Keszycki Rachel, Kawles Allegra, Minogue Grace, Zouridakis Antonia, Macomber Alyssa, Gill Nathan, Vu My, Zhang Hui, Coventry Christina, Rogalski Emily, Weintraub Sandra, Mesulam M-Marsel, Geula Changiz, Gefen Tamar
Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.
Department of Psychiatry and Behavioral Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States.
Front Aging Neurosci. 2023 Jun 9;15:1164581. doi: 10.3389/fnagi.2023.1164581. eCollection 2023.
Frontotemporal lobar degeneration (FTLD) with tau pathology (FTLD-tau) commonly causes dementia syndromes that include primary progressive aphasia (PPA) and behavioral variant frontotemporal dementia (bvFTD). Cognitive decline in PPA and bvFTD is often accompanied by debilitating neuropsychiatric symptoms. In 44 participants with PPA or bvFTD due to autopsy-confirmed FTLD-tau, we characterized neuropsychiatric symptoms at early and late disease stages and determined whether the presence of certain symptoms predicted a specific underlying FTLD-tauopathy. Participants completed annual research visits at the Northwestern University Alzheimer's Disease Research Center. All participants had an initial Global Clinical Dementia Rating (CDR) Scale score ≤ 2, and neuropsychiatric symptoms were evaluated the Neuropsychiatric Inventory-Questionnaire (NPI-Q). We assessed the frequency of neuropsychiatric symptoms across all participants at their initial and final visits and performed logistic regression to determine whether symptoms predicted a specific FTLD-tau pathologic diagnosis. Across the FTLD-tau cohort, irritability and apathy were most frequently endorsed at initial and final visits, respectively, whereas psychosis was highly uncommon at both timepoints. Irritability at initial visit predicted greater odds of a 4-repeat compared to a 3-repeat tauopathy (OR = 3.95, 95% CI = 1.10-15.83, < 0.05). Initial sleep disturbance predicted greater odds of progressive supranuclear palsy (PSP) compared to other FTLD-tau subtypes (OR = 10.68, 95% CI = 2.05-72.40, < 0.01). Appetite disturbance at final evaluation predicted lower odds of PSP (OR = 0.15, 95% CI = 0.02-0.74, < 0.05). Our findings suggest that characterization of neuropsychiatric symptoms can aid in the prediction of underlying FTLD-tauopathies. Given considerable pathologic heterogeneity underlying dementias, neuropsychiatric symptoms may be useful for differential diagnosis and treatment planning.
伴有tau蛋白病变的额颞叶变性（FTLD-tau）通常会引发痴呆综合征，包括原发性进行性失语（PPA）和行为变异型额颞叶痴呆（bvFTD）。PPA和bvFTD中的认知衰退常常伴有使人衰弱的神经精神症状。在44名因尸检确诊为FTLD-tau而患有PPA或bvFTD的参与者中，我们对疾病早期和晚期的神经精神症状进行了特征描述，并确定某些症状的存在是否能预测特定的潜在FTLD-tau蛋白病变。参与者在西北大学阿尔茨海默病研究中心完成了年度研究访视。所有参与者的初始总体临床痴呆评定量表（CDR）评分≤2，并且使用神经精神问卷（NPI-Q）对神经精神症状进行了评估。我们评估了所有参与者在初次和末次访视时神经精神症状的出现频率，并进行逻辑回归分析以确定症状是否能预测特定的FTLD-tau病理诊断。在整个FTLD-tau队列中，初次和末次访视时最常被认可的症状分别是易怒和冷漠，而在两个时间点精神病症状都非常少见。初次访视时的易怒预示着与3重复tau蛋白病变相比，4重复tau蛋白病变的可能性更大（比值比[OR]=3.95，95%置信区间[CI]=1.10-15.83，P<0.05）。与其他FTLD-tau亚型相比，初次访视时的睡眠障碍预示着进行性核上性麻痹（PSP）的可能性更大（OR=10.68，95%CI=2.05-72.40，P<0.01）。末次评估时的食欲障碍预示着PSP的可能性较低（OR=0.15，95%CI=0.02-0.74，P<0.05）。我们的研究结果表明，神经精神症状的特征描述有助于预测潜在的FTLD-tau蛋白病变。鉴于痴呆症存在相当大的病理异质性，神经精神症状可能对鉴别诊断和治疗规划有用。
