Clinical Utility & Appropriate Use Criteria of Amyloid PET imaging
May 18, 2019
台中中⼭醫學⼤學 中華⺠國核醫學學會
Amyloid PET Imaging Study Symposium
Outline
β-amyloid and Alzheimer's disease
18F amyloid PET tracer
Appropriate use criteria of amyloid PET imaging
Clinical utility of amyloid PET
Summary
β-amyloid and Alzheimer's disease
1906 Alzheimer描述首位病人 1907 Fischer發表對斑塊的描述 1910 阿茲海默氏症命名
1960s 電子顯微鏡可以放大至斑塊與糾結 1970s 阿茲海默氏症被承認為最常見的失智症且與老化做區分,斷層掃描能看見患者的腦萎縮。 1980s 分子與生化技術進步,能辨識出斑塊與糾結分別由amyloid-β及tau組成 1984 NINCDS-ADRADA 診斷指引發表
1990s 辨識出阿茲海默氏症的基因突變、風險因子、失智症的階段分級、腦影像技術改進。
組織學 生物化學
遺傳學 腦影像學
1906
2000s 了解失智症成因的生物進程 遺傳學、分子生物學、腦影像進步 2011 NIA-AA 診斷指引發表 2018 NIA-AA AD研究框架發表
Alzheimer's Disease Research Timeline
1984 NINCDS-ADRDA Alzheimer's Criteria
5 McKhann, Guy, et al. "Clinical diagnosis of Alzheimer's disease: Report of the NINCDS‐ADRDA Work Group* under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease." Neurology 34.7 (1984): 939-939.
National Institute of Neurological and Communicative Disorders and Stroke
and the Alzheimer's Disease and Related Disorders Association
Criteria
Definite AD
• 病患臨床符合Probable AD且經屍檢或活檢確定有阿茲海默氏症並組織病理證據
Probable AD
• 經神經心理學檢測認定為失智症,在兩項以上的認知功能受損 • 記憶力與其他認知功能進行性惡化 • 發病時間介於40-90歲,通常晚於65歲 • 非由系統性或其他腦部疾病造成的記憶與認知功能退化
Possible AD
• 非典型的發病時間、表現或進程 • 沒有已知的病因 • 沒有被認為會導致失智的共病
Unlikely AD
• 失智患者為突發性、中風、局部神經功能缺損、癲癇、疾病早期步態異常等。
[11C]Pittsburgh compound-B (PIB) PET
6
Pittsburgh Compound B (PIB), 半衰期 20 min
or
Negative Positive
Klunk, William E., et al. "Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound‐B." Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society 55.3 (2004): 306-319.
Amyloid PET技術發展, 使腦內類澱粉病理變化可在活體中觀察
[1] Villemagne, Victor L., et al. "Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer's disease: a prospective cohort
study." The Lancet Neurology 12.4 (2013): 357-367.
[2] Bateman, Randall J., et al. "Clinical and biomarker changes in dominantly inherited Alzheimer's disease." New England Journal of Medicine 367.9
(2012): 795-804.
Clinical and biomarker changes in dominantly inherited Alzheimer's disease[2]
The natural history of Aβ deposition in sporadic Alzheimer's disease[1]
Aβ deposition in Alzheimer's disease
類澱粉斑塊在症狀出現20年前開始堆積
Association of Elevated Amyloid Levels With Cognition
整體
記憶
專注
語言
視覺空間
Petersen, Ronald C., et al. "Association of elevated amyloid levels with cognition and biomarkers in cognitively normal people from the community." JAMA neurology 73.1 (2016): 85-92.
564 cognitively normal individuals (medianage, 78 years)
2011 NIA-AA Diagnostic Guidelines Toward defining the preclinical stages of Alzheimer’s disease
Sperling, Reisa A., et al. "Toward defining the preclinical stages of Alzheimer’s disease: Recommendations from the National Institute on Aging-
Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease." Alzheimer's & dementia 7.3 (2011): 280-292.
定義臨床前階段與輕度認知障礙
Preclinical Alzheimer’s disease and it’s outcome
Sperling, Reisa, Elizabeth Mormino, and Keith Johnson. "The
evolution of preclinical Alzheimer’s disease: implications for
prevention trials." Neuron 84.3 (2014): 608-622.
