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Divergent social functioning in behavioral variant frontotemporal dementia and Alzheimer disease: reciprocal networks and neuronal evolution
Seeley WW, Allman JM, Carlin DA, Crawford RK, Macedo MN, Greicius MD, Dearmond SJ, Miller BL.. Alzheimer disease and associated disorders, 2007-10-01
Topic: Amyloid, tau and blood-test diagnosis
Behavioral variant frontotemporal dementia (bvFTD) disrupts our most human social and emotional functions. Early in the disease, patients show focal anterior cingulate cortex (ACC) and orbital frontoinsula (FI) degeneration, accentuated in the right hemisphere. The ACC and FI, though sometimes considered ancient in phylogeny, feature a large bipolar projection neuron, the von Economo neuron (VEN), which is found only in humans, apes, and selected whales-all large-brained mammals with complex social structures. In contrast to bvFTD, Alzheimer disease (AD) often spares social functioning, and the ACC and FI, until late in its course, damaging instead a posterior hippocampal-cingulo-temporal-parietal network involved in episodic memory retrieval. These divergent patterns of functional and regional impairment remain mysterious despite extensive molecular-level characterization of bvFTD and AD. In this report, we further develop the hypothesis that VENs drive the regional vulnerability pattern seen in bvFTD, citing recent evidence from functional imaging in healthy humans, and also structural imaging and quantitative neuropathology data from bvFTD and AD. Our most recent findings suggest that bvFTD and AD target distinct, anticorrelated intrinsic connectivity networks and that bvFTD-related VEN injury occurs throughout the ACC-FI network. We suggest that the regional and neuronal vulnerability patterns seen in bvFTD and AD underlie the divergent impact of these disorders on recently evolved social-emotional functions.
Key findings
- Our most recent findings suggest that bvFTD and AD target distinct, anticorrelated intrinsic connectivity networks and that bvFTD-related VEN injury occurs throughout the ACC-FI network.
- We suggest that the regional and neuronal vulnerability patterns seen in bvFTD and AD underlie the divergent impact of these disorders on recently evolved social-emotional functions.
Why it matters
This report proposes that behavioral variant frontotemporal dementia and Alzheimer disease affect different brain networks, with frontotemporal dementia damaging social-emotional regions and Alzheimer disease sparing them until late. It is a hypothesis about disease patterns and does not test treatment or prevention.
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Study details
- Evidence strengthLow
How this study scored 44/100
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 (Alzheimer disease and associated disorders) |
| Journal's citation record | 1 / 4 | Alzheimer Disease & Associated Disorders: journal h-index 131 (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 | 2007 — 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 165 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 7.9 citations a year over 21 year(s) since 2007 |
| Impact for its field and year | 3 / 6 | Cited 4.7× 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 | 1 / 4 | Cited 11 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Bruce L. Miller: h-index 198 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Stanford University: institution h-index 2,684 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 18090425) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 44 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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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 names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Seeley, W. W., Allman, J. M., Carlin, D. A., Crawford, R. K., Macedo, M. N., Greicius, M. D., et al. (2007). Divergent social functioning in behavioral variant frontotemporal dementia and Alzheimer disease: reciprocal networks and neuronal evolution. Alzheimer disease and associated disorders. https://doi.org/10.1097/wad.0b013e31815c0f14
Vancouver
Seeley WW, Allman JM, Carlin DA, Crawford RK, Macedo MN, Greicius MD, et al. Divergent social functioning in behavioral variant frontotemporal dementia and Alzheimer disease: reciprocal networks and neuronal evolution. Alzheimer disease and associated disorders. 2007. doi:10.1097/wad.0b013e31815c0f14. PMID: 18090425.
BibTeX
@article{seeley2007-18090425,
author = {Seeley, W. W. and Allman, J. M. and Carlin, D. A. and Crawford, R. K. and Macedo, M. N. and Greicius, M. D. and Dearmond, S. J. and Miller, B. L.},
title = {{Divergent social functioning in behavioral variant frontotemporal dementia and Alzheimer disease: reciprocal networks and neuronal evolution}},
journal = {Alzheimer disease and associated disorders},
year = {2007},
doi = {10.1097/wad.0b013e31815c0f14},
pmid = {18090425},
url = {https://doi.org/10.1097/wad.0b013e31815c0f14}
}
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