Impairment In Euthymic Bipolar Patients Research Articles

The Impact of Obesity on Cognitive Functioning in Euthymic Bipolar Patients: A Cross-Sectional and Longitudinal Study.

To determine the influence of body mass index (BMI) on cognition in euthymic bipolar patients and healthy matched controls in a post hoc study of 2 cross-sectional and longitudinal exploratory studies. A total sample of 121 individuals was examined, which included 52 euthymic bipolar disorder I or II patients (DSM-IV-TR criteria) and 69 healthy controls matched by age and gender, categorized in 2 subgroups in terms of body mass index (BMI-factor): normal weight (BMI: 18.5-24.9 kg/m²) versus overweight-obesity (overweight, BMI: 25.0-29.9 kg/m²; and obese, BMI ≥ 30 kg/m²). Demographic, clinical, cognitive, and psychosocial functioning data were collected from 2003 until 2011. Cognitive domains studied were executive function, attention, processing speed, verbal memory, and visual memory. Fifty-four subjects (28 bipolar and 26 healthy controls) were reevaluated after 6 years of follow-up. Obesity and bipolar disorder showed a significant effect on cognition in cross-sectional and long-term MANOVA analyses (F₇,₁₁₁ = 2.54, P = .018 and F₁₉,₂₃ = 2.25, P = .033, respectively). In the cross-sectional linear regression model, global cognitive functioning was predicted by the interaction of BMI-factor by group (β = -0.44, SE = 0.14, P = .002), current age (β = -0.44, P < .0001), and premorbid IQ (β = 0.28, P = .0002), which explained 56% of variance (F₅,₁₁₅ = 29.6, P < .0001). Change in cognitive functioning over time was predicted by the interaction of BMI-factor by group (β = -0.8, SE = 0.33, P = .022) and cognition at baseline (β = -0.46, SE = 0.15, P = .004), which explained 27.65% of variance (F₆,₄₀ = 2.548, P = .0349). Generalized estimating equations analysis showed that interaction of group by BMI (Wald χ²₁ = 5.37, P = .02), age (Wald χ²₁ = 22.08, P < .0001), and premorbid IQ (Wald χ²₁ = 25.65, P < .0001) were the significant predictors. Obesity was significantly associated with cognitive impairment in euthymic bipolar patients, and it also appeared to affect cognition in the long term.

Structural and Functional Brain Correlates of Cognitive Impairment in Euthymic Patients with Bipolar Disorder.

IntroductionCognitive impairment in the euthymic phase is a well-established finding in bipolar disorder. However, its brain structural and/or functional correlates are uncertain.MethodsThirty-three euthymic bipolar patients with preserved memory and executive function and 28 euthymic bipolar patients with significant memory and/or executive impairment, as defined using two test batteries, the Rivermead Behavioural Memory Test (RBMT) and the Behavioural Assessment of the Dysexecutive Syndrome (BADS), plus 28 healthy controls underwent structural MRI using voxel-based morphometry (VBM). Twenty-seven of the cognitively preserved patients, 23 of the cognitively impaired patients and 28 controls also underwent fMRI during performance of the n-back working memory task.ResultsNo clusters of grey or white matter volume difference were found between the two patient groups. During n-back performance, the cognitively impaired patients showed hypoactivation compared to the cognitively preserved patients in a circumscribed region in the right dorsolateral prefrontal cortex. Both patient groups showed failure of de-activation in the medial frontal cortex compared to the healthy controls.ConclusionsCognitive impairment in euthymic bipolar patients appears from this study to be unrelated to structural brain abnormality, but there was some evidence for an association with altered prefrontal function.