Progression to clinical dementia rating scale at least 0.5, symptomatic Alzheimer’s disease by preclinical Alzheimer’s disease stage
Vos, Stephanie JB, et al. "Preclinical Alzheimer's disease and its outcome: a
longitudinal cohort study." The Lancet Neurology12.10 (2013): 957-965.
Clinical outcomes of amyloid positivity in persons without dementia
由正常至失憶型MCI風險提高2.3倍 由MCI至clinical AD風險提高1.9倍
Roberts, Rosebud O., et al. "Prevalence and outcomes of amyloid positivity among persons without dementia in
a longitudinal, population-based setting." JAMA neurology 75.8 (2018): 970-979.
2018 NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease
Jack, Clifford R., et al. "NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease." Alzheimer's & Dementia 14.4 (2018): 535-562
18F amyloid PET tracer
Commercial 18F-Aβ PET tracer approved by FDA & EMA
18F-florbetaben (NeuraceqTM)
U.S. FDA approved March 2014
18F-florbetapir (AmyvidTM)
U.S. FDA approved April 2012
18F-flutemetamol (VizamylTM)
U.S. FDA approved October 2013
Amyloid Positive Amyloid Negative
Sabri, Osama, et al. "Florbetaben PET imaging to detect amyloid beta plaques in Alzheimer's disease: phase 3 study." Alzheimer's & Dementia 11.8 (2015): 964-974.
Aβ
ne
gati
ve
A
β p
osi
tive
MRI Amyloid PET Histopathology Bielschowsky silver staining
74位患者過世後捐出大腦,與生前18F-Florbetaben PET 影像作比對 Gold standard: 中度至高度神經炎斑塊 (CERAD) 敏感度: 97.9% [95% CI 93.8–100%], 特異性: 88.9% [95% CI 77.0–100%]
18F-Florbetaben PET phase III clinical trial
18F-florbetaben indications • For Positron Emission Tomography (PET) imaging of the
brain to estimate β-amyloid neuritic plaque density in adult patients with cognitive impairment who are being evaluated for Alzheimer’s Disease (AD) and other causes of cognitive decline.
16
FBB Positive FBB Negative
Negative FBB scan: sparse to no amyloid neuritic plaques and Positive FBB scan: moderate to frequent amyloid neuritic plaques
18F-florbetaben dosage and administration
• 300 MBq (8.1 mCi) as a slow single intravenous bolus (6 sec/mL) in a total volume of up to 10 mL。
• Obtain 15-20 minute PET images starting from 45 to 130 minutes after intravenous administration
17
18F-florbetaben Image Interpretation
18F-florbetaben Image Interpretation (cont.)
β型澱粉樣蛋白神經炎斑塊沉積評分定義 (BAPL-brain amyloid plaque load)
判讀
BAPL 分數 判讀原則
掃描陰性
1
掃描為 無 β型澱粉樣蛋白沉積
在腦部四個區域(側顳葉、額葉、後扣帶回/
楔前葉、頂葉)中各得RCTU 1分。
掃描陽性
2
掃描為 中度 β型澱粉樣蛋白沉積
在腦部四個區域之任一或全部區域評為RCTU 2分,且在腦部四個區域都沒有被評為RCTU 3分。
3
掃描為 顯著 β型澱粉樣蛋白沉積
RCTU評分為3分:在腦部四個區域中至少一個得到RCTU 3分。
腦皮質區域示踪劑攝取的定義 (RCTU- regional cortical tracer uptake)
RCTU 分數 判讀條件
1 無-示踪劑攝取
灰質攝取示踪劑的程度 (如:訊號強度)低於白質的攝取程度。
2 中度-示踪劑攝取
有一個或多個小面積區域(
從白質邊緣至外皮質邊緣)
攝取示踪劑程度等同或高於白質的攝取程度,影響個別區域大部分的切面影像。
3 顯著-示踪劑攝取
有一大片融合的面積區域(
從白質邊緣至外皮質邊緣)
攝取示踪劑程度等同或高於白質的攝取程度(延伸超過白質邊緣至外皮質邊緣);影響全部的區域,涵括個別區域大部分的切面影像。
註:皮質攝取示踪劑程度的評分,取決於問題區域大部分的切片影像。
18F-Florbetaben safety profile and radiation dosimetry
20
安全性 總體安全性檔案基於1090次給藥的數據,其中包含872名受試者。
無發生與本藥相關的嚴重不良反應報告。
受試者中觀察到最常見的藥物不良反應為注射部位紅疹、刺激、疼痛,所有不良反應為輕至中度,且持續時間短。
輻射劑量
NEURACEQ [US package insert]. Matran, Switzerland: Piramal Imaging, S.A.; April 2014.
