Functional autonomy, comorbidities and cognitive decline: a mediation analysis in neurocognitive disorders

Neurocognitive Disorders (NCDs) represent a growing global health concern, significantly impacting both quality of life and healthcare systems. Emerging evidence suggests that functional autonomy, measured through Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL), as well as comorbidity and educational attainment, influence the trajectory of cognitive decline. However, the interplay among these factors remains insufficiently understood. This study investigates the mediating role of IADL between comorbidity and disorder severity, while examining the direct and IADL-mediated effects of educational attainment (as a proxy of cognitive reserve).

To explore the interrelationships between comorbidity (Cumulative Illness Rating Scale-CIRS), functional autonomy (ADL and IADL), educational attainment, and the severity of Neurocognitive Disorders. Specifically, the study aims to assess the mediating effect of IADL and examine how demographic and clinical variables (including age, gender, and education level) are associated with cognitive impairment.

An observational study was conducted on a sample of 1,033 individuals, including patients diagnosed with major or mild Neurocognitive Disorder, as well as individuals without dementia but reporting subjective memory complaints. Functional autonomy was assessed using the ADL and IADL scales, comorbidity through the Cumulative Illness Rating Scale (CIRS), and educational attainment was measured in total years of formal schooling. Multiple linear regression analyses and mediation testing were carried out using Structural Equation Modeling (SEM).

Comorbidity (CIRS) was the strongest predictor of disorder severity (B = 0.259, p = 0.001), followed by age (B = 0.012, p < 0.001), educational attainment (B = -0.018, p = 0.003), and IADL scores (B = -0.109, p < 0.001). In multiple regression, diagnostic severity was significantly associated with comorbidity (CIRS; B = 0.259), age (B = 0.012), educational attainment (B = -0.018), and functional autonomy (IADL; B = -0.109). SEM supported partial mediation of the CIRS-severity association via IADL (indirect effect = 0.222), with excellent model fit (CFI = 0.95; RMSEA = 0.03).

Comorbidity, functional autonomy, and educational attainment play critical roles in the progression of Neurocognitive Disorders. Higher comorbidity is linked to more severe cognitive deficits, whereas greater functional independence and educational background are protective factors. Incorporating ADL, IADL, and CIRS assessments into diagnostic and care planning, alongside demographic profiling, may enhance the precision of clinical interventions, support functional independence, and reduce caregiver burden.