{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T01:41:19Z","timestamp":1791423679507,"version":"4.3.3"},"reference-count":33,"publisher":"American Medical Association (AMA)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Neurol"],"published-print":{"date-parts":[[2026,1,1]]},"abstract":"\n Importance<\/jats:title>\n Treatment for cognitive dysfunction due to postacute sequelae of long COVID (ie, symptoms of fatigue, malaise, weakness, confusion that persist beyond 12 weeks after an initial COVID infection) remains a significant unmet need.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To test evidence-based rehabilitation strategies for improving cognitive symptoms in persons with long COVID.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This was a 5-arm, multicenter, randomized clinical trial of 3 remotely delivered interventions conducted between August 17, 2023, and June 10, 2024. The study took place at 22 trial sites and included the screening of individuals with cognitive long COVID.<\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n Participants were randomized to 1 of 5 arms: adaptive computerized cognitive training (BrainHQ [Posit Science]), cognitive-behavioral rehabilitation involving both group and individual counseling sessions (PASC-Cognitive Recovery [PASC-CoRE]) paired with BrainHQ, and transcranial direct current stimulation (tDCS) paired with BrainHQ. Two comparator arms were included as follows: unstructured computer puzzles and games (active comparator) and sham tDCS paired with BrainHQ. The interventions occurred 5 times per week over 10 weeks.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Cognitive and behavioral in-person assessments were performed at baseline, midintervention, at the end of intervention, and 3 months after the end of the intervention. The primary outcome measure was the modified Everyday Cognition Scale 2 (ECog2) completed at the end of the intervention compared to the baseline visit based on participant self-report looking back over the prior 7 days.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n A total of 378 individuals were screened, from which there were 328 participants (median [IQR] age, 48.0 [37.0-58.0] years; 241 female [73.5%]; race: 15 Asian [4.6%], 47 Black [14.3%], and 235 White [71.6%]; ethnicity: 52 Hispanic [15.9%]). None of the 3 active interventions demonstrated benefits on the modified ECog2 in the intention-to-treat population by the end of the intervention period. The adjusted differences in mean change were 0.0 (95% CI, \u22120.2 to 0.2) for BrainHQ vs active comparator, 0.1 (95% CI, \u22120.1 to 0.3) for PASC-CoRE + BrainHQ vs active comparator, 0.0 (95% CI, \u22120.2 to 0.2) for tDCS-active + BrainHQ vs tDCS-sham + BrainHQ, and 0.1 (95% CI, \u22120.1 to 0.3) for PASC-CoRE + BrainHQ vs BrainHQ alone. Secondary participant-reported outcomes and neuropsychological tests showed no differential benefits for any treatment arm. All 5 arms demonstrated some improvements over time on the modified ECog2 and on secondary outcomes. There were no serious adverse events attributable to the interventions.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n This phase 2 randomized clinical trial failed to demonstrate differential benefits for online cognitive training, a structured cognitive rehabilitation program, and tDCS for cognitive long COVID.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT05965739<\/jats:ext-link>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamaneurol.2025.4415","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T16:30:56Z","timestamp":1762792256000},"page":"49","source":"Crossref","is-referenced-by-count":12,"title":["Evaluation of Interventions for Cognitive Symptoms in Long COVID"],"prefix":"10.1001","volume":"83","author":[{"given":"David S.","family":"Knopman","sequence":"first","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Rochester, 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