Equivalent linear change in cognition between individuals with bipolar disorder and healthy controls over 5 years.

OBJECTIVES: Cognitive dysfunction is a key feature of bipolar disorder (BD). However, not much is known about its temporal stability, as some studies have demonstrated a neurodegenerative model in BD while others have shown no change in cognitive functioning over time. Building upon our prior work, which examined the natural course of executive functioning, the current study aimed to investigate the natural course of memory, emotion processing, and fine motor dexterity over a 5-year period in BD and healthy control (HC) samples. METHODS: Using a 5-year longitudinal cohort, 90 individuals with BD and 17 HCs were administered a battery of neuropsychological tests at study baseline and at 1 and 5 years after study entry that captured four areas of cognitive performance: visual memory, auditory memory, emotion processing, and fine motor dexterity. RESULTS: Latent growth curve modeling showed no group differences in the slopes of any of the cognitive factors between the BD and HC groups. Age at baseline was negatively associated with visual memory, emotion processing, and fine motor dexterity. Education level was positively associated with auditory and visual memory and fine motor. Female gender was negatively associated with emotion processing. CONCLUSIONS: Extending our prior work on longitudinal evaluation of executive functioning, individuals with BD show similar linear change in other areas of cognitive functioning including memory, emotion processing, and fine motor dexterity as compared to unaffected HCs. Age, education, and gender may have some differential effects on cognitive changes.

Influence of cognitive reserve on neuropsychological functioning in bipolar disorder: Findings from a 5-year longitudinal study.

OBJECTIVES: The present study examined the 5-year longitudinal course of cognitive functioning in a large sample of well-characterized patients with bipolar disorder (BP), compared to healthy controls (HCs), and the influence of cognitive reserve factors (e.g., education and IQ) on cognitive change over time. METHODS: Participants included 159 individuals diagnosed with BP and 54 HCs recruited as part of a longitudinal naturalistic study of BP who had completed neuropsychological testing at the time of their enrollment and again 5 years later. RESULTS: The overall relative rate of change did not differ between the BP and HC groups. In total, 46.5% of the BP group and 37% of the HC group showed evidence of decline on at least one measure over time. T-test analyses did not find differences between BP 'decliners' and 'non-decliners' in cognitive reserve variables. However, we found that higher baseline intellectual ability was associated with more stability in cognitive test scores over time for the BP group. Results of linear regression modeling revealed that lower verbal IQ and education were related to increased cognitive decline in specific domains in the BP group. CONCLUSIONS: This study has explored the influence of cognitive reserve on preservation of specific cognitive abilities over time in BP. The BP group did not demonstrate accelerated cognitive decline over 5 years compared to the HC group. Although the trajectory of cognitive change over time was similar between BP patients and HCs, higher overall intellectual ability may be a protective factor against cognitive decline, particularly for BP patients.

Similar Trajectory of Executive Functioning Performance over 5 years among individuals with Bipolar Disorder and Unaffected Controls using Latent Growth Modeling.

OBJECTIVE: Executive Functioning (EF) deficits in bipolar disorder (BD) are commonly present regardless of mood state and therefore are considered core features of the illness. However, very little is known about the temporal stability of these deficits. We examined the natural course of EF over a five year period in BD and healthy control (HC) samples. METHOD: Using a 5-year longitudinal cohort, 91 individuals with BD and 17 HC were administered a battery of neuropsychological tests that captured four main areas of EF: Processing Speed with Interference Resolution, Verbal Fluency with Processing Speed, Inhibitory Control, and Conceptual Reasoning and Set Shifting. Evaluations occurred at study entry, one, and five years later. RESULTS: Latent Growth Curve Modeling demonstrated that the BD group performed significantly worse in all EF areas than the HC group. Changes in EF from baseline to 5-year follow-up were similar across both diagnostic groups. Older age at baseline, above and beyond education and diagnosis, was associated with worse initial performance in EF. Being of older age was associated with greater decline in Processing Speed with Interference Resolution, and Verbal Fluency with Processing Speed. Higher education was marginally associated with a smaller declining slope for Processing Speed with Interference Resolution. CONCLUSIONS: Executive functioning deficits in BD persist over time, and in the context of normative age-related decline, may place individuals at greater risk for cognitive disability as the disease progresses. Age and having a BD diagnosis together, however, do not accelerate executive functioning decline over time.

