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43/100

✓ Peer-reviewed alzhub usefulness score 43 out of 100. Biomarkers

Topic: Amyloid, tau and blood-test diagnosis

There is considerable interest in designing therapeutic studies of individuals at risk of Alzheimer disease (AD) to prevent the onset of symptoms. Cortical β-amyloid plaques, the first stage of AD pathology, can be detected in vivo using positron emission tomography (PET), and several studies have shown that ~1/3 of healthy elderly have significant β-amyloid deposition. Here we assessed whether asymptomatic amyloid-PET-positive controls have increased rates of brain atrophy, which could be harnessed as an outcome measure for AD prevention trials. We assessed 66 control subjects (age = 73.5±7.3 yrs; MMSE = 29±1.3) from the Australian Imaging Biomarkers & Lifestyle study who had a baseline Pittsburgh Compound B (PiB) PET scan and two 3T MRI scans ~18-months apart. We calculated PET standard uptake value ratios (SUVR), and classified individuals as amyloid-positive/negative. Baseline and 18-month MRI scans were registered, and brain, hippocampal, and ventricular volumes and annualized volume changes calculated. Increasing baseline PiB-PET measures of β-amyloid load correlated with hippocampal atrophy rate independent of age (p = 0.014). Twenty-two (1/3) were PiB-positive (SUVR>1.40), the remaining 44 PiB-negative (SUVR≤1.31). Compared to PiB-negatives, PiB-positive individuals were older (76.8±7.5 vs. 71.7±7.5, p<0.05) and more were APOE4 positive (63.6% vs. 19.2%, p<0.01) but there were no differences in baseline brain, ventricle or hippocampal volumes, either with or without correction for total intracranial volume, once age and gender were accounted for. The PiB-positive group had greater total hippocampal loss (0.06±0.08 vs. 0.02±0.05 ml/yr, p = 0.02), independent of age and gender, with non-significantly higher rates of whole brain (7.1±9.4 vs. 4.7±5.5 ml/yr) and ventricular (2.0±3.0 vs. 1.1±1.0 ml/yr) change. Based on the observed effect size, recruiting 384 (95%CI 195-1080) amyloid-positive subjects/arm will provide 80% power to detect 25% absolute slowing of hippocampal atrophy rate in an 18-month treatment trial. We conclude that hippocampal atrophy may be a feasible outcome measure for secondary prevention studies in asymptomatic amyloidosis.

Cite this study APA, Vancouver, BibTeX · download .bib or .ris

APA 7th

Andrews, K. A., Modat, M., Macdonald, K. E., Yeatman, T., Cardoso, M. J., Leung, K. K., et al. (2013). Atrophy rates in asymptomatic amyloidosis: implications for Alzheimer prevention trials. PloS one. https://doi.org/10.1371/journal.pone.0058816

Vancouver

Andrews KA, Modat M, Macdonald KE, Yeatman T, Cardoso MJ, Leung KK, et al. Atrophy rates in asymptomatic amyloidosis: implications for Alzheimer prevention trials. PloS one. 2013. doi:10.1371/journal.pone.0058816. PMID: 23554933.

BibTeX

@article{andrews2013-23554933,
  author  = {Andrews, K. A. and Modat, M. and Macdonald, K. E. and Yeatman, T. and Cardoso, M. J. and Leung, K. K. and Barnes, J. and Villemagne, V. L. and others},
  title   = {{Atrophy rates in asymptomatic amyloidosis: implications for Alzheimer prevention trials}},
  journal = {PloS one},
  year    = {2013},
  doi     = {10.1371/journal.pone.0058816},
  pmid    = {23554933},
  url     = {https://doi.org/10.1371/journal.pone.0058816}
}

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Key findings

Cortical β-amyloid plaques, the first stage of AD pathology, can be detected in vivo using positron emission tomography (PET), and several studies have shown that ~1/3 of healthy elderly have significant β-amyloid deposition.
Compared to PiB-negatives, PiB-positive individuals were older (76.8±7.5 vs. 71.7±7.5, p<0.05) and more were APOE4 positive (63.6% vs. 19.2%, p<0.01) but there were no differences in baseline brain, ventricle or hippocampal volumes, either with or without correction for total intracranial volume, once age and gender were accounted for.
The PiB-positive group had greater total hippocampal loss (0.06±0.08 vs. 0.02±0.05 ml/yr, p = 0.02), independent of age and gender, with non-significantly higher rates of whole brain (7.1±9.4 vs. 4.7±5.5 ml/yr) and ventricular (2.0±3.0 vs. 1.1±1.0 ml/yr) change.
We conclude that hippocampal atrophy may be a feasible outcome measure for secondary prevention studies in asymptomatic amyloidosis.

Why it matters

In cognitively normal older adults, higher baseline amyloid load on PET correlated with a faster rate of hippocampal shrinkage over about 18 months, even though amyloid-positive and amyloid-negative people did not differ in brain, ventricle or hippocampal volumes at the start. This supports using brain atrophy rates as an outcome measure in trials aimed at preventing Alzheimer's symptoms, but it is an observational imaging study, not a test of any treatment.

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Study details

Effect size63.6%; 19.2%
Evidence strengthLow

How this study scored 43/100

Published in a peer-reviewed journal. Scored zero for study design, sample size, studied in people 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 41 of the 96 points we could judge it on, which is 43 out of 100.

Component	Points	Why
Journal tier	7 / 10	Tier 3 — peer-reviewed journal (PloS one)
Journal's citation record	4 / 4	PLoS ONE: journal h-index 594 (OpenAlex, 2026-10-29)
Study design	0 / 12	No study design recorded — scores zero, not guessed (not stated in the record — scored 0)
Strength of evidence	1 / 5	Rated “low” in our summary
Peer-review validation	10 / 10	Peer-reviewed. Published as an article in a named peer-reviewed journal.
How recent	1 / 5	2013 — within 20 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	2 / 3	Effect reported as a number, without an interval or test
Studied in people	0 / 3	Not stated whether this was studied in people — scores zero (not stated in the record — scored 0)
Randomised / blinded	0 / 2	No randomisation or blinding stated — scores zero (not stated in the record — scored 0)
Times cited	4 / 7	Cited 44 times (OpenAlex, 2026-10-10)
Citations per year	1 / 5	2.9 citations a year over 15 year(s) since 2013
Impact for its field and year	3 / 6	Cited 3.4× the average for papers of its field and year (OpenAlex FWCI)
Cited by studies here	1 / 6	Cited by 1 other studies in this library
Still being cited	0 / 4	Cited 1 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	2 / 3	University College London: institution h-index 2,029 (OpenAlex)
Multi-centre collaboration	1 / 3	OpenAlex lists 2 institution(s) in 2 countries
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 23554933)
Free to read	2 / 2	Free to read
Points	41 / 96	Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 41 of the 96 points we could judge it on is 43 out of 100.
Total	43 / 100	—

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