Center for Cognitive Neuroscience and Aging, Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, USA.
1Florida Alzheimer's Disease Research Center, Miami Beach, FL, USA.
Int Psychogeriatr. 2022 Nov;34(11):991-1001. doi: 10.1017/S1041610220004007. Epub 2021 Jan 18.
To examine the direct and indirect effects of age, APOE ϵ4 genotype, amyloid positivity, and volumetric reductions in AD-prone brain regions as it relates to semantic intrusion errors reflecting proactive semantic interference (PSI) and the failure to recover from proactive semantic interference (frPSI) on the Loewenstein-Acevedo Scales of Semantic Interference and Learning (LASSI-L), a cognitive stress test that has been consistently more predictive of preclinical and prodromal Alzheimer's disease (AD) than traditional list-learning tests.
Cross-sectional study.
1Florida Alzheimer's Disease Research Center baseline study.
Two-hundred and twelve participants with Mini-Mental State Examination (MMSE) score above 16 and a broad array of cognitive diagnoses ranging from cognitively normal (CN) to dementia, of whom 58% were female, mean age of 72.1 (SD 7.9).
Participants underwent extensive clinical and neuropsychological evaluations, MR and amyloid Positron Emission Tomography/Computer/Computer Tomography (PET/CT) imaging, and analyses of APOE ϵ4 genotype. Confirmatory path analyses were conducted in the structural equation modeling framework that estimated multiple equations simultaneously while controlling for important covariates such as sex, education, language of evaluation, and global cognitive impairment.
Both amyloid positivity and decreased brain volumes in AD-prone regions were directly related to LASSI-L Cued B1 and Cued B2 intrusions (sensitive to PSI and frPSI effects) even after controlling for covariates. APOE ϵ4 status did not evidence direct effects on these LASSI-L cognitive markers, but rather exerted their effects on amyloid positivity, which in turn related to PSI and frPSI. Similarly, age did not have a direct relationship with LASSI-L scores, but exerted its effects indirectly through amyloid positivity and volumes of AD-prone brain regions.
Our study provides insight into the relationships among age, APOE ϵ4, amyloid, and brain volumetric reductions as it relates to semantic intrusion errors. The investigation expands our understanding of the underpinnings of PSI and frPSI intrusions in a large cohort.
探讨年龄、APOE ϵ4 基因型、淀粉样蛋白阳性、AD 易感脑区容积减少与 AD 患者认知压力测试（Loewenstein-Acevedo 语义干扰和学习量表，LASSI-L）中反映前摄性语义干扰（PSI）和无法从前摄性语义干扰中恢复（frPSI）的语义侵入错误之间的直接和间接影响。LASSI-L 是一种认知压力测试，其对临床前和前驱期阿尔茨海默病（AD）的预测性一直优于传统的列表学习测试。
横断面研究。
佛罗里达 AD 研究中心基线研究。
212 名参与者，其简易精神状态检查（MMSE）评分高于 16 分，且认知诊断广泛，包括从认知正常（CN）到痴呆，其中 58%为女性，平均年龄为 72.1（标准差 7.9）岁。
参与者接受了广泛的临床和神经心理学评估、磁共振成像（MRI）和淀粉样蛋白正电子发射断层扫描/计算机/计算机断层扫描（PET/CT）成像，以及 APOE ϵ4 基因型分析。在结构方程模型框架中进行了验证性路径分析，该框架同时估计了多个方程，同时控制了性别、教育、评估语言和整体认知障碍等重要协变量。
淀粉样蛋白阳性和 AD 易感脑区的脑容积减少与 LASSI-L 线索 B1 和线索 B2 侵入直接相关，即使在控制了协变量后也是如此（对 PSI 和 frPSI 效应敏感）。APOE ϵ4 状态对这些 LASSI-L 认知标志物没有直接影响，而是通过淀粉样蛋白阳性对其产生影响，进而与 PSI 和 frPSI 相关。同样，年龄与 LASSI-L 评分没有直接关系，但通过淀粉样蛋白阳性和 AD 易感脑区的容积间接产生影响。
我们的研究提供了对年龄、APOE ϵ4、淀粉样蛋白和脑容积减少与语义侵入错误之间关系的深入了解。该研究扩大了我们对大量队列中 PSI 和 frPSI 侵入的基础的理解。
