Home › Research › Biomarkers
Cognitive and Brain Reserve as Modifiers of Early Alzheimer Disease–Related Cognitive Vulnerability
Kelsey R. Sewell, Patricio Solis‐Urra, Haiqing Huang, Thomas K. Karikari, George Grove, Arthur F. Kramer, Edward McAuley, Jeffrey Murray Burns et al.. Neurology, 2026-04-14
Topic: Amyloid, tau and blood-test diagnosis
A total of 621 participants (aged 69.9 ± 3.8, 71% female) had available data for the main analyses and 355 had PET Centiloid data available. Brain-PAD moderated the association between AD pathology (measured by p-tau217) and multiple cognitive domains, including episodic memory (β = -0.09 [-0.16 to -0.02]), processing speed (β = -0.08 [-0.15 to -0.01]), working memory (β = -0.10 [-0.18 to -0.03]), and executive function/attentional control (β = -0.08 [-0.15 to -0.01]). Specifically, the negative association of greater AD pathology with poorer cognition was weakest in individuals with younger appearing brains. A latent SES score also moderated the relationship between p-tau217 and episodic memory (β = 0.08 [0.01-0.16]), but this did not survive correction for multiple comparisons. Neither years of education nor the volumetric AD signature moderated pathology-cognition associations. These results support the hypothesis that higher cognitive and brain reserve may help buffer the cognitive consequences of AD pathology. Strategies to increase both cognitive and brain reserve could help to boost resilience against emerging AD pathology; however, longitudinal studies are needed to confirm these conclusions.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Sewell, K. R., Solis‐Urra, P., Huang, H., Karikari, T. K., Grove, G., Kramer, A. F., et al. (2026). Cognitive and Brain Reserve as Modifiers of Early Alzheimer Disease–Related Cognitive Vulnerability. Neurology. https://doi.org/10.1212/wnl.0000000000214833
Vancouver
Sewell KR, Solis‐Urra P, Huang H, Karikari TK, Grove G, Kramer AF, et al. Cognitive and Brain Reserve as Modifiers of Early Alzheimer Disease–Related Cognitive Vulnerability. Neurology. 2026. doi:10.1212/wnl.0000000000214833. PMID: 41980229.
BibTeX
@article{sewell2026-41980229,
author = {Sewell, Kelsey R. and Solis‐Urra, Patricio and Huang, Haiqing and Karikari, Thomas K. and Grove, George and Kramer, Arthur F. and McAuley, Edward and Burns, Jeffrey Murray and others},
title = {{Cognitive and Brain Reserve as Modifiers of Early Alzheimer Disease–Related Cognitive Vulnerability}},
journal = {Neurology},
year = {2026},
doi = {10.1212/wnl.0000000000214833},
pmid = {41980229},
url = {https://doi.org/10.1212/wnl.0000000000214833}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
Key findings
- A total of 621 participants (aged 69.9 ± 3.8, 71% female) had available data for the main analyses and 355 had PET Centiloid data available.
- Brain-PAD moderated the association between AD pathology (measured by p-tau217) and multiple cognitive domains, including episodic memory (β = -0.09 [-0.16 to -0.02]), processing speed (β = -0.08 [-0.15 to -0.01]), working memory (β = -0.10 [-0.18 to -0.03]), and executive function/attentional control (β = -0.08 [-0.15 to -0.01]).
- Specifically, the negative association of greater AD pathology with poorer cognition was weakest in individuals with younger appearing brains.
- A latent SES score also moderated the relationship between p-tau217 and episodic memory (β = 0.08 [0.01-0.16]), but this did not survive correction for multiple comparisons.
- Neither years of education nor the volumetric AD signature moderated pathology-cognition associations.
Why it matters
People with younger-appearing brains showed a weaker link between Alzheimer's pathology (p-tau217) and poorer cognition across several domains, supporting the idea that brain reserve may buffer the cognitive effects of pathology. The authors note longitudinal studies are needed to confirm this, and it does not show that reserve prevents or cures the disease.
New to this subject? Start with our plain-English guide: Blood tests & biomarkers →
Study details
- Study designcross-sectional
- Participants621
- Evidence strengthHigh
How this study scored 61/100
Published in a leading specialty journal, and it is a snapshot of people at one point in time. Scored zero for effect reported and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (OpenAlex, 2026-10-29) |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| Strength of evidence | 5 / 5 | Rated “high” 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 | 621 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 | 1 / 7 | Cited 3 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.5 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 4 / 6 | Cited 14.2× 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 | 1 / 4 | Cited 3 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Kirk I. Erickson: h-index 94 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Columbia University: institution h-index 1,824 (OpenAlex) |
| Multicenter collaboration | 3 / 3 | OpenAlex lists 11 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41980229) |
| Free to read | 2 / 2 | Free to read |
| Total | 61 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Related
Studies in the library that share something with this one. The line above each title says what.
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.
Related studies in Biomarkers
Also tagged “cerebrospinal”
820 studies in the library carry the topic tag “cerebrospinal”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 820 tagged studies.