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Background: Caregivers of patients with mild cognitive impairment (MCI) need similar levels of support services as Alzheimer’s disease (AD) caregivers, but it is unclear if this translates to increased caregiver burden. Methods: 135 participants and their caregivers (40 MCI, 55 AD and 40 normal controls, NC) completed questionnaires, and the patients were administered neuropsychological tests. Results: The MCI caregivers reported significantly more overall caregiving burden than the NC, but less than the AD. They showed similar levels of emotional, physical and social burden as the AD caregivers. Among the MCI caregivers, the neuropsychiatric symptoms and executive functioning of the patients were related to a greater burden, and the caregivers with a greater burden reported lower life satisfaction and social support, and a greater need for support services. Conclusion: These results indicate that MCI caregivers are at increased risk for caregiver stress, and they require enhanced assistance and/or education in caring for their loved ones.

The Tactual Performance Test (TPT) and a version of the TPT with unfamiliar geometric designs were presented to American, Lao, and Senegalese children. The nonstandard TPT was designed to evaluate the importance of familiarity of forms in improved performance between successive TPT learning trials. The nonstandard board was more difficult for all the groups, with poorer time-per-block performance across learning trials and poorer TPT memory measures. Irrespective, the transfer-of-learning (ToL) effect for the standard and nonstandard boards was consistent for all the cultural groups. ToL effect is not dependent on familiarity of the TPT forms and is consistent across cultures.

Objective: The aim of this study was to evaluate the short-term stability and reliability of a brief computerized cognitive battery in established dementia types. Method: Patients were administered the computerized battery twice with administrations approximately 2 hours apart, with intervening conventional neuropsychological tests. Patients were classified clinically, via consensus conference, as healthy controls (n = 23), mild cognitive impairment (n = 20), Alzheimer’s disease (n = 52), dementia with Lewy Bodies ([DLB], n = 10), or frontotemporal dementia (n = 9). Results: Minimal practice effects were evident across Cog-State test administrations. Small magnitude improvements were seen across all groups on a working memory task, and healthy controls showed a mild practice effect on the accuracy of associative learning. Conclusions: In established dementia, administration of the CogState tasks appears sensitive to cognitive impairment in dementia. Repeat administration also provided acceptable stability and test-retest reliability with minimal practice effects at short test-retest intervals despite intervening cognitive challenges.

Background: Rivipansel is a pan-selectin inhibitor in phase 3 development for treatment of sickle cell disease vaso-occlusive crises. Previous studies have shown almost complete elimination of unchanged drug in urine following an intravenous (IV) infusion. The objective of this study was to evaluate the effect of varying degrees of renal impairment on the pharmacokinetics (PK), safety, and tolerability of rivipansel. Methods: A single 840-mg dose of open-label rivipansel was administered IV over 20 minutes to 7 subjects with mild, 7 with moderate, and 7 with severe renal impairment, and to 7 healthy subjects with normal renal function. Classification of renal impairment groups was based on the Cockroft-Gault estimated glomerular filtration rate (CGeGFR): 60-89 mL/min (mild), 30-59 mL/min (moderate), and Results: All 28 subjects completed the study. A summary of PK parameters is presented in Table 1. Overall rivipansel exposure was greater in subjects with mild, moderate, and severe renal impairment, with values 1.4×, 2.3×, and 5.5× that of subjects with normal renal function, respectively. Renal clearance decreased with decreasing renal function. Total clearance was lower by 31%, 56%, and 82% in the mild, moderate, and severe renal impairment groups, respectively, compared with the normal renal function group. Five treatment-emergent adverse events (TEAEs) were reported in 3 subjects in the mild renal impairment group, and 3 TEAEs were reported in 2 subjects in the severe renal impairment group. None of the TEAEs reported was considered to be treatment-related. Conclusions: Greater rivipansel exposure and decreased clearance were observed in subjects with renal impairment compared with subjects with normal renal function. A single 840-mg IV dose of rivipansel was well tolerated in all groups. Disclosures Tammara: Pfizer Inc.: Employment. Ryan:Pfizer Inc.: Employment. Plotka:Pfizer Inc.: Employment. Shafer:Pfizer Inc.: Employment. Wei:Pfizer Inc.: Employment. Readett:Pfizer Inc.: Employment. Fang:Pfizer Inc.: Employment. Korth-Bradley:Pfizer Inc.: Employment.