藥物不良反應 不良反應次數 (百分比比例)
注射部位紅疹 18 (1.7%)
注射部位刺激 12 (1.1%)
注射部位疼痛 37 (3.4%)
Appropriate use criteria of amyloid PET imaging
2013 Appropriate use criteria for amyloid PET
When should brain amyloid imaging be considered?
For patients with all of the following core elements:
1. A cognitive complaint with objectively confirmed impairment.
2. Alzheimer’s disease is a possible diagnosis, but upon comprehensive evaluation by a dementia expert, the diagnosis remains uncertain.
3. The presence or absence of amyloid would increase certainty in the diagnosis and alter the treatment plan.
由阿茲海默氏症協會與核醫與分子影像學會組織工作小組共同發表在Journal of Nuclear Medicine
Johnson, Keith A., et al. "Appropriate use criteria for amyloid PET: a report of the Amyloid Imaging Task Force, the Society of Nuclear Medicine and Molecular Imaging, and the Alzheimer’s Association." Journal of Nuclear Medicine, (2013)
Amyloid imaging appropriate Amyloid imaging inappropriate
1. Persistent or progressive unexplained MCI
2. core clinical criteria for possible AD because of unclear clinical presentation (either an atypical clinical course or an etiologically mixed presentation)
3. Patients with progressive dementia and atypically early age of onset (<65 yrs)
4. core clinical criteria for probable AD with typical age of onset
5. To determine dementia severity 6. Based solely on a positive family
history of dementia or presence of APOE4
7. Solely subjective th a cognitive complaint that is unconfirmed on clinical examination
8. In lieu of genotyping for suspected autosomal mutation carriers
9. In asymptomatic individuals 10. Nonmedical use (e.g., legal, insurance
coverage, or employment screening)
Appropriate use criteria for Amyloid PET
Johnson, Keith A., et al. "Appropriate use criteria for amyloid PET: a report of the Amyloid Imaging Task Force, the Society of Nuclear Medicine and Molecular Imaging, and the Alzheimer’s Association." Journal of Nuclear Medicine, (2013)
Appropriate use criteria for Amyloid PET
Johnson, Keith A., et al. "Appropriate use criteria for amyloid PET: a report of the Amyloid Imaging Task Force, the Society of Nuclear Medicine and Molecular Imaging, and the Alzheimer’s Association." Journal of Nuclear Medicine, (2013)
1. 持續或漸進之不明原因輕度認知障礙(MCI)患者。Persistent or progressive
unexplained MCI
2. 臨床表徵不明確(非典型或混和型),符合“Possible AD” 臨床標準患者
3. 早發型失智症患者(65歲前發病)
輕度認知障礙與失智症進程
根據台灣流行病學調查 [1]
65歲以上長者每12人中 • 有2位患有輕度認知障礙 • 有1位患有失智症 (base on NIA-AA criteria and CDR score)
輕度認知障礙(MCI) 失智症(Dementia) 認知正常
1. Sun, Y. et al. A Nationwide Survey of Mild Cognitive Impairment and Dementia , Including Very Mild Dementia , in Taiwan. 9, (2014). 2. 衛生福利部 失智症診療手冊106年2月 3版,第一章 失智症的認識 page 3 (2017)
經確診輕度認知障礙的患者,五年內高達40-50%的比例會發展成失智症[2]
Jansen, Willemijn J., et al. "Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis." Jama313.19 (2015): 1924-1938.
