From the The Norwegian National Centre for Ageing and Health (G.G.T.), Vestfold Hospital Trust, Oslo ; Department of Geriatric Medicine (G.G.T.), Oslo University Hospital, Norway; Department of Health Sciences (M.H.N.), Lund Universityl Memory Clinic (M.H.N., E.S., S.P., O.H.), Skåne University Hospital, Malmö; and Clinical Memory Research Unit (M.H.N., E.S., S.P., O.H.), Department of Clinical Sciences Malmö, Lund University, Sweden.
Neurology. 2022 Nov 8;99(19):e2081-e2091. doi: 10.1212/WNL.0000000000201106. Epub 2022 Aug 26.
Impaired spatial navigation is considered an early sign in many neurodegenerative diseases. We aimed to determine whether spatial navigation was associated with future dementia in patients with subjective cognitive decline (SCD) or mild cognitive impairment (MCI) and to explore associations between spatial navigation and biomarkers of Alzheimer disease (AD) and neurodegeneration.
This study included memory clinic patients without dementia in the longitudinal BioFINDER cohort. The Floor Maze Test (FMT) was used to assess spatial navigation at baseline. Conversion to dementia was evaluated at 2-year and 4-year follow-ups. At baseline, amyloid-β 42/40 ratio, phosphorylated-tau (P-tau), and neurofilament light (NfL) were analyzed in CSF. Cortical thickness and volume of regions relevant for navigation and white matter lesion volume were quantified from MRI. The predictive role of the FMT for conversion to all-cause dementia was analyzed using logistic regression analyses in 2 models: (1) controlled for age, sex, and education and (2) adding baseline cognitive status and MMSE. Associations between FMT and biomarkers were adjusted for age, sex, and cognitive status (SCD or MCI).
One hundred fifty-six patients with SCD and 176 patients with MCI were included. FMT total time was associated with progression to all-cause dementia in model 2 at 2-year (OR 1.10, 95% CI 1.04-1.16) and at 4-year follow-up (OR 1.10, 95% CI 1.04-1.16), i.e., a 10% increase in odds of developing dementia per every 10 seconds increase in FMT. In the adjusted analyses, P-tau and NfL were associated with FMT total time, as well as hippocampal volume, parahippocampal, and inferior parietal cortical thickness. Amyloid-β 42/40 ratio was not associated with FMT total time.
Impaired spatial navigation was associated with conversion to dementia within 2 and 4 years and with key CSF and MRI biomarkers for AD and neurodegeneration in patients with SCD and MCI. This supports its use in early cognitive assessments, but the predictive accuracy should be validated in other cohorts.
This is a Class I prospective cohort study demonstrating association of baseline markers of spatial recognition with development of dementia in patients with SCD or MCI at baseline.
空间导航障碍被认为是许多神经退行性疾病的早期征象。我们旨在确定空间导航是否与主观认知下降（SCD）或轻度认知障碍（MCI）患者的未来痴呆有关，并探讨空间导航与阿尔茨海默病（AD）和神经退行性变的生物标志物之间的关系。
本研究纳入了纵向 BioFINDER 队列中无痴呆的记忆诊所患者。在基线时使用地板迷宫测试（FMT）评估空间导航。在 2 年和 4 年的随访中评估转化为痴呆的情况。在基线时，分析了 CSF 中的β淀粉样蛋白 42/40 比值、磷酸化 tau（P-tau）和神经丝轻链（NfL）。从 MRI 中量化了与导航相关的皮质厚度和区域体积以及白质病变体积。使用逻辑回归分析在 2 个模型中分析了 FMT 对所有原因痴呆转化的预测作用：（1）控制年龄、性别和教育；（2）添加基线认知状态和 MMSE。调整 FMT 与生物标志物之间的关联，以适应年龄、性别和认知状态（SCD 或 MCI）。
纳入了 156 名 SCD 患者和 176 名 MCI 患者。在模型 2中，FMT 总时间与 2 年（OR 1.10，95%CI 1.04-1.16）和 4 年随访（OR 1.10，95%CI 1.04-1.16）时向所有原因痴呆的进展相关，即 FMT 每增加 10 秒，患痴呆的几率就会增加 10%。在调整后的分析中，P-tau 和 NfL 与 FMT 总时间以及海马体体积、海马旁回和下顶叶皮质厚度相关，而β淀粉样蛋白 42/40 比值与 FMT 总时间无关。
在 SCD 和 MCI 患者中，受损的空间导航与 2 年内和 4 年内向痴呆的转化以及 AD 和神经退行性变的关键 CSF 和 MRI 生物标志物相关。这支持在早期认知评估中使用它，但应在其他队列中验证其预测准确性。
这是一项 I 级前瞻性队列研究，证明了 SCD 或 MCI 患者基线时空间识别的基线标志物与基线时痴呆发展的相关性。
