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Left frontal cortex connectivity underlies cognitive reserve in prodromal Alzheimer disease
Franzmeier N, Duering M, Weiner M, Dichgans M, Ewers M, Alzheimer's Disease Neuroimaging Initiative (ADNI).. Neurology, 2017-02-10
Topic: Amyloid, tau and blood-test diagnosis
Objective To test whether higher global functional connectivity of the left frontal cortex (LFC) in Alzheimer disease (AD) is associated with more years of education (a proxy of cognitive reserve [CR]) and mitigates the association between AD-related fluorodeoxyglucose (FDG)-PET hypometabolism and episodic memory. Methods Forty-four amyloid-PET-positive patients with amnestic mild cognitive impairment (MCI-Aβ+) and 24 amyloid-PET-negative healthy controls (HC) were included. Voxel-based linear regression analyses were used to test the association between years of education and FDG-PET in MCI-Aβ+, controlled for episodic memory performance. Global LFC (gLFC) connectivity was computed through seed-based resting-state fMRI correlations between the LFC (seed) and each voxel in the gray matter. In linear regression analyses, education as a predictor of gLFC connectivity and the interaction of gLFC connectivity × FDG-PET hypometabolism on episodic memory were tested. Results FDG-PET metabolism in the precuneus was reduced in MCI-Aβ+ compared to HC ( p = 0.028), with stronger reductions observed in MCI-Aβ+ with more years of education ( p = 0.006). In MCI-Aβ+, higher gLFC connectivity was associated with more years of education ( p = 0.021). At higher levels of gLFC connectivity, the association between precuneus FDG-PET hypometabolism and lower memory performance was attenuated ( p = 0.027). Conclusions Higher gLFC connectivity is a functional substrate of CR that helps to maintain episodic memory relatively well in the face of emerging FDG-PET hypometabolism in early-stage AD.
Key findings
- Objective To test whether higher global functional connectivity of the left frontal cortex (LFC) in Alzheimer disease (AD) is associated with more years of education (a proxy of cognitive reserve [CR]) and mitigates the association between AD-related fluorodeoxyglucose (FDG)-PET hypometabolism and episodic memory.
- Results FDG-PET metabolism in the precuneus was reduced in MCI-Aβ+ compared to HC ( p = 0.028), with stronger reductions observed in MCI-Aβ+ with more years of education ( p = 0.006).
- In MCI-Aβ+, higher gLFC connectivity was associated with more years of education ( p = 0.021).
Why it matters
In 44 patients with amnestic mild cognitive impairment who were amyloid-PET positive, higher global left frontal cortex connectivity was associated with more years of education and weakened the link between precuneus hypometabolism and lower memory performance. This concerns cognitive reserve, not treating, curing or preventing Alzheimer disease.
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Study details
- Evidence strengthLow
How this study scored 50/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, 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 48 of the 96 points we could judge it on, which is 50 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (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 | 2 / 5 | 2017 — within 10 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 147 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 13.4 citations a year over 11 year(s) since 2017 |
| Impact for its field and year | 4 / 6 | Cited 11.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 5 other studies in this library |
| Still being cited | 2 / 4 | Cited 39 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 of California, San Francisco: institution h-index 1,915 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 28188306) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 48 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 48 of the 96 points we could judge it on is 50 out of 100. |
| Total | 50 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1212/wnl.0000000000003711
- PubMed: 28188306
- Original source →
- Free full text: PubMed Central →
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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. Check the citation against the original before you use it.
APA 7th
Franzmeier, N., Duering, M., Weiner, M., Dichgans, M., & Ewers, M. (2017). Left frontal cortex connectivity underlies cognitive reserve in prodromal Alzheimer disease. Neurology. https://doi.org/10.1212/wnl.0000000000003711
Vancouver
Franzmeier N, Duering M, Weiner M, Dichgans M, Ewers M. Left frontal cortex connectivity underlies cognitive reserve in prodromal Alzheimer disease. Neurology. 2017. doi:10.1212/wnl.0000000000003711. PMID: 28188306.
BibTeX
@article{franzmeier2017-28188306,
author = {Franzmeier, N. and Duering, M. and Weiner, M. and Dichgans, M. and Ewers, M.},
title = {{Left frontal cortex connectivity underlies cognitive reserve in prodromal Alzheimer disease}},
journal = {Neurology},
year = {2017},
doi = {10.1212/wnl.0000000000003711},
pmid = {28188306},
url = {https://doi.org/10.1212/wnl.0000000000003711}
}
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