MCI患者類澱粉斑塊堆積發生率是認知正常者的兩倍
60~80歲的MCI病患半數為Amyloid 陽性
Amyloid positive versus negative in Mild Cognitive Impairments (MCI) patient
1. Ewers, Michael, et al. "CSF biomarker and PIB-PET–derived beta-amyloid signature predicts metabolic, gray matter, and cognitive changes in nondemented subjects." Cerebral cortex, (2011)
2. Nordberg, Agneta, et al. "A European multicentre PET study of fibrillar amyloid in Alzheimer’s disease." European journal of nuclear medicine and molecular imaging, (2013)
3. Roberts, Rosebud O., et al. "Prevalence and outcomes of amyloid positivity among persons without dementia in a longitudinal, population-based setting." JAMA neurology 75.8 (2018): 970-979.
Nordberg, Agneta, et al., 2013 Roberts, Rosebud O., et al., 2018 Ewers, Michael, et al., 2011
Amyloid PET 可釐清輕度認知障礙患者腦內是否有阿茲海默氏症的病理變化,評估疾病進展為AD的可能性
Survival plot for conversion from MCI to AD Percentage of participants with MCI without AD over time
45 MCI patient
24 of 45
FBB +
18 of 24(75%)
Progressed to AD
21 of 24 (87%)
progressed to AD
1 death, 2 MCI worsening
21 of 45
FBB -
2 of 21 (9.5%)
Progressed to AD
1 back to MCI
1 met FTLD criteria
4 of 21 (19%)
non-AD dementia*
1 PSP/ 2 FTLD/ 1 DLB
AD: “probable AD” according to the NINCDS-ADRDA criteria PSP: progressive supranuclear palsy FTLD: frontotemporal lobar degeneration DLB: dementia with Lewy bodies
2 year follow-up 4 year follow-up Baseline
Ong, Kevin T., et al. "Aβ imaging with 18F-florbetaben in prodromal Alzheimer's disease: a prospective outcome study." J Neurol Neurosurg Psychiatry, (2015)
18F-florbetaben 早期偵測阿茲海默氏症
釐清輕度認知障礙病患之初期突觸失能
Brendel, Matthias, et al. "Additive value of amyloid-PET in routine cases of clinical dementia work-up after FDG-PET." European journal of nuclear medicine and molecular imaging, (2017)
73歲女性 • FDG-PET顯示後扣帶
皮層代謝下降,中度相似AD。
• FBB-PET 陽性 最終診斷: 阿茲海默氏症
77歲女性 • FDG-PET顯示後扣帶
皮層代謝下降,中度相似AD。
• FBB-PET 陰性 最終診斷: 無最終診斷
Appropriate use criteria for Amyloid PET
Johnson, Keith A., et al. "Appropriate use criteria for amyloid PET: a report of the Amyloid Imaging Task Force, the Society of Nuclear Medicine and Molecular Imaging, and the Alzheimer’s Association." Journal of Nuclear Medicine, (2013)
1. 持續或漸進之不明原因輕度認知障礙(MCI)患者。
2. 臨床表徵不明確(非典型或混和型),符合“Possible AD” 臨床標準患者 core
clinical criteria for possible AD because of unclear clinical presentation
3. 早發型失智症患者(65歲前發病)
18F-florbetaben 用於AD與non-AD失智症
Villemagne, Victor L., et al. "Amyloid imaging with 18F-florbetaben in Alzheimer
disease and other dementias." Journal of Nuclear Medicine, (2011).
