W4 T2 P4

• Assessment of cognition should be undertaken and adapted from an International Society of Bipolar paper by Kamilla Miskowiak.
• Delay cognitive assessment until remission is achieved, as mood symptoms influence cognition.
• Assess cognition of fully remitted patients with objective and subjective screeners.
• Instruments: SCIP in COBRA, MOCA, and MMSE (Mini-Mental State Exam) for older patients.
• If a patient is cognitively impaired, determine if it’s illness related.
• Consider secondary causes (medication, comorbidity, unhealthy lifestyle, organic brain illness, dementia).
• If impairments persist, assess secondary causes or refer for dementia assessment.
• If impairment seems mood disorder-related, provide information and recommendations, and consider compensation strategies.
• Track cognition over time, ideally every five years or if assessment is anticipated.

Pro-Cognitive Treatments

• Some evidence supports drugs like vortioxetine (antidepressant), mifepristone (hormonal antagonist), pramipexole (dopamine active drug), duloxetine (antidepressant), lurasidone (antipsychotic).
• Also erythropoietin (stimulates red blood cell formation), and modafinil (cognitive enhancer).
• Current antidepressants generally don't cause cognitive improvement.
• A study showed no difference among escitalopram, sertraline, and venlafaxine in cognitive improvement.
• Antidepressants showed no effect above time and practice; patients remained impaired.
• Impairment degree correlated with chronicity, not depression severity.
• Antidepressants which treat depression do not necessarily improve cognitive impairment related to depression.
• Cognition may be an objective marker of antidepressant response.
• Methodological problems exist in antidepressant trials using cognitive outcomes due to the increased placebo response.
• Raskin et al. showed duloxetine had beneficial effects in elderly depression using a cognitive battery.
• Vortioxetine improves cognition in recovered major depressive patients, suggesting a mood-independent pro-cognitive effect.
• Phillip Harvey showed Lurasidone benefits cognition in schizophrenia.
• Underestimation of treatment effect for a pro-cognitive agent could be caused by not using the right measures.

Vortioxetine Effects

• Improving cognitive performance happens during depression episodes across multiple domains.
• Tests include the digit symbol substitution test with two vortioxetine doses.
• Benefits include executive function effects, attention and speed of processing, and memory effects.
• Improvements were replicated in people recovered from depression.
• Improvement in neuropsychological tests generalises to everyday functioning (UPSA).
• UPSA measures factors such as household chores, communication, finance, and recreation.
• Vortioxetine, but not duloxetine, had a greater beneficial effect than placebo.

Mechanisms for Cognitive Impairment

• Stress and stressful life events are associated with mood disorder episodes.
• Stress weakens prefrontal networks.
• Under normal conditions the prefrontal cortex regulates thought, action, and emotion.
• Under stress, excess hormones cause the amygdala to affect the basal ganglia.
• Can result conditional emotion responses and reflexive/habitual responding from primitive brain circuits.
• Activation of the autonomic nervous system also happens.

Mifepristone

• Potentially pro-cognitive, formulated in 1981 for high stress hormone-related conditions.
• Approved in Europe/Asia in 1988, in US in 2000.
• Blocks glucocorticoids and progesterone receptors.
• Used for pregnancy termination; not licensed for that purpose in the UK during a study.
• Used to treat cognitive impairments in bipolar depression.
• It has large, delayed benefit in cognitive performance specifically, spatial working memory and verbal learning saw improvements
• No secondary antidepressant effect was observed with mifepristone.

Erythropoietin

• Kamilla Miskowiak researched its efficacy in depression.
• Intravenous erythropoietin improved cognition at Weeks 9 and 14.
• Erythropoietin produces mood-independent memory improvements, persisting beyond the active treatment phase.
• Erythropoietin is not a practicable treatment, but shows potential.
• Erythropoietin improved the speed of complex cognitive processing in bipolar disorder, also persisting beyond treatment.

Lithium

• Worral and Telford (1978) examined the effect of lithium on cognition
• There has been a belief lithium may impair cognition.
• Katherine Burdick's data may revise the cognition lithium belief.
• In baseline comparisons of 262 participants, lithium therapy improved verbal learning, memory, executive skills, and cognitive index.
• Results do not suggest lithium impairs cognition, and lithium may be neuroprotective.
• Prospective comparisons showed mood stabilisation improved global cognitive index, memory, and executive skills.
• Lithium is suggests beneficial for cognition in bipolar disorder.

Lurasidone

• Lurasidone may improve cognitive function in schizophrenia.
• Lurasidone, approved for bipolar disorder, may improve cognitive impairment in euthymic/recovered patients.

Non-Pharmacological Strategies

• Functional remediation is a psychoeducative strategy (Torrent et al.).
• FAST measures functional assessment score
• Treatment options include: treatment as usual, psychoeducation, or functional remediation.
• The primary endpoint measures change in FAST.
• Functional remediation saw the greatest improvement, followed by psychoeducation.
• The study was single-blind; possibility exists that functional remediation was associated with a greater placebo effect.
• CIRCuiTS is a cognitive remediation therapy approach by Professor Dame Til Wykes et al.
• Emphasises strategy use and metacognitive skills.
• Therapy includes personalised goal setting, and promotes applying new skills to real-life activities.
• CRIB study: Cognitive Remediation and Bipolar Study.
• Patients were randomised to treatment as usual or treatment as usual plus cognitive remediation and evaluated at 13 and 25 weeks.
• Retention was improved with cognitive remediation therapy.
• Benefits of cognitive remediation were shown in both groups at Week 25, and sometimes at Week 13.
• Showing improvements in global cognitive score, memory, verbal fluency, processing speed, and attention.
• Showing improvements in intellectual performance, working memory, and executive functioning.
• Improvements were seen across the board, with no detrimental effect from cognitive remediation.
• Intention-to-treat showed increased improvements from CRT than treatment as usual.
• FAST showed improvement at Weeks 13 and 25.
• The general attainment score and UPSA improved at Week 13 and 25.
• A larger trial will recruit 250 patients to further examine these effects in euthymic bipolar disorder.

Summary

• Cognitive impairment occurs in neuropsychiatric disorders, including major depressive and bipolar disorder.
• Cognitive deficits may endure beyond illness episodes.
• Deficits may be independent from depressive symptomology.
• These deficits impact psychosocial functioning and workplace performance.
• Screening for cognitive deficits and decline is important.
• Studies are limited, but promising, and a focus of interest.
• Potential benefits of pharmacotherapy drugs (vortioxetine, mifepristone, lurasidone, lithium) are evident.
• Cognitive remediation shows potential, mentioning preliminary results from cognitive remediation and the Bipolar Study.

Overview of cognitive assessment and treatment strategies, adapted from an International Society of Bipolar paper. It emphasizes assessment timing, instruments like SCIP and MOCA, and addressing secondary causes. Recommendations for tracking cognitive function over time are also highlighted.