Cognitive and psychosocial impairment in remitted bipolar patients

There is growing evidence showing that bipolar disorder is associated with persistent cognitive deficits. However, the exact meaning and impact of cognitive deficits in bipolar disorder is still not entirely known, even though they have been associated with poor psychosocial functioning. This study aims to summarize cognitive and psychosocial functioning findings of remitted bipolar patients. We conducted an extensive Medline search of the published English literature for the period January 2000– March 2014 using a variety of search terms to find relevant articles. Bibliographies of retrieved papers were further analysed for publications of interest. Our results showed that: (1) all mood states of bipolar disorder are associated with cognitive impairment. However, the euthymic state is associated with less impairment than the other states; (2) there is a strong association between clinical factors (i.e, duration of illness, number of episodes, residual mood symptoms, comorbidities) and cognitive impairment in euthymic bipolar patients, although these factors do not account fully for these deficits; (3) cognitive deficits, in particular, verbal learning and executive dysfunctions may contribute to poor functioning. In conclusion, our review suggests that cognitive deficits are strongly associated with mood episodes; such deficits persist, in lower degree, during remission. Impairment on cognitive performance may explain, in part, poor long–term functioning in remitted bipolar patients. It highlights that psychosocial interventions in combination with pharmacotherapy should be considered to improve cognition and enhance the level of functioning. Therefore, studies assessing the efficacy of novel strategies focused on cognitive and functional status are an important area of future investigation in bipolar disorder.

Neurocognitive impairment and psychosocial functioning in bipolar II disorder

There is a growing body of evidence on neurocognitive impairment in euthymic bipolar patients, but this issue has been studied mostly in bipolar I disorder, data on bipolar II (BD-II) are scant and discrepant. The two aims of this study were to ascertain whether strictly defined euthymic BD-II patients would present neurocognitive disturbances and to evaluate their impact on functional outcome. Forty-three BD-II patients and 42 demographically and educationally matched healthy subjects were assessed with a comprehensive neuropsychological test battery and with the Social and Occupational Functioning Assessment Scale (SOFAS). The euthymia criteria were reduced (Hamilton Rating Scale for Depression score ≤6 and a Young Mania Rating Scale score ≤6) to minimize the influence of subdepressive symptomatology on cognition and functioning. BD-II patients showed a significantly lower performance on several measures of attention, learning and verbal memory, and executive function compared with healthy controls. The presence of subthreshold depressive symptomatology and one measure related to executive function (Trail Making Test, part B) was the variables that best predicted psychosocial functioning measured with the SOFAS. This report provides further evidence that euthymic BD-II patients present cognitive impairment which may impact psychosocial functioning.

Treatment Nonadherence and Neurocognitive Impairment in Bipolar Disorder

Little is known regarding the relationship between treatment adherence and residual cognitive dysfunction in euthymic bipolar disorder patients. This study aimed to investigate whether poor treatment adherence is associated with cognitive impairment in euthymic bipolar patients and whether other factors may be associated with both adherence and cognitive functioning. Euthymic DSM-IV bipolar I or II disorder patients (N = 103: 61 with high levels of treatment adherence and 42 with poor treatment adherence) were assessed using a neuropsychological battery targeting attention, psychomotor speed, verbal memory, and executive functions and compared with 35 healthy controls of similar age, sex distribution, and education. Data were collected from September 2005 to June 2007. Bipolar patients with poor treatment adherence had more hospitalizations than those with high adherence. After controlling for age, gender, estimated IQ score, and Young Mania Rating Scale and 17-item Hamilton Rating Scale for Depression scores, non-treatment-adherent patients performed less well than normal controls in verbal learning and some executive functions. Among treatment-adherent and poorly adherent bipolar disorder patients, performance was similar in attention tasks and short-term and long-term verbal recall, but non-treatment-adherent patients were more impaired in ability to inhibit interferences and in spatial working memory. Poorer treatment adherence also was associated with the bipolar I subtype and with greater illness severity, as indicated by number of manic episodes and hospitalizations and history of psychosis. Pharmacologic factors, such as treatment with lithium, may also influence the relationship between neurocognition and adherence. There is a close relationship between poor treatment adherence and cognitive impairment, but the causal inferences of these findings are uncertain. Poor treatment adherence may worsen the course of bipolar disorder and so indirectly worsen cognitive performance, or cognitive impairment may contribute to poor treatment adherence and reflect more severe illness.