鑑別診斷:額顳葉型失智症 vs. 阿茲海默症額葉亞型
Brendel, Matthias, et al. "Additive value of amyloid-PET in routine cases of clinical dementia work-up after FDG-PET." European journal of nuclear medicine and molecular imaging, (2017)
63歲女性 • FDG-PET 似額顳葉失智症
的代謝下降特徵。 • FBB-PET 陰性 最終診斷: 額顳葉型失智症
66歲男性 • FDG-PET 似額顳葉失智症
的代謝下降特徵。 • FBB-PET 陽性 最終診斷: 阿茲海默氏症額顳葉亞型
frontal variants of AD
FTLD with coexisting parietal hypometabolism
鑑別診斷: 血管型失智症 vs. 混和型失智症
Brendel, Matthias, et al. "Additive value of amyloid-PET in routine cases of clinical dementia work-up after FDG-PET." European journal of nuclear medicine and molecular imaging, (2017)
78歲女性 • 輕度認知障礙 • 腦白質病變 (MRI) • FDG-PET 似血管型失智症
的散佈代謝下降特徵 • FBB-PET 陰性 最終診斷: 血管型失智症
77歲女性 • 輕度認知障礙 • 腦白質病變 (MRI) • FDG-PET 似血管型失智症
的散佈代謝下降特徵 • FBB-PET 陽性 最終診斷: 混和型失智症 (AD+VaD)
Appropriate use criteria for Amyloid PET
Johnson, Keith A., et al. "Appropriate use criteria for amyloid PET: a report of the Amyloid Imaging Task Force, the Society of Nuclear Medicine and Molecular Imaging, and the Alzheimer’s Association." Journal of Nuclear Medicine, (2013)
1. 持續或漸進之不明原因輕度認知障礙(MCI)患者。
2. 臨床表徵不明確(非典型或混和型),符合“Possible AD” 臨床標準患者
3. 早發型失智症患者(65歲前發病) Patients with progressive dementia and
atypically early age of onset
早發型失智症
由於正值中壯年,患者可能仍在職場工作、照顧長輩及子女,對家庭與社會的衝擊重大。
1. World Health Organization. "Global action plan on the public health response to dementia 2017–2025." (2017).
根據世界衛生組織全球失智症行動計劃摘要,失智症病
人中,約有 9%屬於65歲前發病的早發型失智症[1]
認知症狀出現年齡與起始診斷類別
Van Der Flier, Wiesje M., and Philip Scheltens. "Amsterdam dementia cohort: performing research to optimize care." Journal of Alzheimer's Disease 62.3 (2018): 1091-1111.
早發型阿茲海默氏症的診斷挑戰
Liana G. Apostolova, lecture in Dementia Care Expo 2018, Tainan
阿茲海默氏症的非典型亞型: PCA, lvPPA, fvAD在年輕發病的族群中常被誤診
Smits, Lieke L., et al. "Early onset Alzheimer's disease is associated with a distinct
neuropsychological profile." Journal of Alzheimer's Disease 30.1 (2012): 101-108.
記憶 語言 視空間 執行力 專注力
65歲前發病
65歲後發病
• 相較晚發型AD多以記憶力下降為特徵,早發型的症狀常發生在其他認知領域
早發性失智症的延遲確診 失智症自症狀出現至確診的時間(年)
診斷種類
早發型失智症(65歲前) 晚發型失智症(65歲後)
Mean (S.D.) n Mean (S.D.) n
All 4.4 (3.1) 235 2.8 (2.1) 167
AD 4.2 (3.0) 139 3.0 (2.2) 122
FTD 6.4 (3.6) 29 3.3 (2.1) 3
VaD 3.9 (2.7) 35 2.2 (1.8) 33
Other 4.1 (3.3) 32 3.4 (1.3) 9
早發行失智症患者的容易發生延遲確診,
自發病到確診的平均時間,比65歲以上發病者多1.6年[1]
1. Van Vliet, D., et al. "Time to diagnosis in young-onset dementia as compared with late-onset dementia." Psychological medicine 43.2 (2013): 423-432.
鑑別診斷: 原發性進行性失語症
Brendel, Matthias, et al. "Additive value of amyloid-PET in routine cases of clinical dementia work-up after FDG-PET." European journal of nuclear medicine and molecular imaging, (2017)
59歲女性 • 臨床表現原發漸進性失語
症(分類未確定) • FDG-PET 似額顳葉失智症
的代謝下降特徵。 • FBB-PET 陽性 最終診斷: 阿茲海默氏症導致lvPPA
59歲男性 • 臨床表現原發漸進性失語
症(分類未確定) • FDG-PET 似額顳葉失智症
的代謝下降特徵。 • FBB-PET 陰性 Final diagnosis: 額顳葉失智症導致svPPA
logopenic variant primary progressive aphasia PPA (lvPPA), 85% +
semantic variant primary progressive aphasia PPA (svPPA), 13% +
Clinical utility of amyloid PET
Date: September 27, 2013
A. “Evidence at this time is insufficient to conclude that the use of PET-Aβ imaging is
reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the
functioning of Medicare beneficiaries with dementia or neurodegenerative disease”.
