German Center for Neurodegenerative Diseases (DZNE) within the Helmholtz Association, 39120, Magdeburg, Germany.
Department of Consultation-Liaison-Psychiatry and Psychosomatic Medicine, University Hospital Zurich, University of Zurich, Culmannstrasse 8, Zurich, 8091, Switzerland.
Alzheimers Res Ther. 2024 Sep 4;16(1):196. doi: 10.1186/s13195-024-01519-3.
While several studies in cerebral amyloid angiopathy (CAA) focus on cognitive function, data on neuropsychiatric symptoms (NPS) and lifelong mental activities in these patients are scarce. Since NPS are associated with functional impairment, faster cognitive decline and faster progression to death, replication studies in more diverse settings and samples are warranted.
We prospectively recruited n = 69 CAA patients and n = 18 cognitively normal controls (NC). The number and severity of NPS were assessed using the Alzheimer's Disease (AD) Assessment Scale's (ADAS) noncognitive subscale. We applied different regression models exploring associations between NPS number or severity and group status (CAA vs. NC), CAA severity assessed with magnetic resonance imaging (MRI) or cognitive function (Mini-Mental State Examination (MMSE), ADAS cognitive subscale), adjusting for age, sex, years of education, arterial hypertension, AD pathology, and apolipoprotein E status. Mediation analyses were performed to test indirect effects of lifelong mental activities on CAA severity and NPS.
Patients with CAA had 4.86 times (95% CI 2.20-10.73) more NPS and 3.56 units (95% CI 1.94-5.19) higher expected NPS severity than NC. Higher total CAA severity on MRI predicted 1.14 times (95% CI 1.01.-1.27) more NPS and 0.57 units (95% CI 0.19-0.95) higher expected NPS severity. More severe white matter hyperintensities were associated with 1.21 times more NPS (95% CI 1.05-1.39) and 0.63 units (95% CI 0.19-1.08) more severe NPS. NPS number (MMSE mean difference - 1.15, 95% CI -1.67 to -0.63; ADAS cognitive mean difference 1.91, 95% CI 1.26-2.56) and severity (MMSE - 0.55, 95% CI -0.80 to -0.30; ADAS cognitive mean difference 0.89, 95% CI 0.57-1.21) predicted lower cognitive function. Greater lifelong mental activities partially mediated the relationship between CAA severity and NPS (indirect effect 0.05, 95% CI 0.0007-0.13), and greater lifelong mental activities led to less pronounced CAA severity and thus to less NPS (indirect effect - 0.08, 95% CI -0.22 to -0.002).
This study suggests that NPS are common in CAA, and that this relationship may be driven by CAA severity. Furthermore, NPS seem to be tied to lower cognitive function. However, lifelong mental activities might mitigate the impact of NPS in CAA.
虽然有几项关于脑淀粉样血管病（CAA）的研究侧重于认知功能，但关于这些患者的神经精神症状（NPS）和终身精神活动的数据却很少。由于 NPS 与功能障碍、认知衰退更快和死亡更快有关，因此需要在更多样化的环境和样本中进行复制研究。
我们前瞻性招募了 n = 69 名 CAA 患者和 n = 18 名认知正常对照者（NC）。使用阿尔茨海默病评估量表（ADAS）的非认知子量表评估 NPS 的数量和严重程度。我们应用了不同的回归模型，探讨 NPS 数量或严重程度与组状态（CAA 与 NC）、用磁共振成像（MRI）评估的 CAA 严重程度或认知功能（简易精神状态检查（MMSE）、ADAS 认知子量表）之间的关系，调整了年龄、性别、受教育年限、动脉高血压、AD 病理学和载脂蛋白 E 状态。进行中介分析以测试终身精神活动对 CAA 严重程度和 NPS 的间接影响。
CAA 患者的 NPS 数量多 4.86 倍（95%CI 2.20-10.73），预期 NPS 严重程度高 3.56 个单位（95%CI 1.94-5.19）。MRI 上 CAA 总严重程度越高，预测 NPS 数量多 1.14 倍（95%CI 1.01.-1.27），预期 NPS 严重程度高 0.57 个单位（95%CI 0.19-0.95）。更严重的白质高信号与 NPS 数量多 1.21 倍（95%CI 1.05-1.39）和 NPS 严重程度高 0.63 个单位（95%CI 0.19-1.08）有关。NPS 数量（MMSE 平均差异 -1.15，95%CI -1.67 至 -0.63；ADAS 认知平均差异 1.91，95%CI 1.26-2.56）和严重程度（MMSE -0.55，95%CI -0.80 至 -0.30；ADAS 认知平均差异 0.89，95%CI 0.57-1.21）预测认知功能较低。更大的终身精神活动部分介导了 CAA 严重程度与 NPS 之间的关系（间接效应 0.05，95%CI 0.0007-0.13），并且更大的终身精神活动导致 CAA 严重程度降低，从而导致 NPS 减少（间接效应 -0.08，95%CI -0.22 至 -0.002）。
本研究表明，NPS 在 CAA 中很常见，这种关系可能是由 CAA 严重程度驱动的。此外，NPS 似乎与较低的认知功能有关。然而，终身精神活动可能会减轻 CAA 中 NPS 的影响。
