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Interactive Associations of Vascular Risk and β-Amyloid Burden With Cognitive Decline in Clinically Normal Elderly Individuals: Findings From the Harvard Aging Brain Study
Rabin JS, Schultz AP, Hedden T, Viswanathan A, Marshall GA, Kilpatrick E, Klein H, Buckley RF et al.. JAMA neurology, 2018-09-01
Topic: Amyloid, tau and blood-test diagnosis
Importance Identifying asymptomatic individuals at high risk of impending cognitive decline because of Alzheimer disease is crucial for successful prevention of dementia. Vascular risk and β-amyloid (Aβ) pathology commonly co-occur in older adults and are significant causes of cognitive impairment. Objective To determine whether vascular risk and Aβ burden act additively or synergistically to promote cognitive decline in clinically normal older adults; and, secondarily, to evaluate the unique influence of vascular risk on prospective cognitive decline beyond that of commonly used imaging biomarkers, including Aβ burden, hippocampal volume, fludeoxyglucose F18-labeled (FDG) positron emission tomography (PET), and white matter hyperintensities, a marker of cerebrovascular disease. Design, setting, and participants In this longitudinal observational study, we examined clinically normal older adults from the Harvard Aging Brain Study. Participants were required to have baseline imaging data (FDG-PET, Aβ-PET, and magnetic resonance imaging), baseline medical data to quantify vascular risk, and at least 1 follow-up neuropsychological visit. Data collection began in 2010 and is ongoing. Data analysis was performed on data collected between 2010 and 2017. Main outcomes and measures Vascular risk was quantified using the Framingham Heart Study general cardiovascular disease (FHS-CVD) risk score. We measured Aβ burden with Pittsburgh Compound-B PET. Cognition was measured annually with the Preclinical Alzheimer Cognitive Composite. Models were corrected for baseline age, sex, years of education, and apolipoprotein E ε4 status. Results Of the 223 participants, 130 (58.3%) were women. The mean (SD) age was 73.7 (6.0) years, and the mean (SD) follow-up time was 3.7 (1.2) years. Faster cognitive decline was associated with both a higher FHS-CVD risk score (β = -0.064; 95% CI, -0.094 to -0.033; P Conclusions and relevance In this study, vascular risk was associated with prospective cognitive decline in clinically normal older adults, both alone and synergistically with Aβ burden. Vascular risk may complement imaging biomarkers in assessing risk of prospective cognitive decline in preclinical Alzheimer disease.
Key findings
- Vascular risk and β-amyloid (Aβ) pathology commonly co-occur in older adults and are significant causes of cognitive impairment.
- Results Of the 223 participants, 130 (58.3%) were women.
- Faster cognitive decline was associated with both a higher FHS-CVD risk score (β = -0.064; 95% CI, -0.094 to -0.033; P < .001) and higher Aβ burden (β = -0.058; 95% CI, -0.079 to -0.037; P < .001).
Why it matters
In 223 clinically normal older adults followed for about 3.7 years on average, a higher Framingham cardiovascular risk score was linked to faster cognitive decline. The authors report this effect was stronger in people with more amyloid in the brain ("synergistically with Aβ burden"). They suggest vascular risk "may complement imaging biomarkers" in spotting who may decline. This was an observational study and did not test whether treating vascular risk changes the outcome.
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Study details
- Study designlongitudinal study
- Participants223
- Effect size58.3%
- Evidence strengthModerate
How this study scored 69/100
Published in a leading specialty 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.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (JAMA neurology) |
| Journal's citation record | 2 / 4 | JAMA Neurology: journal h-index 235 (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 | 2 / 5 | 2018 — within 10 year(s) of the newest study here |
| Sample size | 2 / 4 | 223 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 | 5 / 7 | Cited 223 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 22.3 citations a year over 10 year(s) since 2018 |
| Impact for its field and year | 4 / 6 | Cited 16.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 19 other studies in this library |
| Still being cited | 3 / 4 | Cited 62 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Jasmeer P. Chhatwal: h-index 64 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 29799986) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 69 / 100 | — |
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Read the original
- DOI: 10.1001/jamaneurol.2018.1123
- PubMed: 29799986
- Original source →
- Free full text: JAMA Neurology →
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
Rabin, J. S., Schultz, A. P., Hedden, T., Viswanathan, A., Marshall, G. A., Kilpatrick, E., et al. (2018). Interactive Associations of Vascular Risk and β-Amyloid Burden With Cognitive Decline in Clinically Normal Elderly Individuals: Findings From the Harvard Aging Brain Study. JAMA neurology. https://doi.org/10.1001/jamaneurol.2018.1123
Vancouver
Rabin JS, Schultz AP, Hedden T, Viswanathan A, Marshall GA, Kilpatrick E, et al. Interactive Associations of Vascular Risk and β-Amyloid Burden With Cognitive Decline in Clinically Normal Elderly Individuals: Findings From the Harvard Aging Brain Study. JAMA neurology. 2018. doi:10.1001/jamaneurol.2018.1123. PMID: 29799986.
BibTeX
@article{rabin2018-29799986,
author = {Rabin, J. S. and Schultz, A. P. and Hedden, T. and Viswanathan, A. and Marshall, G. A. and Kilpatrick, E. and Klein, H. and Buckley, R. F. and others},
title = {{Interactive Associations of Vascular Risk and β-Amyloid Burden With Cognitive Decline in Clinically Normal Elderly Individuals: Findings From the Harvard Aging Brain Study}},
journal = {JAMA neurology},
year = {2018},
doi = {10.1001/jamaneurol.2018.1123},
pmid = {29799986},
url = {https://doi.org/10.1001/jamaneurol.2018.1123}
}
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