significantly contribute to cognitive impairment in either cohort.
- These results indicate that PART pathology in isolation does not significantly impair cognition, which is instead primarily influenced by comorbid neuropathologic features.
Why it matters
In people with definite or possible primary age-related tauopathy, Alzheimer's-related pathologies did not significantly contribute to cognitive impairment; decline was instead linked to other comorbid pathologies such as TDP-43, Lewy bodies and arteriolosclerosis. This suggests that primary age-related tauopathy alone does not significantly impair cognition, but much of the variance in decline remained unexplained.
Study details
- Study designlongitudinal study
- Participants174
- Effect size67.8%; 75.7%
- Evidence strengthModerate
How this study scored 50/100
Published in a peer-reviewed journal, and it is a longitudinal study following the same people over time. Scored zero for randomised / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 48 of the 96 points we could judge it on, which is 50 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Neuropathology & Experimental Neurology) |
| Journal's citation record | 2 / 4 | Journal of Neuropathology & Experimental Neurology: journal h-index 239 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A longitudinal study following the same 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 | 2 / 4 | 174 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) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 0 / 7 | Cited 0 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.0 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 0 / 6 | Cited 0.0× 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 0 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | OpenAlex's profile for last-listed author Timothy E. Richardson holds only 9 work(s), too few to judge a track record — left out of this score |
| Institution's track record | 1 / 3 | The University of Texas Southwestern Medical Center: institution h-index 1,356 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 7 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 42215016) |
| Free to read | 2 / 2 | Free to read |
| Points | 48 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 48 of the 96 points we could judge it on is 50 out of 100. |
| Total | 50 / 100 | — |
What each of these 20 components measures, and what this score is not →
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