B. “However, there is sufficient evidence that the use of PET Aβ imaging is promising in two
scenarios:
(1) to exclude Alzheimer’s disease (AD) in narrowly defined and clinically difficult
differential diagnoses, such as AD versus frontotemporal dementia (FTD)
(2) to enrich clinical trials seeking better treatments or prevention strategies for AD”.
CMS will cover one PET Aβ scan per patient through coverage with evidence
development (CED), under §1862(a)(1)(E) of the Act, in clinical studies that meet the CED
criteria.
https://www.cms.gov/medicare-coverage-database/details/nca-decision-memo.aspx?NCAId=265
Imaging Dementia—Evidence for Amyloid Scanning (IDEAS) Study Aim 1: To assess the impact of amyloid PET on the management of patients meeting Appropriate Use Criteria (AUC) [ Time Frame: 90 days ] • Goal: ≥ 30% change between intended and actual patient management in the following:
AD drug therapy Other drug therapy Counseling about safety and future planning
Aim 2: To assess the impact of amyloid PET on hospital admissions and emergency room visits in patients enrolled in the cohort (amyloid PET-known) compared to matched patients not in the cohort (amyloid PET-naïve) over 12 months [ Time Frame: 12 months ] • Goal: ≥ 10% relative reduction in amyloid PET-known patients in the following:
Inpatient hospital admissions over 12 months. Emergency room visits over 12 months.
Rabinovici, Gil D., et al. "Association of Amyloid Positron Emission Tomography With Subsequent Change in Clinical Management Among Medicare Beneficiaries With Mild Cognitive Impairment or Dementia." JAMA 321.13 (2019): 1286-1294.
Patient Characteristics
Positive 3154 70%
Negative 1347 30%
失智症
(n=4504)
Positive 3817 55%
Negative 3082 45%
輕度認知障礙
(n=6905)
Rabinovici, Gil D., et al. "Association of Amyloid Positron Emission Tomography With Subsequent Change in Clinical Management Among Medicare Beneficiaries With Mild Cognitive Impairment or Dementia." JAMA 321.13 (2019): 1286-1294.
Primary End Point Goal: 30.0% composite change in each group significantly exceeding (P < .001, 1-sided)
Amyloid PET改變了60%以上案例的病患處置計畫,遠超出目標的30%
Rabinovici, Gil D., et al. "Association of Amyloid Positron Emission Tomography With Subsequent Change in Clinical Management Among Medicare Beneficiaries With Mild Cognitive Impairment or Dementia." JAMA 321.13 (2019): 1286-1294.
Counseling, 20.7%
Counseling, 24.3%
non-AD durg, 25.4%
non-AD durg, 22.9%
AD drug, 44.9%
AD drug, 43.6%
Composite, 63.5%
Composite, 60.2%
Dementia(n=4,504)
MCI(n=6905)
Management changed between the pre- & post- amyloid PET
Secondary End Point The proportion of changes in diagnosis between pre- and post-PET visits.
After amyloid PET scan: • From AD to non-AD: 2,860/11,409 (25.1%
[95% CI, 24.3%-25.9%]) • From non–AD to AD: 1,201/11,409
(10.5% [95% CI, 10.0%-11.1%]) AD to non-AD
25%
non-AD to AD 11% no changed
64%
Diagnosis changes between pre- and post-PET visit
Amyloid PET改變了 36%案例的病因診斷
Rabinovici, Gil D., et al. "Association of Amyloid Positron Emission Tomography With Subsequent Change in Clinical Management Among Medicare Beneficiaries With Mild Cognitive Impairment or Dementia." JAMA 321.13 (2019): 1286-1294.
