Plasma markers of Alzheimer’s Disease and changes in postoperative cognition

阿尔茨海默病的血浆标志物和术后认知的变化

• 批准号: 10284747
• 负责人: JACQUELINE M LEUNG
• 金额: $ 40.34万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-24 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10284747
• 关键词: Activities of Daily Living; Acute; Affect; Alzheimer disease detection; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease related dementia; Alzheimer' s disease test; Alzheimer’s disease biomarker; Amyloid; Amyloid beta-42; Amyloid beta-Protein; Anesthesia procedures; Anesthetics; Benchmarking; Biological Markers; Brain; Clinical; Cognition; Cognitive; Delirium; Dementia; Deposition; Development; Diagnosis; Early Diagnosis; Elderly; Environment; Evaluation; Exposure to; Family; Functional disorder; Health Personnel; Healthcare Systems; Human Resources; Impaired cognition; Individual; Informed Consent; Intervention; Measurement; Memory impairment; Nerve Degeneration; Neuropsychology; Operative Surgical Procedures; Opioid; Pain; Patients; Perioperative; Pharmaceutical Preparations; Phase; Physicians; Plasma; Postoperative Period; Prevalence; Process; Progressive Disease; Public Health; Research; Risk; Sleep disturbances; Societies; Specialist; Stress; Symptoms; Syndrome; Tissues; Training; Work; adverse outcome; aged; base; clinically significant; cognitive function; cognitive testing; cohort; daily functioning; follow-up; functional decline; functional status; in vivo; instrumental activity of daily living; mild cognitive impairment; neuroimaging; older patient; parent grant; postoperative delirium; pre-clinical; prodromal Alzheimer' s disease; protein aggregation; screening; slow potential; tau Proteins; tau-1

Dementia is a major public health problem with direct consequences to the individual, family, society, and the healthcare system. The pathophysiology of Alzheimer's disease and related dementias (ADRD) is incompletely understood despite its prevalence. The pathology of ADRD begins years before clinical symptoms emerge, therefore the need to provide early diagnosis in order to develop follow up and potential therapy is urgently needed before the neurodegenerative process advances to a later stage. The central hypothesis of this supplement is that patients with seemingly intact cognition, but with positive plasma AD biomarkers are vulnerable to the stress of major surgery and anesthesia, resulting in a higher likelihood of developing postoperative delirium, subsyndromal delirium, and acute cognitive decline. Therefore, perioperative period provides an earlier window to diagnosing cognitive impairment including AD before clinically significant symptoms are recognized, thus providing an earlier path to follow-up and intervention to potentially slow the rate of cognitive decline. The surgical setting provides a unique natural environment to study how the vulnerable brain may respond in the setting of perioperative stress such as pain, exposure to new medications, or sleep disruption. Routine preoperative evaluation does not formally assess for early signs of memory impairment because most individuals with AD and their families don't seek evaluation for cognitive impairment until it affects their daily functioning, which occurs later in the pathophysiology of AD. Recent research has shown that plasma AD biomarkers, including Aβ42/40 and p-tau181, are highly correlated with brain amyloid and tau burden detected by neuropathological assessment and amyloid and tau neuroimaging. Plasma AD biomarkers have high sensitivity in predicting AD, therefore can provide a relatively non-invasive benchmark for AD detection, even in asymptomatic or prodromal phases. This supplement will leverage cognitive, surgical, clinical, and tissue banking from over 672 patients aged 65 years or older undergoing major elective surgery, a cohort selected from the parent grant. Cognitive tests were conducted before and daily in the first 2-3 days after surgery; incident delirium was assessed each day after surgery; and functional status (activities of daily living, instrumental activities of daily living) was assessed at 1 month after surgery. We hypothesize that patients with postoperative delirium/subsyndromal delirium are more likely to have positive plasma AD biomarkers, and those with preoperative plasma biomarkers of AD are more likely to decline in cognitive functioning and daily functioning in the days after surgery through 1 month after surgery. Our study will not only inform the pathophysiology of delirium, but will also provide an earlier window to diagnosing patients at risk for developing AD in order to guide interventions that may slow the rate of longer-term cognitive and functional decline.

