Cognitive impairment in older persons with bipolar disorder

Beekman, A.T.F. [Promotor]Stek, M.L. [Copromotor]Comijs, H.C. [Copromotor

Interrogating Associations Between Polygenic Liabilities and Electroconvulsive Therapy Effectiveness

BACKGROUND: Electroconvulsive therapy (ECT) is the most effective treatment for severe major depressive episodes (MDEs). Nonetheless, firmly established associations between ECT outcomes and biological variables are currently lacking. Polygenic risk scores (PRSs) carry clinical potential, but associations with treatment response in psychiatry are seldom reported. Here, we examined whether PRSs for major depressive disorder, schizophrenia (SCZ), cross-disorder, and pharmacological antidepressant response are associated with ECT effectiveness. METHODS: A total of 288 patients with MDE from 3 countries were included. The main outcome was a change in the 17-item Hamilton Depression Rating Scale scores from before to after ECT treatment. Secondary outcomes were response and remission. Regression analyses with PRSs as independent variables and several covariates were performed. Explained variance (R2) at the optimal p-value threshold is reported. RESULTS: In the 266 subjects passing quality control, the PRS-SCZ was positively associated with a larger Hamilton Depression Rating Scale decrease in linear regression (optimal p-value threshold = .05, R2 = 6.94%, p < .0001), which was consistent across countries: Ireland (R2 = 8.18%, p = .0013), Belgium (R2 = 6.83%, p = .016), and the Netherlands (R2 = 7.92%, p = .0077). The PRS-SCZ was also positively associated with remission (R2 = 4.63%, p = .0018). Sensitivity and subgroup analyses, including in MDE without psychotic features (R2 = 4.42%, p = .0024) and unipolar MDE only (R2 = 9.08%, p < .0001), confirmed the results. The other PRSs were not associated with a change in the Hamilton Depression Rating Scale score at the predefined Bonferroni-corrected significance threshold. CONCLUSIONS: A linear association between PRS-SCZ and ECT outcome was uncovered. Although it is too early to adopt PRSs in ECT clinical decision making, these findings strengthen the positioning of PRS-SCZ as relevant to treatment response in psychiatry

Risk factors for cognitive impairment in elderly bipolar patients

Objective: Cognitive impairment in elderly bipolar patients persists during euthymic state, yet the aetiology of such impairment is not well understood. The objective of this study is to identify factors contributing to cognitive impairment in elderly patients with bipolar disorder. Method: 119 older patients (age > 60) with bipolar I or II disorder in a euthymic state were extensively tested on cognitive functioning including attention, memory, visuoconstruction, executive function and verbal fluency with regard to potential risk factors. Results: Regression analysis shows that health related factors, medication and illness characteristics are associated with cognitive impairment in several cognitive domains: attention, memory, visuoconstruction, executive function and verbal fluency. More vascular burden factors are related to poorer outcome of cognitive functioning. Patients with lithium pharmacotherapy performed worse compared to those with other mood stabilizers, but this was no longer significant in multivariate analysis. Conclusions: In elderly bipolar patients, more vascular risk factors and more hospital admissions are associated with more cognitive impairment. © 2010 Elsevier B.V. All rights reserved

Cognitive decline in elderly bipolar disorder patients: a follow-up study

Objective: Older individuals with bipolar disorder may exhibit greater cognitive decline over time compared to mentally healthy elderly individuals. We aimed to investigate neurocognitive performance in bipolar disorder over a period of two years. Methods: A comprehensive neuropsychological test battery was applied at baseline and two years later to 65 euthymic elderly outpatients with bipolar disorder (mean age=68.35, range: 60-90years) and to a demographically comparable sample of 42 healthy elderly controls. A general linear model was used to measure changes over time for the two groups. The impact of baseline illness characteristics on intra-individual change in neurocognitive performance within the bipolar group was studied by using logistic regression analysis. Results: At baseline and at follow up, bipolar disorder patients performed worse on all neurocognitive measures compared to the healthy elderly group. However, there was no significant group-by-time interaction between the bipolar disorder patients and the comparison group. Conclusions: Although older bipolar disorder patients have worse cognitive function than normal controls, they did not have greater cognitive decline over a period of two years. © 2012 John Wiley and Sons A/S

Cognitive impairment in late life schizophrenia and bipolar I disorder

Objective Evidence in younger populations suggests quantitative but not categorical differences in cognitive impairments between schizophrenia and bipolar disorder. It is uncertain whether a similar distinction applies to patients in later life. Methods We compared the cognitive abilities of older, community-living schizophrenia patients, controlling for their state of symptomatic remission, with those of older euthymic patients with bipolar I disorder. The study included 67 patients with schizophrenia (20 in symptomatic remission, 47 not in symptomatic remission; mean age 68 years) and 74 euthymic bipolar I patients (mean age 70 years), who were compared using analysis of covariance on clinical and neuropsychological variables (e.g., attention/working memory, verbal memory, executive function and verbal fluency) and contrasted with 69 healthy controls. Results Remitted (SR) and non-remitted (SN) schizophrenia patients and bipolar I (BP) patients were impaired relative to healthy controls, with mostly large effect sizes for verbal memory (Cohen's d: SR 1.34, SN 1.48, BP 1.09), executive function (Cohen's d: SR 0.87, SN 1.29, BP 0.71) and verbal fluency (Cohen's d: SR 1.09, SN 1.25, BP 0.88), but smaller effect sizes for the domain of attention/working memory (Cohen's d: SR 0.26, SN 0.18, BP 0.52). Differences in cognitive performance between the remitted schizophrenia patients and the bipolar I patients were not significant. Conclusions In both older patients with schizophrenia and with bipolar disorder, serious and pervasive cognitive deficits can be demonstrated. Trait-related cognitive deficits in schizophrenia and bipolar disorder may share major phenotypic similarity in later life. Copyright © 2012 John Wiley & Sons, Ltd. Copyright © 2012 John Wiley & Sons, Ltd