晚发性精神病 (LOP) 中的 Tau 生物标志物
Hallucinations or delusions that occur for the first time in older people with no acute medical problems or mood symptoms may be related to impending dementia. This study aims to confirm this hypothesis using novel blood biomarkers and Positron Emission Tomography (PET) imaging tracers, as well as non-invasive testing.
研究概览
详细说明
Psychotic symptoms that occur in advanced age in the absence of an acute medical condition or prominent mood symptoms can represent the late appearance of primary psychotic disorders such as very late-onset schizophrenia-like psychosis (VLOSP) or delusional disorder, or can presage the appearance of a neurodegenerative condition such as Alzheimer's disease (AD). An episode of non-affective psychosis late in life more than doubles the risk of subsequent neurodegenerative disease, with an average time from psychosis to AD diagnosis of 18 months. The biologic mechanisms responsible for the increased risk of dementia in those who experience psychosis are unclear. One hypothesis is reverse causality, in which inchoate neurodegeneration is responsible for psychotic symptoms that emerge in the absence of traditional cognitive hallmarks of dementia. The psychosis then heralds the inception of illness that will eventuate in cognitive decline. The investigators will utilize neurodegenerative biomarkers in the form of novel PET imaging tracers, plasma immunoassays and non-invasive neurophysiologic measurements to test this hypothesis in a pilot cohort of elderly subjects suffering with psychosis occurring in late-life without dementia for comparison with a cohort of healthy elderly controls (HEC)s who are participating in a study focused on those with dementia.
研究类型
注册 (估计的)
联系人和位置
学习联系方式
- 姓名:Erica Christen, MS
- 电话号码:516-562-3492
- 邮箱:EChriste@northwell.edu
研究联系人备份
- 姓名:Nichole Hoehn, MS
- 电话号码:516-562-3492
- 邮箱:nhoehn@northwell.edu
学习地点
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New York
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Manhasset、New York、美国、11030
- 招聘中
- The Feinstein Institutes for Medical Research
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接触:
- Erica Christen, MS
- 电话号码:516-562-3492
- 邮箱:EChriste@northwell.edu
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接触:
- Michelle Gong, AS
- 电话号码:516-562-3492
- 邮箱:MGong@northwell.edu
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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
取样方法
研究人群
Very late-onset schizophrenia-like psychosis (VLSOP) diagnostic criteria:
VLSOP is a schizophrenia-like condition characterized by the onset of delusions (primarily persecutory but also bizarre delusions) and/or hallucinations (auditory, visual, tactile, or olfactory) after age 60 in the absence of negative symptoms, formal thought disorder, and affective flattening that are common in early-onset schizophrenia.
Delusional disorder diagnostic criteria:
Delusional disorder comprises the presences of non-bizarre delusions including erotomanic, grandiose, jealous, persecutory, or somatic subtypes.
The presence of one (or more) above delusions with a duration of 1 month or longer.
描述
Inclusion Criteria:
- Male or female, aged 65-85 years.
- Diagnosis of late-onset non-affective primary psychotic disorder consistent with either very late-onset schizophrenia-like psychosis (VLOSP, International Late-Onset Schizophrenia Group consensus criteria, Howard et al., 2000) or delusional disorder (DSM-5 criteria)
- Caregiver available to provide collateral history and participation in informant-based ratings (NPI,CDR)
- Clinical Dementia Rating (CDR) score of 0 or 0.5.
- Mini-Mental State Examination (MMSE) score ≥ 24 and at the screening visit.
- Normal memory function (to rule-out mild cognitive impairment, MCI) documented by scoring within 1.5 SD range in education adjusted norms of the Logical Memory II subscale
- Ability to hear 500, 1000 and 1500 Hz bilaterally on a hearing evaluation (hearing aids permitted).
Exclusion Criteria:
- Participants with affective and psychotic disorders including bipolar disorder, schizoaffective disorder, active major depression; insulin dependent type 2 diabetes; a history of CVD; a history of epilepsy; a history of TBI with greater than 15 minutes of loss of consciousness; a movement disorder including Parkinson's disease; stroke; autoimmune disease affecting the CNS; substance abuse disorder; or active delirium/encephalopathy.
- Evidence of a clinically relevant neurological disorder
- Modified Hachinski ischemia score of more than 4.
- History of alcoholism or drug dependency/abuse within the last 5 years before screening.
- Presence of metal implants such as pacemakers, ear implants, internal bullet fragments or shrapnel.
- Inability to lie flat for 1 hour approximately.
- Hearing impairment as evidenced by the inability to hear 500, 1000 and 1500 Hz bilaterally on a hearing evaluation. Subjects with hearing aids will be allowed to participate if they meet minimum hearing requirements.
学习计划
研究是如何设计的?
设计细节
- 观测模型:COHORT
- 时间观点:PROSPECTIVE
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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Quantification of neurofibrillary tangle pathology in subjects via PET [18F]PI-2620 radiotracer uptake.
大体时间:Each subject will have one PET imaging scan at visit 3 (week 4).
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To determine whether there are increases in tau pathology in those with psychotic episodes that occur late in life employing tau PET ligands, and whether those increases are etiologic contributors to a stable psychosis or are a presage of an incipient cognitive decline. |
Each subject will have one PET imaging scan at visit 3 (week 4).
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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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Measurement of peripheral soluble tau pathology with tau plasma immunoassays.
大体时间:Each subject will have blood collected at visit 1 or 2 (week 1 or 2).
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Plasma samples will be collected via venipuncture from LOP subjects and batch shipped to Quanterix Inc. for ptau analyses and quantification on the SiMOA SR-X analyzer platform. |
Each subject will have blood collected at visit 1 or 2 (week 1 or 2).
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其他结果措施
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Evaluation of sensorimotor gating integrity and it's association to tau PET ligand uptake.
大体时间:Each subject will participate in this assessment at visit 2 (week 2).
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Prepulse Inhibition of Acoustic Startle (PPI) sessions will be assessed using eyeblink response (electromyography of the orbicularis oculi muscle) to a 115-dB startle stimulus. |
Each subject will participate in this assessment at visit 2 (week 2).
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合作者和调查者
调查人员
- 首席研究员:Jeremy Koppel, MD、Northwell Health
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
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
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- 23-0874
- 1R21MH135148 (美国 NIH 拨款/合同)
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)?
IPD 计划说明
Raw imaging files and neurocognitive data will be made available to other researchers via the NIMH Data Repository. Demographic data including age, sex, ethnicity and diagnosis will be shared. Information needed to generate a global unique identifier for the NIMH Data Archive (NDA) will be collected for each subject. In addition to the subject level data described above, all PET and MRI designs and experiment definitions, and study protocols will be deposited in the NDA.
IPD 共享时间框架
Data will be made available as soon as possible or at the time of associated publication, whichever comes first.
IPD 共享访问标准
To request access of the data, researchers will use the standard processes at NDA, and the NDA Data Access Committee will decide which requests to grant. The standard NDA data access process allows access for one year and is renewable.
IPD 共享支持信息类型
- 研究方案
- 企业社会责任
药物和器械信息、研究文件
研究美国 FDA 监管的药品
研究美国 FDA 监管的设备产品
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