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Greater White Matter Hyperintensity Volume Is Associated with the Number of Microhemorrhages in Preclinical Alzheimer's Disease
Shirzadi Z, Schultz AP, Properzi M, Yaari R, Yau WW, Brickman AM, Rafii MS, Donohue MC et al.. The journal of prevention of Alzheimer's disease, 2024-01-01
Topic: Plasma and spinal-fluid biomarkers
Background Increased white matter hyperintensity (WMH) volume visible on MRI is a common finding in Alzheimer's disease (AD). We hypothesized that WMH in preclinical AD is associated with the presence of advanced vessel amyloidosis manifested as microhemorrhages (MCH). Objectives 1) To assess the relationship between baseline WMH volume and baseline MCH. 2) To assess the relationship between longitudinal WMH accumulation and last MRI MCH during the double-blind phase of the A4 trial. Design A multicenter, randomized, double-blind, placebo-controlled, Phase 3 study comparing solanezumab with placebo given as infusions once every 4 weeks over 4.5 years in subjects with preclinical AD, defined as having evidence of elevated brain amyloid before the stage of clinically evident cognitive impairment, with an optional open-label extension period. Setting Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study. Participants A sample of 1157 cognitively unimpaired older adults (mean age = 71.9 years [SD = 4.8 years], 59% women, 59% APOE ε4 carriers). Measurements A linear regression model was used to assess the impact of baseline MCH amount (0, 1, 2+) on WMH volume. A linear mixed-effects model was used to assess the impact of last MRI MCH on longitudinal WMH. All models were corrected for age, sex, grey matter volume, cortical amyloid PET, APOE ε4 status, and treatment group. Results Baseline WMH volume was greater in individuals with more than one MCH compared to those with no MCH (t=4.8, p<0.001). The longitudinal increase in WMH amongst individuals with one (t=2.3, p=0.025) and more than one MCH (t=6.7, p<0.001) at the last MRI was greater than those with no MCH. Conclusion These results indicate a strong association between WMH and MCH, a common manifestation of cerebral amyloid angiopathy and ARIA-H. These results suggest that increased WMH volume may represent an early sign of vessel amyloidosis, likely prior to the emergence of MCH.
Key findings
- We hypothesized that WMH in preclinical AD is associated with the presence of advanced vessel amyloidosis manifested as microhemorrhages (MCH).
- Results Baseline WMH volume was greater in individuals with more than one MCH compared to those with no MCH (t=4.8, p<0.001).
- Conclusion These results indicate a strong association between WMH and MCH, a common manifestation of cerebral amyloid angiopathy and ARIA-H.
- These results suggest that increased WMH volume may represent an early sign of vessel amyloidosis, likely prior to the emergence of MCH.
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Study details
- Study designlongitudinal study
- Evidence strengthHigh
How this study scored 79/100
Published in a peer-reviewed journal, and it is a large phase 3 trial. Scored zero for sample size and effect reported because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record and institution's track record, so those were left out: it earned 48 of the 61 points we could judge it on, which is 79 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The journal of prevention of Alzheimer's disease) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 11 / 12 | A large phase 3 trial (from PubMed type “Clinical Trial, Phase III”) |
| 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 | 4 / 5 | 2024 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| 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 (pubmed indexes it as a clinical or observational study) |
| Randomised / blinded | 2 / 2 | Randomised and blinded or placebo-controlled (as stated in the record) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| 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 | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | 2 / 3 | PubMed indexes it as a multicentre study |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39044495) |
| Free to read | 2 / 2 | Free to read |
| Points | 48 / 61 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 48 of the 61 points we could judge it on is 79 out of 100. |
| Total | 79 / 100 | — |
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APA 7th
Shirzadi, Z., Schultz, A. P., Properzi, M., Yaari, R., Yau, W. W., Brickman, A. M., et al. (2024). Greater White Matter Hyperintensity Volume Is Associated with the Number of Microhemorrhages in Preclinical Alzheimer's Disease. The journal of prevention of Alzheimer's disease. https://doi.org/10.14283/jpad.2024.139
Vancouver
Shirzadi Z, Schultz AP, Properzi M, Yaari R, Yau WW, Brickman AM, et al. Greater White Matter Hyperintensity Volume Is Associated with the Number of Microhemorrhages in Preclinical Alzheimer's Disease. The journal of prevention of Alzheimer's disease. 2024. doi:10.14283/jpad.2024.139. PMID: 39044495.
BibTeX
@article{shirzadi2024-39044495,
author = {Shirzadi, Z. and Schultz, A. P. and Properzi, M. and Yaari, R. and Yau, W. W. and Brickman, A. M. and Rafii, M. S. and Donohue, M. C. and others},
title = {{Greater White Matter Hyperintensity Volume Is Associated with the Number of Microhemorrhages in Preclinical Alzheimer's Disease}},
journal = {The journal of prevention of Alzheimer's disease},
year = {2024},
doi = {10.14283/jpad.2024.139},
pmid = {39044495},
url = {https://doi.org/10.14283/jpad.2024.139}
}