Abstract：
BACKGROUND: Olfactory dysfunction has been reported for its association with cognitive impairment and incident dementia. However, the underlying role of neurodegeneration in this relationship is not fully understood.
METHODS: This prospective cohort study included participants from the Shanghai Aging Study (SAS) who were 60 years or older and diagnosed as dementia-free at baseline and completed at least one follow-up interview between 2010 and 2022. At baseline, olfactory identification function was assessed by the 12-item Sniffin\' Sticks Smell test (SSST-12). Olfactory dysfunction was defined as SSST-12 < 7, 6, and 5 in three age groups of participants with (age < 70, 70 ≤ age < 80, and age ≥ 80), respectively, according to previously reported normative data of olfaction in the SAS. Baseline blood Neurofilament Light Chain (NfL) was quantified using the ultra-sensitive Single Molecular Array technology (Quanterix), and dichotomized into low and high levels according to the median concentration. Multiple cognitive function assessments were administered by the Mini-mental State Examination (MMSE) at baseline and follow-ups. We used the linear mixed-effect model to fit the MMSE trajectories in participants with and without olfactory dysfunction adjusting for baseline age, sex, education year, smoking, and APOE ε4, with person-specific MMSE intercept and slope. Stratified analysis was conducted in participants with low and high NfL.
RESULTS: Among 1125 participants included in this study, 296 were defined as having olfactory dysfunction at baseline. Less education, higher proportion of APOE ε4 allele, and lower baseline and follow-up MMSE scores were observed in participants with olfactory dysfunction (Table 1). During the median 9.4 years follow-up, participants with olfactory dysfunction at baseline evidenced a faster MMSE decline compared with those without olfactory dysfunction (b [95% CI]: -0.08 [-0.15, -0.02], P = 0.02) (Figure 1). Such association remained statistically significant (-0.18 [-0.31, -0.06], P = 0.005) in the subgroup with high NfL, but not in the subgroup with low NfL (0.004 [-0.07, 0.07], P = 0.92) (Figure 2).
CONCLUSIONS: Blood NfL may modify the association of olfactory dysfunction with long-term cognitive decline in community-dwelling older adults. In individuals with high potential neurodegeneration, olfactory dysfunction may be an independent indicator of future cognitive deterioration.
METHODS: This prospective cohort study included participants from the Shanghai Aging Study (SAS) who were 60 years or older and diagnosed as dementia-free at baseline and completed at least one follow-up interview between 2010 and 2022. At baseline, olfactory identification function was assessed by the 12-item Sniffin\' Sticks Smell test (SSST-12). Olfactory dysfunction was defined as SSST-12 < 7, 6, and 5 in three age groups of participants with (age < 70, 70 ≤ age < 80, and age ≥ 80), respectively, according to previously reported normative data of olfaction in the SAS. Baseline blood Neurofilament Light Chain (NfL) was quantified using the ultra-sensitive Single Molecular Array technology (Quanterix), and dichotomized into low and high levels according to the median concentration. Multiple cognitive function assessments were administered by the Mini-mental State Examination (MMSE) at baseline and follow-ups. We used the linear mixed-effect model to fit the MMSE trajectories in participants with and without olfactory dysfunction adjusting for baseline age, sex, education year, smoking, and APOE ε4, with person-specific MMSE intercept and slope. Stratified analysis was conducted in participants with low and high NfL.
RESULTS: Among 1125 participants included in this study, 296 were defined as having olfactory dysfunction at baseline. Less education, higher proportion of APOE ε4 allele, and lower baseline and follow-up MMSE scores were observed in participants with olfactory dysfunction (Table 1). During the median 9.4 years follow-up, participants with olfactory dysfunction at baseline evidenced a faster MMSE decline compared with those without olfactory dysfunction (b [95% CI]: -0.08 [-0.15, -0.02], P = 0.02) (Figure 1). Such association remained statistically significant (-0.18 [-0.31, -0.06], P = 0.005) in the subgroup with high NfL, but not in the subgroup with low NfL (0.004 [-0.07, 0.07], P = 0.92) (Figure 2).
CONCLUSIONS: Blood NfL may modify the association of olfactory dysfunction with long-term cognitive decline in community-dwelling older adults. In individuals with high potential neurodegeneration, olfactory dysfunction may be an independent indicator of future cognitive deterioration.
