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Amyloid-β deposition in mild cognitive impairment is associated with increased hippocampal activity, atrophy and clinical progression
Huijbers W, Mormino EC, Schultz AP, Wigman S, Ward AM, Larvie M, Amariglio RE, Marshall GA et al.. Brain : a journal of neurology, 2015-02-11
Topic: Amyloid, tau and blood-test diagnosis
Cross-sectional functional magnetic resonance imaging studies using a memory task in patients with mild cognitive impairment have produced discordant results, with some studies reporting increased hippocampal activity--consistent with findings in genetic at-risk populations--and other studies reporting decreased hippocampal activity, relative to normal controls. However, previous studies in mild cognitive impairment have not included markers of amyloid-β, which may be particularly important in prediction of progression along the Alzheimer's disease continuum. Here, we examine the contribution of amyloid-β deposition to cross-sectional and longitudinal measures of hippocampal functional magnetic resonance imaging activity, hippocampal volume, global cognition and clinical progression over 36 months in 33 patients with mild cognitive impairment. Amyloid-β status was examined with positron emission tomography imaging using Pittsburg compound-B, hippocampal functional magnetic resonance imaging activity was assessed using an associative face-name memory encoding task, and hippocampal volume was quantified with structural magnetic resonance imaging. Finally global cognition was assessed using the Mini-Mental State Examination and clinical progression was assessed using the Clinical Dementia Rating (Sum of Boxes). At baseline, amyloid-β positive patients with mild cognitive impairment showed increased hippocampal activation, smaller hippocampal volumes, and a trend towards lower Mini-Mental State Examination scores and higher Clinical Dementia Ratings compared to amyloid-β negative patients with mild cognitive impairment. Longitudinally, amyloid-β positive patients with mild cognitive impairment continued to show high levels of hippocampal activity, despite increasing rates of hippocampal atrophy, decline on the Mini-Mental State Examination and faster progression on the Clinical Dementia Ratings. When entered simultaneously into the same linear mixed model, amyloid-β status, hippocampal activation, and hippocampal volume independently predicted clinical progression. These results indicate that amyloid-β positive patients with mild cognitive impairment are more likely on a path towards Alzheimer's disease dementia than amyloid-β negative patients. Increased hippocampal activity is discussed in relation to neuronal compensation and/or amyloid-β induced excitoxicity.
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APA 7th
Huijbers, W., Mormino, E. C., Schultz, A. P., Wigman, S., Ward, A. M., Larvie, M., et al. (2015). Amyloid-β deposition in mild cognitive impairment is associated with increased hippocampal activity, atrophy and clinical progression. Brain : a journal of neurology. https://doi.org/10.1093/brain/awv007
Vancouver
Huijbers W, Mormino EC, Schultz AP, Wigman S, Ward AM, Larvie M, et al. Amyloid-β deposition in mild cognitive impairment is associated with increased hippocampal activity, atrophy and clinical progression. Brain : a journal of neurology. 2015. doi:10.1093/brain/awv007. PMID: 25678559.
BibTeX
@article{huijbers2015-25678559,
author = {Huijbers, W. and Mormino, E. C. and Schultz, A. P. and Wigman, S. and Ward, A. M. and Larvie, M. and Amariglio, R. E. and Marshall, G. A. and others},
title = {{Amyloid-β deposition in mild cognitive impairment is associated with increased hippocampal activity, atrophy and clinical progression}},
journal = {Brain : a journal of neurology},
year = {2015},
doi = {10.1093/brain/awv007},
pmid = {25678559},
url = {https://doi.org/10.1093/brain/awv007}
}
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Key findings
- Cross-sectional functional magnetic resonance imaging studies using a memory task in patients with mild cognitive impairment have produced discordant results, with some studies reporting increased hippocampal activity--consistent with findings in genetic at-risk populations--and other studies reporting decreased hippocampal activity, relative to normal controls.
- At baseline, amyloid-β positive patients with mild cognitive impairment showed increased hippocampal activation, smaller hippocampal volumes, and a trend towards lower Mini-Mental State Examination scores and higher Clinical Dementia Ratings compared to amyloid-β negative patients with mild cognitive impairment.
- These results indicate that amyloid-β positive patients with mild cognitive impairment are more likely on a path towards Alzheimer's disease dementia than amyloid-β negative patients.
Why it matters
In 33 patients with mild cognitive impairment, those who were amyloid-β positive showed increased hippocampal activation, smaller hippocampal volumes, and a trend towards lower Mini-Mental State Examination scores at baseline. The study examined how amyloid-β deposition relates to brain activity, atrophy and clinical progression, and did not test any treatment.
Study details
- Study designcross-sectional
- Participants33
- Evidence strengthModerate
How this study scored 63/100
Published in a leading specialty journal, and it is a snapshot of people at one point in time. Scored zero for effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain : a journal of neurology) |
| Journal's citation record | 4 / 4 | Brain: journal h-index 503 (OpenAlex, 2026-10-29) |
| Study design | 4 / 12 | A snapshot of people at one point in 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 | 1 / 5 | 2015 — within 20 year(s) of the newest study here |
| Sample size | 1 / 4 | 33 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 | 5 / 7 | Cited 249 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 19.2 citations a year over 13 year(s) since 2015 |
| Impact for its field and year | 4 / 6 | Cited 17.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 6 other studies in this library |
| Still being cited | 3 / 4 | Cited 55 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Reisa Anne Sperling: h-index 157 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 25678559) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 63 / 100 | — |
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