Department of Pediatrics, Albert Einstein College of Medicine, Van Etten Building, Suite 1C, 1225 Morris Park Avenue, Bronx, NY, 10461, USA.
Department of Neuroscience, Rose F. Kennedy Center, Albert Einstein College of Medicine, Bronx, NY, USA.
Orphanet J Rare Dis. 2021 Apr 13;16(1):177. doi: 10.1186/s13023-021-01818-0.
Cystinosis, a rare lysosomal storage disease, is characterized by cystine crystallization and accumulation within tissues and organs, including the kidneys and brain. Its impact on neural function appears mild relative to its effects on other organs, but therapeutic advances have led to substantially increased life expectancy, necessitating deeper understanding of its impact on neurocognitive function in adulthood. We previously demonstrated intact auditory sensory processing, accompanied by mild sensory memory difficulties, in children and adolescents with cystinosis.
We investigated whether further progressive decrements in these processes would be observed in adults with cystinosis, comparing high-density auditory-evoked potential (AEP) recordings from adults with cystinosis (N = 15; ages: 19-38 years) to those of age-matched controls (N = 17). We employed a duration oddball paradigm with different stimulation rates, in which participants passively listened to regularly occurring standard tones interspersed with infrequently occurring deviant tones. Analyses focused on AEP components reflecting auditory sensory-perceptual processing (N1 and P2), sensory memory (mismatch negativity, MMN), and attentional orienting (P3a).
Overall, adults with cystinosis produced highly similar sensory-perceptual AEP responses to those observed in controls suggesting intact early auditory cortical processing. However, significantly increased P2 and P3a amplitudes and reduced MMN at slower stimulation rates were observed, suggesting mild-to-moderate changes in auditory sensory memory and attentional processing. While cognitive testing revealed lower scores on verbal IQ and perceptual reasoning in cystinosis, these did not correlate with the AEP measures.
These neurophysiological data point to the emergence of subtle auditory processing deficits in early adulthood in cystinosis, warranting further investigation of memory and attentional processes in this population, and of their consequences for perceptual and cognitive function.
胱氨酸贮积症是一种罕见的溶酶体贮积病，其特征是胱氨酸在组织和器官内结晶和积累，包括肾脏和大脑。与其他器官相比，它对神经功能的影响似乎较轻，但治疗的进步导致预期寿命大大延长，因此需要更深入地了解其对成年期神经认知功能的影响。我们之前证明了胱氨酸贮积症儿童和青少年的听觉感觉处理完好，伴有轻微的感觉记忆困难。
我们研究了胱氨酸贮积症成人是否会出现这些过程的进一步进行性下降，将胱氨酸贮积症成人（N=15；年龄：19-38 岁）的高密度听觉诱发电位（AEPs）记录与年龄匹配的对照组（N=17）进行比较。我们采用了不同刺激率的时长Oddball 范式，其中参与者被动地听规则出现的标准音，同时穿插出现不常出现的偏差音。分析集中在反映听觉感觉知觉处理的 AEPs 成分上（N1 和 P2）、感觉记忆（失匹配负波，MMN）和注意定向（P3a）。
总体而言，胱氨酸贮积症成人的感觉知觉 AEP 反应与对照组非常相似，表明早期听觉皮质处理完好。然而，在较慢的刺激率下观察到 P2 和 P3a 振幅增加和 MMN 减少，表明听觉感觉记忆和注意力处理有轻度到中度变化。虽然认知测试显示胱氨酸贮积症的言语智商和知觉推理得分较低，但这些与 AEP 测量值没有相关性。
这些神经生理学数据表明胱氨酸贮积症在成年早期出现微妙的听觉处理缺陷，需要进一步研究该人群的记忆和注意力过程，以及它们对感知和认知功能的影响。
