Longitudinal Intraindividual Cognitive Variability Is Associated With Reduction in Regional Cerebral Blood Flow Among Alzheimer's Disease Biomarker-Positive Older Adults.
Longitudinal Intraindividual Cognitive Variability Is Associated With Reduction in Regional Cerebral Blood Flow Among Alzheimer's Disease Biomarker-Positive Older Adults.
复制标题
DOI：
10.3389/fnagi.2022.859873
复制
发表时间：
2022
影响因子：
4.8
通讯作者：
中科院分区：
文献类型：
--
作者：
个体内变异（IIV）在一个单一的测试会话内的神经心理学措施是一个有前途的标志物预测认知能力下降和阿尔茨海默病（AD）的发展。我们之前已经表明，在淀粉样蛋白β（Aβ）阳性的无痴呆的老年人中，较大的IIV与脑血流量（CBF）减少有关，但与皮质厚度或脑体积无关。然而，人们对IIV和CBF随时间变化之间的关联知之甚少。因此，我们研究了IIV的12个月纵向变化以及IIV和AD生物标志物状态对区域CBF变化的相互作用。53名非痴呆阿尔茨海默病神经影像学倡议（ADNI）参与者在基线时接受腰椎穿刺以获得脑脊液（CSF），并在基线和12个月随访评估时进行神经心理学测试和磁共振成像（MRI）检查。IIV计算为6个经人口统计学校正的神经心理学指标的个体内标准差。采集脉冲动脉自旋标记（ASL）MRI以量化CBF，并检查FreeSurfer推导的先验CBF感兴趣区（ROI）。使用已发表的CSF p-tau/Aβ比值临界评分确定AD生物标志物阳性。计算IIV、CBF和平均神经心理学表现从基线到12个月的变化评分。分层线性回归模型显示，在调整年龄和性别后，内嗅和海马CBF变化的IIV变化和生物标志物阳性（p-tau/Aβ+）之间存在显著的相互作用，但其他ROI则无此作用。具体而言，在生物标志物阳性的个体中，IIV的增加与内嗅和海马CBF的减少相关（n = 21）。相反，在生物标志物阴性的患者中，IIV和CBF的变化之间没有显著相关性（n = 32）。结果仍然是相似的分析时，调整神经心理学表现的平均水平的变化。IIV的变化可能对AD生物标志物阳性个体中AD易感区域的局部灌注不足变化敏感，高于人口统计学和平均神经心理学表现。这些发现提供了进一步的证据支持IIV作为痴呆风险个体脑血管脑变化的潜在标志物。
Intraindividual variability (IIV) across neuropsychological measures within a single testing session is a promising marker predictive of cognitive decline and development of Alzheimer’s disease (AD). We have previously shown that greater IIV is cross-sectionally associated with reduced cerebral blood flow (CBF), but not with cortical thickness or brain volume, in older adults without dementia who were amyloid beta (Aβ) positive. However, there is little known about the association between change in IIV and CBF over time. Therefore, we examined 12-month longitudinal change in IIV and interactions of IIV and AD biomarker status on changes in regional CBF. Fifty-three non-demented Alzheimer’s Disease Neuroimaging Initiative (ADNI) participants underwent lumbar puncture to obtain cerebrospinal fluid (CSF) at baseline and neuropsychological testing and magnetic resonance imaging (MRI) exams at baseline and 12-month follow-up evaluation. IIV was calculated as the intraindividual standard deviation across 6 demographically-corrected neuropsychological measures. Pulsed arterial spin labeling (ASL) MRI was acquired to quantify CBF and FreeSurfer-derived a priori CBF regions of interest (ROIs) were examined. AD biomarker positivity was determined using a published CSF p-tau/Aβ ratio cut-score. Change scores were calculated for IIV, CBF, and mean neuropsychological performance from baseline to 12 months. Hierarchical linear regression models showed that after adjusting for age and gender, there was a significant interaction between IIV change and biomarker-positivity (p-tau/Aβ+) for change in entorhinal and hippocampal CBF but not for the other ROIs. Specifically, increases in IIV were associated with reductions in entorhinal and hippocampal CBF among individuals who were biomarker-positive (n = 21). In contrast, there were no significant associations between change in IIV and CBF among those who were biomarker-negative (n = 32). Findings remained similar when analyses were performed adjusting for change in mean level of neuropsychological performance. Changes in IIV may be sensitive to changes in regional hypoperfusion in AD-vulnerable regions among AD biomarker-positive individuals, above and beyond demographics and mean neuropsychological performance. These findings provide further evidence supporting IIV as a potential marker of cerebrovascular brain changes in individuals at risk for dementia.