作者：Pauline Anderson
出處：WebMD醫學新聞
December 24, 2008 — 新研究顯示，快速動眼(REM)睡眠異常(RBD)者，發生巴金森氏症(Parkinson's disease，PD)或者失智症的5年風險達20%，且此一風險在10年後超過40%、在12年後超過50%。
RBD患者缺乏REM睡眠期的正常肌肉張力，且在這段睡眠時期有過度的運動力，如猛擊或踢。
研究作者、魁北克McGill大學的Ronald B. Postuma醫師表示，RBD患者的PD與失智風險對於諮商和預防來說是不可或缺的。
Postuma醫師向Medscape Psychiatry表示，重點在於這些病患必須每年或者定期追蹤，以確認和治療這些神經異常。
這項研究線上登載於12月24日的Neurology期刊。
【可治療的狀況】
根據情況看來，早期PD與失智通常無法辨識。Postuma醫師表示，不幸的是，病患未尋求醫療照顧，而是試圖跟上同儕，或者是從喜愛的活動俱樂部退出、或者是提早退休。
他表示，這些是可以治療的；我們可以幫助病患走快一點以及活動好一點。如果我們可以及早治療他們，他們的生活品質將大不相同。
研究者使用生活表格分析來確認93名在1989至2006年間診斷有自發RBD而轉診到睡眠異常中心之病患的風險隨時間變化情況。每位研究對象接受完整的醫療史、神經檢查與認知檢測。病患須在開始時沒有神經退化徵兆。使用多頻睡眠生理檢查確認RBD，以及REM睡眠期間的動作表現史。
【男性比較常見】
5、60歲的男性比較可能有一般的RBD表現；不過，原因還不清楚。研究對象參與時的平均年紀為65.4歲，80.4%為男性。
在93名病患中，整個研究期間有26人發生神經退化疾病—15人發生巴金森症、11人發生失智。發生巴金森症者中，14 人有自發性PD診斷、1人有多元系統性病變。
發生失智者中，7人達到路易氏體失智症(Lewy Body Dementia，LBD)規範，4 人為阿茲海默氏症(Alzheimer's disease，AD)。發生異常者以及未發生異常者的年紀、性別、發生這些異常時的RBD期間均無顯著差異。
根據分析，5年後，發生PD或者失智的風險為17.5%；10年後的風險為40.6%、12年後為52.4%。
Postuma醫師表示，這個風險因為一些可能因素而低於之前的研究數據。例如，他們使用嚴格的PD定義，且失智定義也未納入輕微認知不佳者。
他表示，你經常在這些人發現微妙的疾病徵兆— 一點點遲緩或者一點點認知不佳— 對於我們來說，這些不算在內。我們需要確定他們真的罹患疾病。
Postuma醫師表示，此外，研究對象比之前的研究更早確認RBD，因此他們可以被監測。
我們較早發現病患、發現較輕微案例。也許從現在開始的20年，如果任何人已經確認此異常，我們可以說其風險較低，因為我們比以往更早發現它。
【RBD是PD的開始徵兆】
該研究確認RBD是PD的標記。Postuma醫師表示，它告訴我們，疾病開始發生。神經退化過程持續數年。我們不知道會有多少年— 也許只是幾年、也許十幾、二十年 —但是最先影響的就是睡眠。
Postuma醫師之前的研究發現，有約半數的RBD病患味覺和彩色視覺減少。這使得他相信，PD可能是LBD的型態且來自RBD，而不是源自腦部的運動區域。
他表示，大部份的巴金森症案例發生在控制味覺、彩色視覺、動作調節與血壓的區域。
他指出，疾病惡化後漸漸擴展到整個腦幹，直到重創運動控制的區域，就在此時，超過某特定閾值後，病患成為醫師診間中的巴金森症患者。還不清楚哪些RBD病患會變成PD患者。他表示，我們專注於釐清如何預測哪些人會發生。我們必須持續追蹤這些病患數年後才可以得知。
為了找到PD或者失智的預防與治療，Postuma 醫師相信，後續研究需鎖定RBD病患。這些病患還沒有此疾病，隨著時間變成巴金森氏症後才介入就太遲了。
【反射夢境】
和夢遊病患半睡半醒的狀態不同，RBD只發生在REM睡眠時期。RBD病患會把夢境付諸實現，所以若夢中有人在追逐他們，他們會模擬跑步的動作；如果夢見有人攻擊他們，他們會用拳頭反擊。Postuma 醫師表示，但是一旦有人控制並喚醒他們，他們會馬上恢復正常。
估計每200人有1人有RBD，但因很難確認所有案例，所以這樣的數字可能低估了。Postuma 醫師表示，不是每個人都會傷害自己，也不是每個人都知道這個問題。如果你自己睡，你永遠不會知道自己有這個疾病。
這不僅是迄今最大型的研究，也是追蹤病患時間最長的。他表示，我們在12年和15年時都還有許多病患。
研究作者 J. Montplaisir博士來自蒙特婁的Sacre-Coeur醫院，指出接受 Boehringer Ingelheim、Servier與Shire Biochem 的顧問費用以及擔任 Boehringer與Shire的講師，且接受Sanofi Synthelabo與GlaxoSmithKline的研究活動資金。
Neurology. 線上登載於2008年12月24日。
Sleep Disorder May Lead to Parkinson's Disease or Dementia
By Pauline Anderson
Medscape Medical News
December 24, 2008 — Patients with rapid-eye-movement (REM)–sleep behavior disorder (RBD) face close to a 20% 5-year risk of developing Parkinson's disease (PD) or dementia, and that risk rises to more than 40% after 10 years and exceeds 50% after 12 years, new research shows.