Little is known about the service needs for persons caring for individuals with mild cognitive impairment (MCI). In this study, the level of support service need for caregivers of individuals diagnosed with Alzheimer disease (AD; N=55) and MCI (N=25) was compared with normal controls (N=44). Study partners (ie, caregivers) completed questionnaires about their service needs and participants' neurobehavioral symptoms, functional abilities, and frailty. Total, social, and mental health service needs were significantly different among the 3 groups (P

Nickel superoxide dismutase (NiSOD) is unique among the family of SOD enzymes in that it coordinates cysteine residues (Cys2 and Cys6) to the redox-active metal center and exhibits a hexameric quaternary structure. To assess the role of the Cys residues with respect to the activity of NiSOD, mutations of Cys2 and Cys6 to serine (C2S-, C6S-, and C2S/C6S-NiSOD) were carried out. The resulting mutants do not catalyze the disproportionation of superoxide, but retain the hexameric structure found for wild-type (WT) NiSOD and bind Ni(II) ions in a 1:1 stoichiometry. X-ray absorption spectroscopic (XAS) studies of the Cys mutants reveal that the nickel active-site structure for each mutant resembles that of C2S/C6S-NiSOD and demonstrate that mutation of either Cys2 or Cys6 inhibits coordination of the remaining Cys residue. Mutation of one or both Cys residue(s) in NiSOD induces the conversion of the low-spin Ni(II) site in the native enzyme to a high-spin Ni(II) center in the mutants. This result that indicates that coordination of both Cys residues is required to generate the native low-spin configurations and maintain catalytic activity. Analysis of the quaternary structure of the cysteine mutants by differential scanning calorimetry, mass spectrometry, and size-exclusion chromatography reveal that the cysteine ligands, particularly Cys2, are also important for stabilizing the hexameric quaternary structure of the native enzyme.

Antennae are important sensory organs in insects because they enable the perception of chemical and tactile cues believed to be important in sex recognition and mating in various species. To examine the role of the antennae in the mating behaviour of decorated crickets, Gryllodes sigillatus, we experimentally manipulated the chemosensory ability of males and females and altered the chemical cues present on the female cuticle. Our results suggest that males rely heavily on their antennae to recognize conspecific females, because antennectomized and chemically ablated males were less likely to produce the courtship song upon contact with a female. The chemical cues used by males to recognize females appear to be sex specific, because males courted dead females that had been stripped of their surface hydrocarbons and imbued with hydrocarbons extracted from other females, but ignored females similarly stripped of their cues and imbued with extracts derived from males. Females, in contrast, did not seem to rely on their antennae for sex recognition, because antennectomized females frequently mounted males, although they took significantly longer to do so. Males lacking antennae almost never showed mate-guarding behaviour, while males with intact antennae almost always did. Collectively, these results suggest that sensory information provided by the antennae is critical to the mating success of both male and female crickets.

