Parkinson’s Disease May Have Link to Stroke
Parkinson risk in idiopathic REM sleep behavior disorder
Preparing for neuroprotective trials
Ronald B. Postuma, MD, Jean-Francois Gagnon, PhD, Josie-Anne Bertrand, PhD, Daphné Génier Marchand, BSc, and Jacques Y. Montplaisir, MD
This article has been cited by other articles in PMC.
Abstract
Objective:
To
precisely delineate clinical risk factors for conversion from
idiopathic REM sleep behavior disorder (RBD) to Parkinson disease,
dementia with Lewy bodies, and multiple system atrophy, in order to
enable practical planning and stratification of neuroprotective trials
against neurodegenerative synucleinopathy.
Methods:
In
a 10-year prospective cohort, we tested prodromal Parkinson disease
markers in 89 patients with idiopathic RBD. With Kaplan-Meier analysis,
we calculated risk of neurodegenerative synucleinopathy, and using Cox
proportional hazards, tested the ability of prodromal markers to
identify patients at higher disease risk. By combining predictive
markers, we then designed stratification strategies to optimally select
patients for definitive neuroprotective trials.
Results:
The
risk of defined neurodegenerative synucleinopathy was high: 30%
developed disease at 3 years, rising to 66% at 7.5 years. Advanced age
(hazard ratio [HR] = 1.07), olfactory loss (HR = 2.8), abnormal color
vision (HR = 3.1), subtle motor dysfunction (HR = 3.9), and nonuse of
antidepressants (HR = 3.5) identified higher risk of disease conversion.
However, mild cognitive impairment (HR = 1.8), depression (HR = 0.63),
Parkinson personality, treatment with clonazepam (HR = 1.3) or melatonin
(HR = 0.55), autonomic markers, and sex (HR = 1.37) did not clearly
predict clinical neurodegeneration. Stratification with prodromal
markers increased risk of neurodegenerative disease conversion by 200%,
and combining markers allowed sample size reduction in neuroprotective
trials by >40%. With a moderately effective agent (HR = 0.5), trials
with fewer than 80 subjects per group can demonstrate definitive
reductions in neurodegenerative disease.
Conclusions:
Using
stratification with simply assessed markers, it is now not only
possible, but practical to include patients with RBD in neuroprotective
trials against Parkinson disease, multiple system atrophy, and dementia
with Lewy bodies.
No comments:
Post a Comment