Pang Chunyang, Cao Wen, Xie Jiali, Li Yaojia, Zhu Luyi, Yu Huan, Fan Dongsheng, Deng Binbin
Department of Rehabilitation Medicine, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Neurology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
J Cachexia Sarcopenia Muscle. 2025 Aug;16(4):e70003. doi: 10.1002/jcsm.70003.
Amyotrophic lateral sclerosis (ALS) has a prolonged latency period, though its preclinical characteristics remain poorly understood. This study uses UK Biobank data to explore and compare ALS's pre-diagnostic features, including symptoms and medication use, aiming to provide insights into the disease's underlying mechanisms.
Clinical symptoms and medications were identified from self-reports, hospital records, and death registry data. Propensity score matching was used to match ALS with Alzheimer's disease (AD) and Parkinson's disease (PD), ensuring balance in socioeconomic factors to compare symptoms 0-5 years before diagnosis. Cox regression analysis was applied to assess the associations between medication use and the risk of incident ALS and mortality after ALS diagnosis.
A total of 753 ALS cases were observed in 502 417 participants, with an incidence rate of 10.58 per 100 000 person-years. In the ALS cohort, the male-to-female ratio was 2.9, with a median age at onset of 64.61 years (Interquartile range (IQR): 56.80-71.31) and a median survival time post-diagnosis of 9.08 months (IQR: 3.18-18.98), while females (log-rank p = 0.038) and individuals with earlier (< 64.61 years) disease onset (log-rank p < 0.001) had longer survival periods. In the 5 years prior to diagnosis, ALS showed a higher incidence of falls compared to ad (11.3% vs. 3.2%, p < 0.001), but a lower incidence than PD (10.7% vs. 28.3%, p < 0.001). Additionally, ALS had a lower incidence of depression (4.6% vs. 25.6%, p < 0.001), anxiety (3.5% vs. 18.1%, p < 0.001), sleep disorders (1.4% vs. 7.2%, p < 0.001), hypotension (3.4% vs. 30.5%, p < 0.001), constipation (0.3% vs. 4.9%, p < 0.001), and urinary dysfunction (2.2% vs. 8.7%, p < 0.001) compared with PD. The use of calcium channel blockers may be a risk factor for incident ALS (adjusted HR 1.61, 95% CI: 1.22-2.12, p < 0.001).
Pre-diagnostic presentations of falls are more frequent in ALS than in AD, but less frequent than in PD. However, ALS exhibits fewer psychiatric symptoms and autonomic dysfunction compared with PD. The use of calcium channel blockers may be associated with an increased risk of developing ALS in the future.
肌萎缩侧索硬化症（ALS）有较长的潜伏期，但其临床前特征仍了解甚少。本研究利用英国生物银行的数据来探索和比较ALS的诊断前特征，包括症状和药物使用情况，旨在深入了解该疾病的潜在机制。
从自我报告、医院记录和死亡登记数据中识别临床症状和药物。采用倾向得分匹配法将ALS与阿尔茨海默病（AD）和帕金森病（PD）进行匹配，确保社会经济因素平衡，以比较诊断前0至5年的症状。应用Cox回归分析评估药物使用与ALS发病风险及ALS诊断后死亡率之间的关联。
在502417名参与者中，共观察到753例ALS病例，发病率为每10万人年10.58例。在ALS队列中，男女比例为2.9，发病年龄中位数为64.61岁（四分位间距（IQR）：56.80 - 71.31），诊断后中位生存时间为9.08个月（IQR：3.18 - 18.98），而女性（对数秩检验p = 0.038）和发病较早（<64.61岁）的个体（对数秩检验p < 0.001）生存期更长。在诊断前5年，ALS的跌倒发生率高于AD（11.3%对3.2%，p < 0.001），但低于PD（10.7%对28.3%，p < 0.001）。此外，与PD相比，ALS的抑郁症（4.6%对25.6%，p < 0.001）、焦虑症（3.5%对18.1%，p < 0.001）、睡眠障碍（1.4%对7.2%，p < 0.001）、低血压（3.4%对30.5%，p < 0.001）、便秘（0.3%对4.9%，p < 0.001）和排尿功能障碍（2.2%对8.7%，p < 0.001）发生率更低。使用钙通道阻滞剂可能是ALS发病的一个危险因素（调整后HR 1.61，95%CI：1.22 - 2.12，p < 0.001）。
ALS诊断前跌倒的表现比AD更频繁，但比PD少。然而，与PD相比，ALS的精神症状和自主神经功能障碍较少。使用钙通道阻滞剂可能与未来发生ALS的风险增加有关。
