SNM 2009:PET可以用於釐清失智類型


  June 23, 2009 (多倫多) — 一篇進行中研究的初步結果顯示,使用正子放射型電腦斷層攝影(PET)可以幫助改善失智診斷的準確度。
  
  密西根大學醫院核子醫學科、放射與精神科教授Kirk Frey醫師在核子醫學協會第56屆年會中接受訪問時表示,我們知道失智會被誤診。迄今,最佳的診斷方法是比較臨床診斷和解剖所見。
  
  研究對象診斷有輕微認知缺損或者輕微失智(簡易智能評估分數≧18),接受標準的神經學、神經心理學、與組織腦部影像評估。由本領域的3位專家評估這些結果。達成阿茲海默氏症(AD)、額顳葉失智症(frontotemporal dementia,FTD)或Lewy體失智症(dementia with Lewy bodies,DLB)等診斷。
  
  研究人員進行PET影像,包括以碳11標記的螢光物質顯影劑(11C-PiB)偵測澱粉樣蛋白沉積,以及用碳11 [11C]dihydrotetrabenazine(DTBZ)測量黑質紋狀體投影完整性。FTD類型患者顯示PiB和DTBZ都有正常攝入。DLB類型患者顯示有嚴重的紋狀體DTBZ缺損。AD類型患者有正常DTBZ攝入,以及放大的前額皮質PiB結合。
  
  有26%的研究對象,其臨床評估與PET分類之間缺乏一致性。特別的是,9名PET顯示有黑質紋狀體病灶者中,有3人臨床上並未被辨識。43名陽性PiB中有9人無臨床診斷,314名FTD病患中有3人根據臨床發現而被錯誤分類為AD。
  
  Frey醫師認為這種誤診率相當嚴重。Frey醫師表示,如果將影像檢查視為真,我們的臨床診斷有24%是錯誤的,如同之前發表的臨床解剖研究發現的範圍。
  
  研究者計畫收集目前追蹤中的150名病患的兩年資料。Frey醫師表示,這些病患已經被縱向追蹤。兩年後的臨床診斷有可能會不一樣。
  
  他警告,誤診的後果包括不適當的病患處置。
  
  Frey醫師在Medscape Radiology的訪問中表示,在診間,臨床上不太可能分辨DLB和阿茲海默氏症。這些病患的多巴胺神經元退化,前腦的神經細胞也是,這些都與認知衰退有關。
  
  Frey醫師解釋,如果你有此類病患,且不知道病患有DLB,你可能會給他抗精神病藥物來幫助行為改善。對這類病患來說,那可能是致命的。
  根據Frey醫師表示,同樣地,經常用於失智症狀處置的乙醯膽鹼酯酶抑制劑,現在認為對於治療DLB比治療AD更有效,對於治療FTD則無幫助。
  
  Frey醫師表示,就病患的觀點來說,這不是必要的安全風險,非必要性的使用乙醯膽鹼酯酶抑制劑對病患或健康照護體系而言,是相當大的代價。
  
  再者,使用PET和新型的影像示蹤劑協助分辨失智的亞型,將開啟更多標靶治療的研究方向,且將研究對象設定為更合適的族群。Frey醫師表示,如果藥物是針對澱粉樣蛋白病理,你會將試驗限制於那些有澱粉樣蛋白問題的病患。
  
  他強調,臨床核准的放射性示蹤劑未能分辨失智症亞型之間的神經化學特徵差異,本研究中所用的示蹤劑尚未獲得美國食品藥物管理局核准。
  本研究發表時的主持人、麻州綜合醫院/哈佛大學放射科訪問助理教授Alexander Drzezga醫師表示,這是一個非常相關的研究。對於不清楚的案例,影像檢查有其好處。即使是有經驗的醫師也可能誤判。
  
  Drzezga醫師表示,臨床實務可能發生誤診,病患因為不恰當的疾病分類而被處方不適當的藥物。
  
  Drzezga醫師表示,有可以提供客觀答案的方法是件好事。症狀可能誤判,影像提供你有關病患狀況的更明確證據。
  
  Frey醫師與 Drzezga醫師宣告沒有相關財務關係。
  
  核子醫學協會2009年年會,摘要251。發表於2009年6月15日。
  

SNM 2009: PET Can Be Used to Classify Dementia Subtype

By Louise Gagnon
Medscape Medical News

June 23, 2009 (Toronto, Ontario) — Preliminary results of an ongoing study show that the use of positron emission tomography (PET) can help improve the accuracy of a dementia diagnosis.

