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A clinico-pathological study of subtypes in Parkinson's disease
Selikhova M, Williams DR, Kempster PA, Holton JL, Revesz T, Lees AJ.. Brain : a journal of neurology, 2009-09-16
Topic: Risk, prevention and care in population studies
We have carried out a systematic review of the case files of 242 donors with pathologically verified Parkinson's disease at the Queen Square Brain Bank for Neurological Disorders in an attempt to corroborate the data-driven subtype classification proposed by Lewis and colleagues (Heterogeneity of Parkinson's disease in the early clinical stages using a data driven approach. J Neurol Neurosurg Psychiatry 2005; 76: 343-8). Cases were segregated into earlier disease onset (25%), tremor dominant (31%), non-tremor dominant (36%) and rapid disease progression without dementia (8%) subgroups. We found a strong association between a non-tremor dominant disease pattern and cognitive disability. The earlier disease onset group had the longest duration to death, and greatest delay to the onset of falls and cognitive decline. Patients with a tremor dominant disease pattern did not live significantly longer than non-tremor dominant patients and showed no difference in mean time to onset of falls and hallucinations. Rapid disease progression was associated with older age, early depression and early midline motor symptoms, and in 70% of the cases, tremulous onset. The non-tremor dominant subgroup had a significantly higher mean pathological grading of cortical Lewy bodies than all other groupings (P < 0.05) and more cortical amyloid-beta plaque load and cerebral amyloid angiopathy than early disease onset and tremor dominant groups (P = 0.047). An analysis of cases with pathologically defined neocortical Lewy body disease confirmed the link between bradykinetic onset, cognitive decline and Lewy body deposition in the neocortex. Although neuropathological examination failed to distinguish the other subtypes, the classification scheme was supported by an analysis of clinical data that were independent of the basic subgroup definitions.
Key findings
- We found a strong association between a non-tremor dominant disease pattern and cognitive disability.
- Patients with a tremor dominant disease pattern did not live significantly longer than non-tremor dominant patients and showed no difference in mean time to onset of falls and hallucinations.
- Rapid disease progression was associated with older age, early depression and early midline motor symptoms, and in 70% of the cases, tremulous onset.
- The non-tremor dominant subgroup had a significantly higher mean pathological grading of cortical Lewy bodies than all other groupings (P < 0.05) and more cortical amyloid-beta plaque load and cerebral amyloid angiopathy than early disease onset and tremor dominant groups (P = 0.047).
Why it matters
This study of Parkinson's disease subtypes found that a non-tremor dominant pattern was strongly associated with cognitive disability and more cortical Lewy bodies and amyloid-beta plaque load. It does not test any treatment or prevention for Alzheimer's disease, so it has no direct implications for treating, curing, or preventing the disease.
Study details
- Study designsystematic review
- Evidence strengthHigh
How this study scored 69/100
Published in a leading specialty journal, and it is a systematic review of all the studies on the question. Scored zero for sample size, effect reported and studied in people because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain : a journal of neurology) |
| Journal's citation record | 4 / 4 | Brain: journal h-index 503 (OpenAlex, 2026-10-29) |
| Study design | 12 / 12 | A systematic review of all the studies on the question |
| Strength of evidence | 5 / 5 | Rated “high” 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 | A review of other studies — randomisation is not credited here |
| Times cited | 6 / 7 | Cited 463 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 24.4 citations a year over 19 year(s) since 2009 |
| Impact for its field and year | 4 / 6 | Cited 16.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 13 other studies in this library |
| Still being cited | 3 / 4 | Cited 51 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author A. J. Lees: h-index 24 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University College London: institution h-index 2,029 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 7 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 19759203) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 69 / 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
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APA 7th
Selikhova, M., Williams, D. R., Kempster, P. A., Holton, J. L., Revesz, T., & Lees, A. J. (2009). A clinico-pathological study of subtypes in Parkinson's disease. Brain : a journal of neurology. https://doi.org/10.1093/brain/awp234
Vancouver
Selikhova M, Williams DR, Kempster PA, Holton JL, Revesz T, Lees AJ. A clinico-pathological study of subtypes in Parkinson's disease. Brain : a journal of neurology. 2009. doi:10.1093/brain/awp234. PMID: 19759203.
BibTeX
@article{selikhova2009-19759203,
author = {Selikhova, M. and Williams, D. R. and Kempster, P. A. and Holton, J. L. and Revesz, T. and Lees, A. J.},
title = {{A clinico-pathological study of subtypes in Parkinson's disease}},
journal = {Brain : a journal of neurology},
year = {2009},
doi = {10.1093/brain/awp234},
pmid = {19759203},
url = {https://doi.org/10.1093/brain/awp234}
}
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