Dementia prevalence is predicted to triple to 152 million globally by 2050. Alzheimer’s disease (AD) constitutes 70% of cases. There is an urgent need to identify individuals with preclinical AD, a 10–20-year period of progressive brain pathology without noticeable cognitive symptoms, for targeted risk reduction. Current tests of AD pathology are either too invasive, specialised or expensive for population-level assessments. Cognitive tests are normal in preclinical AD. Emerging evidence demonstrates that movement analysis is sensitive to AD across the disease continuum, including preclinical AD. Our new smartphone test, TapTalk, combines analysis of hand and speech-like movements to detect AD risk. This study aims to [1] determine which combinations of hand-speech movement data most accurately predict preclinical AD [2], determine usability, reliability, and validity of TapTalk in cognitively asymptomatic older adults and [3], prospectively validate TapTalk in older adults who have cognitive symptoms against cognitive tests and clinical diagnoses of Mild Cognitive Impairment and AD dementia. Aim 1 will be addressed in a cross-sectional study of at least 500 cognitively asymptomatic older adults who will complete computerised tests comprising measures of hand motor control (finger tapping) and oro-motor control (syllabic diadochokinesis). So far, 1382 adults, mean (SD) age 66.20 (7.65) years, range 50–92 (72.07% female) have been recruited. Motor measures will be compared to a blood-based AD biomarker, phosphorylated tau 181 to develop an algorithm that classifies preclinical AD risk. Aim 2 comprises three sub-studies in cognitively asymptomatic adults: (i) a cross-sectional study of 30–40 adults to determine the validity of data collection from different types of smartphones, (ii) a prospective cohort study of 50–100 adults ≥ 50 years old to determine usability and test-retest reliability, and (iii) a prospective cohort study of ~1,000 adults ≥ 50 years old to validate against cognitive measures. Aim 3 will be addressed in a cross-sectional study of ~200 participants with cognitive symptoms to validate TapTalk against Montreal Cognitive Assessment and interdisciplinary consensus diagnosis. This study will establish the precision of TapTalk to identify preclinical AD and estimate risk of cognitive decline. If accurate, this innovative smartphone app will enable low-cost, accessible screening of individuals for AD risk. This will have wide applications in public health initiatives and clinical trials. ClinicalTrials.gov identifier: NCT06114914, 29 October 2023. Retrospectively registered.

中文翻译：

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开发针对临床前阿尔茨海默病的智能手机筛查测试并在整个痴呆症连续体中进行验证

预计到 2050 年，全球痴呆症患病率将增加两倍，达到 1.52 亿。阿尔茨海默病 (AD) 占病例的 70%。迫切需要识别患有临床前 AD 的个体，以有针对性地降低风险，AD 是一种持续 10-20 年的进行性脑病理学，没有明显的认知症状。目前的 AD 病理学测试对于人群水平的评估来说要么侵入性太强、专业性太强，要么成本高昂。临床前 AD 的认知测试是正常的。新出现的证据表明，运动分析对整个疾病连续体（包括临床前 AD）很敏感。我们的新智能手机测试 TapTalk 结合了手部和类似语音动作的分析来检测 AD 风险。本研究旨在 [1] 确定哪些手部言语运动数据组合最准确地预测临床前 AD [2]，确定 TapTalk 在无认知症状的老年人中的可用性、可靠性和有效性，以及 [3] 前瞻性地验证 TapTalk 在老年人中的效果患有针对认知测试和临床诊断的轻度认知障碍和 AD 痴呆症的认知症状的人。目标 1 将通过对至少 500 名无认知症状老年人的横断面研究来解决，这些老年人将完成计算机化测试，包括手部运动控制（手指敲击）和口腔运动控制（音节双动运动）的测量。到目前为止，已招募了 1382 名成年人，平均 (SD) 年龄为 66.20 (7.65) 岁，范围为 50-92 岁（72.07% 为女性）。运动测量将与基于血液的 AD 生物标志物磷酸化 tau 181 进行比较，以开发一种对临床前 AD 风险进行分类的算法。目标 2 包括针对无认知症状成年人的三项子研究：(i) 一项针对 30-40 名成年人的横断面研究，以确定从不同类型智能手机收集的数据的有效性，(ii) 一项针对 50-100 名成年人的前瞻性队列研究≥ 50 岁的成年人，以确定可用性和重测可靠性，以及 (iii) 对约 1,000 名 ≥ 50 岁的成年人进行前瞻性队列研究，以验证认知测量。目标 3 将在一项对约 200 名有认知症状的参与者进行的横断面研究中得到解决，以根据蒙特利尔认知评估和跨学科共识诊断来验证 TapTalk。这项研究将确定 TapTalk 识别临床前 AD 和评估认知能力下降风险的精确度。如果准确的话，这款创新的智能手机应用程序将能够以低成本、便捷的方式对个人进行 AD 风险筛查。这将在公共卫生倡议和临床试验中得到广泛应用。 ClinicalTrials.gov 标识符：NCT06114914，2023 年 10 月 29 日。回顾注册。