We know that dementia is misdiagnosed," Kirk Frey, MD, professor of radiology and psychiatry at the University of Michigan Hospitals' Division of Nuclear Medicine in Ann Arbor, said in an interview here at the Society of Nuclear Medicine 56th Annual Meeting. To date, "the best way [to diagnose it is] to compare the clinical diagnosis with what is found at autopsy."

Study subjects diagnosed with mild cognitive impairment or mild dementia (Mini-Mental State Examination score ? 18) received standard neurological, neuropsychometric, and anatomic brain-imaging evaluations. Three experts in the field were asked to evaluate the results. They arrived at a diagnosis of Alzheimer's disease (AD), frontotemporal dementia (FTD), or dementia with Lewy bodies (DLB).

Investigators performed PET imaging with both carbon-11-labelled Pittsburgh-compound B (11C-PiB) to detect amyloid deposits and [11C]dihydrotetrabenazine (DTBZ) to measure nigrostriatal projection integrity. Individuals with FTD showed normal uptake of both PiB and DTBZ. Individuals with DLB showed severe striatal DTBZ defects. Those with AD had normal DTBZ uptake and augmented frontal cortical PiB binding.

There was a lack of agreement between clinical evaluations and PET classifications in 26% of subjects. Specifically, 3 of 9 patients had nigrostriatal lesions on PET that were not identified clinically. Nine of 43 patients were positive for PiB but were not clinically diagnosed as such, and 3 of 14 FTD patients were incorrectly classified, based on clinical findings, as having AD.

Dr. Frey described the rate of misdiagnosis as "significant." "If you take the imaging as truth, our clinical diagnosis was in error 24% of the time, which is well within the range of what clinical autopsy studies that have been previously published found," said Dr. Frey.

The researchers plan to compile 2 years of data on 150 patients who are currently being followed. "The patients are being followed longitudinally," said Dr. Frey. "It could be that the clinical diagnosis may be different after 2 years."

The consequence of misdiagnosis can be inappropriate management of patients, he cautioned.

"In the clinic, it is often impossible [clinically] to distinguish between DLB and Alzheimer's disease," said Dr. Frey in an interview with Medscape Radiology. "These patients have a degeneration of their dopamine neurons, as well as the nerve cells in the forebrain, that relate to cognitive decline.

"If you have such a patient and you don't know the patient has DLB, you may administer an antipsychotic medication to help with behavioral management," explained Dr. Frey. "In these patients, that can be lethal."

Similarly, acetylcholinesterase inhibitors, which are frequently prescribed for symptom management of dementia, are believed now to be more effective in treating DLB than AD and are regarded as having no benefit in treating FTD, according to Dr. Frey.

"This is not necessarily a safety risk from the standpoint of the patient, but unnecessary use of acetylcholinesterase inhibitors is a significant expense to the patient or the healthcare system," said Dr. Frey.

Moreover, being able to identify the subtypes of dementia using PET with emerging imaging tracers will open the research door to more targeted therapies and narrow the study populations to more suitable candidates. "If the drug is targeting an amyloid pathology, you would want to restrict a trial of that drug to patients who have the amyloid problem," said Dr. Frey.

He stressed that clinically approved radiotracers are not able to identify neurochemical features that differentiate between dementia subtypes and that the tracers used in this study are not yet approved by the US Food and Drug Administration.

"It is a very relevant study," said Alexander Drzezga, MD, a visiting assistant professor in the Department of Radiology at Harvard University/Massachusetts General Hospital in Boston, who moderated the oral session at which the research was presented. "There is a benefit of imaging procedures in cases that are not clear. Even experienced clinicians may judge the cases wrong."

Dr. Drzezga said it does occur in clinical practice that patients are prescribed inappropriate medications because of inappropriate disease classification.

"It's good to have measures that give you an objective answer," said Dr. Drzezga. "The symptoms can be misleading, and imaging may give you a more definite proof of what patients are suffering from."

Dr. Frey and Dr. Drzezga have disclosed no relevant financial relationships.

Society of Nuclear Medicine 2009 Annual Meeting, Abstract 251. Presented June 15, 2009.
J Nuclear Med. 2009;50:65P.

    
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