Multimodal Detection of Cognitive Impairment in Non-Neurological Rehabilitation Settings: The COGinREHAB Study Protocol

Background/Objectives: Cognitive impairment is highly prevalent among hospitalised adults but often remains under-recognised, particularly in non-neurological rehabilitation settings where clinical attention is mainly focused on physical recovery. Undetected cognitive impairment may adversely affect rehabilitation outcomes, functional recovery, and long-term care planning. Methods: A multicentre, prospective, longitudinal study, with a single-group assignment and a diagnostic purpose, will be conducted across three rehabilitation centres of the Don Carlo Gnocchi Foundation (Italy), enrolling 384 patients aged ≥45 years without severe psychiatric or neurological disorders, other than cognitive impairment, admitted to cardiac, pulmonary, orthopaedic rehabilitation, or intermediate care units for non-neurological conditions. At baseline (T0), all participants will undergo standardised clinical and cognitive screening. Individuals with suspected cognitive impairment, operationally defined as an Equivalent Score (ES) of 1 on the Montreal Cognitive Assessment–MoCA total score and/or an ES of 0 or 1 on at least one MoCA cognitive domain, including the Memory Index Score (MIS), and a random sample of those without, will undergo a comprehensive neuropsychological assessment. Participants with neuropsychologically defined cognitive impairment, based on objective deficits in the comprehensive neuropsychological assessment, will undergo plasma biomarker testing (GFAP, NfL, pTau-217), APOE genotyping, and brain CT. Participants with a MoCA total ES of 0 will be classified as having cognitive impairment on the basis of screening alone. At two prespecified sites, consecutive consenting participants with neuropsychologically defined cognitive impairment will additionally undergo an EEG vigilance protocol, auditory P300 recording, seven-day actigraphy, and overnight polysomnography. Patients with neuropsychologically defined cognitive impairment at T0 will undergo a 12-month follow-up assessment (T1) of the progression of cognitive impairment and plasma biomarkers; those enrolled in the neurophysiological substudy will additionally repeat the EEG vigilance protocol. Expected Results: The study will provide a conservative (lower-bound) estimate of the prevalence of documented and non-documented cognitive impairment, together with an estimate corrected for partial verification bias, in non-neurological rehabilitation settings. It will further characterise the cognitive profiles and examine their correlations with biomarkers of neurodegeneration (GFAP, NfL, pTau-217), APOE genotype, relative EEG spectral power and sleep intrusion measures, P300 latency and amplitude, actigraphy-derived Sleep Efficiency, and polysomnography-derived sleep stage proportions. Longitudinal data will enable the evaluation of cognitive trajectories and their biological correlates. Conclusions: The COGinREHAB study addresses a critical gap in rehabilitation medicine by implementing a structured, multimodal approach to the identification and characterisation of cognitive impairment in patients with non-neurological conditions. Its findings may facilitate earlier detection of cognitive impairment and inform the development of personalised rehabilitation and care pathways. Trial registration: ClinicalTrials.gov, NCT07731334.