背景:创伤性脑损伤(TBI)和重复性头部撞击(RHI)与多种类型的神经退行性疾病的风险增加有关,痴呆风险更高,痴呆症症状出现的年龄较早,提示转诊对晚年大脑健康的影响。额颞叶痴呆(FTD)和原发性进行性失语症(PPA)代表了一系列神经病理多样的临床表型。由于复杂的认知和行为症状,FTD/PPA诊断带来了独特的挑战,这些症状不成比例地表现为早发性痴呆(65岁之前)。我们对FTD和PPA患者与健康对照者的终生头部创伤暴露进行了详细表征,以检查终生TBI和RHI的频率以及相关的临床意义。
方法:我们研究了132名FTD/PPA(年龄68.9±8.1,65%男性)和132名性别匹配的健康对照(HC;年龄73.4±7.6)。我们比较了FTD/PPA和HC(卡方,逻辑回归,方差分析)。在FTD/PPA内,我们评估了与症状发病年龄的相关性(方差分析).在行为变异FTD中,我们评估了与认知功能和神经精神症状的关联(线性回归控制年龄,性别,和多年的教育)。
结果:对于任何接触/碰撞运动,FTD/PPA的参与年限均大于HC(8.5±6.7yrsvs.5.3±4.5yrs,p=.008)和美式足球(6.2yrs±4.3yrsvs.3.1±2.4yrs;p=.003)。在FTD/PPA内,与TBI的症状发作年龄较早(0TBI:62.1±8.1,1TBI:59.9±6.9,2+TBI:57.3±8.4;p=.03)和美式足球年数(0yrs:62.2±8.7,1-4yrs:59.7±7.0,5+yrs:55.9±6.3;p=.009)相关。在bvFTD内,那些踢过美式足球的人记忆力较差(z得分:-2.4±1.2vs.-1.4±1.6,p=.02,d=1.1)。
结论:终身头部外伤可能是FTD/PPA可预防的环境危险因素。剂量依赖性暴露于TBI或RHI影响bvFTD的FTD/PPA症状发作和记忆功能。需要进行临床病理研究,以更好地了解RHI或TBI与FTD/PPA发作和症状之间的神经病理学相关性。
BACKGROUND: Traumatic brain injury (TBI) and repetitive head impacts (RHI) have been linked to increased risk for multiple types of neurodegenerative disease, higher dementia risk, and earlier age of dementia symptom onset, suggesting transdiagnostic implications for later-life brain health. Frontotemporal dementia (FTD) and primary progressive aphasia (PPA) represent a spectrum of clinical phenotypes that are neuropathologically diverse. FTD/PPA diagnoses bring unique challenges due to complex cognitive and behavioral symptoms that disproportionately present as an early-onset dementia (before age 65). We performed a detailed characterization of lifetime head trauma exposure in individuals with FTD and PPA compared to healthy controls to examine frequency of lifetime TBI and RHI and associated clinical implications.
METHODS: We studied 132 FTD/PPA (age 68.9 ± 8.1, 65% male) and 132 sex-matched healthy controls (HC; age 73.4 ± 7.6). We compared rates of prior TBI and RHI (contact/collision sports) between FTD/PPA and HC (chi-square, logistic regression, analysis of variance). Within FTD/PPA, we evaluated associations with age of symptom onset (analysis of variance). Within behavioral variant FTD, we evaluated associations with cognitive function and neuropsychiatric symptoms (linear regression controlling for age, sex, and years of education).
RESULTS: Years of participation were greater in FTD/PPA than HC for any contact/collision sport (8.5 ± 6.7yrs vs. 5.3 ± 4.5yrs, p = .008) and for American football (6.2yrs ± 4.3yrs vs. 3.1 ± 2.4yrs; p = .003). Within FTD/PPA, there were dose-dependent associations with earlier age of symptom onset for TBI (0 TBI: 62.1 ± 8.1, 1 TBI: 59.9 ± 6.9, 2 + TBI: 57.3 ± 8.4; p = .03) and years of American football (0yrs: 62.2 ± 8.7, 1-4yrs: 59.7 ± 7.0, 5 + yrs: 55.9 ± 6.3; p = .009). Within bvFTD, those who played American football had worse memory (z-score: -2.4 ± 1.2 vs. -1.4 ± 1.6, p = .02, d = 1.1).
CONCLUSIONS: Lifetime head trauma may represent a preventable environmental risk factor for FTD/PPA. Dose-dependent exposure to TBI or RHI influences FTD/PPA symptom onset and memory function in bvFTD. Clinico-pathological studies are needed to better understand the neuropathological correlates linking RHI or TBI to FTD/PPA onset and symptoms.