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Natural history of pure autonomic failure: A United States prospective cohort
Kaufmann H, Norcliffe-Kaufmann L, Palma JA, Biaggioni I, Low PA, Singer W, Goldstein DS, Peltier AC et al.. Annals of neurology, 2017-02-01
Topic: Risk, prevention and care in population studies
Objective To define the clinical features and biomarkers that predict which patients with pure autonomic failure will develop Parkinson disease, dementia with Lewy bodies, or multiple system atrophy. Methods One hundred patients who presented with pure autonomic failure were recruited at 5 medical centers in the United States. Seventy-four patients agreed to be followed prospectively. Patients underwent clinical evaluations including neurological rating scales, sleep questionnaires, smell test, and sympathetic and parasympathetic cardiovascular autonomic function tests. Results At enrollment, patients were 68 ± 12 years old (median ± interquartile range) and had had autonomic failure for 5 ± 7 years. Within 4 years of follow-up, 25 of 74 subjects (34%) developed dementia with Lewy bodies (n = 13), Parkinson disease (n = 6), or multiple system atrophy (n = 6). The presence of probable rapid eye movement (REM) sleep behavior disorder was strongly associated with the development of a manifest central nervous system (CNS) synucleinopathy (odds ratio = 7.1). Patients who phenoconverted to multiple system atrophy had younger age at onset of autonomic failure, severe bladder/bowel dysfunction, preserved olfaction, and a cardiac chronotropic response upon tilt > 10 beats per minute. Those who phenoconverted to Parkinson disease or dementia with Lewy bodies had decreased olfaction, a lesser chronotropic response to tilt, and a longer duration of illness. The small group of patients retaining the pure autonomic failure phenotype had very low plasma norepinephrine levels, slow resting heart rate, no REM sleep behavior disorder, and preserved smell. Interpretation Patients presenting with pure autonomic failure are at high risk of phenoconverting to a manifest CNS synucleinopathy. Specific clinical features predict future diagnosis. Ann Neurol 2017;81:287-297.
Key findings
- Results At enrollment, patients were 68 ± 12 years old (median ± interquartile range) and had had autonomic failure for 5 ± 7 years.
- The presence of probable rapid eye movement (REM) sleep behavior disorder was strongly associated with the development of a manifest central nervous system (CNS) synucleinopathy (odds ratio = 7.1).
Why it matters
This prospective cohort study found that within 4 years of follow-up, 34% of patients with pure autonomic failure developed dementia with Lewy bodies, Parkinson disease, or multiple system atrophy. The presence of probable REM sleep behavior disorder was strongly associated with the development of a manifest central nervous system synucleinopathy.
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Study details
- Participants13
- Evidence strengthLow
How this study scored 56/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / 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 | 2017 — within 10 year(s) of the newest study here |
| Sample size | 1 / 4 | 13 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 299 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 27.2 citations a year over 11 year(s) since 2017 |
| Impact for its field and year | 4 / 6 | Cited 19.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 7 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 | 2 / 4 | Last-listed author David L. Robertson: h-index 29 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 8 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 28093795) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 56 / 100 | — |
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Read the original
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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.
APA 7th
Kaufmann, H., Norcliffe-Kaufmann, L., Palma, J. A., Biaggioni, I., Low, P. A., Singer, W., et al. (2017). Natural history of pure autonomic failure: A United States prospective cohort. Annals of neurology. https://doi.org/10.1002/ana.24877
Vancouver
Kaufmann H, Norcliffe-Kaufmann L, Palma JA, Biaggioni I, Low PA, Singer W, et al. Natural history of pure autonomic failure: A United States prospective cohort. Annals of neurology. 2017. doi:10.1002/ana.24877. PMID: 28093795.
BibTeX
@article{kaufmann2017-28093795,
author = {Kaufmann, H. and Norcliffe-Kaufmann, L. and Palma, J. A. and Biaggioni, I. and Low, P. A. and Singer, W. and Goldstein, D. S. and Peltier, A. C. and others},
title = {{Natural history of pure autonomic failure: A United States prospective cohort}},
journal = {Annals of neurology},
year = {2017},
doi = {10.1002/ana.24877},
pmid = {28093795},
url = {https://doi.org/10.1002/ana.24877}
}
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