痴呆症是一个重大的公共卫生问题，对个人、家庭、社会和社会产生直接影响 医疗保健系统。阿尔茨海默病和相关痴呆 (ADRD) 的病理生理学尚不完全 尽管它很流行，但仍被理解。 ADRD 的病理学在临床症状出现前数年就已开始， 因此，迫切需要提供早期诊断，以便开展后续行动和潜在的治疗 在神经退行性过程进展到后期之前需要。这个假设的中心假设 补充的是，认知能力看似完好，但血浆 AD 生物标志物呈阳性的患者 容易受到大手术和麻醉的压力，导致患上这种疾病的可能性更高 术后谵妄、亚综合征谵妄和急性认知能力下降。因此，围手术期 为在出现临床意义之前诊断包括 AD 在内的认知障碍提供了一个更早的窗口 症状得到识别，从而提供更早的跟进和干预途径，以减缓病情的发展 认知能力下降的速度。手术环境提供了一个独特的自然环境来研究如何 脆弱的大脑可能会在围手术期压力下做出反应，例如疼痛、接触新药物、 或睡眠中断。常规术前评估并不能正式评估早期记忆迹象 因为大多数 AD 患者及其家人不会寻求认知障碍评估 直到它影响他们的日常功能，这在 AD 的病理生理学后期发生。最近的研究有 表明血浆 AD 生物标志物，包括 Aβ42/40 和 p-tau181，与脑淀粉样蛋白高度相关 和 tau 负荷通过神经病理学评估和淀粉样蛋白和 tau 神经影像学检测。等离子AD 生物标志物对预测AD具有较高的敏感性，因此可以提供相对无创的基准 用于 AD 检测，即使是在无症状或前驱期。该补充品将利用认知、外科、 来自超过 672 名 65 岁或以上接受重大选择性手术的患者的临床和组织库， 从家长补助金中选择的队列。认知测试在前 2-3 天内每天进行 手术后；手术后每天评估谵妄事件；和功能状态（日常活动 术后1个月评估生活（日常生活的工具性活动）。我们假设 术后谵妄/亚综合征谵妄患者更有可能出现血浆 AD 阳性 生物标志物，以及术前血浆生物标志物具有 AD 的患者认知能力更可能下降 术后几天至术后 1 个月的功能和日常功能。我们的学习不仅 为谵妄的病理生理学提供信息，同时也为诊断有谵妄风险的患者提供更早的窗口 发展AD以指导可能减缓长期认知和功能速度的干预措施 衰退。

项目成果

The Impact of Surgery duration and Surgery End Time on Postoperative Sleep in Older Adults.

手术持续时间和手术结束时间对老年人术后睡眠的影响。

• DOI: 10.23937/2572-4053.1510034
• 发表时间: 2021
• 期刊: Journal of sleep disorders and management
• 作者: Tran,Danielle;Tang,Christopher;Tabatabai,Sanam;Pleasants,Devon;Choukalas,Christopher;Min,Jie;Do,Quyen;Sands,Laura;Lee,Kathryn;Leung,JacquelineM
• 通讯作者: Leung,JacquelineM

Lidocaine Infusion for the Management of Postoperative Pain and Delirium (LIMPP): protocol for a randomised control trial.

• DOI: 10.1136/bmjopen-2021-059416
• 发表时间: 2022-06-06
• 期刊: BMJ OPEN
• 影响因子: 2.9
• 作者: Buren, Marc Alan;Theologis, Alekos;Zuraek, Ariadne;Behrends, Matthias;Clark, Aaron J.;Leung, Jacqueline M.
• 通讯作者: Leung, Jacqueline M.