The effect of previous psychotic mood episodes on cognitive impairment in euthymic bipolar patients

Cognitive dysfunctions in several domains were proposed to be trait markers of bipolar patients. The aim of this study was to evaluate the effect of previous psychotic features on neuropsychological measures, including sustained attention, in remitted bipolar patients. The study participants were 40 euthymic psychotic, 25 non-psychotic bipolar I patients and 30 healthy control subjects. Participants were assessed with a battery of neuropsychological tests targeting attention, executive functions, psychomotor speed, verbal learning and memory. Euthymic psychotic bipolar patients performed worse than controls on most of the measures, after controlling for the confounding effects of education, age and residual symptoms. Non-psychotic patients were also impaired on tasks of attention, fluency and psychomotor speed. 'Number of Wisconsin Card Sorting Test (WCST) categories' achieved was the only measure on which psychotic patients performed significantly worse compared to non-psychotic patients. Differences among patient groups were not explained by illness severity measures. The duration of illness was related to slowness in psychomotor speed tasks. Verbal memory deficits may be related to serum lithium levels and age of onset of disease. Deficits in cognitive flexibility may be a candidate for being a trait marker of psychotic features among bipolar patients. However, verbal fluency, psychomotor speed and sustained attention deficits may be candidates for vulnerability indicators of bipolar disorder in general.

Impaired verbal memory and otherwise spared cognition in remitted bipolar patients on monotherapy with lithium or valproate

Patients with bipolar disorder have been reported to have neurocognitive deficits; however, it is not known whether the cognitive dysfunctions are state-dependent or a stable trait. Lithium and valproate, 2 of the most widely used mood stabilizers in the treatment of bipolar disorder, have also been associated with cognitive impairment. However, the degree and pattern of neurocognitive impairment in euthymic bipolar patients on either monotherapy with lithium or valproate have not been compared before in depth. We compared 17 euthymic outpatients with bipolar disorder (BD) on lithium monotherapy to 11 euthymic outpatients with BD on valproate monotherapy and 29 comparison subjects using tests measuring immediate verbal memory and executive functions in addition to 3 subtests of the Wechsler Adult Intelligence Scale Revised. The groups were similar in terms of level of education, duration and severity of illness, and gender distribution. Patients on lithium monotherapy were older than patients on valproate and healthy controls. Mood symptoms as assessed by standardized scales were mild to non-existent in both patient groups. Immediate verbal memory was impaired in both patient groups compared to controls, where the main effect of age was not significant. No significant differences could be found on the other cognitive measures. Both lithium and valproate may be associated with immediate verbal memory impairment, sparing other cognitive functions. Presence of a similar verbal memory deficit in the lithium and valproate groups suggests that this deficit might be intrinsic to BD or that the 2 medications influence immediate verbal memory similarly. Larger samples of remitted bipolar patients on monotherapy should be studied for more precise conclusions.

Association of cognitive deficits with elevated homocysteine levels in euthymic bipolar patients and its impact on psychosocial functioning: preliminary results

