Supplementary Material for: Timed Up and Go in People with Subjective Cognitive Decline Is Associated with Faster Cognitive Deterioration and Cortical Thickness

<b><i>Introduction:</i></b> Early markers of neurodegeneration provide an opportunity to detect, monitor, and initiate interventions in individuals who have an increased risk of developing dementia. Here, we investigated whether the Timed Up and Go (TUG) test is associated with early brain neurodegeneration and whether the TUG test could be a marker of cognitive decline in people with subjective cognitive decline (SCD). <b><i>Methods:</i></b> This is a longitudinal analysis of the Dementia Disease Initiation Study, a prospective, community-based, cohort study from Norway, designed to investigate early markers of cognitive impairment and dementia. Participants were classified as SCD and healthy controls (HC). The main studied variables were the TUG test and cognition as measured by the Mini-Mental State Examination and the Consortium to Establish a Registry for Alzheimer’s Disease memory composite score. Additionally, we investigated the cross-sectional association of brain morphology with the TUG using 1.5T-MRI. <b><i>Results:</i></b> The sample included 45 participants (SCD = 21, HC = 24) followed during a mean time of 1.50 ± 0.70 years. At baseline, the cognitive performance did not differ between the groups, but TUG was longer in SCD. Slower baseline TUG was associated with a faster cognitive decline in both groups and it was also associated with reduced cortical thickness especially in motor, executive, associative, and somatosensory cortical regions in people with SCD. <b><i>Discussion/Conclusion:</i></b> TUG predicted cognitive change in individuals with SCD, and there was a negative association between TUG and cortical thickness. TUG is a promising cheap and noninvasive marker of early cognitive decline and may help initiate interventions in individuals who have an increased risk of dementia.

**引言**：神经退行性病变的早期生物标志物，可为痴呆发病风险升高人群提供检测、监测与干预启动的契机。本研究旨在探索定时起立行走测试（Timed Up and Go, TUG）是否与早期脑神经退行性病变相关，以及该测试能否作为主观认知下降（subjective cognitive decline, SCD）人群认知下降的生物标志物。

**研究方法**：本研究为一项针对「痴呆发病启动研究（Dementia Disease Initiation Study）」的纵向分析。该研究是一项来自挪威的前瞻性社区队列研究，旨在探索认知损害与痴呆的早期生物标志物。研究对象分为主观认知下降组（SCD）与健康对照组（healthy controls, HC）。本研究的核心观测变量为TUG测试结果与认知水平，认知水平通过简易精神状态检查表（Mini-Mental State Examination）及阿尔茨海默病登记联盟记忆组合评分（Consortium to Establish a Registry for Alzheimer’s Disease memory composite score）进行评估。此外，本研究借助1.5T磁共振成像（1.5T-MRI）探索了脑形态学与TUG测试的横断面关联。

**研究结果**：本研究共纳入45名研究对象（SCD组21例，HC组24例），平均随访时长为1.50±0.70年。基线时，两组的认知表现无显著差异，但SCD组的TUG测试耗时更长。基线时较慢的TUG测试速度与两组更快的认知下降速率相关；此外，在SCD人群中，较慢的基线TUG测试还与皮层厚度降低存在关联，尤其累及运动、执行、联合及体感皮层区域。

**讨论与结论**：TUG测试可预测SCD人群的认知变化，且TUG测试耗时与皮层厚度呈负相关。TUG测试是一种极具应用前景的低成本、无创性早期认知下降生物标志物，或可助力为痴呆发病风险升高人群启动干预措施。