摘要：
背景：据报道，嗅觉功能障碍与认知障碍和偶发性痴呆有关。然而,神经变性在这种关系中的潜在作用尚不完全清楚。
方法：这项前瞻性队列研究纳入了来自上海老龄化研究（SAS）的参与者，这些参与者年龄在60岁或以上，在基线时被诊断为无痴呆，并在2010年至2022年间完成了至少一次随访访谈。在基线,嗅觉识别功能通过12项Sniffin棒嗅觉测试(SSST-12)进行评估。嗅觉功能障碍定义为SSST-12<7、6和5，在三个年龄组的参与者中（年龄<70，70≤年龄<80，和年龄≥80），分别,根据先前报道的SAS嗅觉的规范数据。使用超敏感单分子阵列技术（Quanterix）定量基线血液神经丝轻链（NfL），并根据中位数浓度分为低水平和高水平。在基线和随访时，通过迷你精神状态检查（MMSE）进行多项认知功能评估。我们使用线性混合效应模型来拟合有和没有嗅觉功能障碍的参与者的MMSE轨迹，调整基线年龄，性别,教育年,吸烟,和APOEε4，具有特定于人的MMSE截距和斜率。对NfL低和高的参与者进行了分层分析。
结果：在本研究的1125名参与者中，296被定义为在基线时具有嗅觉功能障碍。教育较少，APOEε4等位基因比例较高，在嗅觉功能障碍的参与者中观察到较低的基线和随访MMSE评分(表1).在中位9.4年的随访期间，基线时嗅觉功能障碍的参与者与无嗅觉功能障碍的参与者相比MMSE下降更快(b[95%CI]:-0.08[-0.15,-0.02],P=0.02)(图1)。这种关联仍然具有统计学意义(-0.18[-0.31，-0.06]，P=0.005）在具有高NfL的亚组中，但在低NfL的亚组中没有(0.004[-0.07,0.07]，P=0.92)(图2)。
结论：在社区居住的老年人中，血液NfL可能改变嗅觉功能障碍与长期认知能力下降的关系。在具有高潜在神经变性的个体中，嗅觉功能障碍可能是未来认知功能恶化的独立指标.
方法：这项前瞻性队列研究纳入了来自上海老龄化研究（SAS）的参与者，这些参与者年龄在60岁或以上，在基线时被诊断为无痴呆，并在2010年至2022年间完成了至少一次随访访谈。在基线,嗅觉识别功能通过12项Sniffin棒嗅觉测试(SSST-12)进行评估。嗅觉功能障碍定义为SSST-12<7、6和5，在三个年龄组的参与者中（年龄<70，70≤年龄<80，和年龄≥80），分别,根据先前报道的SAS嗅觉的规范数据。使用超敏感单分子阵列技术（Quanterix）定量基线血液神经丝轻链（NfL），并根据中位数浓度分为低水平和高水平。在基线和随访时，通过迷你精神状态检查（MMSE）进行多项认知功能评估。我们使用线性混合效应模型来拟合有和没有嗅觉功能障碍的参与者的MMSE轨迹，调整基线年龄，性别,教育年,吸烟,和APOEε4，具有特定于人的MMSE截距和斜率。对NfL低和高的参与者进行了分层分析。
结果：在本研究的1125名参与者中，296被定义为在基线时具有嗅觉功能障碍。教育较少，APOEε4等位基因比例较高，在嗅觉功能障碍的参与者中观察到较低的基线和随访MMSE评分(表1).在中位9.4年的随访期间，基线时嗅觉功能障碍的参与者与无嗅觉功能障碍的参与者相比MMSE下降更快(b[95%CI]:-0.08[-0.15,-0.02],P=0.02)(图1)。这种关联仍然具有统计学意义(-0.18[-0.31，-0.06]，P=0.005）在具有高NfL的亚组中，但在低NfL的亚组中没有(0.004[-0.07,0.07]，P=0.92)(图2)。
结论：在社区居住的老年人中，血液NfL可能改变嗅觉功能障碍与长期认知能力下降的关系。在具有高潜在神经变性的个体中，嗅觉功能障碍可能是未来认知功能恶化的独立指标.
