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Brain connectivity in neurodegenerative diseases--from phenotype to proteinopathy
Pievani M, Filippini N, van den Heuvel MP, Cappa SF, Frisoni GB, Frisoni GB.. Nature reviews. Neurology, 2014-10-07
Topic: Brain proteins, microglia and lab models
Functional and structural connectivity measures, as assessed by means of functional and diffusion MRI, are emerging as potential intermediate biomarkers for Alzheimer disease (AD) and other disorders. This Review aims to summarize current evidence that connectivity biomarkers are associated with upstream and downstream disease processes (molecular pathology and clinical symptoms, respectively) in the major neurodegenerative diseases. The vast majority of studies have addressed functional and structural connectivity correlates of clinical phenotypes, confirming the predictable correlation with topography and disease severity in AD and frontotemporal dementia. In neurodegenerative diseases with motor symptoms, structural--but, to date, not functional--connectivity has been consistently found to be associated with clinical phenotype and disease severity. In the latest studies, the focus has moved towards the investigation of connectivity correlates of molecular pathology. Studies in cognitively healthy individuals with brain amyloidosis or genetic risk factors for AD have shown functional connectivity abnormalities in preclinical disease stages that are reminiscent of abnormalities observed in symptomatic AD. This shift in approach is promising, and may aid identification of early disease markers, establish a paradigm for other neurodegenerative disorders, shed light on the molecular neurobiology of connectivity disruption and, ultimately, clarify the pathophysiology of neurodegenerative diseases.
Key findings
- This Review aims to summarize current evidence that connectivity biomarkers are associated with upstream and downstream disease processes (molecular pathology and clinical symptoms, respectively) in the major neurodegenerative diseases.
- In neurodegenerative diseases with motor symptoms, structural--but, to date, not functional--connectivity has been consistently found to be associated with clinical phenotype and disease severity.
Why it matters
This 2014 review gathers MRI studies of how brain regions connect, functionally and structurally, across Alzheimer's, frontotemporal dementia and movement-related neurodegenerative diseases. It reports that these measures track symptom location and severity in Alzheimer's and frontotemporal dementia, and that cognitively healthy people with brain amyloid or genetic risk for Alzheimer's show functional connectivity changes "reminiscent of" those in symptomatic disease. The authors present connectivity as a "potential" early marker, not a proven test, and note that in movement-related diseases only structural connectivity, not functional, had consistently matched symptoms.
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Study details
- Evidence strengthLow
How this study scored 49/100
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 (Nature reviews. Neurology) |
| Journal's citation record | 3 / 4 | Nature Reviews Neurology: journal h-index 269 (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 | 2014 — 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 | 6 / 7 | Cited 312 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 22.3 citations a year over 14 year(s) since 2014 |
| Impact for its field and year | 2 / 6 | Cited 1.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 7 other studies in this library |
| Still being cited | 3 / 4 | Cited 64 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Giovanni Battista Frisoni: h-index 120 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Oxford: institution h-index 2,205 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 7 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 25287597) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 49 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1038/nrneurol.2014.178
- PubMed: 25287597
- Original source →
- Free full text: Archive ouverte UNIGE (University of Geneva) →
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. Check the citation against the original before you use it.
APA 7th
Pievani, M., Filippini, N., van den Heuvel, M. P., Cappa, S. F., & Frisoni, G. B. (2014). Brain connectivity in neurodegenerative diseases--from phenotype to proteinopathy. Nature reviews. Neurology. https://doi.org/10.1038/nrneurol.2014.178
Vancouver
Pievani M, Filippini N, van den Heuvel MP, Cappa SF, Frisoni GB. Brain connectivity in neurodegenerative diseases--from phenotype to proteinopathy. Nature reviews. Neurology. 2014. doi:10.1038/nrneurol.2014.178. PMID: 25287597.
BibTeX
@article{pievani2014-25287597,
author = {Pievani, M. and Filippini, N. and van den Heuvel, M. P. and Cappa, S. F. and Frisoni, G. B.},
title = {{Brain connectivity in neurodegenerative diseases--from phenotype to proteinopathy}},
journal = {Nature reviews. Neurology},
year = {2014},
doi = {10.1038/nrneurol.2014.178},
pmid = {25287597},
url = {https://doi.org/10.1038/nrneurol.2014.178}
}
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