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Association Between Elevated Brain Amyloid and Subsequent Cognitive Decline Among Cognitively Normal Persons
Donohue MC, Sperling RA, Petersen R, Sun CK, Weiner MW, Aisen PS, Alzheimer’s Disease Neuroimaging Initiative.. JAMA, 2017-06-01
Topic: Amyloid, tau and blood-test diagnosis
Importance Among cognitively normal individuals, elevated brain amyloid (defined by cerebrospinal fluid assays or positron emission tomography regional summaries) can be related to risk for later Alzheimer-related cognitive decline. Objective To characterize and quantify the risk for Alzheimer-related cognitive decline among cognitively normal individuals with elevated brain amyloid. Design, setting, and participants Exploratory analyses were conducted with longitudinal cognitive and biomarker data from 445 cognitively normal individuals in the United States and Canada. Participants were observed from August 23, 2005, to June 7, 2016, for a median of 3.1 years (interquartile range, 2.0-4.2 years; maximum follow-up, 10.3 years) as part of the Alzheimer's Disease Neuroimaging Initiative (ADNI). Exposures Individuals were classified at baseline as having normal (n = 243) or elevated (n = 202) brain amyloid using positron emission tomography amyloid imaging or a cerebrospinal fluid assay of amyloid β. Main outcomes and measures Outcomes included scores on the Preclinical Alzheimer Cognitive Composite (PACC; a sum of 4 baseline standardized z scores, which decreases with worse performance), Mini-Mental State Examination (MMSE; 0 [worst] to 30 [best] points), Clinical Dementia Rating Sum of Boxes (CDR-Sum of Boxes; 0 [best] to 18 [worst] points), and Logical Memory Delayed Recall (0 [worst] to 25 [best] story units). Results Among the 445 participants (243 with normal amyloid, 202 with elevated amyloid), mean (SD) age was 74.0 (5.9) years, mean education was 16.4 (2.7) years, and 52% were women. The mean score for PACC at baseline was 0.00 (2.60); for MMSE, 29.0 (1.2); for CDR-Sum of Boxes, 0.04 (0.14); and for Logical Memory Delayed Recall, 13.1 (3.3). Compared with the group with normal amyloid, those with elevated amyloid had worse mean scores at 4 years on the PACC (mean difference, 1.51 points [95% CI, 0.94-2.10]; P Conclusions and relevance Exploratory analyses of a cognitively normal cohort followed up for a median of 3.1 years suggest that elevation in baseline brain amyloid level, compared with normal brain amyloid level, was associated with higher likelihood of cognitive decline, although the findings are of uncertain clinical significance. Further research is needed to assess the clinical importance of these differences and measure longer-term associations.
Key findings
- Results Among the 445 participants (243 with normal amyloid, 202 with elevated amyloid), mean (SD) age was 74.0 (5.9) years, mean education was 16.4 (2.7) years, and 52% were women.
- Compared with the group with normal amyloid, those with elevated amyloid had worse mean scores at 4 years on the PACC (mean difference, 1.51 points [95% CI, 0.94-2.10]; P < .001), MMSE (mean difference, 0.56 points [95% CI, 0.32-0.80]; P < .001), and CDR-Sum of Boxes (mean difference, 0.23 points [95% CI, 0.08-0.38]; P = .002).
Why it matters
In 445 cognitively normal older adults followed for a median of 3.1 years in the ADNI study, the 202 with elevated brain amyloid on PET or spinal-fluid testing scored on average 1.51 points lower (95% CI 0.94–2.10) at 4 years on the PACC thinking-test composite than the 243 with normal amyloid. The authors call these analyses exploratory and say the differences are "of uncertain clinical significance", so the study shows an association with later decline, not that amyloid causes it or that any one person will develop dementia.
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Study details
- Study designlongitudinal study
- Participants243
- Evidence strengthModerate
How this study scored 73/100
Published in a top-tier journal, and it is a longitudinal study following the same people over time. Scored zero for effect reported and randomised / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 70 of the 96 points we could judge it on, which is 73 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 10 / 10 | Tier 1 — top-tier general journal (JAMA) |
| Journal's citation record | 4 / 4 | JAMA: journal h-index 1,011 (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 | 2017 — within 10 year(s) of the newest study here |
| Sample size | 2 / 4 | 243 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 | 6 / 7 | Cited 457 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 41.5 citations a year over 11 year(s) since 2017 |
| Impact for its field and year | 5 / 6 | Cited 34.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 44 other studies in this library |
| Still being cited | 3 / 4 | Cited 151 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 7 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 28609533) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 70 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 70 of the 96 points we could judge it on is 73 out of 100. |
| Total | 73 / 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).
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 names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Donohue, M. C., Sperling, R. A., Petersen, R., Sun, C. K., Weiner, M. W., Aisen, P. S., et al. (2017). Association Between Elevated Brain Amyloid and Subsequent Cognitive Decline Among Cognitively Normal Persons. JAMA. https://doi.org/10.1001/jama.2017.6669
Vancouver
Donohue MC, Sperling RA, Petersen R, Sun CK, Weiner MW, Aisen PS, et al. Association Between Elevated Brain Amyloid and Subsequent Cognitive Decline Among Cognitively Normal Persons. JAMA. 2017. doi:10.1001/jama.2017.6669. PMID: 28609533.
BibTeX
@article{donohue2017-28609533,
author = {Donohue, M. C. and Sperling, R. A. and Petersen, R. and Sun, C. K. and Weiner, M. W. and Aisen, P. S. and {Alzheimer’s Disease Neuroimaging Initiative}},
title = {{Association Between Elevated Brain Amyloid and Subsequent Cognitive Decline Among Cognitively Normal Persons}},
journal = {JAMA},
year = {2017},
doi = {10.1001/jama.2017.6669},
pmid = {28609533},
url = {https://doi.org/10.1001/jama.2017.6669}
}
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