Koch Dook W, Klinkhammer Simona, Verveen Anouk, Visser Denise, Nieuwkerk Pythia T, Verwijk Esmée, van Berckel Bart N M, Horn Janneke, Tolboom Nelleke, van Heugten Caroline M, Verfaillie Sander C J, Knoop Hans
Department of Medical Psychology, Amsterdam UMC Location AMC, Amsterdam, The Netherlands.
Department of Radiology and Nuclear Medicine, Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.
Clin Neuropsychol. 2026 Jan;40(1):109-127. doi: 10.1080/13854046.2025.2496212. Epub 2025 May 2.
Objective cognitive impairment has been shown in a minority of hospitalized COVID-19 patients, and longitudinal studies with a relatively long follow-up duration are scarce. We sought to investigate the presence and long-term change of objective cognitive functioning. Forty-six initially hospitalized (18 ± 19 days) COVID-19 survivors (male/female: 30/16; age: 61 ± 11) underwent extensive neuropsychological assessment (including performance validity) approximately 1 (T1) and 2.5 years (T2) post-infection. Cognitive domains assessed were: memory, attention, executive functioning, processing speed, and language ( = 14 (sub)tests). We used normative data to derive age, sex, and education-adjusted T-scores ( ≤ 35 [≤-1.5SD], deficit cut-off). Repeated measures AN(C)OVAs were used to investigate cognitive functioning over time. Mean neuropsychological performance ( = 14 tests) was within normal range at both timepoints, and number of individuals with objective cognitive deficits ranged from 0-20% (T1), and 2-22% (T2). Number of subjective cognitive complaints remained unchanged. A minority (17%) showed objective cognitive deficits on ≥2 tests at both 1 and 2.5 years post-infection, but not consistently within one cognitive domain. Longitudinal analyses on the total sample showed improvement in performance over time on phonemic fluency (<.001), but stable cognitive performance on all other tests, independent of prior comorbidities, subjective cognitive complaints, depressive symptoms, and ICU admission. There were no consistent objective cognitive deficits or major cognitive disorders years after SARS-CoV-2 infection in the majority of cases. Neuropsychological functioning remained essentially unchanged over time. Future larger longitudinal studies are necessary to unravel COVID-19-related cognitive phenotypes of persisting deficits and how these can be modulated.
少数住院的新冠病毒疾病（COVID-19）患者出现了客观认知障碍，而随访时间相对较长的纵向研究却很匮乏。我们试图调查客观认知功能的存在情况及其长期变化。46名最初住院（18±19天）的COVID-19幸存者（男性/女性：30/16；年龄：61±11岁）在感染后约1年（T1）和2.5年（T2）接受了广泛的神经心理学评估（包括效标效度）。评估的认知领域包括：记忆、注意力、执行功能、处理速度和语言（=14项（子）测试）。我们使用常模数据得出年龄、性别和教育程度调整后的T分数（≤35[≤-1.5SD]，缺陷临界值）。采用重复测量方差分析（AN(C)OVA）来研究随时间变化的认知功能。两个时间点的平均神经心理学表现（=14项测试）均在正常范围内，存在客观认知缺陷的个体数量在0-20%（T1）和2-22%（T2）之间。主观认知主诉的数量保持不变。少数人（17%）在感染后1年和2.5年时在≥2项测试中表现出客观认知缺陷，但并非始终集中在一个认知领域。对整个样本的纵向分析显示，随着时间推移，音素流畅性测试的表现有所改善（<.001），但所有其他测试的认知表现保持稳定，与既往合并症、主观认知主诉、抑郁症状和入住重症监护病房无关。在大多数病例中，感染严重急性呼吸综合征冠状病毒2（SARS-CoV-2）数年后并未出现一致的客观认知缺陷或重大认知障碍。神经心理学功能随时间基本保持不变。未来有必要开展更大规模的纵向研究，以阐明与COVID-19相关的持续存在的认知缺陷表型以及如何对其进行调节。
