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56/100

✓ Peer-reviewed alzhub usefulness score 56 out of 100. Genetics

Topic: Amyloid, tau and blood-test diagnosis

Plain-language summary

Individuals with rapid progression were more likely to have at least one APOE ε4 allele (OR: 2.08 [95% CI: 1.16–3.74], p < 0.01), higher Braak stage (2.19 [1.20–3.98], p < 0.01), higher Thal phase (2.45 [1.24–4.83], p < 0.01), more severe white matter rarefaction (1.68 [1.21–2.35], p < 0.01), and in the final 24 months of life, more frequent untreated/undertreated hyperlipidemia (1.74 [1.35–5.56], p < 0.01) and less frequent untreated/undertreated depression (0.40 [0.17–0.91], p < 0.05). Conversely, resilient individuals harbored less frequent APOE ε4 alleles (0.17 [0.06–0.55], p < 0.01), lower Thal phase (0.33 [0.12–0.95], p < 0.05), lower CERAD neuritic plaque score (0.32 [0.11–0.97], p < 0.05), less frequent untreated/undertreated psychosis (0.06 [0.01–0.39], p < 0.01), and more frequent untreated/undertreated depression (8.73 [2.12–35.85], p < 0.01). These data suggest that resilience and progression in ADNC are impacted by AD-relevant genetics and the severity of late-stage ADNC (even within the narrow range of values compatible with high-level ADNC), additional pathologic features, and potentially the clinical management of underlying systemic disorders.

What this study adds

Evidence grade: Moderate

This is a follow-up (cohort) study of 75 participants. Among people with high-level Alzheimer disease neuropathologic change, rapid progression was linked to having at least one APOE ε4 allele and to more severe pathology, while resilient individuals less often carried APOE ε4. Reported effect size: OR: 2.08.

Taken from this record’s own fields, not from reading the paper. The grade is assigned from the abstract’s wording; what that means.

Cite this study APA, Vancouver, BibTeX · download .bib or .ris

APA 7th

Richardson, T. E., Kandoi, S., Almeida, F., Rohde, S. K., Marx, G. A., Canbeldek, L., et al. (2025). Longitudinal assessment of cognitive decline and resilience in high-level Alzheimer disease neuropathologic change. Alzheimer s Research & Therapy. https://doi.org/10.1186/s13195-025-01904-6

Vancouver

Richardson TE, Kandoi S, Almeida F, Rohde SK, Marx GA, Canbeldek L, et al. Longitudinal assessment of cognitive decline and resilience in high-level Alzheimer disease neuropathologic change. Alzheimer s Research & Therapy. 2025. doi:10.1186/s13195-025-01904-6. PMID: 41339920.

BibTeX

@article{richardson2025-41339920,
  author  = {Richardson, Timothy E. and Kandoi, Shrishtee and Almeida, Francisco and Rohde, Susan Karijn and Marx, Gabriel A. and Canbeldek, Leyla and Hiya, Satomi and Maldonado‐Díaz, Carolina and others},
  title   = {{Longitudinal assessment of cognitive decline and resilience in high-level Alzheimer disease neuropathologic change}},
  journal = {Alzheimer s Research \& Therapy},
  year    = {2025},
  doi     = {10.1186/s13195-025-01904-6},
  pmid    = {41339920},
  url     = {https://doi.org/10.1186/s13195-025-01904-6}
}

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How to read this study

Design: this is a follow-up (cohort) study. People are observed over time and not assigned to anything, so an association can reflect other differences between groups. Look at how long follow-up lasted, how many dropped out, and whether the authors adjusted for age, education and other health conditions.
Size: the record lists 75 participants. Ask whether that is enough for the question, and who they were.
Effect: the record reports “OR: 2.08”. A statistically significant result can still be small in daily life.

What the evidence grade means here

This page is graded moderate. alzhub.org assigns the grade automatically from keywords in the abstract, not from reading the paper. Moderate means the abstract mentions a cohort, case-control or longitudinal design. It can add at most 5 of the 100 points in the study score, and it is a label about design, not a verdict on whether the findings are true.

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Key findings

Individuals with rapid progression were more likely to have at least one APOE ε4 allele (OR: 2.08 [95% CI: 1.16–3.74], p < 0.01), higher Braak stage (2.19 [1.20–3.98], p < 0.01), higher Thal phase (2.45 [1.24–4.83], p < 0.01), more severe white matter rarefaction (1.68 [1.21–2.35], p < 0.01), and in the final 24 months of life, more frequent untreated/undertreated hyperlipidemia (1.74 [1.35–5.56], p < 0.01) and less frequent untreated/undertreated depression (0.40 [0.17–0.91], p < 0.05).
Conversely, resilient individuals harbored less frequent APOE ε4 alleles (0.17 [0.06–0.55], p < 0.01), lower Thal phase (0.33 [0.12–0.95], p < 0.05), lower CERAD neuritic plaque score (0.32 [0.11–0.97], p < 0.05), less frequent untreated/undertreated psychosis (0.06 [0.01–0.39], p < 0.01), and more frequent untreated/undertreated depression (8.73 [2.12–35.85], p < 0.01).
These data suggest that resilience and progression in ADNC are impacted by AD-relevant genetics and the severity of late-stage ADNC (even within the narrow range of values compatible with high-level ADNC), additional pathologic features, and potentially the clinical management of underlying systemic disorders.

Why it matters

Among people with high-level Alzheimer disease neuropathologic change, rapid progression was linked to having at least one APOE ε4 allele and to more severe pathology, while resilient individuals less often carried APOE ε4. The authors suggest resilience and progression may be affected by AD-relevant genetics, pathology severity, and possibly clinical management of underlying systemic disorders.

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Study details

Study designcohort study
Participants75
Effect sizeOR: 2.08
Evidence strengthModerate

How this study scored 56/100

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 (Alzheimer s Research & Therapy)
Journal's citation record	1 / 4	Alzheimer s Research & Therapy: journal h-index 146 (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	1 / 4	75 participants
Effect reported	3 / 3	Effect reported with a statistic (interval, p-value, ratio or similar)
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	2 / 7	Cited 5 times (OpenAlex, 2026-10-10)
Citations per year	1 / 5	1.7 citations a year over 3 year(s) since 2025
Impact for its field and year	3 / 6	Cited 3.2× the average for papers of its field and year (OpenAlex FWCI)
Cited by studies here	1 / 6	Cited by 2 other studies in this library
Still being cited	1 / 4	Cited 5 times in 2024–2026 (2026 still in progress; OpenAlex)
Senior author's track record	2 / 4	Last-listed author Jamie M. Walker: h-index 26 (OpenAlex, whole career)
Institution's track record	1 / 3	The University of Texas Southwestern Medical Center: institution h-index 1,356 (OpenAlex)
Multicenter collaboration	2 / 3	OpenAlex lists 7 institution(s) in 3 countries
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 41339920)
Free to read	2 / 2	Free to read
Total	56 / 100	—

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