Co-LEsions in Alzheimer Disease and Related Disorders (CLEM)
One of the crucial challenges for the future of Alzheimer's disease (AD) therapeutic approaches in elderly is to target the main pathological process responsible for disability and dependency. However, a progressive cognitive impairment occurring after the age of 70 is often related to mixed lesions of neurodegenerative and vascular origins. Whereas young patients are mostly affected by pure lesions, aging favors the occurrence of co-lesions of AD, vascular and Lewy body types. Pure DLB (Dementia with Lewy Body) and AD are distinct disorders but they often coexist in old age patients, the Abeta pathology of DLB/AD cases being different to that observed in patients with AD alone. Vascular dementia (VD) and AD with cerebrovascular disease (AD+CVD) are the leading causes of dementia next to AD alone. Lack of consensus persists about the diagnosis criteria for VD and AD+CVD, due in part to their clinical, pathological heterogeneity and the multiple pathological subtypes.
We do not know the precise role and weight of each brain lesion type in the disability progression in elderly. To target the actual pathological process, we need to disclose the functional weight of AD, Lewy body and vascular lesion types in elderly. Most of the studies report on functional and clinical abnormalities in patients with pure pathologies. Thus, co-morbid processes involved in the transition from an independent functional status to disability in the elderly with co-lesions still remain to be elucidated. Neuropathological examination often performed at late stages cannot answer this question at mild or moderate stages.
Brain MRI, Single Photon Emission Computed Tomography (SPECT) with DaTscan® and CSF biomarkers help routinely in performing the diagnosis of pure or mixed lesions responsible for dementia. The topography of the atrophy in MRI helps to provide information about the etiological diagnosis. Medial temporal lobe atrophy on MRI has good discriminatory power for AD compared to DLB and VD in pathologically confirmed cases. DaTscan® SPECT presents with good sensitivity and specificity at early stages of DLB. The good diagnosis value of CSF biological markers has led recently to their inclusion in the research diagnosis criteria of AD. Low Aβ1-42 and high levels of total tau and hyperphosphorylated tau isoforms appear to be the most sensitive and specific CSF biomarkers. Aβ1-42 is lowered in AD, as well as in other neurodegenerative diseases like DLB, VD. The combination of MRI, particularly medial temporal atrophy measures and vascular lesions on FLAIR MRI sequences, SPECT and CSF biomarkers seem to be of incremental value for the diagnosis AD, VD, DLB and mixed profiles.
The aim of this study is to identify the biomarkers (MRI, SPECT-DaTscan® and CSF), and their combination, that are the most predictive of functional disability in elderly presenting with a progressive cognitive decline related to AD, DLB, VD and all mixed patterns.
研究概览
研究类型
注册 (预期的)
阶段
- 不适用
联系人和位置
学习地点
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Villeurbanne、法国、69100
- 招聘中
- Hopital Charpennes
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接触:
- Nawele Boublay
- 电话号码:00334.27.85.63.02
- 邮箱:nawale.boublay@chu-lyon.fr
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首席研究员:
- Pierre KROLAK-SALMON
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Male or female subject aged over 70 years
- Out-patient consulting at one of the Memory Centres participating to the study
- Patients meeting diagnosis criteria for dementia due to Alzheimer's disease (McKhann, Knopman et al. 2011), vascular dementia (NINCDS-AIREN criteria, Roma´n, G. C., Tatemichi, T. K., Erkinjuntti, T., et al. (1993), Lewy body disease (McKeith, Dickson et al. 2005), and patients presenting with mixed signs and symptoms suggesting a combination of these diagnosis
- Mild or moderate dementia stage (MMSE criteria > 15)
- Being affiliated to health insurance
- Patient with sufficient visual, auditory and oral and written French language skills to complete the clinical and neuropsychological evaluations
- Accompanied by a close relation in sufficient contact with the subject to assess their dependency
Exclusion Criteria:
- Patients with psychiatric disorders (Axe 1 DSMIV (Diagnostic and Statistical Manual of Mental Disorders) disease) excepted patients with depressive or anxious disorders stabilized for more than 3 months
- Patients taking any neuroleptic psychotropic medication
- Patients taking other psychotropic medication, with the exception of any antidepressant, hypnotic, anxiolytic, acetylcholinesterase inhibitors or memantine which has been prescribed and stabilised for more than 3 months
- Patients with signs and symptoms suggestive of dementia related to other diseases than AD, vascular and Lewy diseases, or mixed forms
- Patients with other neurological diseases
- Patients with progressive and unstable pathologies which could interfere with the variables under consideration
- Deafness or blindness which could compromise evaluation of the patient
- Patients being not able to undergo DaTscan®: with moderate or severe hepatic or renal impairment, a known hypersensitivity to ioflupane or any of the excipients
- Patient living in an institution
- Patient meeting brain MRI exclusion criteria (pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments or foreign objects in the eyes, skin, or body) or refusing MRI
- Patient being under guardianship
学习计划
研究是如何设计的?
设计细节
- 主要用途:放映
- 分配:不适用
- 介入模型:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
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其他:SPEC-DaTscan
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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Disability progression
大体时间:2 years
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defined by the Disability Assessment in Dementia (DAD) scale (Gauthier, Gelinas et al. 1997; Gelinas, Gauthier et al. 1999)
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2 years
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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Neuropsychological inventory
大体时间:2 years
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For the diagnosis and initial correlation with imaging and CSF markers, o For longitudinal assessments : MMSE (Folstein, Folstein et al. 1975), Batterie Rapide d'Efficience Frontale (BREF) (Dubois, Slachevsky et al. 2000) Adas-Cog (Rosen, Mohs et al. 1984)
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2 years
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NeuroPsychiatric inventory
大体时间:2 years
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Inventory described in Cummings, Mega et al. 1994
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2 years
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Clinical/serum markers
大体时间:2 years
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Disability progression and cognitive decline
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2 years
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合作者和调查者
出版物和有用的链接
研究记录日期
研究主要日期
学习开始
初级完成 (预期的)
研究完成 (预期的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.
SPECT-DaTscan的临床试验
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Assistance Publique - Hôpitaux de ParisAssociation Française contre les Myopathies (AFM), Paris; ARS (Association pour la Recherche... 和其他合作者完全的
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GE HealthcareQuintiles, Inc.; H2O Clinical LLC完全的
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GE HealthcarePPD完全的特发性震颤 | 多系统萎缩 (MSA) | 帕金森综合症 | 帕金森病(PD) | 进行性核上性麻痹 (PSP)中国