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Epidemiological pathology of dementia: attributable-risks at death in the Medical Research Council Cognitive Function and Ageing Study
Matthews FE, Brayne C, Lowe J, McKeith I, Wharton SB, Ince P.. PLoS medicine, 2009-11-10
Topic: Risk, prevention and care in population studies
Background Dementia drug development aims to modulate pathological processes that cause clinical syndromes. Population data (epidemiological neuropathology) will help to model and predict the potential impact of such therapies on dementia burden in older people. Presently this can only be explored through post mortem findings. We report the attributable risks (ARs) for dementia at death for common age-related degenerative and vascular pathologies, and other factors, in the MRC Cognitive Function and Ageing Study (MRC CFAS). Methods and findings A multicentre, prospective, longitudinal study of older people in the UK was linked to a brain donation programme. Neuropathology of 456 consecutive brain donations assessed degenerative and vascular pathologies. Logistic regression modelling, with bootstrapping and sensitivity analyses, was used to estimate AR at death for dementia for specific pathologies and other factors. The main contributors to AR at death for dementia in MRC CFAS were age (18%), small brain (12%), neocortical neuritic plaques (8%) and neurofibrillary tangles (11%), small vessel disease (12%), multiple vascular pathologies (9%), and hippocampal atrophy (10%). Other significant factors include cerebral amyloid angiopathy (7%) and Lewy bodies (3%). Conclusions Such AR estimates cannot be derived from the living population; rather they estimate the relative contribution of specific pathologies to dementia at death. We found that multiple pathologies determine the overall burden of dementia. The impact of therapy targeted to a specific pathology may be profound when the dementia is relatively "pure," but may be less impressive for the majority with mixed disease, and in terms of the population. These data justify a range of strategies, and combination therapies, to combat the degenerative and vascular determinants of cognitive decline and dementia. Please see later in the article for the Editors' Summary.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Matthews, F. E., Brayne, C., Lowe, J., McKeith, I., Wharton, S. B., & Ince, P. (2009). Epidemiological pathology of dementia: attributable-risks at death in the Medical Research Council Cognitive Function and Ageing Study. PLoS medicine. https://doi.org/10.1371/journal.pmed.1000180
Vancouver
Matthews FE, Brayne C, Lowe J, McKeith I, Wharton SB, Ince P. Epidemiological pathology of dementia: attributable-risks at death in the Medical Research Council Cognitive Function and Ageing Study. PLoS medicine. 2009. doi:10.1371/journal.pmed.1000180. PMID: 19901977.
BibTeX
@article{matthews2009-19901977,
author = {Matthews, F. E. and Brayne, C. and Lowe, J. and McKeith, I. and Wharton, S. B. and Ince, P.},
title = {{Epidemiological pathology of dementia: attributable-risks at death in the Medical Research Council Cognitive Function and Ageing Study}},
journal = {PLoS medicine},
year = {2009},
doi = {10.1371/journal.pmed.1000180},
pmid = {19901977},
url = {https://doi.org/10.1371/journal.pmed.1000180}
}
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Key findings
- Other significant factors include cerebral amyloid angiopathy (7%) and Lewy bodies (3%).
- We found that multiple pathologies determine the overall burden of dementia.
Why it matters
In 456 consecutive brain donations from a UK study of older people, no single pathology dominated dementia at death: the largest estimated shares were age (18%), small brain (12%), small vessel disease (12%), tangles (11%) and hippocampal atrophy (10%), with plaques at 8%. The authors conclude that a treatment aimed at one pathology "may be less impressive for the majority with mixed disease," and argue for combination strategies against both degenerative and vascular damage. These are post-mortem estimates that, in the study's words, "cannot be derived from the living population," and the study tested no treatment.
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Study details
- Study designlongitudinal study
- Evidence strengthModerate
How this study scored 61/100
Published in a peer-reviewed 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 | 7 / 10 | Tier 3 — peer-reviewed journal (PLoS medicine) |
| Journal's citation record | 3 / 4 | PLoS Medicine: journal h-index 350 (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 | 2009 — 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 281 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 14.8 citations a year over 19 year(s) since 2009 |
| Impact for its field and year | 4 / 6 | Cited 10.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 41 other studies in this library |
| Still being cited | 2 / 4 | Cited 17 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Paul G. Ince: h-index 102 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Cambridge: institution h-index 1,973 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 19901977) |
| Free to read | 2 / 2 | Free to read |
| Total | 61 / 100 | — |
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Read the original
- DOI: 10.1371/journal.pmed.1000180
- PubMed: 19901977
- Original source →
- Free full text: PLoS Medicine →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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