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

Introduction: 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). Methods: 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. Results: 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. Discussion/Conclusion: 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：神经退行性疾病的早期生物标志物，可为痴呆发病风险升高人群提供检测、监测及启动干预措施的契机。本研究旨在探究计时起身行走（Timed Up and Go, TUG）测试是否与早期脑神经退行性变相关，以及该测试能否作为主观认知下降（Subjective Cognitive Decline, SCD）人群认知衰退的标志物。

方法：本研究针对挪威一项旨在探究认知损害与痴呆早期生物标志物的前瞻性社区队列研究——《痴呆疾病启动研究》（Dementia Disease Initiation Study）开展纵向分析。研究对象被分为主观认知下降组与健康对照（Healthy Controls, HC）组。本研究的核心观测变量为计时起身行走测试结果，以及通过简易精神状态检查表（Mini-Mental State Examination, MMSE）与阿尔茨海默病注册联盟（Consortium to Establish a Registry for Alzheimer’s Disease, CERAD）记忆综合评分测得的认知水平。此外，本研究借助1.5T磁共振成像（1.5T-MRI）分析了脑形态学特征与计时起身行走测试结果的横断面关联。

结果：本研究共纳入45名研究对象（主观认知下降组21名，健康对照组24名），平均随访时长为1.50±0.70年。基线时两组认知表现无显著差异，但主观认知下降组的计时起身行走测试耗时更长。基线时计时起身行走测试耗时越长，两组受试者的认知下降速度均越快；此外，主观认知下降组中，测试耗时越长还与皮层厚度降低显著相关，尤其累及运动皮层、执行皮层、联合皮层及体感皮层区域。

讨论与结论：计时起身行走测试可预测主观认知下降人群的认知变化，且测试耗时与皮层厚度呈负相关。该测试是一种颇具应用前景的低成本、无创早期认知下降生物标志物，或可为痴呆发病风险升高人群提供干预启动的依据。