Cognitive decline in Cushing's syndrome: A systematic review

Area of Science:

• Neuroendocrinology
• Neuropsychiatry
• Neurosurgery

Background:

• Cushing's syndrome (CS) significantly impairs neurocognitive function, psychiatric health, and quality of life.
• Neurocognitive deficits and psychiatric symptoms in CS patients may persist post-surgery.
• Comparison with non-functioning pituitary adenoma (NFPA) and healthy controls is crucial for understanding CS-specific effects.

Purpose of the Study:

• To systematically review and compare neurocognitive, psychiatric, and structural brain changes in Cushing's disease (CD)/CS versus NFPA patients.
• To evaluate these changes before and after surgical treatment.
• To identify predictors of persistent neurocognitive symptoms and reduced quality of life in CS patients.

Main Methods:

• Systematic review of English literature (Medline/Pubmed) up to 2021, adhering to PRISMA guidelines.
• Inclusion criteria: studies on CD/CS patients, reporting psychiatric symptoms, published in peer-reviewed journals.
• Analysis of 40 eligible studies involving 2603 participants, using validated questionnaires and comparing with NFPA controls.

Main Results:

• Patients with CD/CS showed worse cognitive function than NFPA controls, particularly with higher baseline serum cortisol levels, persisting even after remission.
• Longer duration of uncontrolled CS correlated with poorer cognitive function.
• While overall brain volume increased post-remission, frontal and temporal lobe volumes remained reduced compared to controls.

Conclusions:

• Neurocognitive dysfunction, psychiatric disorders, and diminished quality of life are common in CS and can persist after curative surgery.
• Predictors of persistent symptoms include high pre-operative cortisol, longer disease duration, baseline cognitive/neuropsychiatric deficits, and frontal/temporal lobe atrophy.
• Larger prospective studies are needed to validate these findings and guide management.