From the Department of Psychiatry and Behavioral Sciences (M.C.-K.); Center for Aging and Human Development (M.C.-K., C.F.P., B.L.P.), Duke University Medical Center, Durham, NC; Departments of Biostatistics and Bioinformatics (C.F.P.); Departments of Psychiatry and Behavioral Sciences, Neurology and Epidemiology and Biostatistics (K.Y.), University of California, San Francisco and San Francisco Veterans Affairs Medical Center; and Department of Neurology (B.L.P.), Duke University Medical Center, Durham, NC.
Neurology. 2023 Oct 31;101(18):e1761-e1770. doi: 10.1212/WNL.0000000000207819. Epub 2023 Sep 6.
Traumatic brain injuries (TBIs) are associated with increased risk of dementia, but whether lifetime TBI influences cognitive trajectories in later life is less clear. Cognitive interventions after TBI may improve cognitive trajectories and delay dementia. Because twins share many genes and environmental factors, we capitalize on the twin study design to examine the association between lifetime TBI and cognitive decline.
Participants were members of the National Academy of Sciences-National Research Council's Twin Registry of male veterans of World War II with self or proxy-reported history of TBI and with up to 4 observations over 12 years of the modified Telephone Interview for Cognitive Status (TICS-m). We used linear random-effects mixed models to analyze the association between TBI and TICS-m in the full sample and among co-twins discordant for TBI. Additional TBI predictor variables included number of TBIs, severity (loss of consciousness [LOC]), and age of first TBI (age <25 vs 25+ years [older age TBI]). Models were adjusted for age (centered at 70 years), age-squared, education, wave, twin pair, lifestyle behaviors, and medical conditions.
Of 8,662 participants, 25% reported TBI. History of any TBI (β = -0.56, 95% CI -0.73 to -0.39), TBI with LOC (β = -0.51, 95% CI -0.71 to -0.31), and older age TBI (β = -0.66, 95% CI -0.90 to -0.42) were associated with lower TICS-m scores at 70 years. TBI with LOC (β = -0.03, 95% CI -0.05 to -0.001), more than one TBI (β = -0.05, 95% CI -0.09 to -0.002,), and older age TBI (β = -0.06, 95% CI -0.09 to -0.03) were associated with faster cognitive decline. Among monozygotic pairs discordant for TBI (589 pairs), history of any TBI (β = -0.55, 95% CI -0.91 to -0.19) and older age TBI (β = -0.74, 95% CI -1.22 to -0.26) were associated with lower TICS-m scores at 70 years. Those with more than one TBI (β = -0.13, 95% CI -0.23 to -0.03) and older age TBI (β = -0.07, 95% CI -0.13 to -0.002) showed greater cognitive decline compared with their co-twin without TBI.
These findings support an association of the effect of TBI on cognitive score and the rapidity of cognitive decline in later life. The results in monozygotic pairs, who share all genes and many exposures, particularly in early life, provide additional evidence of a causal relationship between TBI and poorer late-life cognitive outcomes.
创伤性脑损伤（TBI）与痴呆风险增加有关，但一生中 TBI 是否会影响晚年的认知轨迹尚不清楚。TBI 后的认知干预可能会改善认知轨迹并延迟痴呆的发生。由于双胞胎共享许多基因和环境因素，我们利用双胞胎研究设计来研究一生中 TBI 与认知下降之间的关联。
参与者是美国国家科学院-国家研究理事会双胞胎登记处的二战男性退伍军人，他们自我或通过代理人报告了 TBI 病史，并在 12 年的时间内进行了多达 4 次修改后的电话认知状态测试（TICS-m）。我们使用线性随机效应混合模型来分析 TBI 与 TICS-m 在全样本中的关联，以及在 TBI 不一致的同卵双胞胎中的关联。其他 TBI 预测变量包括 TBI 的次数、严重程度（意识丧失[LOC]）和首次 TBI 的年龄（年龄<25 岁与 25 岁以上[老年 TBI]）。模型调整了年龄（以 70 岁为中心）、年龄平方、教育、波次、双胞胎对、生活方式行为和医疗状况。
在 8662 名参与者中，有 25%报告了 TBI。任何 TBI 的病史（β=-0.56，95%CI-0.73 至-0.39）、伴有 LOC 的 TBI（β=-0.51，95%CI-0.71 至-0.31）和老年 TBI（β=-0.66，95%CI-0.90 至-0.42）与 70 岁时的 TICS-m 评分较低有关。伴有 LOC 的 TBI（β=-0.03，95%CI-0.05 至-0.001）、多次 TBI（β=-0.05，95%CI-0.09 至-0.002）和老年 TBI（β=-0.06，95%CI-0.09 至-0.03）与认知下降较快有关。在 TBI 不一致的同卵双胞胎中（589 对），任何 TBI 的病史（β=-0.55，95%CI-0.91 至-0.19）和老年 TBI（β=-0.74，95%CI-1.22 至-0.26）与 70 岁时的 TICS-m 评分较低有关。多次 TBI（β=-0.13，95%CI-0.23 至-0.03）和老年 TBI（β=-0.07，95%CI-0.13 至-0.002）与无 TBI 的同卵双胞胎相比，认知衰退更为明显。
这些发现支持 TBI 对认知评分和晚年认知衰退速度的影响的关联。在同卵双胞胎中的结果，他们共享所有的基因和许多暴露，特别是在早期生活中，为 TBI 与较差的晚年认知结果之间的因果关系提供了额外的证据。
