Structural and Clinical Predictors of Cognitive Impairment After Surgical Treatment for Ruptured Cerebral Aneurysms

Aneurysmal subarachnoid hemorrhage (aSAH) is associated with substantial morbidity, even among patients who remain functionally independent after treatment. Late cognitive deficits, particularly involving memory, attention, and executive function, are common in patients undergoing microsurgical clipping of ruptured cerebral aneurysms; however, the underlying mechanisms remain poorly understood. This study aims to identify clinical, acute radiological, and late structural predictors associated with cognitive impairment in these patients.

Participants will undergo a standardized late postoperative brain magnetic resonance imaging (MRI) evaluation (>1 year after treatment). Structural imaging variables to be analyzed as potential predictors of cognitive impairment include the presence or absence of hippocampal atrophy, frontal lobe atrophy, posterior cerebellar atrophy, pituitary gland atrophy, and deep gray nuclei atrophy, as well as quantitative measurements of white matter hyperintensity volume on FLAIR MRI, residual infarct volume, and cerebral perfusion. These imaging variables will be evaluated in combination with clinical and acute radiological characteristics to identify independent predictors of late cognitive impairment.

Primary outcomes

• Montreal Cognitive Assessment (MoCA) score [Through study completion, an average of 3 years]: The MoCA is a global cognitive screening test with scores ranging from 0 to 30, where higher scores indicate better cognitive function. Cognitive impairment is defined as a MoCA score <25, adjusted for educational level. A secondary analysis will also classify participants with MoCA <23, adjusted for educational level, representing unfavorable functional outcome.

Secondary outcomes

• EuroQol 5-Dimension 5-Level (EQ-5D-5L) [Through study completion, an average of 3 years]: The EQ-5D-5L descriptive system generates a health utility index score ranging from less than 0 (health states considered worse than death) to 1.0 (full health), depending on the country-specific value set. Higher scores indicate better health-related quality of life.
• Hospital Anxiety and Depression Scale (HADS) [Through study completion, an average of 3 years]: proportion of patients with anxiety or depression. The HADS consists of two subscales: HADS-Anxiety (HADS-A) and HADS-Depression (HADS-D), each ranging from 0 to 21, with higher scores indicating greater symptom severity. The outcome is defined as the proportion of participants with a score ≥8 on either the HADS-A (anxiety) or HADS-D (depression) subscale, consistent with clinically significant symptoms.
• Modified Rankin Scale (mRS) [Through study completion, an average of 3 years]: proportion of patients with favorable functional outcome. The Modified Rankin Scale ranges from 0 to 6, where 0 indicates no symptoms, 5 indicates severe disability requiring constant care, and 6 indicates death. Higher scores indicate worse functional outcome. The outcome is defined as the proportion of participants with a favorable functional outcome (mRS 0-2) versus an unfavorable functional outcome (mRS 3-6).
• Return to work [Through study completion, an average of 3 years]: proportion of patients returning to work. This outcome is defined as the proportion of participants who returned to paid employment after aneurysmal subarachnoid hemorrhage and microsurgical clipping (yes/no). Among participants who returned to work, the proportion requiring workplace adaptations or modifications (yes/no) will also be assessed.
• In-hospital complications [Through study completion, an average of 3 years]: Proportion of participants experiencing in-hospital complications. Each complication will be recorded as a binary outcome (yes/no) during the index hospitalization for aneurysmal subarachnoid hemorrhage. Complications include aneurysm rebleeding, hydrocephalus, need for surgical revision, infection, and delayed cerebral ischemia.

Sex: All

Inclusion Criteria:

* Age ≥18 years at the time of aSAH.
* Treatment by microsurgical clipping of a ruptured cerebral aneurysm.
* Survival until study recruitment.
* Ability to understand and sign informed consent.

Exclusion Criteria:

* Non-aneurysmal subarachnoid hemorrhage.
* Exclusively endovascular treatment.
* Previous diagnosis of dementia.
* Severe neurological or psychiatric disorders unrelated to aSAH with significant cognitive impact.
* Absolute contraindication to MRI.
* Severe aphasia preventing adequate neuropsychological evaluation.
* Incomplete clinical data.
* Inability to attend in-person assessment.