Home › Research › Disparities
Combined neuropathological pathways account for age-related risk of dementia
Power MC, Mormino E, Soldan A, James BD, Yu L, Armstrong NM, Bangen KJ, Delano-Wood L et al.. Annals of neurology, 2018-06-26
Topic: Risk, prevention and care in population studies
Objective Our objectives were to characterize the inter-relation of known dementia-related neuropathologies in one comprehensive model and quantify the extent to which accumulation of neuropathologies accounts for the association between age and dementia. Methods We used data from 1,362 autopsied participants of three community-based clinicopathological cohorts: the Religious Orders Study, the Rush Memory and Aging Project, and the Minority Aging Research Study. We estimated a series of structural equation models summarizing a priori hypothesized neuropathological pathways between age and dementia risk individually and collectively. Results At time of death (mean age, 89 years), 44% of our sample had a clinical dementia diagnosis. When considered individually, our vascular, amyloid/tau, neocortical Lewy body, and TAR DNA-binding protein 43 (TDP-43)/hippocampal sclerosis pathology pathways each accounted for a substantial proportion of the association between age and dementia. When considered collectively, the four pathways fully accounted for all variance in dementia risk previously attributable to age. Pathways involving amyloid/tau, neocortical Lewy bodies, and TDP-43/hippocampal sclerosis were interdependent, attributable to the importance of amyloid beta plaques in all three. The importance of the pathways varied, with the vascular pathway accounting for 32% of the association between age and dementia, wheraes the remaining three inter-related degenerative pathways together accounted for 68% (amyloid/tau, 24%; the Lewy body, 1%; and TDP-43/hippocampal sclerosis, 43%). Interpretation Age-related increases in dementia risk can be attributed to accumulation of multiple pathologies, each of which contributes to dementia risk. Multipronged approaches may be necessary if we are to develop effective therapies. Ann Neurol 2018;84:10-22.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Power, M. C., Mormino, E., Soldan, A., James, B. D., Yu, L., Armstrong, N. M., et al. (2018). Combined neuropathological pathways account for age-related risk of dementia. Annals of neurology. https://doi.org/10.1002/ana.25246
Vancouver
Power MC, Mormino E, Soldan A, James BD, Yu L, Armstrong NM, et al. Combined neuropathological pathways account for age-related risk of dementia. Annals of neurology. 2018. doi:10.1002/ana.25246. PMID: 29944741.
BibTeX
@article{power2018-29944741,
author = {Power, M. C. and Mormino, E. and Soldan, A. and James, B. D. and Yu, L. and Armstrong, N. M. and Bangen, K. J. and Delano-Wood, L. and others},
title = {{Combined neuropathological pathways account for age-related risk of dementia}},
journal = {Annals of neurology},
year = {2018},
doi = {10.1002/ana.25246},
pmid = {29944741},
url = {https://doi.org/10.1002/ana.25246}
}
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's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
Key findings
- Results At time of death (mean age, 89 years), 44% of our sample had a clinical dementia diagnosis.
Why it matters
In 1,362 autopsied participants from three community cohorts (mean age at death 89), four brain-pathology pathways together fully accounted for the statistical link between older age and dementia: TDP-43/hippocampal sclerosis 43%, vascular 32%, amyloid/tau 24% and neocortical Lewy body 1%. The authors conclude that rising dementia risk with age reflects several pathologies building up at once, and that "multipronged approaches may be necessary" for effective therapies. This is an observational autopsy analysis, so it shows association, not cause.
New to this subject? Start with our plain-English guide: Disparities →
Study details
- Evidence strengthLow
How this study scored 56/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Annals of neurology) |
| Journal's citation record | 3 / 4 | Annals of Neurology: journal h-index 437 (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 | 2018 — 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) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 220 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 22.0 citations a year over 10 year(s) since 2018 |
| Impact for its field and year | 4 / 6 | Cited 16.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 23 other studies in this library |
| Still being cited | 3 / 4 | Cited 70 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Julie A. Schneider: h-index 151 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multicenter collaboration | 3 / 3 | OpenAlex lists 14 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 29944741) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 56 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Related
Studies in the library that share something with this one. The line above each title says what.
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 22.
Later studies that cite this one
23 studies in the alzhub library list this one in their references. Showing the 8 highest-scoring.
Related studies in Disparities
Also tagged “incidence”
1,084 studies in the library carry the topic tag “incidence”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 1,084 tagged studies.