Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
JAMA Netw Open. 2024 Oct 1;7(10):e2441505. doi: 10.1001/jamanetworkopen.2024.41505.
It remains unclear which risk factors accelerate brain atrophy along with a progression from normal cognition to mild cognitive impairment (MCI).
To examine risk factors associated with the acceleration of brain atrophy and progression from normal cognition to MCI based on long-term longitudinal data for middle-aged and older adults.
DESIGN, SETTING, AND PARTICIPANTS: Data for this cohort study were extracted from the Biomarkers for Older Controls at Risk for Dementia (BIOCARD) cohort, initiated at the National Institutes of Health from January 1, 1995, to December 31, 2005, and continued at Johns Hopkins University from January 1, 2015, to October 31, 2023. All participants were cognitively normal at baseline. The participants whose structural magnetic brain imaging (MRI) of the brain and cerebrospinal fluid (CSF) measures were available for over 10 years were included.
Longitudinal structural MRI of the brain and measurement of CSF biomarkers for Alzheimer disease pathology (ratio of amyloid β peptide 42 [Aβ42] to Aβ40, tau phosphorylated at threonine 181, and total tau).
Annual change rates of segmental brain volumes, Kaplan-Meier survival curves plotting time to event for progression to MCI symptom onset, and hazard ratios (HRs) determined by Cox proportional hazards regression models.
A total of 185 participants (mean [SD] age, 55.4 [8.4] years; 116 women [63%]) were included and followed up for a maximum of 27 years (median, 20 [IQR, 18-22] years). The groups with high levels of atrophy in the white matter and enlargement in the ventricles had an earlier progression from normal cognition to MCI symptom onset (HR for white matter, 1.86 [95% CI, 1.24-2.49]; P = .001; HR for ventricles, 1.71 [95% CI, 1.19-2.24]; P = .009). Diabetes was associated with progression to MCI (HR, 1.41 [95% CI, 1.06-1.76]; P = .04), as was a low CSF Aβ42:Aβ40 ratio (HR, 1.48 [95% CI, 1.09-1.88]; P = .04), and their combination had a higher HR of 1.55 (95% CI, 1.13-1.98]; P = .03), indicating a synergic association of diabetes and amyloid pathology with MCI progression.
In this cohort study of middle-aged and older adults, higher rates of volume change in the white matter and ventricles, along with the presence of diabetes and a low CSF Aβ42:Aβ40 ratio, were identified as important risk factors for the progression to MCI. These results support the importance of identifying individuals who have accelerated brain atrophy to optimize preventive strategies for progression to MCI.
目前尚不清楚哪些风险因素会加速大脑萎缩，并导致从正常认知到轻度认知障碍（MCI）的进展。
根据中年和老年人的长期纵向数据，研究与大脑萎缩加速和从正常认知到 MCI 进展相关的风险因素。
设计、地点和参与者：本队列研究的数据来自 Biomarkers for Older Controls at Risk for Dementia（BIOCARD）队列，该队列于 1995 年 1 月 1 日至 2005 年 12 月 31 日在国立卫生研究院启动，并于 2015 年 1 月 1 日至 2023 年 10 月 31 日在约翰霍普金斯大学继续进行。所有参与者在基线时认知正常。纳入了大脑结构磁共振成像（MRI）和脑脊髓液（CSF）测量值超过 10 年的参与者。
大脑的纵向结构 MRI 和用于检测阿尔茨海默病病理的 CSF 生物标志物（Aβ42 与 Aβ40 的比值、磷酸化的 tau 181 位苏氨酸和总 tau）。
节段性脑容量的年变化率、Kaplan-Meier 生存曲线绘制 MCI 症状发作的时间事件，以及 Cox 比例风险回归模型确定的危险比（HR）。
共纳入 185 名参与者（平均[标准差]年龄 55.4[8.4]岁；116 名女性[63%]），随访时间最长达 27 年（中位数 20[IQR，18-22]年）。白质萎缩程度较高和脑室扩大程度较高的组，从正常认知进展到 MCI 症状发作的时间更早（白质的 HR 为 1.86[95%CI，1.24-2.49]；P=0.001；脑室的 HR 为 1.71[95%CI，1.19-2.24]；P=0.009）。糖尿病与进展为 MCI 相关（HR 为 1.41[95%CI，1.06-1.76]；P=0.04），CSF Aβ42:Aβ40 比值较低也与进展为 MCI 相关（HR 为 1.48[95%CI，1.09-1.88]；P=0.04），两者的结合具有更高的 HR 为 1.55（95%CI，1.13-1.98]；P=0.03），表明糖尿病和淀粉样蛋白病理与 MCI 进展存在协同关联。
在这项针对中年和老年人的队列研究中，白质和脑室体积变化率较高，加上存在糖尿病和 CSF Aβ42:Aβ40 比值较低，被确定为进展为 MCI 的重要风险因素。这些结果支持识别大脑萎缩加速的个体的重要性，以优化进展为 MCI 的预防策略。
