Longitudinal Cognitive Assessment After CAR-T Cell Immunotherapy: A Prospective Cohort Study

(1) Background: Cognitive dysfunction represents an emerging concern in chimeric antigen receptor T-cell (CAR-T) therapy recipients, yet longitudinal data using simple, clinically applicable tools are lacking. (2) Methods: We conducted a single-center prospective cohort study of consecutive adults with hematologic malignancies treated with commercially available CAR-T cell products between May 2023 and November 2025 at our center. Cognitive function was evaluated with the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) at baseline (before the administration of lymphodepleting chemotherapy) (T1), 6 h after infusion (T2), at 3 months (T3), and at 6 months (T4). MoCA scores ≤ 25 and/or MMSE scores ≤ 23 were considered indicative of impaired cognitive function. (3) Results: Thirty-six patients were enrolled in the present study, while cytokine release syndrome occurred in 33/36 patients (91.7%), and immune effector cell-associated neurotoxicity syndrome of any grade occurred in 23/36 (63.9%). At baseline (T1), cognitive impairment was identified in 12/36 patients (33.3%) by MoCA. Following infusion (T2), 11/35 (31.4%) exhibited cognitive impairment, while baseline cognitive impairment and older age were associated with early post-infusion cognitive dysfunction. Across follow-up (T3 and T4), no significant overall changes were observed in MoCA- or MMSE-defined cognitive status or in total test scores. However, abstraction in MoCA and attention/calculation in MMSE showed time-dependent variation. (4) Conclusions: These findings support the use of simple longitudinal cognitive assessment in CAR-T recipients.