It has been commonly noted that RBD often precedes the development of parkinsonism and dementia.2,8
Obtaining an accurate picture of the risk of developing a neurodegenerative disorder is essential for accurate counseling of patients and for planning of any potential neuroprotective trials. However, definition of the risk of developing a neurodegenerative condition has been published only in two relatively small-scale studies.5,9
The initial report of RBD as a predictor of neurodegenerative disease found that 38% of 29 male patients had developed a parkinsonian disorder 5 years after the diagnosis of idiopathic RBD. More recently, a study of 44 patients with an initial diagnosis of idiopathic REM sleep behavior disorder found that after a median of 5 years of follow-up, 20 of 44 patients (45%) went on to develop a neurodegenerative condition; the commonest diagnoses were PD,9
and mild cognitive impairment.4
Two case series, reported in abstract form only, have suggested that at a mean follow-up of 10 years, 65% of patients had developed neurodegenerative disease.22,23
No published studies have described 10- and 12-year follow-up of idiopathic RBD.
We have demonstrated a risk of disease that is somewhat lower than found in the two previous case series. Some of this variation may be due to differences in disease definition—mild cognitive impairment was not considered a disease outcome in our study, and we used a systematic strict definition of parkinsonism which excluded those with mild parkinsonian signs or a single cardinal manifestation of parkinsonism. It is also possible that disease risk can be changing with time, perhaps related to earlier diagnosis and recognition of milder cases. In support of this notion, the interval between RBD symptom onset and diagnosis in those patients diagnosed between 1989 and 1996 was 10.3 ± 9.2 years (n = 18) compared to an interval of 5.7 ± 5.0 years in those diagnosed from 2004 to 2006 (n = 22, p = 0.052). Therefore symptom to diagnosis latency seems to be changing in time, which no doubt reflects increased awareness and recognition of the disorder. Finally, differences in analytic method between studies can result in important differences in estimation of disease risk. Whereas our method of analysis was a life table analysis, the two previous case series estimating risk of disease in RBD described the proportion developing disease, with mean follow-up duration. If we analyze our results in the same way, we find a similar, although slightly lower proportion developing neurodegenerative disease (i.e., 27.9% over a mean of 5.2 years follow-up [to last clinical visit]). An important advantage of the life table method is that it utilizes censored data—that is, patients, who are censored because of death, loss to follow-up, or recent diagnoses, can contribute in a systematic manner to estimation of risk at later time points. Because of this method and the size of the cohort, we were able to estimate disease risk at 10- and 12-year time points.
Some limitations of this study should be noted. Because persons who agree to participate in prospective annual protocols may have important differences in disease risk between those who refuse or who are unable to participate, we felt that it was essential to include all patients for whom follow-up information was available. This warranted the inclusion of 15 (of 93) patients for whom at least some information was collected from clinical records or telephone follow-up. This information is probably less reliable than that gleaned from a systematic research-based in-person examination—in particular, subtle parkinsonism is often missed by patients, and can be picked up only on examination. However, the large majority of patients had a thorough standardized examination by a movement disorders specialist, and a second analysis that included only these individuals did not find differences in disease risk. All diagnoses were clinical, without autopsy confirmation; inevitably, some patients may have been misdiagnosed. In particular, the diagnosis of LBD requires the presence of clinical hallmarks which may not be apparent early in disease. Given that pathologic studies have found Lewy bodies in all cases of RBD with dementia,24
it will be of exceptional interest to see if the four patients diagnosed with clinical AD will eventually develop hallmarks of LBD. Preliminary analysis of our patients with dementia (presently in progress) has suggested that our patients with clinical diagnosis of AD are indistinguishable from our LBD patients, suggesting that our clinical AD patients in fact have LBD (data not shown). Finally, although this study is the largest study following patients with idiopathic RBD, sample size restrictions prevented analysis of subgroups—in particular, it would be of interest to assess whether risk of developing dementia may be lower in women with idiopathic RBD.