Predictors of Cognitive Decline and Delirium in Older Women With Ovarian Cancer

Cognitive decline and delirium are frequent and clinically relevant geriatric syndromes among older adults with cancer. These conditions are associated with reduced treatment adherence, functional decline, poorer quality of life, increased hospitalization, and mortality. In older women with ovarian cancer, cognitive outcomes are influenced by a complex interaction between aging-related vulnerability, frailty, multimorbidity, cancer characteristics, and oncological treatments. Despite the increasing use of Comprehensive Geriatric Assessment (CGA) in oncology, important gaps remain in identifying patients at highest risk for cognitive decline and delirium and in understanding the biological mechanisms underlying these conditions.

The C.R.O.W.N. (Identification of clinical, functional and biological predictors of Cognitive decline and deliRium in Older Women affected by ovarian caNcer) study is a prospective, longitudinal, single-center observational cohort study designed to identify clinical, functional, and biological predictors of cognitive decline and delirium in older women with ovarian cancer undergoing active treatment.

Women aged 70 years or older with newly diagnosed ovarian cancer, regardless of disease stage, or with first disease recurrence will be enrolled before the initiation of any oncological treatment or invasive procedure. All participants will undergo a standardized Comprehensive Geriatric Assessment, including evaluation of comorbidities, medications, frailty, nutritional status, physical performance, disability, mood, quality of life, and cognitive function.

Cognitive assessment will combine subjective and objective measures. Standardized neuropsychological tests will evaluate memory, executive function, attention, verbal fluency, and global cognition, while validated patient-reported outcome measures will assess perceived cognitive impairment. Participants will undergo evaluations at baseline, 6 months, and 12 months to characterize longitudinal cognitive trajectories.

During hospital admissions, including postoperative hospitalization, participants will be systematically screened for delirium using validated assessment tools. In addition, a structured telemonitoring program based on telephone contacts, video consultations when necessary, and remote cognitive screening will support follow-up, minimize missing data, and facilitate early identification of cognitive changes.

Blood samples collected before treatment initiation will be analyzed to measure biomarkers of neurodegeneration and systemic inflammation, including neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), phosphorylated tau, amyloid-beta peptides, inflammatory cytokines, C-reactive protein, and other laboratory markers. These biomarkers will be integrated with clinical and geriatric assessment data to investigate their contribution to cognitive decline and delirium.

The primary objective is to determine the prevalence and incidence of cognitive decline and to identify clinical, functional, and biological predictors associated with longitudinal cognitive deterioration. Secondary objectives include evaluating the incidence and predictors of delirium, assessing the association of cognitive disorders with disability, hospitalization, mortality, and quality of life, and developing a multivariable risk prediction model capable of stratifying patients according to their probability of adverse cognitive outcomes.

By integrating comprehensive geriatric assessment with blood-based biomarkers and longitudinal follow-up, the C.R.O.W.N. study aims to improve the early identification of vulnerable older women with ovarian cancer, support individualized oncogeriatric care, and provide evidence to inform future preventive and therapeutic strategies targeting cancer-related cognitive impairment and delirium.

Inclusion criteria

• Female sex with ovarian cancer.
• Age ≥70 years.
• Newly diagnosed ovarian cancer (any stage) or first disease recurrence.
• Evaluation before initiation of any anticancer treatment or invasive procedure (e.g., primary cytoreductive surgery, neoadjuvant chemotherapy, image-guided biopsy, or exploratory laparoscopy).
• Ability to understand and provide written informed consent, or availability of a legally authorized representative to provide consent.

Exclusion criteria

• Age <70 years.
• Refusal or inability to provide written informed consent and absence of a legally authorized representative.