Neuropathologic basis of age-associated brain atrophy
Erten-Lyons D, Dodge HH, Woltjer R, Silbert LC, Howieson DB, Kramer P, Kaye JA.. JAMA neurology, 2013-05-01
Topic: Amyloid, tau and blood-test diagnosis
Importance While brain volume changes are used as surrogate markers for Alzheimer disease neuropathology in clinical studies, the extent to which these changes are due to pathologic features of Alzheimer disease in the aging brain is not well established. This study aims to clarify the neuropathologic correlates of longitudinal brain atrophy. Objective To examine the association between brain atrophy during life and neuropathology in an elderly population. Design Autopsy study of a cohort of elderly individuals. Setting Community-based population. Participants Seventy-one healthy elderly individuals were selected from participants of the Oregon Brain Aging Study for having an autopsy, more than 1 magnetic resonance imaging scan, and the last magnetic resonance imaging scan within 36 months of death. Main outcomes and measures The associations between brain volume trajectories (ventricular, total brain, and hippocampal) and time interaction terms for neurofibrillary tangles, neuritic plaques, gross infarcts, microinfarcts, amyloid angiopathy, Lewy bodies, APOE ε4 presence, and clinical diagnosis (no cognitive impairment, mild cognitive impairment, or dementia as time-varying covariates) were examined in mixed-effects models, adjusting for duration of follow-up and age at death. Results Ventricular volume trajectory was significantly associated with age, presence of infarcts, neurofibrillary tangle and neuritic plaque scores, APOE ε4 allele presence, and dementia diagnosis. Total brain volume trajectory was significantly associated with age and mild cognitive impairment diagnosis. Hippocampal volume trajectory was significantly associated with amyloid angiopathy. Conclusions and relevance Ventricular volume trajectory is more sensitive than total brain and hippocampal volume trajectories as a marker of accruing Alzheimer disease and vascular pathology in elderly individuals. The association between brain volume trajectories and cognitive impairment (mild cognitive impairment and dementia) remained after controlling for the degree of neuropathology and other covariates. This suggests that there may be other factors not measured in this study that could be contributing to brain atrophy in those with cognitive impairment.
Key findings
- Results Ventricular volume trajectory was significantly associated with age, presence of infarcts, neurofibrillary tangle and neuritic plaque scores, APOE ε4 allele presence, and dementia diagnosis.
- Total brain volume trajectory was significantly associated with age and mild cognitive impairment diagnosis.
- Hippocampal volume trajectory was significantly associated with amyloid angiopathy.
- This suggests that there may be other factors not measured in this study that could be contributing to brain atrophy in those with cognitive impairment.
Why it matters
This autopsy study found that brain shrinkage over time was linked to several factors including infarcts, tangles, plaques, APOE ε4, and dementia diagnosis. The authors note there may be other factors not measured in this study contributing to brain atrophy.
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Study details
- Study designlongitudinal study
- Evidence strengthModerate
How this study scored 54/100
Published in a leading specialty journal, and it is a longitudinal study following the same people over time. Scored zero for sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (JAMA neurology) |
| Journal's citation record | 2 / 4 | JAMA Neurology: journal h-index 235 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A longitudinal study following the same people over time |
| 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 | 2013 — 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 120 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 8.0 citations a year over 15 year(s) since 2013 |
| Impact for its field and year | 3 / 6 | Cited 6.8× 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 21 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Jeffrey Alan Kaye: h-index 122 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Oregon Health & Science University: institution h-index 1,025 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 23552688) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 54 / 100 | — |
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Read the original
- DOI: 10.1001/jamaneurol.2013.1957
- PubMed: 23552688
- 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. The record names 7 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
Erten-Lyons, D., Dodge, H. H., Woltjer, R., Silbert, L. C., Howieson, D. B., Kramer, P., et al. (2013). Neuropathologic basis of age-associated brain atrophy. JAMA neurology. https://doi.org/10.1001/jamaneurol.2013.1957
Vancouver
Erten-Lyons D, Dodge HH, Woltjer R, Silbert LC, Howieson DB, Kramer P, et al. Neuropathologic basis of age-associated brain atrophy. JAMA neurology. 2013. doi:10.1001/jamaneurol.2013.1957. PMID: 23552688.
BibTeX
@article{ertenlyons2013-23552688,
author = {Erten-Lyons, D. and Dodge, H. H. and Woltjer, R. and Silbert, L. C. and Howieson, D. B. and Kramer, P. and Kaye, J. A.},
title = {{Neuropathologic basis of age-associated brain atrophy}},
journal = {JAMA neurology},
year = {2013},
doi = {10.1001/jamaneurol.2013.1957},
pmid = {23552688},
url = {https://doi.org/10.1001/jamaneurol.2013.1957}
}
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