Pink Anna, Krell-Roesch Janina, Syrjanen Jeremy A, Christenson Luke R, Lowe Val J, Vemuri Prashanthi, Fields Julie A, Stokin Gorazd B, Kremers Walter K, Scharf Eugene L, Jack Clifford R, Knopman David S, Petersen Ronald C, Vassilaki Maria, Geda Yonas E
First Department of Medicine Paracelsus Medical University Salzburg Austria.
Department of Quantitative Health Sciences Mayo Clinic Rochester Rochester Minnesota USA.
Psychiatr Res Clin Pract. 2023 Jan 20;5(1):4-15. doi: 10.1176/appi.prcp.20220036. eCollection 2023 Spring.
To examine interactions between Neuropsychiatric symptoms (NPS) with Pittsburgh Compound B (PiB) and fluorodeoxyglucose positron emission tomography (FDG-PET) in predicting cognitive trajectories.
We conducted a longitudinal study in the setting of the population-based Mayo Clinic Study of Aging in Olmsted County, MN, involving 1581 cognitively unimpaired (CU) persons aged ≥50 years (median age 71.83 years, 54.0% males, 27.5% APOE ɛ4 carriers). NPS at baseline were assessed using the Neuropsychiatric Inventory Questionnaire (NPI-Q). Brain glucose hypometabolism was defined as a SUVR ≤ 1.47 (measured by FDG-PET) in regions typically affected in Alzheimer's disease. Abnormal cortical amyloid deposition was measured using PiB-PET (SUVR ≥ 1.48). Neuropsychological testing was done approximately every 15 months, and we calculated global and domain-specific (memory, language, attention, and visuospatial skills) cognitive z-scores. We ran linear mixed-effect models to examine the associations and interactions between NPS at baseline and z-scored PiB- and FDG-PET SUVRs in predicting cognitive z-scores adjusted for age, sex, education, and previous cognitive testing.
Individuals at the average PiB and without NPS at baseline declined over time on cognitive z-scores. Those with increased PiB at baseline declined faster (two-way interaction), and those with increased PiB and NPS declined even faster (three-way interaction). We observed interactions between time, increased PiB and anxiety or irritability indicating accelerated decline on global z-scores, and between time, increased PiB and several NPS (e.g., agitation) showing faster domain-specific decline, especially on the attention domain.
NPS and increased brain amyloid deposition synergistically interact in accelerating global and domain-specific cognitive decline among CU persons at baseline.
研究神经精神症状（NPS）与匹兹堡化合物B（PiB）及氟脱氧葡萄糖正电子发射断层扫描（FDG-PET）之间的相互作用，以预测认知轨迹。
我们在明尼苏达州奥尔姆斯特德县基于人群的梅奥诊所衰老研究中进行了一项纵向研究，纳入了1581名年龄≥50岁的认知未受损（CU）者（中位年龄71.83岁，男性占54.0%，APOEε4携带者占27.5%）。使用神经精神科问卷（NPI-Q）评估基线时的NPS。脑葡萄糖低代谢定义为阿尔茨海默病典型受累区域的标准化摄取值（SUVR）≤1.47（通过FDG-PET测量）。使用PiB-PET测量异常皮质淀粉样蛋白沉积（SUVR≥1.48）。大约每15个月进行一次神经心理学测试，并计算总体及特定领域（记忆、语言、注意力和视觉空间技能）的认知z分数。我们运行线性混合效应模型，以检验基线时NPS与z评分的PiB和FDG-PET SUVR之间在预测经年龄、性别、教育程度和既往认知测试校正后的认知z分数方面的关联和相互作用。
基线时PiB平均且无NPS的个体认知z分数随时间下降。基线时PiB升高的个体下降更快（双向相互作用），而PiB升高且有NPS的个体下降甚至更快（三向相互作用）。我们观察到时间、PiB升高与焦虑或易怒之间存在相互作用，表明总体z分数加速下降，以及时间、PiB升高与几种NPS（如激越）之间存在相互作用，显示特定领域下降更快，尤其是在注意力领域。
在基线时，NPS与脑淀粉样蛋白沉积增加在加速CU个体的总体和特定领域认知衰退方面存在协同相互作用。
