From the Veterans Affairs Northwest Mental Illness Research, Education, and Clinical Center (MIRECC) (G.L., J.I., J.S., C.L.M., J.M., K.F.P., M.A.R., E.R.P.) and Geriatric Research Education and Clinical Center (GRECC) (G.L., D.C.), Veterans Affairs Puget Sound Health Care System, Seattle, WA; Departments of Psychiatry and Behavioral Sciences (G.L., J.I., J.S., D.C., M.A.R., E.R.P.), Neurology (J.I.), Radiology (C.L.M.), Pharmacology (D.C.), Rehabilitation Medicine (K.F.P.), and Division of Gerontology and Geriatric Medicine Department of Medicine, (D.C.), University of Washington School of Medicine, Seattle, WA; Department of Psychiatry and Neurochemistry (K.B.), Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), UCL Institute of Neurology, Queen Square; UK Dementia Research Institute at UCL (H.Z.), London, United Kingdom; Hong Kong Center for Neurodegenerative Diseases (H.Z.), Clear Water Bay, Hong Kong, China; and Wisconsin Alzheimer's Disease Research Center (H.Z.), University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, WI.
Neurology. 2024 Apr 9;102(7):e209197. doi: 10.1212/WNL.0000000000209197. Epub 2024 Mar 13.
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.
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).
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 ≤ 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 < 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 ( ≤ 0.05) in older participants.
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.
中重度创伤性脑损伤（TBI）已被报道会增加阿尔茨海默病（AD）的风险。轻度 TBI（mTBI）是否会使退伍军人患 AD 的风险增加尚不清楚。本研究使用 CSF 生物标志物调查了经历爆炸相关 mTBI 的退伍军人的早期 AD 变化。
这是一项来自 2 个研究来源的经历 mTBI 和无 mTBI 的退伍军人及平民的横断面病例对照研究。经历爆炸相关 mTBI 的退伍军人至少有 1 次符合退伍军人事务部（VA）和国防部（DoD）mTBI 标准的战区爆炸或联合爆炸/撞击 mTBI。无 mTBI 参与者一生中没有 TBI 史。所有参与者均接受了标准化的临床和神经心理学评估以及腰椎穿刺以采集 CSF。使用 MesoScale Discovery 测定法测量 CSF 生物标志物以检测 Aβ40 和 Aβ42，以及 INNOTEST ELISA 检测磷酸化 tau181（p-tau181）和总 tau（t-tau）。
我们的样本包括 51 名经历 mTBI 的参与者和 85 名无 mTBI 的参与者，他们的平均（SD）年龄分别为 34.0（10.1）和 33.5 岁（8.9）。除 1 名参与者（99%）外，所有参与者均为男性。mTBI 组和无 mTBI 组之间 CSF AD 生物标志物的差异与年龄有关，在年龄较大时最为明显（整体检验 ≤ 0.08）。在 50 岁时，mTBI 组 CSF Aβ42 和 Aβ40 分别比无 mTBI 组低 154[-12 至 319]和 1864[610-3118]pg/mL。相比之下，mTBI 组 CSF p-tau181 和 t-tau 的平均水平随年龄变化相对稳定，而无 mTBI 组的平均水平随着年龄的增长而升高。mTBI 组在年龄较大时的认知表现也较差（整体检验 < 0.08）：在 50 岁时，TMT-B 时间平均延长 34 秒[10-58]，CVLT-II 短延迟回忆平均减少 4.2 分[1.9-6.6]。年龄较大的参与者中，认知表现较差与 CSF Aβ42 降低有关（ ≤ 0.05）。
经历爆炸相关 mTBI 的中年退伍军人的 CSF Aβ 水平降低。这些数据表明，与爆炸相关的 mTBI 相关的慢性神经病理过程与已知预示 AD 发病的致病过程具有共同特征，因此人们担心经历爆炸相关 mTBI 的退伍军人可能会在以后的生活中患上痴呆症。
