Douglas Mental Health University Institute, Montreal, QC, Canada.
McGill University, Montreal, QC, Canada.
J Alzheimers Dis. 2017;60(4):1589-1600. doi: 10.3233/JAD-170545.
Prevention of dementia due to Alzheimer's disease (d/AD) requires interventions that slow the disease process prior to symptom onset. To develop such interventions, one needs metrics that assess pre-symptomatic disease progression. Familiar measures of progression include cerebrospinal fluid (CSF) biochemical and imaging analyses, as well as cognitive testing. Changes in the latter can sometimes be difficult to distinguish from effects of "normal" aging. A different approach involves testing of "central auditory processing" (CAP), which enables comprehension of auditory stimuli amidst a distracting background (e.g., conversation in a noisy bar or restaurant). Such comprehension is often impaired in d/AD. Similarly, effortful or diminished auditory comprehension is sometimes reported by cognitively healthy elders, raising the possibility that CAP deficit may be a marker of pre-symptomatic AD. In 187 cognitively and physically healthy members of the aging, AD family history-positive PREVENT-AD cohort, we therefore evaluated whether CAP deficits were associated with known markers of AD neurodegeneration. Such markers included CSF tau concentrations and magnetic resonance imaging volumetric and cortical thickness measures in key AD-related regions. Adjusting for age, sex, education, pure-tone hearing, and APOEɛ4 status, we observed a persistent relationship between CAP scores and CSF tau levels, entorhinal and hippocampal cortex volumes, cortical thickness, and deficits in cognition (Repeatable Battery for Assessment of Neuropsychological Status total score, and several of its index scales). These cross-sectional observations suggest that CAP may serve as a novel metric for pre-symptomatic AD pathogenesis. They are therefore being followed up longitudinally with larger samples.
预防阿尔茨海默病（AD）导致的痴呆症（d/AD）需要在症状出现前干预减缓疾病进程。为了开发这种干预措施，人们需要评估疾病进展的指标。常见的进展指标包括脑脊液（CSF）生化和影像学分析以及认知测试。后者的变化有时难以与“正常”衰老的影响区分开来。另一种方法涉及“中枢听觉处理”（CAP）的测试，这可以使人们在嘈杂的背景（例如嘈杂的酒吧或餐厅中的对话）中理解听觉刺激。在 d/AD 中，这种理解通常会受到损害。同样，认知健康的老年人有时会报告需要努力或听力理解能力下降，这增加了 CAP 缺陷可能是 AD 前驱期的标志物的可能性。在认知和身体都健康的 AD 家族史阳性 PREVENT-AD 队列的 187 名成员中，我们评估了 CAP 缺陷是否与 AD 神经退行性变的已知标志物有关。这些标志物包括 CSF 中的 tau 浓度以及关键 AD 相关区域的磁共振成像体积和皮质厚度测量。调整年龄、性别、教育程度、纯音听力和 APOEɛ4 状态后，我们观察到 CAP 评分与 CSF 中的 tau 水平、内嗅皮质和海马皮质体积、皮质厚度以及认知缺陷（重复神经心理状况评估量表总评分及其几个指数量表）之间存在持续的关系。这些横断面观察表明，CAP 可能成为 AD 前驱期发病机制的新指标。因此，我们正在用更大的样本进行纵向随访。
