Region-specific cerebral blood flow differentiates cognitively impaired and unimpaired individuals with core Alzheimer's disease pathology
Fernandes-Taylor, S.; Driscoll, I.; Glittenberg, M.; Breidenbach, B.; Paulsen, A. J.; Hauge, K.; Rhodes, A.; Rivera-Rivera et al.. medRxiv (preprint), 2026-08-25
Topic: Amyloid, tau and blood-test diagnosis
BackgroundUp to 30% of individuals harboring core Alzheimers disease (AD) neuropathology--amyloid-{beta} (A{beta};A) and tau (T)--remain cognitively unimpaired. ObjectiveWe examine whether MRI measures of cerebral blood flow (CBF) and white matter hyperintensities (WMH) differentiate cognitively impaired (AD or mild cognitive impairment (MCI);AD+MCI) from non-demented individuals with (NDAN) and without (Controls) core AD neuropathology. MethodsA retrospective cohort study (2018-2023) using data from The Wisconsin Registry for Alzheimers Prevention and Wisconsin Alzheimers Disease Research Center studies employed linear models comparing group differences in regional gray matter (GM) CBF and whole brain WMH volume. Participants (N=500) underwent 3T MRI, A{beta}-(11C-Pittsburgh Compound B) and tau-(18F-MK6240) PET, and neuropsychological assessments. We categorized participants based on PET and cognitive status as Controls (n=416; cognitively unimpaired, A-T-), NDAN (n=38; cognitively unimpaired, A+T+), or AD+MCI (n=46; cognitively impaired, A+T+). ResultsParticipants were 67 years old (mean), 68% female, and 37% APOE {varepsilon}4+. NDAN, like Controls, had significantly higher CBF than AD+MCI in GM regions susceptible to neurofibrillary tangle formation in early AD (frontal and temporal cortices, and limbic regions (ps<0.05)). Largest CBF differences (22-34%) were observed in GM regions that accumulate A{beta} early but remain largely tangle-free during early AD progression, namely the occipital and parietal cortices. WMH volume differentiated AD+MCI from Controls (p=0.002) but not NDAN (p=0.16). ConclusionCBF differentiated NDAN from AD+MCI, highlighting vascular contributions to cognitive resilience. Most pronounced CBF preservation in NDAN was observed in parietal and occipital cortices, regions typically free of tau until late stages of AD progression.
Key findings
- NDAN, like Controls, had significantly higher CBF than AD+MCI in GM regions susceptible to neurofibrillary tangle formation in early AD (frontal and temporal cortices, and limbic regions (ps<0.05)).
Why it matters
In this cohort, cognitively unimpaired people with core Alzheimer's pathology had significantly higher cerebral blood flow than cognitively impaired people with the same pathology in regions vulnerable in early disease. This observational imaging finding may help explain why some people with pathology stay cognitively intact, but it is not a treatment or cure.
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Study details
- Study designcohort study
- Participants500
- Evidence strengthModerate
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 37 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for effect reported and randomised / blinded because the record does not state it. We have no data on impact for its field and year and senior author's track record, so those were left out: it earned 33 of the 90 points we could judge it on, which is 37 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (medRxiv (preprint)) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 7 / 12 | A cohort study following people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 2 / 4 | 500 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) |
| 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 | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| 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 Ozioma Okonkwo holds only 9 work(s), too few to judge a track record — left out of this score |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 2 / 2 | Free to read |
| Points | 33 / 90 | Scored on 18 of 20 parts. We have no data for the rest, so they are left out: 33 of the 90 points we could judge it on is 37 out of 100. |
| Total | 37 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
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.
APA 7th
Fernandes-Taylor, S., Driscoll, I., Glittenberg, M., Breidenbach, B., Paulsen, A. J., Hauge, K., et al. (2026). Region-specific cerebral blood flow differentiates cognitively impaired and unimpaired individuals with core Alzheimer's disease pathology. medRxiv (preprint). https://doi.org/10.64898/2026.08.22.26361093
Vancouver
Fernandes-Taylor S, Driscoll I, Glittenberg M, Breidenbach B, Paulsen AJ, Hauge K, et al. Region-specific cerebral blood flow differentiates cognitively impaired and unimpaired individuals with core Alzheimer's disease pathology. medRxiv (preprint). 2026. doi:10.64898/2026.08.22.26361093.
BibTeX
@article{fernandestaylor2026-79f3be3a,
author = {Fernandes-Taylor, S. and Driscoll, I. and Glittenberg, M. and Breidenbach, B. and Paulsen, A. J. and Hauge, K. and Rhodes, A. and Rivera-Rivera and others},
title = {{Region-specific cerebral blood flow differentiates cognitively impaired and unimpaired individuals with core Alzheimer's disease pathology}},
journal = {medRxiv (preprint)},
year = {2026},
doi = {10.64898/2026.08.22.26361093},
url = {https://doi.org/10.64898/2026.08.22.26361093}
}
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