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Can Ketones Help Rescue Brain Fuel Supply in Later Life? Implications for Cognitive Health during Aging and the Treatment of Alzheimer's Disease
Cunnane SC, Courchesne-Loyer A, Vandenberghe C, St-Pierre V, Fortier M, Hennebelle M, Croteau E, Bocti C et al.. Frontiers in molecular neuroscience, 2016-07-08
Topic: Risk, prevention and care in population studies
We propose that brain energy deficit is an important pre-symptomatic feature of Alzheimer's disease (AD) that requires closer attention in the development of AD therapeutics. Our rationale is fourfold: (i) Glucose uptake is lower in the frontal cortex of people >65 years-old despite cognitive scores that are normal for age. (ii) The regional deficit in brain glucose uptake is present in adults <40 years-old who have genetic or lifestyle risk factors for AD but in whom cognitive decline has not yet started. Examples include young adult carriers of presenilin-1 or apolipoprotein E4, and young adults with mild insulin resistance or with a maternal family history of AD. (iii) Regional brain glucose uptake is impaired in AD and mild cognitive impairment (MCI), but brain uptake of ketones (beta-hydroxybutyrate and acetoacetate), remains the same in AD and MCI as in cognitively healthy age-matched controls. These observations point to a brain fuel deficit which appears to be specific to glucose, precedes cognitive decline associated with AD, and becomes more severe as MCI progresses toward AD. Since glucose is the brain's main fuel, we suggest that gradual brain glucose exhaustion is contributing significantly to the onset or progression of AD. (iv) Interventions that raise ketone availability to the brain improve cognitive outcomes in both MCI and AD as well as in acute experimental hypoglycemia. Ketones are the brain's main alternative fuel to glucose and brain ketone uptake is still normal in MCI and in early AD, which would help explain why ketogenic interventions improve some cognitive outcomes in MCI and AD. We suggest that the brain energy deficit needs to be overcome in order to successfully develop more effective therapeutics for AD. At present, oral ketogenic supplements are the most promising means of achieving this goal.
Key findings
- These observations point to a brain fuel deficit which appears to be specific to glucose, precedes cognitive decline associated with AD, and becomes more severe as MCI progresses toward AD.
- Since glucose is the brain's main fuel, we suggest that gradual brain glucose exhaustion is contributing significantly to the onset or progression of AD.
- We suggest that the brain energy deficit needs to be overcome in order to successfully develop more effective therapeutics for AD.
Why it matters
This paper proposes that brain energy deficit, specific to glucose, is an important pre-symptomatic feature of Alzheimer's disease, while brain uptake of ketones remains the same in Alzheimer's disease and mild cognitive impairment as in healthy controls. The authors suggest that the brain energy deficit needs to be overcome in order to successfully develop more effective therapeutics for Alzheimer's disease.
Study details
- Evidence strengthLow
How this study scored 43/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Frontiers in molecular neuroscience) |
| Journal's citation record | 1 / 4 | Frontiers in Molecular Neuroscience: journal h-index 143 (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 | 2016 — 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 | 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 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 219 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 18.2 citations a year over 12 year(s) since 2016 |
| 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 | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 3 / 4 | Cited 59 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Christian‐Alexandre Castellano: h-index 29 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Université de Sherbrooke: institution h-index 498 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 27458340) |
| Free to read | 2 / 2 | Free to read |
| Total | 43 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.3389/fnmol.2016.00053
- PubMed: 27458340
- Original source →
- Free full text: Frontiers in Molecular Neuroscience →
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
Cunnane, S. C., Courchesne-Loyer, A., Vandenberghe, C., St-Pierre, V., Fortier, M., Hennebelle, M., et al. (2016). Can Ketones Help Rescue Brain Fuel Supply in Later Life? Implications for Cognitive Health during Aging and the Treatment of Alzheimer's Disease. Frontiers in molecular neuroscience. https://doi.org/10.3389/fnmol.2016.00053
Vancouver
Cunnane SC, Courchesne-Loyer A, Vandenberghe C, St-Pierre V, Fortier M, Hennebelle M, et al. Can Ketones Help Rescue Brain Fuel Supply in Later Life? Implications for Cognitive Health during Aging and the Treatment of Alzheimer's Disease. Frontiers in molecular neuroscience. 2016. doi:10.3389/fnmol.2016.00053. PMID: 27458340.
BibTeX
@article{cunnane2016-27458340,
author = {Cunnane, S. C. and Courchesne-Loyer, A. and Vandenberghe, C. and St-Pierre, V. and Fortier, M. and Hennebelle, M. and Croteau, E. and Bocti, C. and others},
title = {{Can Ketones Help Rescue Brain Fuel Supply in Later Life? Implications for Cognitive Health during Aging and the Treatment of Alzheimer's Disease}},
journal = {Frontiers in molecular neuroscience},
year = {2016},
doi = {10.3389/fnmol.2016.00053},
pmid = {27458340},
url = {https://doi.org/10.3389/fnmol.2016.00053}
}
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