背景:创伤后应激障碍(PTSD)和创伤性脑损伤(TBI)与自我报告的认知问题以及阿尔茨海默病和相关痴呆(ADRD)的风险相关。在认知障碍中观察到的重叠症状特征,精神疾病,和环境暴露(例如,头部受伤)可能会使ADRD早期体征的检测复杂化。创伤后应激障碍之间的相互作用,头部受伤,主观(自我报告)认知担忧和ADRD的遗传风险也没有得到很好的理解,特别是在不同的祖先群体中。
方法:使用美国退伍军人事务部(VA)百万退伍军人计划(MVP)的数据,我们检查了痴呆危险因素(APOEε4,PTSD,在欧洲人(n=140,921)中测量的TBI)和主观认知担忧(SCC),非洲(n=15,788),和西班牙裔(n=8064)血统(EA,AA,HA,分别)。然后,我们使用VA电子病历中的数据进行回顾性生存分析,评估PTSD,TBI,APOEε4和SCC及其与65岁及以上退伍军人转换为ADRD的风险的关联。
结果:PTSD症状(B=0.50-0.52,p<1E-250)和可能的TBI(B=0.05-0.19,p=1.51E-07-0.002)在所有三个祖先组中与SCC呈正相关。在65岁及以上的EA退伍军人中,APOEε4与更大的SCC相关(B=0.037,p=1.88E-12)。Cox模型的结果表明PTSD症状(风险比[HR]=1.13-1.21),在所有三个祖先组中,APOEε4(HR=1.73-2.05)和SCC(HR=1.18-1.37)与ADRD风险呈正相关。在EA组中,可能的TBI也导致ADRD风险增加(HR=1.18)。
结论:这些发现强调了SCC作为65岁及65岁以上退伍军人ADRD风险指标的价值,临床,和人口危险因素。
BACKGROUND: Posttraumatic stress disorder (PTSD) and traumatic brain injury (
TBI) are associated with self-reported problems with cognition as well as risk for Alzheimer\'s disease and related dementias (ADRD). Overlapping symptom profiles observed in cognitive disorders, psychiatric disorders, and environmental exposures (e.g., head injury) can complicate the detection of early signs of ADRD. The interplay between PTSD, head injury, subjective (self-reported) cognitive concerns and genetic risk for ADRD is also not well understood, particularly in diverse ancestry groups.
METHODS: Using data from the U.S. Department of Veterans Affairs (VA) Million Veteran Program (MVP), we examined the relationship between dementia risk factors (APOE ε4, PTSD,
TBI) and subjective cognitive concerns (SCC) measured in individuals of European (n = 140,921), African (n = 15,788), and Hispanic (n = 8,064) ancestry (EA, AA, and HA, respectively). We then used data from the VA electronic medical record to perform a retrospective survival analysis evaluating PTSD,
TBI, APOE ε4, and SCC and their associations with risk of conversion to ADRD in Veterans aged 65 and older.
RESULTS: PTSD symptoms (B = 0.50-0.52, p < 1E-250) and probable
TBI (B = 0.05-0.19, p = 1.51E-07 - 0.002) were positively associated with SCC across all three ancestry groups. APOE ε4 was associated with greater SCC in EA Veterans aged 65 and older (B = 0.037, p = 1.88E-12). Results of Cox models indicated that PTSD symptoms (hazard ratio [HR] = 1.13-1.21), APOE ε4 (HR = 1.73-2.05) and SCC (HR = 1.18-1.37) were positively associated with risk for ADRD across all three ancestry groups. In the EA group, probable
TBI also contributed to increased risk of ADRD (HR = 1.18).
CONCLUSIONS: The findings underscore the value of SCC as an indicator of ADRD risk in Veterans 65 and older when considered in conjunction with other influential genetic, clinical, and demographic risk factors.