Zimmer Aline R, Bourourou Miled, Lesage Frédéric, Hamel Edith
Graduate Program in Pharmaceutical Science, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
Laboratory of Cerebrovascular Research, Montreal Neurological Institute-Hospital, McGill University, Montréal, Quebec, Canadá.
Alzheimers Dement. 2025 Aug;21(8):e70402. doi: 10.1002/alz.70402.
Alzheimer's disease (AD) is a leading cause of dementia, with vascular dysfunction being an early pathogenic event. Cardiovascular interventions show therapeutic promise, hence may improve neurovascular coupling (NVC) and resting-state functional connectivity (RSFC) hemodynamic responses.
NVC and RSFC were recorded longitudinally in control and AD transgenic mice treated or not with simvastatin (SV) using optical imaging of intrinsic signals (OIS), together with memory testing.
AD mice showed early decreases in NVC and bilateral connectivity (BC) in motor and cingulate cortex, and hypoconnectivity within the sensory-motor network. Early default-mode network (DMN) hyperconnectivity was followed by hypoconnectivity, together with a decreased BC in somatosensory (S) cortex. SV restored NVC, prevented aberrant DMN hyperconnectivity, improved BC of S, and preserved memory.
Our results indicate that OIS can detect early AD-related changes in NVC and RSFC, and that a preventive cardiovascular strategy may bear therapeutic promise in at-risk individuals.
Optical imaging of intrinsic signals captures Alzheimer's disease (AD) progression and response to therapy. Neurovascular coupling (NVC) and resting-state functional connectivity (RSFC) disruptions precede memory decline in AD transgenic mice. Simvastatin prevented NVC and AD-specific RSFC disruptions and protected memory. This study supports translational value of hemodynamic signal in early AD detection.
阿尔茨海默病（AD）是痴呆症的主要病因，血管功能障碍是早期致病事件。心血管干预显示出治疗前景，因此可能改善神经血管耦合（NVC）和静息态功能连接（RSFC）的血流动力学反应。
使用内在信号光学成像（OIS）对接受或未接受辛伐他汀（SV）治疗的对照小鼠和AD转基因小鼠进行NVC和RSFC的纵向记录，并进行记忆测试。
AD小鼠在运动和扣带回皮层的NVC和双侧连接性（BC）早期下降，感觉运动网络内连接减少。早期默认模式网络（DMN）的高连接性随后出现低连接性，同时体感（S）皮层的BC降低。SV恢复了NVC，防止了异常的DMN高连接性，改善了S的BC，并保留了记忆。
我们的结果表明，OIS可以检测到NVC和RSFC中与AD相关的早期变化，并且预防性心血管策略可能对高危个体具有治疗前景。
内在信号光学成像可捕捉阿尔茨海默病（AD）的进展和对治疗的反应。在AD转基因小鼠中，神经血管耦合（NVC）和静息态功能连接（RSFC）的破坏先于记忆衰退。辛伐他汀可预防NVC和AD特异性RSFC破坏并保护记忆。本研究支持血流动力学信号在AD早期检测中的转化价值。
