Division of Geriatric Psychiatry, Department of Psychiatry, Brigham and Women's Hospital (SL, BSZ, NJD), Harvard Medical School, Boston, MA; Center for Brain Circuit Therapeutics, Brigham and Women's Hospital (SL, STP, WJD, SHS), Boston, MA.
Division of Geriatric Psychiatry, Department of Psychiatry, Brigham and Women's Hospital (SL, BSZ, NJD), Harvard Medical School, Boston, MA.
Am J Geriatr Psychiatry. 2024 Oct;32(10):1203-1214. doi: 10.1016/j.jagp.2024.04.016. Epub 2024 May 4.
Anxiety disorders and subsyndromal anxiety symptoms are highly prevalent in late life. Recent studies support that anxiety may be a neuropsychiatric symptom during preclinical Alzheimer's disease (AD) and that higher anxiety is associated with more rapid cognitive decline and progression to cognitive impairment. However, the associations of specific anxiety symptoms with AD pathologies and with co-occurring subjective and objective cognitive changes have not yet been established.
Baseline data from the A4 and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration studies were analyzed. Older adult participants (n = 4,486) underwent assessments of anxiety (State-Trait Anxiety Inventory-6 item version [STAI]), and cerebral amyloid-beta (Aβ; F-florbetapir) PET and a subset underwent tau (F-flortaucipir) PET. Linear regressions estimated associations of Aβ in a cortical composite and tau in the amygdala, entorhinal, and inferior temporal regions with STAI-Total and individual STAI item scores. Models adjusted for age, sex, education, marital status, depression, Apolipoprotein ε4 genotype, and subjective and objective cognition (Cognitive Function Index-participant; Preclinical Alzheimer Cognitive Composite).
Greater Aβ deposition was significantly associated with higher STAI-Worry, adjusting for all covariates, but not with other STAI items or STAI-Total scores. In mediation analyses, the association of Aβ with STAI-Worry was partially mediated by subjective cognition with a stronger direct effect. No associations were found for regional tau deposition with STAI-Total or STAI-Worry score.
Greater worry was associated with Aβ but not tau deposition, independent of subjective and objective cognition in cognitively unimpaired (CU) older adults. These findings implicate worry as an early, specific behavioral marker and a possible therapeutic target in preclinical AD.
焦虑症和亚综合征焦虑症状在老年人群中高发。最近的研究支持，在临床前阿尔茨海默病（AD）中，焦虑可能是一种神经精神症状，并且更高的焦虑与更快的认知下降和向认知障碍进展相关。然而，特定焦虑症状与 AD 病理学以及同时存在的主观和客观认知变化的关联尚未确定。
对 A4 和纵向评估淀粉样蛋白风险和神经退行性变研究的基线数据进行了分析。老年参与者（n=4486）接受了焦虑（状态-特质焦虑量表-6 项版本[STAI]）、脑淀粉样蛋白-β（Aβ；F-氟比他滨 PET）和部分 tau（F-氟拉他滨 PET）的评估。线性回归估计了皮质复合 Aβ和杏仁核、内嗅皮质和下颞叶 tau 与 STAI-总分和个体 STAI 项目评分的关联。模型调整了年龄、性别、教育、婚姻状况、抑郁、载脂蛋白 E4 基因型以及主观和客观认知（参与者认知功能指数；临床前阿尔茨海默认知复合评分）。
在调整所有协变量后，更大的 Aβ沉积与更高的 STAI-担忧显著相关，但与其他 STAI 项目或 STAI-总分无关。在中介分析中，Aβ与 STAI-担忧的关联部分由主观认知介导，直接效应更强。在认知正常（CU）老年人中，未发现区域 tau 沉积与 STAI-总分或 STAI-担忧评分之间存在关联。
与 tau 沉积相比，更大的担忧与 Aβ相关，但与主观和客观认知无关，这提示担忧是临床前 AD 中的一种早期、特异性行为标志物，并且可能是一个治疗靶点。
