Research Service, VA San Diego Healthcare System, San Diego, CA, USA.
Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.
J Alzheimers Dis. 2021;81(4):1711-1725. doi: 10.3233/JAD-201474.
Altered cerebral blood flow (CBF) has been linked to increased risk for Alzheimer's disease (AD). However, whether altered CBF contributes to AD risk by accelerating cognitive decline remains unclear. It also remains unclear whether reductions in CBF accelerate neurodegeneration and development of small vessel cerebrovascular disease.
To examine associations between CBF and trajectories of memory performance, regional brain atrophy, and global white matter hyperintensity (WMH) volume.
147 Alzheimer's Disease Neuroimaging Initiative participants free of dementia underwent arterial spin labeling (ASL) magnetic resonance imaging (MRI) to measure CBF and serial neuropsychological and structural MRI examinations. Linear mixed effects models examined 5-year rate of change in memory and 4-year rate of change in regional brain atrophy and global WMH volumes as a function of baseline regional CBF. Entorhinal and hippocampal CBF were examined in separate models.
Adjusting for demographic characteristics, pulse pressure, apolipoprotein E ɛ4 positivity, cerebrospinal fluid p-tau/Aβ ratio, and neuronal metabolism (i.e., fluorodeoxyglucose standardized uptake value ratio), lower baseline entorhinal CBF predicted faster rates of decline in memory as well as faster entorhinal thinning and WMH progression. Hippocampal CBF did not predict cognitive or brain structure trajectories.
Findings highlight the importance of early cerebrovascular dysfunction in AD risk and suggest that entorhinal CBF as measured by noninvasive ASL MRI is a useful biomarker predictive of future cognitive decline and of risk of both.
大脑血流（CBF）的改变与阿尔茨海默病（AD）风险增加有关。然而，CBF 的改变是否通过加速认知能力下降来增加 AD 风险尚不清楚。CBF 的减少是否会加速神经退行性变和小血管脑血管疾病的发展也尚不清楚。
检查 CBF 与记忆表现、区域脑萎缩和全脑白质高信号（WMH）体积轨迹之间的关联。
147 名无痴呆的阿尔茨海默病神经影像学倡议参与者接受动脉自旋标记（ASL）磁共振成像（MRI）以测量 CBF，并进行了一系列神经心理学和结构 MRI 检查。线性混合效应模型检查了记忆的 5 年变化率和区域脑萎缩和全脑 WMH 体积的 4 年变化率，作为基线区域 CBF 的函数。在单独的模型中检查了内嗅皮层和海马体的 CBF。
调整人口统计学特征、脉压、载脂蛋白 E ɛ4 阳性、脑脊液 p-tau/Aβ 比值和神经元代谢（即氟脱氧葡萄糖标准化摄取值比）后，基线内嗅皮层 CBF 较低预测了记忆的下降速度更快，以及内嗅皮层变薄和 WMH 进展更快。海马体 CBF 不能预测认知或大脑结构轨迹。
研究结果强调了早期脑血管功能障碍在 AD 风险中的重要性，并表明非侵入性 ASL MRI 测量的内嗅皮层 CBF 是预测未来认知能力下降和两者风险的有用生物标志物。