Elevated homocysteine (Hcy) levels have been demonstrated to have a negative impact on cognitive functioning in healthy elderly people. Further studies suggest that they are an independent risk factor for dementia, in particular for Alzheimer's disease. Bipolar disorder is also associated with cognitive impairment. However, the pathophysiological mechanisms of these deficits have not been elucidated yet. This study examines the role of Hcy on cognition and its impact on psychosocial functioning in euthymic bipolar patients. A total of 55 euthymic bipolar patients and 17 healthy controls were enrolled in the study. Neuropsychological assessments consisted of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), the Trail Making Test (TMT), the Weschler Adult Intelligence Scale, 3(rd) edition (WAIS-III) subtest Letter-Number Sequencing Test (LNST) and the HAWIE-R (German version of the WAIS-R) subtest Information. Psychosocial functioning was assessed using the Social Adjustment Scale (SAS). To obtain plasma levels of Hcy, blood samples were collected in EDTA tubes, immediately put on ice, centrifuged within 15 min and stored at -80 degrees C. Total Hcy concentration was measured using high-performance liquid chromatography. In the neuropsychological tests, patients differed significantly from healthy controls on the TMT B and the RBANS composite indices Language, Attention and Total Score. No differences were found on the HAWIE-R subtest Information, the TMT A, LNST or the RBANS composite indices Immediate Memory, Visuospatial/Constructional Abilities and Delayed Memory. Mean Hcy levels were 9.8 +/- 3.2 microm/L in the patient group and 7.8 +/- 2.1 microm/L in the control group, respectively (p = 0.012). In the patient group Hcy levels significantly correlated with gender, diagnosis and RBANS index scores for Immediate Memory, Language, Attention and Total Score. Linear regression analyses revealed a significant and independent association of Hcy levels with Immediate Memory and TMT B scores in the patient group. Homocysteine levels did not correlate with any measure in the control group. Spearman's correlations indicated that psychosocial functioning in bipolar patients is not associated with clinical variables apart from time in remission. However, it correlated significantly with working memory measures (LNST). No relationship could be determined between psychosocial functioning and Hcy plasma levels. Elevated Hcy levels seem to be associated with cognitive impairment in euthymic bipolar patients, but not with psychosocial functioning. More studies are needed to clarify the role of Hcy in cognition in bipolar disorder.

Cognitive Impairment in Euthymic Bipolar Patients

Accumulating evidence has suggested that bipolar illness is associated with neurocognitive impairment, even in the euthymic phase. However, those studies did not clearly control for the potential effects of mood symptoms or hypercortisolemic states associated with depression, did not report proportions of patients with this impairment, and used measurements that lacked obvious …

Cognitive impairment in euthymic bipolar patients: implications for clinical and functional outcome.

Cognitive impairment in bipolar disorder may be a stable characteristic of the illness, although discrepancies have emerged with regard to what dysfunctions remain during remission periods. The aim of this study was to ascertain whether euthymic bipolar patients would show impairment in verbal learning and memory and in executive functions compared with healthy controls. Secondly, to establish if there was a relationship between clinical data and neuropsychological performance. Forty euthymic bipolar patients were compared with 30 healthy controls through a battery of neuropsychological tests assessing estimated premorbid IQ, attention, verbal learning and memory, and frontal executive functioning. The effect of subsyndromal symptomatology was controlled. Remitted bipolar patients performed worse than controls in several measures of memory and executive function, after controlling for the effect of subclinical symptomatology, age and premorbid IQ. Verbal memory impairment was related to global assessment of function scores, as well as to a longer duration of illness, a higher number of manic episodes, and prior psychotic symptoms. Results provide evidence of neuropsychological impairment in euthymic bipolar patients, after controlling for the effect of subsyndromal depressive symptoms, suggesting verbal memory and executive dysfunctions. Cognitive impairment seems to be related to a worse clinical course and poor functional outcome.

Cognitive Impairment in Euthymic Bipolar Patients With and Without Prior Alcohol Dependence

Few studies of the neurocognitive performance of patients with bipolar disorder have been performed while patients are in the euthymic state. Twenty-five euthymic bipolar patients (12 with and 13 without a history of alcohol dependence) were compared with 22 normal control subjects on a neuropsychological test battery assessing a range of cognitive domains. The relationship between subjects' neurocognitive performance and the course-of-illness variables (lifetime episodes and duration of mania, depression, or both), as well as current lithium level, was determined. The results indicated differences across the groups, with the bipolar patients with and without alcohol dependence performing more poorly than controls on tests of verbal memory. Furthermore, bipolar subjects with a history of alcohol dependence had additional decrements in executive (i.e., frontal lobe) functions when compared with controls. For subjects in the bipolar group, lifetime months of mania and depression were negatively correlated with performance in verbal memory and several executive function measures. Our findings support the presence of persistent neurocognitive difficulties in patients with long-standing bipolar disorder who are not in the psychiatrically acute state or who are suffering the effects of alcohol abuse and suggest that there may be an aggregate negative effect of lifetime duration of bipolar illness on memory and frontal or executive systems.