Post hoc analysis (事後分析)
MCI, Aβ(+) AD用藥比例
40.4%81.5%
Dementia, Aβ(+) AD用藥比例
63.2%91.2%
Rabinovici, Gil D., et al. "Association of Amyloid Positron Emission Tomography With Subsequent Change in Clinical Management Among Medicare Beneficiaries With Mild Cognitive Impairment or Dementia." JAMA 321.13 (2019): 1286-1294.
Early Diagnosis of Cognitive Impairment Is Important
48
1. Alzheimer’s Association. http://www.alz.org/documents_custom/public-health/2013-Value-of-Knowing.pdf. Accessed March 5, 2015. 2. Geldmacher DS et al. Alzheimers Dement. 2014;10(2):214-224. 3. Alzheimer’s Disease International. 2014. 4. Prince M, Bryce R, Ferri C; Alzheimer’s Disease International. http://www.alz.co.uk/research/worldalzheimerreport2011.pdf. Accessed January 28, 2015. 5. Ngandu T et al. Lancet. 2015. pii: S0140-6736(15)60461-5. [Epub ahead of print]. 6. de Vugt ME, Verhey FRJ. Prog Neurobiol. 2013;110:54-62. 7. https://www.gov.uk/government/publications/dementia-care-and-support. © Crown, 2013. Published November 2013. Accessed January 28, 2015. 8. Kremen WS et al. Int J Epidemiol. 2013;1-11.
Benefits of identifying people at risk for dementia
Allows for the earlier initiation of therapies and positive impact on health outcomes1,2
Allows for initiation of lifestyle modification3-5
Allows caregivers more time to adapt and develop positive coping strategies, which benefits both patients and caregivers6-7
Allows patients ability to take part in planning for their future6-7
Sheds light on early trajectories leading toward different types of cognitive impairment or maintenance of function8
35% of risk factors to dementia are potentially modifiable
Livingston, Gill, et al. "Dementia prevention, intervention, and care." The Lancet 390.10113 (2017): 2673-2734.
Dementia prevention, intervention, and care
Preventive strategies in dementia
Summary
18F-florbetaben 以影像呈現腦中有無類澱粉斑塊堆積
Appropriate use criteria for Amyloid PET
Johnson, Keith A., et al. "Appropriate use criteria for amyloid PET: a report of the Amyloid Imaging Task Force, the Society of Nuclear Medicine and Molecular Imaging, and the Alzheimer’s Association." Journal of Nuclear Medicine, (2013)
1. 持續或漸進之不明原因輕度認知障礙(MCI)患者。
2. 臨床表徵不明確(非典型或混和型),符合“Possible AD” 臨床標準患者
3. 早發型失智症患者(65歲前發病)
阿茲海默氏症病程、醫療處置與預防
National Institute on Aging, USA.
疾病進程
沒有疾病 沒有症狀
早期腦部病變 沒有症狀
阿茲海默病變 輕度症狀
中度到重度障礙
正常 阿茲海默氏症 臨床症狀前
阿茲海默氏症 輕度認知障礙
次級預防 醫療處置 初級預防 醫療介入
臨床階段
腦病理階段
找出有風險者 預防AD
預防或延緩症狀出現
刺激記憶 延緩退化
認知症狀治療 行為症狀治療 延緩退化
策略
Case Scenario 1
• 80 year old patient with a typical course and uncomplicated clinical history who has been adequately evaluated
• AD dementia highly likely
Amyloid PET would not be appropriate
Case Scenario 2
• 75 year old patient with mild impairment and an unusual presentation
• Cause of syndrome uncertain; understanding the pathology may or may not be pivotal
Amyloid PET may or may not be appropriate, depending on the determination of the dementia expert after completing the
comprehensive evaluation
Case Scenario 3
• 80 year old patient with clear impairments and multiple comorbidities that may be contributing the syndrome
Could be a candidate for amyloid PET because of the uncertainty of the cause of the
impairments
Case Scenario 4
• 55 year old with objectively documented impairments of uncertain cause
An AD diagnosis would have value, affecting his social and financial life and prognosis. Therefore, he would be an appropriate
candidate for PET