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Memory decline accompanies subthreshold amyloid accumulation
Landau SM, Horng A, Jagust WJ, Alzheimer's Disease Neuroimaging Initiative.. Neurology, 2018-03-23
Topic: Amyloid, tau and blood-test diagnosis
Objective Extensive cortical β-amyloid (Aβ positivity) has been linked to cognitive decline, but the clinical significance of elevations in Aβ within the negative range is unknown. Methods We examined amyloid and cognitive trajectories (memory, executive function) in 142 cognitively normal older individuals enrolled in the Alzheimer's Disease Neuroimaging Initiative who were Aβ-negative at baseline and who had at least 2 [ 18 F]-florbetapir PET scans over 3.9 ± 1.4 years. We determined whether Aβ accumulation was associated with longitudinal changes in memory or executive function. Results Among baseline-negative individuals, florbetapir slope (mean annual increase 0.002 ± 0.008 standardized uptake value ratio units/y) was not related to age, sex, education, APOE4 status, baseline memory or executive function, temporoparietal glucose metabolism, baseline hippocampal volume, or hippocampal volume change; but it was related to higher baseline cortical florbetapir, indicating that Aβ accumulation was ongoing at baseline in those who accumulated during the study. Over the course of follow-up, 13 individuals converted to florbetapir+ and 14 nearly nonoverlapping individuals converted to mild cognitive impairment or Alzheimer disease. Amyloid accumulation among baseline-negative individuals was associated with poorer longitudinal memory performance ( p = 0.019), but it was not associated with changes in executive function. Reducing the sample to individuals with at least 3 timepoints to estimate the florbetapir slope strengthened the relationship further between florbetapir accumulation and memory decline ( p = 0.007). Conclusions Memory decline accompanies Aβ accumulation in otherwise healthy, Aβ-negative older adults. Amyloid increases within the negative range may represent the earliest detectable indication of pathology with domain-specific cognitive consequences.
Key findings
- We determined whether Aβ accumulation was associated with longitudinal changes in memory or executive function.
- Results Among baseline-negative individuals, florbetapir slope (mean annual increase 0.002 ± 0.008 standardized uptake value ratio units/y) was not related to age, sex, education, APOE4 status, baseline memory or executive function, temporoparietal glucose metabolism, baseline hippocampal volume, or hippocampal volume change; but it was related to higher baseline cortical florbetapir, indicating that Aβ accumulation was ongoing at baseline in those who accumulated during the study.
- Amyloid accumulation among baseline-negative individuals was associated with poorer longitudinal memory performance ( p = 0.019), but it was not associated with changes in executive function.
Study details
- Study designlongitudinal study
- Participants13
- Evidence strengthModerate
How this study scored 64/100
Published in a leading specialty 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 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 39 of the 61 points we could judge it on, which is 64 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 1 / 4 | 13 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 | — / 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 29572282) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 39 / 61 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 39 of the 61 points we could judge it on is 64 out of 100. |
| Total | 64 / 100 | — |
What each of these 20 components measures, and what this score is not →
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APA 7th
Landau, S. M., Horng, A., Jagust, W. J., & Alzheimer's Disease Neuroimaging Initiative. (2018). Memory decline accompanies subthreshold amyloid accumulation. Neurology. https://doi.org/10.1212/wnl.0000000000005354
Vancouver
Landau SM, Horng A, Jagust WJ, Alzheimer's Disease Neuroimaging Initiative. Memory decline accompanies subthreshold amyloid accumulation. Neurology. 2018. doi:10.1212/wnl.0000000000005354. PMID: 29572282.
BibTeX
@article{landau2018-29572282,
author = {Landau, S. M. and Horng, A. and Jagust, W. J. and {Alzheimer's Disease Neuroimaging Initiative}},
title = {{Memory decline accompanies subthreshold amyloid accumulation}},
journal = {Neurology},
year = {2018},
doi = {10.1212/wnl.0000000000005354},
pmid = {29572282},
url = {https://doi.org/10.1212/wnl.0000000000005354}
}