Mulholland Michele M, Stuifbergen Alexa, De La Torre Schutz Alexa, Franco Rocha Oscar Y, Blayney Douglas W, Kesler Shelli R
Department of Comparative Medicine, The University of Texas MD Anderson Cancer Center, Bastrop, TX, USA.
Division of Adult Health, School of Nursing, University of Texas at Austin, Austin, TX, USA.
medRxiv. 2024 Apr 22:2024.04.22.24306190. doi: 10.1101/2024.04.22.24306190.
Chemotherapy-related cognitive impairment (CRCI) remains poorly understood in terms of the mechanisms of cognitive decline. Neural hyperactivity has been reported on average in cancer survivors, but it is unclear which patients demonstrate this neurophenotype, limiting precision medicine in this population. We evaluated a retrospective sample of 80 breast cancer survivors and 80 non-cancer controls, age 35-73, for which we had previously identified and validated three data-driven, biological subgroups (biotypes) of CRCI. We measured neural activity using the z-normalized percent amplitude of fluctuation from resting state functional magnetic resonance imaging (MRI). We tested established, quantitative criteria to determine if hyperactivity can accurately be considered compensatory. We also calculated brain age gap by applying a previously validated algorithm to anatomic MRI. We found that neural activity differed across the three CRCI biotypes and controls (F = 13.5, p < 0.001), with Biotype 2 demonstrating significant hyperactivity compared to the other groups (p < 0.004, corrected), primarily in prefrontal regions. Alternatively, Biotypes 1 and 3 demonstrated significant hypoactivity (p < 0.02, corrected). Hyperactivity in Biotype 2 met several of the criteria to be considered compensatory. However, we also found a positive relationship between neural activity and brain age gap in these patients (r = 0.45, p = 0.042). Our results indicated that neural hyperactivity is specific to a subgroup of breast cancer survivors and, while it seems to support preserved cognitive function, it could also increase the risk of accelerated brain aging. These findings could inform future neuromodulatory interventions with respect to the risks and benefits of up or downregulation of neural activity.
化疗相关认知障碍（CRCI）在认知衰退机制方面仍未得到充分理解。据报道，癌症幸存者平均存在神经活动亢进的情况，但尚不清楚哪些患者表现出这种神经表型，这限制了该人群的精准医学发展。我们评估了80名年龄在35 - 73岁的乳腺癌幸存者和80名非癌症对照者的回顾性样本，此前我们已识别并验证了CRCI的三个数据驱动的生物学亚组（生物型）。我们使用静息态功能磁共振成像（MRI）中波动的z标准化百分比幅度来测量神经活动。我们测试了既定的定量标准，以确定活动亢进是否能准确地被视为一种代偿机制。我们还通过将先前验证的算法应用于解剖学MRI来计算脑龄差距。我们发现，三个CRCI生物型与对照组之间的神经活动存在差异（F = 13.5，p < 0.001），生物型2与其他组相比表现出显著的活动亢进（校正后p < 0.004），主要在前额叶区域。相比之下，生物型1和3表现出显著的活动减退（校正后p < 0.02）。生物型2中的活动亢进符合多项被视为代偿机制的标准。然而，我们还发现这些患者的神经活动与脑龄差距之间存在正相关（r = 0.45，p = 0.042）。我们的结果表明，神经活动亢进是乳腺癌幸存者中的一个亚组所特有的，虽然它似乎支持认知功能的保留，但也可能增加脑加速衰老的风险。这些发现可以为未来关于神经活动上调或下调的风险和益处的神经调节干预提供参考。
