Abstract：
OBJECTIVE: Moderate-to-severe traumatic brain injuries (TBI) have been reported to increase the risk of Alzheimer disease (AD). Whether mild TBI (mTBI) in veterans confers a similar increased risk of AD is less known. This study investigated early AD changes using CSF biomarkers in veterans with blast mTBI.
METHODS: This was a cross-sectional case-control study of veterans with mTBI and non-mTBI veterans and civilians from 2 study sources. Blast-mTBI veterans had at least 1 war zone blast or combined blast/impact mTBI meeting Veterans Affairs (VA) and Department of Defense (DoD) criteria for mTBI. Non-mTBI participants had no lifetime history of TBI. All participants underwent standardized clinical and neuropsychological assessments and lumbar puncture for collection of the CSF. CSF biomarkers were measured using MesoScale Discovery assays for Aβ40 and Aβ42 and INNOTEST ELISAs for phosphorylated tau181 (p-tau181) and total tau (t-tau).
RESULTS: Our sample comprised 51 participants with mTBI and 85 non-mTBI participants with mean (SD) ages 34.0 (10.1) and 33.5 years (8.9), respectively. All participants but 1 (99%) were male. Differences in CSF AD biomarkers between mTBI and non-mTBI groups were age dependent and most pronounced at older ages (omnibus test p ≤ 0.08). At age 50 years, the mTBI group had lower mean [95% CI] CSF Aβ42 and Aβ40 than the non-mTBI group by 154 [-12 to 319] and 1864 [610-3,118] pg/mL, respectively. By contrast, CSF p-tau181 and t-tau mean levels remained relatively constant with age in participants with mTBI, while tending to be higher at older ages for the non-mTBI group. The mTBI group also demonstrated poorer cognitive performance at older ages (omnibus p < 0.08): at age 50 years, the mean TMT-B time was higher by 34 seconds [10-58] and the mean CVLT-II short-delay recall was lower by 4.2 points [1.9-6.6]. Poorer verbal memory and verbal fluency performance were associated with lower CSF Aβ42 (p ≤ 0.05) in older participants.
CONCLUSIONS: CSF Aβ levels decreased in middle-aged veterans with blast-related mTBI. These data suggest that chronic neuropathologic processes associated with blast mTBI share properties in common with pathogenic processes known to portend AD onset, thus raising concern that veterans with blast-related mTBI may develop a dementing disorder later in life.
METHODS: This was a cross-sectional case-control study of veterans with mTBI and non-mTBI veterans and civilians from 2 study sources. Blast-mTBI veterans had at least 1 war zone blast or combined blast/impact mTBI meeting Veterans Affairs (VA) and Department of Defense (DoD) criteria for mTBI. Non-mTBI participants had no lifetime history of TBI. All participants underwent standardized clinical and neuropsychological assessments and lumbar puncture for collection of the CSF. CSF biomarkers were measured using MesoScale Discovery assays for Aβ40 and Aβ42 and INNOTEST ELISAs for phosphorylated tau181 (p-tau181) and total tau (t-tau).
RESULTS: Our sample comprised 51 participants with mTBI and 85 non-mTBI participants with mean (SD) ages 34.0 (10.1) and 33.5 years (8.9), respectively. All participants but 1 (99%) were male. Differences in CSF AD biomarkers between mTBI and non-mTBI groups were age dependent and most pronounced at older ages (omnibus test p ≤ 0.08). At age 50 years, the mTBI group had lower mean [95% CI] CSF Aβ42 and Aβ40 than the non-mTBI group by 154 [-12 to 319] and 1864 [610-3,118] pg/mL, respectively. By contrast, CSF p-tau181 and t-tau mean levels remained relatively constant with age in participants with mTBI, while tending to be higher at older ages for the non-mTBI group. The mTBI group also demonstrated poorer cognitive performance at older ages (omnibus p < 0.08): at age 50 years, the mean TMT-B time was higher by 34 seconds [10-58] and the mean CVLT-II short-delay recall was lower by 4.2 points [1.9-6.6]. Poorer verbal memory and verbal fluency performance were associated with lower CSF Aβ42 (p ≤ 0.05) in older participants.
CONCLUSIONS: CSF Aβ levels decreased in middle-aged veterans with blast-related mTBI. These data suggest that chronic neuropathologic processes associated with blast mTBI share properties in common with pathogenic processes known to portend AD onset, thus raising concern that veterans with blast-related mTBI may develop a dementing disorder later in life.
