Cognitive impairment is common among older adults hospitalized for non-neurological conditions but often goes unrecognized, particularly in rehabilitation settings where clinical attention is mainly focused on physical recovery. The COGinREHAB study is a multicenter, prospective, longitudinal interventional study conducted at three rehabilitation centers of the Fondazione Don Carlo Gnocchi in Italy (Florence and Milan).
The study will enroll 384 patients aged 45 years or older who are hospitalized for at least 7-10 days in cardiac, pulmonary, or orthopedic intensive rehabilitation units, or in intermediate care units, for conditions unrelated to the nervous system.
At admission, all participants undergo a clinical and cognitive screening visit. Patients whose screening results suggest possible cognitive impairment then undergo a more extensive neuropsychological evaluation. In those with confirmed cognitive impairment, additional blood tests are performed to measure biomarkers of neurodegeneration (GFAP, neurofilament light chain, and phosphorylated tau-217), together with APOE genotyping and a non-contrast brain CT scan. In a subset of these patients, resting-state EEG, auditory event-related potentials, actigraphy, and overnight polysomnography are also performed. Patients with confirmed cognitive impairment are invited to a follow-up visit 12 months later to assess whether their cognitive profiles and biological markers have changed.
The main purpose of the study is to estimate how frequently cognitive impairment occurs among patients admitted to non-neurological rehabilitation units, including how often it was previously undiagnosed. The study will also describe the clinical, biological, and neurophysiological profile of these patients and examine how cognitive impairment evolves over one year.
Age ≥45 years
Hospitalization for at least 7-10 days for a non-neurological condition, in cardiac, pulmonary, or orthopedic intensive rehabilitation units, or intermediate care units
Adequate fluency in the Italian language
Provision of written informed consent
Illiteracy
Severe, uncorrected visual impairment and/or hearing loss
Severe verbal communication deficit
Inability to remain seated for the duration of the assessment
Single group
Cognitive and clinical screening
Other interventionStructured collection of clinical/sociodemographic variables (Cumulative Illness Rating Scale -CIRS-, Halm's Clinical Instability Scale -SIC-) and administration of the Montreal Cognitive Assessment (MoCA), Hospital Anxiety and Depression Scale (HADS), Lifestyle for Brain Health index (LIBRA), Cognitive Reserve Index Questionnaire-Short Version (S-CRIq), Motor Reserve Index Questionnaire (MRIq), and Current Physical Activity Questionnaire (cPAq), performed at baseline (T0) in all participants.
Extended neuropsychological assessment
Other interventionDigit Span/Corsi Span (forward/backward), Rey Auditory Verbal Learning Test, Rey-Osterrieth Complex Figure, SAND naming subtest, Trail Making Test A/B, Stroop Colour-Word Test, and phonemic/semantic/alternate verbal fluency, administered at T0 in participants with screening results suggestive of cognitive impairment, and repeated at the 12-month follow-up (T1) in those with confirmed impairment.
Blood biomarker sampling and APOE genotyping
Diagnostic testVenous blood draw for APOE genotyping, including APOE ε4 allele dose (0, 1, or 2 copies) and allelic frequency distribution (ε2, ε3, ε4) (T0 only), and quantification of plasma GFAP, NfL, and pTau-217 (all expressed in pg/mL; T0 and T1), performed in participants with cognitive impairment confirmed by the extended neuropsychological assessment.
Non-contrast brain CT scan
Diagnostic testSingle non-contrast brain CT scan performed at T0 in participants with confirmed cognitive impairment.
Multimodal neurophysiological assessment
Diagnostic testResting-state EEG, quantified as relative spectral power in the delta, theta, alpha, and beta bands (T0 and, in participants with confirmed cognitive impairment, repeated at T1); auditory oddball P300 event-related potentials, quantified as latency and amplitude; actigraphy-based sleep-wake monitoring, quantified as Sleep Efficiency; and overnight polysomnography, quantified as percentage of total sleep time in each sleep stage (N1, N2, N3, and REM); performed at T0 in a subset of participants with confirmed cognitive impairment.
Prevalence of cognitive impairment among patients admitted for non-neurological causes to the rehabilitation wards
Proportion of enrolled patients with cognitive impairment (Unit of Measure: % of patients). Confirmed via a two-stage process: (1) MoCA screening (corrected score range 0-30, higher = better), where an Equivalent Score (ES) of 0-1 in ≥1 domain triggers referral to (2) an extended battery, applying criteria adapted from Jak and Bondi (Jak et al., 2009; Bondi et al., 2014): ES ≤1 (Capitani \& Laiacona, 1997; below the 20th percentile, \~equivalent to \>1 SD below norms) on ≥2 tests within one domain, or ≥1 test in each of 3 domains (memory, language, attention/executive functioning). ES ranges 0-4 (0=worse, 4=better). Calculated as (patients with confirmed impairment / total enrolled) × 100, with 95% CI.
Rate of previously undiagnosed cognitive impairment
Proportion of patients with confirmed cognitive impairment (Unit of Measure: % of patients with confirmed cognitive impairment; per the neuropsychological criteria defined in the Primary Outcome Measure) who had no prior documented diagnosis of cognitive impairment in their clinical history, calculated as (number of patients with previously undiagnosed cognitive impairment / number of patients with confirmed cognitive impairment) × 100, with 95% CI.
Clinical and demographic characteristics associated with cognitive status at baseline
Comparison of sociodemographic and clinical variables (Unit of Measure: N/A - descriptive comparison across subgroups) among subgroups defined by Montreal Cognitive Assessment (MoCA) Equivalent Score (ES; derived from the 0-30 corrected MoCA total score, higher scores indicating better performance): ES ≥2 (within normative range), ES=1 (borderline), ES=0 (below normative reference limit, worse performance).
Change in Montreal Cognitive Assessment (MoCA) Total and Domain Scores
Change between T0 and T1 in MoCA total score (corrected score, range 0-30, higher = better) and MoCA cognitive domain scores, including the Memory Index Score (MIS) and other domain-level indices derived from the Italian MoCA normative reference (Dapor et al., 2025), in patients with confirmed cognitive impairment at baseline: Visuo-spatial (MoCA-V corrected score, range 0-4, higher = better); Attention (MoCA-A corrected score, range 0-6, higher = better); Language (MoCA-L corrected score, range 0-5, higher = better); Executive Functions (MoCA-E corrected score, range 0-4, higher = better); Memory (MoCA-DR corrected score, range 0-5, higher = better); Orientation (MoCA-O corrected score, range 0-6, higher = better); and MIS corrected score, range 0-15, higher = better.
Change in Digit Span Performance
Change in forward and backward Digit Span performance (Unit of Measure: number of digits correctly recalled, range 0-9 forward and 0-8 backward; higher = better) between T0 and T1.
Click on the lead sponsor to view all of their trials.
Fondazione Don Carlo Gnocchi ETS
Lead sponsor
University of Florence
Collaborator
