Holmqvist Sophia L, Thomas Kelsey R, Brenner Einat K, Edmonds Emily C, Calcetas Amanda, Edwards Lauren, Bordyug Maria, Bangen Katherine J
Research Service, VA San Diego Healthcare System, San Diego, CA, United States.
Department of Psychiatry, University of California, San Diego, La Jolla, CA, United States.
Front Aging Neurosci. 2022 Jul 6;14:859873. doi: 10.3389/fnagi.2022.859873. eCollection 2022.
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 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 ( = 21). In contrast, there were no significant associations between change in IIV and CBF among those who were biomarker-negative ( = 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.
在单次测试期间，神经心理学测量指标的个体内变异性（IIV）是预测认知衰退和阿尔茨海默病（AD）发展的一个有前景的标志物。我们之前已经表明，在淀粉样β（Aβ）阳性的无痴呆老年成年人中，更大的IIV与脑血流量（CBF）减少呈横断面相关，但与皮质厚度或脑容量无关。然而，关于IIV随时间的变化与CBF之间的关联却知之甚少。因此，我们研究了IIV的12个月纵向变化以及IIV与AD生物标志物状态对局部CBF变化的相互作用。53名非痴呆的阿尔茨海默病神经影像学计划（ADNI）参与者在基线时接受腰椎穿刺以获取脑脊液（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项经人口统计学校正的神经心理学测量指标的个体内标准差。采用脉冲动脉自旋标记（ASL）MRI来量化CBF，并检查基于FreeSurfer得出的CBF感兴趣区域（ROI）。使用已发表的脑脊液磷酸化tau蛋白/ Aβ比值临界值来确定AD生物标志物阳性。计算从基线到12个月的IIV、CBF和平均神经心理学表现的变化分数。分层线性回归模型显示，在调整年龄和性别后，内嗅区和海马区CBF变化的IIV变化与生物标志物阳性（磷酸化tau蛋白/ Aβ+）之间存在显著交互作用，但其他ROI不存在这种情况。具体而言，在生物标志物阳性的个体（n = 21）中，IIV增加与内嗅区和海马区CBF减少相关。相比之下，在生物标志物阴性的个体（n = 32）中，IIV变化与CBF之间无显著关联。在对神经心理学表现平均水平的变化进行调整后进行分析时，结果仍然相似。在AD生物标志物阳性个体中，IIV的变化可能对AD易损区域的局部灌注不足变化敏感，这超出了人口统计学和平均神经心理学表现的影响。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。
