Home › Research › Mild cognitive impairment
Mitochondrial dysfunction, oxidative stress, neuroinflammation, and metabolic alterations in the progression of Alzheimer's disease: A meta-analysis of in vivo magnetic resonance spectroscopy studies
Song T, Song X, Zhu C, Patrick R, Skurla M, Santangelo I, Green M, Harper D et al.. Ageing research reviews, 2021-10-29
Topic: Amyloid, tau and blood-test diagnosis
Accumulating evidence demonstrates that metabolic changes in the brain associated with neuroinflammation, oxidative stress, and mitochondrial dysfunction play an important role in the pathophysiology of mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, the neural signatures associated with these metabolic alterations and underlying molecular mechanisms are still elusive. Accordingly, we reviewed the literature on in vivo human brain 1 H and 31 P-MRS studies and use meta-analyses to identify patterns of brain metabolic alterations in MCI and AD. 40 and 39 studies on MCI and AD, respectively, were classified according to brain regions. Our results indicate decreased N-acetyl aspartate and creatine but increased myo-inositol levels in both MCI and AD, decreased glutathione level in MCI as well as disrupted energy metabolism in AD. In addition, the hippocampus shows the strongest alterations in most of these metabolites. This meta-analysis also illustrates progressive metabolite alterations from MCI to AD. Taken together, it suggests that 1) neuroinflammation and oxidative stress may occur in the early stages of AD, and likely precede neuron loss in its progression; 2) the hippocampus is a sensitive region of interest for early diagnosis and monitoring the response of interventions; 3) targeting bioenergetics associated with neuroinflammation/oxidative stress is a promising approach for treating AD.
Key findings
- Accumulating evidence demonstrates that metabolic changes in the brain associated with neuroinflammation, oxidative stress, and mitochondrial dysfunction play an important role in the pathophysiology of mild cognitive impairment (MCI) and Alzheimer's disease (AD).
- However, the neural signatures associated with these metabolic alterations and underlying molecular mechanisms are still elusive.
- Our results indicate decreased N-acetyl aspartate and creatine but increased myo-inositol levels in both MCI and AD, decreased glutathione level in MCI as well as disrupted energy metabolism in AD.
- Taken together, it suggests that 1) neuroinflammation and oxidative stress may occur in the early stages of AD, and likely precede neuron loss in its progression; 2) the hippocampus is a sensitive region of interest for early diagnosis and monitoring the response of interventions; 3) targeting bioenergetics associated with neuroinflammation/oxidative stress is a promising approach for treating AD.
Why it matters
This analysis of brain spectroscopy studies found patterns of metabolic changes, including signs of oxidative stress and mitochondrial dysfunction, in people with mild cognitive impairment and Alzheimer's disease. The findings suggest these processes may occur early and that the hippocampus is a sensitive region, but they do not show that treating these changes helps patients.
Study details
- Study designmeta-analysis
- Evidence strengthHigh
How this study scored 67/100
Published in a peer-reviewed journal, and it is a meta-analysis pooling many studies. Scored zero for sample size, effect reported and studied in people because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Ageing research reviews) |
| Journal's citation record | 2 / 4 | Ageing Research Reviews: journal h-index 225 (OpenAlex, 2026-10-29) |
| Study design | 12 / 12 | A meta-analysis pooling many studies |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2021 — within 6 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 | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| 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 | A review of other studies — randomisation is not credited here |
| Times cited | 6 / 7 | Cited 339 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 48.4 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 4 / 6 | Cited 9.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 3 other studies in this library |
| Still being cited | 4 / 4 | Cited 260 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Fei Du: h-index 33 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 34751136) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 67 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1016/j.arr.2021.101503
- PubMed: 34751136
- Original source →
- Free full text: Ageing Research Reviews →
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
Song, T., Song, X., Zhu, C., Patrick, R., Skurla, M., Santangelo, I., et al. (2021). Mitochondrial dysfunction, oxidative stress, neuroinflammation, and metabolic alterations in the progression of Alzheimer's disease: A meta-analysis of in vivo magnetic resonance spectroscopy studies. Ageing research reviews. https://doi.org/10.1016/j.arr.2021.101503
Vancouver
Song T, Song X, Zhu C, Patrick R, Skurla M, Santangelo I, et al. Mitochondrial dysfunction, oxidative stress, neuroinflammation, and metabolic alterations in the progression of Alzheimer's disease: A meta-analysis of in vivo magnetic resonance spectroscopy studies. Ageing research reviews. 2021. doi:10.1016/j.arr.2021.101503. PMID: 34751136.
BibTeX
@article{song2021-34751136,
author = {Song, T. and Song, X. and Zhu, C. and Patrick, R. and Skurla, M. and Santangelo, I. and Green, M. and Harper, D. and others},
title = {{Mitochondrial dysfunction, oxidative stress, neuroinflammation, and metabolic alterations in the progression of Alzheimer's disease: A meta-analysis of in vivo magnetic resonance spectroscopy studies}},
journal = {Ageing research reviews},
year = {2021},
doi = {10.1016/j.arr.2021.101503},
pmid = {34751136},
url = {https://doi.org/10.1016/j.arr.2021.101503}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 16.
Later studies that cite this one
3 studies in the alzhub library list this one in their references.
Related studies in Mild cognitive impairment
Also tagged “classification”
835 studies in the library carry the topic tag “classification”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 835 tagged studies.