Abstract：
OBJECTIVE: Parkinson\'s disease (PD) is an age-related condition characterized by substantial phenotypic variability. Consequently, pathways and proteins involved in biological aging, such as the central aging pathway comprising insulin-like growth factor 1-α-Klotho-sirtuin 1-forkhead box O3-peroxisome proliferator-activated receptor γ, may potentially influence disease progression.
METHODS: Cerebrospinal fluid (CSF) levels of α-Klotho in 471 PD patients were examined. Of the 471 patients, 96 carried a GBA1 variant (PD GBA1), whilst the 375 non-carriers were classified as PD wild-type (PD WT). Each patient was stratified into a CSF α-Klotho tertile group based on the individual level. Kaplan-Meier survival curves and Cox regression analysis stratified by tertile groups were conducted. These longitudinal data were available for 255 patients. Follow-up times reached from 8.4 to 12.4 years. The stratification into PD WT and PD GBA1 was undertaken to evaluate potential continuum patterns, particularly in relation to CSF levels.
RESULTS: Higher CSF levels of α-Klotho were associated with a significant later onset of cognitive impairment. Elevated levels of α-Klotho in CSF were linked to higher Montreal Cognitive Assessment scores in male PD patients with GBA1 mutations.
CONCLUSIONS: Our results indicate that higher CSF levels of α-Klotho are associated with a delayed cognitive decline in PD. Notably, this correlation is more prominently observed in PD patients with GBA1 mutations, potentially reflecting the accelerated biological aging profile characteristic of individuals harboring GBA1 variants.
METHODS: Cerebrospinal fluid (CSF) levels of α-Klotho in 471 PD patients were examined. Of the 471 patients, 96 carried a GBA1 variant (PD GBA1), whilst the 375 non-carriers were classified as PD wild-type (PD WT). Each patient was stratified into a CSF α-Klotho tertile group based on the individual level. Kaplan-Meier survival curves and Cox regression analysis stratified by tertile groups were conducted. These longitudinal data were available for 255 patients. Follow-up times reached from 8.4 to 12.4 years. The stratification into PD WT and PD GBA1 was undertaken to evaluate potential continuum patterns, particularly in relation to CSF levels.
RESULTS: Higher CSF levels of α-Klotho were associated with a significant later onset of cognitive impairment. Elevated levels of α-Klotho in CSF were linked to higher Montreal Cognitive Assessment scores in male PD patients with GBA1 mutations.
CONCLUSIONS: Our results indicate that higher CSF levels of α-Klotho are associated with a delayed cognitive decline in PD. Notably, this correlation is more prominently observed in PD patients with GBA1 mutations, potentially reflecting the accelerated biological aging profile characteristic of individuals harboring GBA1 variants.
摘要：
目的：帕金森病（PD）是一种与年龄有关的疾病，其特征是表型变异。因此,参与生物衰老的途径和蛋白质，如包括胰岛素样生长因子1-α-Klotho-sirtuin1-叉头盒O3-过氧化物酶体增殖物激活受体γ的中枢衰老途径，可能会影响疾病进展。
方法：检测471例PD患者脑脊液中α-Klotho的水平。在471名患者中，96携带GBA1变体(PDGBA1)，而375名非携带者被分类为PD野生型（PDWT）。根据个体水平将每位患者分为CSFα-Klotho三元组。按三元组进行Kaplan-Meier生存曲线和Cox回归分析。这些纵向数据可用于255例患者。随访时间从8.4年到12.4年。对PDWT和PDGBA1进行了分层，以评估潜在的连续模式，特别是与CSF水平有关。
结果：较高的脑脊液α-Klotho水平与认知障碍的明显晚期发病有关。CSF中α-Klotho水平的升高与具有GBA1突变的男性PD患者的较高的蒙特利尔认知评估评分有关。
结论：我们的结果表明，较高的CSF水平的α-Klotho与PD的认知功能延迟下降有关。值得注意的是,这种相关性在具有GBA1突变的PD患者中更为突出，可能反映了携带GBA1变体的个体加速的生物衰老特征。
方法：检测471例PD患者脑脊液中α-Klotho的水平。在471名患者中，96携带GBA1变体(PDGBA1)，而375名非携带者被分类为PD野生型（PDWT）。根据个体水平将每位患者分为CSFα-Klotho三元组。按三元组进行Kaplan-Meier生存曲线和Cox回归分析。这些纵向数据可用于255例患者。随访时间从8.4年到12.4年。对PDWT和PDGBA1进行了分层，以评估潜在的连续模式，特别是与CSF水平有关。
结果：较高的脑脊液α-Klotho水平与认知障碍的明显晚期发病有关。CSF中α-Klotho水平的升高与具有GBA1突变的男性PD患者的较高的蒙特利尔认知评估评分有关。
结论：我们的结果表明，较高的CSF水平的α-Klotho与PD的认知功能延迟下降有关。值得注意的是,这种相关性在具有GBA1突变的PD患者中更为突出，可能反映了携带GBA1变体的个体加速的生物衰老特征。