摘要：
目的：据报道，中度至重度创伤性脑损伤（TBI）会增加阿尔茨海默病（AD）的风险。退伍军人的轻度TBI（mTBI）是否会导致类似的AD风险增加尚不清楚。这项研究使用CSF生物标志物调查了患有mTBI的退伍军人的早期AD变化。
方法：这是一项针对2个研究来源的mTBI退伍军人和非mTBI退伍军人和平民的横断面病例对照研究。Blast-mTBI退伍军人至少有一次战区爆炸或爆炸/冲击mTBI会议退伍军人事务（VA）和国防部（DoD）mTBI标准。非mTBI参与者没有TBI的终生病史。所有参与者都接受了标准化的临床和神经心理学评估以及腰椎穿刺收集CSF。使用Aβ40和Aβ42的中尺度发现测定和磷酸化tau181(p-tau181)和总tau(t-tau)的INNOTESTELISA测量CSF生物标志物。
结果：我们的样本包括51名mTBI参与者和85名非mTBI参与者，平均（SD）年龄为34.0（10.1）和33.5岁（8.9），分别。除1名（99%）外，所有参与者均为男性。mTBI和非mTBI组之间的CSFAD生物标志物的差异与年龄有关，并且在年龄较大时最为明显（综合检验p≤0.08）。50岁时,mTBI组的平均[95%CI]CSFAβ42和Aβ40比非mTBI组低154[-12至319]和1864[610-3,118]pg/mL，分别。相比之下,mTBI参与者的CSFp-tau181和t-tau平均水平随年龄保持相对恒定，而非mTBI组往往在年龄较大时更高。mTBI组在年龄较大时也表现出较差的认知能力（综合p<0.08）：在50岁时，平均TMT-B时间较高34秒[10-58],平均CVLT-II短延迟召回时间较低4.2分[1.9-6.6].在老年参与者中，较差的言语记忆力和言语流畅性表现与较低的CSFAβ42（p≤0.05）相关。
结论：患有与爆炸相关的mTBI的中年退伍军人的CSFAβ水平降低。这些数据表明，与初发mTBI相关的慢性神经病变过程与已知预示AD发病的致病过程具有共同的特性。因此，人们担心患有与爆炸相关的mTBI的退伍军人可能会在以后的生活中发展出痴呆障碍。
方法：这是一项针对2个研究来源的mTBI退伍军人和非mTBI退伍军人和平民的横断面病例对照研究。Blast-mTBI退伍军人至少有一次战区爆炸或爆炸/冲击mTBI会议退伍军人事务（VA）和国防部（DoD）mTBI标准。非mTBI参与者没有TBI的终生病史。所有参与者都接受了标准化的临床和神经心理学评估以及腰椎穿刺收集CSF。使用Aβ40和Aβ42的中尺度发现测定和磷酸化tau181(p-tau181)和总tau(t-tau)的INNOTESTELISA测量CSF生物标志物。
结果：我们的样本包括51名mTBI参与者和85名非mTBI参与者，平均（SD）年龄为34.0（10.1）和33.5岁（8.9），分别。除1名（99%）外，所有参与者均为男性。mTBI和非mTBI组之间的CSFAD生物标志物的差异与年龄有关，并且在年龄较大时最为明显（综合检验p≤0.08）。50岁时,mTBI组的平均[95%CI]CSFAβ42和Aβ40比非mTBI组低154[-12至319]和1864[610-3,118]pg/mL，分别。相比之下,mTBI参与者的CSFp-tau181和t-tau平均水平随年龄保持相对恒定，而非mTBI组往往在年龄较大时更高。mTBI组在年龄较大时也表现出较差的认知能力（综合p<0.08）：在50岁时，平均TMT-B时间较高34秒[10-58],平均CVLT-II短延迟召回时间较低4.2分[1.9-6.6].在老年参与者中，较差的言语记忆力和言语流畅性表现与较低的CSFAβ42（p≤0.05）相关。
结论：患有与爆炸相关的mTBI的中年退伍军人的CSFAβ水平降低。这些数据表明，与初发mTBI相关的慢性神经病变过程与已知预示AD发病的致病过程具有共同的特性。因此，人们担心患有与爆炸相关的mTBI的退伍军人可能会在以后的生活中发展出痴呆障碍。