Cognitive reserve and executive function: Effect on judgment of health and safety.

Individuals with the same neurological conditions do not necessarily manifest the same behavioral presentation, which suggests differences in resilience and vulnerability among individuals, a concept known as cognitive reserve. This study sought to explore the relationship among cognitive reserve, executive functioning, and health and safety judgment among a sample of older adult inpatients in an extended medical care unit at a Veterans Health Administration hospital. We hypothesized that cognitive reserve, as determined by an estimate of premorbid intellectual ability, would act as a protective factor against poor judgment in older adults with executive dysfunction. Participants included 200 Veterans who completed a comprehensive neuropsychological assessment, including measures of health and safety judgment, executive functioning, global cognitive functioning, and premorbid intellectual ability. After controlling for global cognitive functioning, executive functioning abilities did not have an effect on judgment abilities among those with high estimated intellectual ability. However, executive functioning had a significant effect on judgment abilities among those with low estimated intellectual ability. Our results suggest that intact executive functioning is critical for making appropriate health and safety decisions for patients with lower measured intellectual abilities and provide further support for the cognitive reserve model. Clinical implications are also discussed.

Epithelial cell adhesion molecule is an independent prognostic marker in clear cell renal carcinoma.

Epithelial cell adhesion molecule (EPCAM) has recently attained a renewed interest as a candidate protein in diagnosis, prognostication and therapy of various tumor entities. The molecular epidemiology and prognostic relevance of EPCAM in renal cell carcinoma (RCC) and amongst the histological subtypes of RCC are unclear. We analyzed the prevalence and prognostic significance of EPCAM in a tumor tissue microarray composed of 1,088 independent RCCs samples by immunohistochemistry (IHC). We found significant variations of EPCAM IHC staining intensities in between the RCC subtypes: in papillary and chromophobe RCC, the majority of tumors (89-93%) showed an at least weak EPCAM protein expression. In the largest subgroup, the clear cell (cc)RCC (n = 767), a negative EPCAM IHC was found in 1/3 of the patients and was associated with high-grade disease and nodal metastases. Kaplan-Meier analyses demonstrated a significant association between positive EPCAM IHC and prolonged overall survival, even in a subset of low-risk ccRCC. In multivariable analyses, EPCAM represented an independent risk factor of survival throughout all subgroups. For localized, low-grade ccRCC, information of EPCAM IHC raised predictive accuracy of a multivariate model by ∼5%, compared to T-stage and grade alone. Our findings indicate that EPCAM is an independent prognostic molecular marker in ccRCC and, especially in localized ccRCC, might be able to provide auxiliary information for a better prognostication.

Sequential use of the tyrosine kinase inhibitors sorafenib and sunitinib in metastatic renal cell carcinoma: a retrospective outcome analysis.

BACKGROUND: To date, few data are available about the sequential use of the tyrosine kinase inhibitors (TKI) sorafenib and sunitinib in metastatic renal cell carcinoma (mRCC). OBJECTIVE: To investigate the effectiveness of the use of sunitinib after progression under sorafenib in mRCC. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of 30 patients with progressive mRCC, treated with sorafenib between May 2005 and February 2008. When radiologic progression was diagnosed, treatment was switched to sunitinib and continued until a further tumour progression occurred. MEASUREMENTS: Radiologic evaluation of the treatment results was performed every 3 mo according to the criteria for Response Evaluation Criteria in Solid Tumors (RECIST). Adverse effects and therapeutic abnormalities (eg, dose reduction) were documented during regular visits. RESULTS AND LIMITATIONS: Of the patients, 50% benefited from the secondary use of sunitinib. In detail, a radiologically confirmed new disease stabilisation or partial response was observed in seven and eight patients, respectively. Median progression-free survival was 8.7 mo and 10.3 mo under sorafenib and sunitinib, respectively. Overall, the median time from the initialisation of the first TKI until progression under therapy with the second TKI was 17.3 mo. To our knowledge, this is the second largest study reporting results of sequential therapy from sorafenib followed by sunitinib. However, the number of patients is still not extensive enough to settle this important question conclusively. CONCLUSIONS: This study supports the hypothesis that sequential TKI therapy with the sorafenib followed by sunitinib has clinical validity in some patients with advanced renal cell carcinoma when progressive disease occurs under the initial TKI therapy.