Topic: Amyloid, tau and blood-test diagnosis
Background Hippocampal sclerosis (HpScl) in the elderly is often associated with neurodegeneration. Methods We studied the clinical and pathologic features of HpScl in 205 consecutive patients with dementia who came to autopsy from 1997 to 2008, focusing on associations with TAR DNA-binding protein 43 (TDP-43) pathology and allelic variants in the progranulin (GRN) and apolipoprotein E (APOE). Results Of the 205 dementia patients, 28 had HpScl (14%). TDP-43 pathology was more frequent in cases with HpScl compared with those without HpScl (89% vs. 24%). GRN rs5848 T-allele but not APOE ε4 was associated with HpScl. In cases of HpScl with TDP-43 pathology and age of onset after 75 years (n=11), 8 had Alzheimer disease (AD)-like amnestic syndrome, but most (6 of 8) had pathology not consistent with AD (Braak stage III or less), including 4 with frontotemporal lobar degeneration with TDP, 1 with diffuse Lewy body disease, and 1 with "pure HpScl." Conclusions HpScl is common in an elderly cohort with dementia, occurring in 14% of the cases in this series, and 89% have TDP-43 pathology, often associated with a risk variant in GRN. Patients with HpScl who present after the age of 75 years often have presentations consistent with AD, but at autopsy have non-Alzheimer pathologies. Elderly patients with HpScl may be mistaken for AD.
Key findings
- Background Hippocampal sclerosis (HpScl) in the elderly is often associated with neurodegeneration.
- Results Of the 205 dementia patients, 28 had HpScl (14%).
- TDP-43 pathology was more frequent in cases with HpScl compared with those without HpScl (89% vs. 24%).
- GRN rs5848 T-allele but not APOE ε4 was associated with HpScl.
- In cases of HpScl with TDP-43 pathology and age of onset after 75 years (n=11), 8 had Alzheimer disease (AD)-like amnestic syndrome, but most (6 of 8) had pathology not consistent with AD (Braak stage III or less), including 4 with frontotemporal lobar degeneration with TDP, 1 with diffuse Lewy body disease, and 1 with "pure HpScl."
Why it matters
Among 205 dementia patients at autopsy, 14% had hippocampal sclerosis, usually with TDP-43 pathology, and some of these had been mistaken for Alzheimer disease clinically. This is an autopsy study that highlights diagnostic overlap and does not test treatment.
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Study details
- Evidence strengthModerate
How this study scored 45/100
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 | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2011 — 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 | 4 / 7 | Cited 99 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.8 citations a year over 17 year(s) since 2011 |
| Impact for its field and year | 3 / 6 | Cited 6.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 12 other studies in this library |
| Still being cited | 2 / 4 | Cited 18 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Neill R. Graff‐Radford: h-index 131 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Mayo Clinic: institution h-index 1,606 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 21346515) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 45 / 100 | — |
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Read the original
- DOI: 10.1097/wad.0b013e31820f8f50
- PubMed: 21346515
- 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
Pao, W. C., Dickson, D. W., Crook, J. E., Finch, N. A., Rademakers, R., & Graff-Radford, N. R. (2011). Hippocampal sclerosis in the elderly: genetic and pathologic findings, some mimicking Alzheimer disease clinically. Alzheimer disease and associated disorders. https://doi.org/10.1097/wad.0b013e31820f8f50
Vancouver
Pao WC, Dickson DW, Crook JE, Finch NA, Rademakers R, Graff-Radford NR. Hippocampal sclerosis in the elderly: genetic and pathologic findings, some mimicking Alzheimer disease clinically. Alzheimer disease and associated disorders. 2011. doi:10.1097/wad.0b013e31820f8f50. PMID: 21346515.
BibTeX
@article{pao2011-21346515,
author = {Pao, W. C. and Dickson, D. W. and Crook, J. E. and Finch, N. A. and Rademakers, R. and Graff-Radford, N. R.},
title = {{Hippocampal sclerosis in the elderly: genetic and pathologic findings, some mimicking Alzheimer disease clinically}},
journal = {Alzheimer disease and associated disorders},
year = {2011},
doi = {10.1097/wad.0b013e31820f8f50},
pmid = {21346515},
url = {https://doi.org/10.1097/wad.0b013e31820f8f50}
}
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