Patients with RBD lack the normal muscle atonia that accompanies REM sleep and exhibit excessive motor activity such as punching or kicking during this sleep stage.
Pinpointing the risk for PD and dementia among RBD patients is integral for counseling and prevention purposes, said study investigator Ronald B. Postuma, MD, from McGill University, in Montreal, Quebec.
"It's important that these patients be followed on an annual basis or at least periodically" to pick up and treat early signs of these neurological disorders, Dr. Postuma told Medscape Psychiatry.
The study is published online December 24 in Neurology.
A Treatable Condition
As it is, early manifestations of PD and dementia often go unrecognized. Unfortunately, instead of seeking medical attention, patients struggling to keep up with their peers might pull out of a favorite hiking club or take early retirement, said Dr. Postuma.
"These things are treatable; we can help patients walk faster and move better. If we can get them early and treat them early, that can make a big difference to their quality of life," he said.
The investigators used a life-table analysis to determine disease risk over time in 93 patients referred to a sleep-disorders center who had been diagnosed with idiopathic RBD between 1989 and 2006. Each subject underwent a complete medical history, neurological exam, and cognitive testing. Patients had to have no sign of neurodegenerative disease at baseline. RBD was confirmed by polysomnogram and a history of motor manifestations during REM sleep.
More Common in Males
Typically RBD manifests in the decades of the 50s and 60s and is most common in men; however, the reason for this is not clear. The mean age of participants was 65.4 years, and 80.4% of the subjects were male.
Of the 93 patients, 26 developed neurodegenerative disease — 15 developed parkinsonism and 11 dementia — over the course of the study. Of the patients with parkinsonism, 14 had a diagnosis of idiopathic PD and 1 had multiple system atrophy.
Of those with dementia, 7 met criteria for Lewy Body Dementia (LBD) and 4 for Alzheimer's disease (AD). There were no significant differences in age, sex, or RBD duration between patients who developed these disorders and those who did not.
According to the analysis, after 5 years, subjects had a 17.5% risk of developing PD or dementia. The risk was 40.6% after 10 years and 52.4% after 12 years.
This risk is somewhat lower than that uncovered in previous studies for a number of possible reasons, said Dr. Postuma. For one, he and his colleagues used a strict definition of PD and did not include mild cognitive impairment in their definition of dementia.
"You often see subtle signs of these diseases in these people — a little bit of slowing down or a little bit of cognitive impairment — and for us, that didn't count. We needed to be sure they had the disease," he said.
Also, patients in this study were identified with RBD earlier than in previous studies and therefore were at a stage where they could be monitored, said Dr. Postuma.
"We're seeing patients earlier, and we're seeing milder cases. Maybe 20 years from now, if everyone readily recognizes this disorder, we'll actually say that it's an even lower risk because we're catching them much earlier than we used to."
RBD Signals Start of PD
The study confirms that RBD is a marker for PD. "It's telling us that the disease process has started," said Dr. Postuma. "That neurodegenerative process has been going on for years. We don't know how many years — maybe it's just a few, maybe a couple of decades — and it affects sleep first."
Dr. Postuma's earlier research found decreased faculties of smell and color vision in about half of patients with RBD. This led him to believe that PD — and probably the form of LBD that emerges from RBD — does not originate in the motor areas of the brain.
"In the majority of Parkinson's cases, the disease probably starts in the areas that control smell, color vision, mood regulation, and blood pressure," he said.
"The disease process then spreads gradually through the brain stem until it hits the areas that are involved in motor control. It's at that point, after it crosses a certain threshold, that a patient is going to be in the doctor's office with Parkinson's disease," he added.
It is not clear which patients with RBD will become those PD patients. "We're very interested in trying to figure out how to predict who gets it. We have to keep following these patients for some years before we'll be able to tell," he said.
To find treatments to prevent PD or dementia, Dr. Postuma believes future research should look closely at patients with RBD. "These are patients who don't even have the disease yet, so maybe by the time a person actually has Parkinson's disease it's too late to intervene."
Acting Out Dreams
Unlike sleepwalking, where people are in a half-awake/half-asleep state, RBD occurs only during REM sleep. RBD patients act out their dreams, so if someone is chasing them in their dream, they will mimic a running action; if someone is attacking them, they will fight them off with their fists. But as soon as someone confronts them, talks to them, and wakes them up, they are instantly normal, said Dr. Postuma.
An estimated 1 in 200 people has RBD, although that figure is probably on the low side, because it is difficult to capture all cases. "Not everyone hurts themselves, and not everyone recognizes the problem," said Dr. Postuma. "And if you sleep alone, you may never know you have this disease."
Not only is this the largest study of its kind to date, it has also followed patients for a longer period than previous studies. "We have lots of patients 12 years out and 15 years out," he said.
Study author J. Montplaisir, MD, PhD, from Sacre-Coeur Hospital in Montreal, reports receiving personal compensation as a consultant to Boehringer Ingelheim, Servier, and Shire Biochem and as a speaker for Boehringer and Shire and receiving financial support for research activities from Sanofi Synthelabo and GlaxoSmithKline.
Neurology. Published online December 24, 2008.
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