Neuropsychological and psychosocial predictors of subjective well-being (SWB) were examined among 74 persons with multiple sclerosis (MS). The multidimensional construct of SWB was assessed by self-report measures of acute psychological distress, global life satisfaction, and health-related quality of life (HRQoL). Objective disease-related indices were obtained from medical records and neuropsychological testing. Unawareness of deficit, a frequent aspect of executive function impairments in MS, was measured as the discrepancy between patient self-report of functional abilities and a caregiver's report of the patient's abilities. Results indicate that a substantial proportion of patients experienced diminished SWB and that disease characteristics such as duration and severity have differential relationships to SWB outcomes. Multiple regression analyses indicated that, in the context of a combined predictive model, social support and unawareness of deficit provided unique information in predicting all three aspects of SWB, beyond that accounted for by disease characteristics. Both social support and unawareness of deficit were associated with positive well-being outcomes. Neuropsychological impairment was adversely related to life satisfaction and HRQoL, but it did not add unique information to the prediction of these outcomes. The findings present a unique view of SWB among individuals with MS in the absence of acute exacerbation of the illness.

Background Second generation antipsychotics (SGAs) are increasingly utilized in Bipolar Disorder (BD) but are potentially associated with cognitive side effects. Also linked to cognitive deficits associated with SGA-treatment are catechol-O-methyltransferase (COMT) gene variants. In this study, we examine the relationship between cognition in SGA use and COMT rs5993883 in cohort sample of subjects with BD. Methods Interactions between SGA-treatment and COMT rs5993883 genotype on cognition was tested using a battery of neuropsychological tests performed in cross-sectional study of 246 bipolar subjects. Results The mean age of our sample was 40.15 years and was comprised of 70 % female subjects. Significant demographic differences included gender, hospitalizations, benzodiazepine/antidepressant use and BD-type diagnosis. Linear regressions showed that the COMT rs5993883 GG genotype predicted lower verbal learning (p = 0.0006) and memory (p = 0.0026) scores, and lower scores on a cognitive control task (p = 0.004) in SGA-treated subjects. Interestingly, COMT GT- or TT-variants showed no intergroup cognitive differences. Further analysis revealed an interaction between SGA-COMT GG-genotype for verbal learning (p = 0.028), verbal memory (p = 0.026) and cognitive control (p = 0.0005). Conclusions This investigation contributes to previous work demonstrating links between cognition, SGA-treatment and COMT rs5993883 in BD subjects. Our analysis shows significant associations between cognitive domains such as verbal-cognition and cognitive control in SGA-treated subjects carrying the COMT rs5993883 GG-genotype. Prospective studies are needed to evaluate the clinical significance of these findings. Electronic supplementary material The online version of this article (doi:10.1186/s40359-016-0118-3) contains supplementary material, which is available to authorized users.

Childhood trauma has been linked to the development and severity of psychiatric disorders as well as deficits in cognitive functioning. This study aimed to investigate the performance of bipolar disorder (BD) patients and healthy controls (HC), with or without a history of childhood trauma, on a parametric Go/No-Go (PGNG) task measuring important aspects of executive functions, namely attention and inhibitory control. Two hundred and thirty-three individuals with BD and 90 HC completed diagnostic interview, childhood trauma questionnaire (CTQ), symptom severity scales, and a PGNG task. Four comparison groups were created using a 1.0 standard deviation cut-off of the mean of the HC total CTQ score: BD-trauma, BD-normative, HC-trauma and HC-normative. We assessed interactions between diagnosis and trauma on Go/No-Go levels of interest by using a two-way multivariate analysis of covariance. Results showed a significant main effect of trauma on inhibitory control accuracy, as the trauma group exhibited significantly poorer accuracy on inhibition trials compared to the normative group. There was also a main effect of diagnosis on response time. These findings suggest that early trauma might adversely impact the development of cognitive systems and brain circuits that support inhibitory aspects of executive functioning in individuals with a history of trauma.

Background Few treatments are available to directly address employment or work functioning among individuals with bipolar disorder (BD) and currently available treatment models have not been evaluated to examine their impact employment outcomes. We examined impact of affective symptoms and health-related quality of life (HRQoL) on longitudinal employment outcomes in a community-based sample of individuals with bipolar disorder who completed the Life Goals-Collaborative Care (LG-CC) intervention. Methods Participants (N=178) were assessed based on HRQoL, employment status, affective symptoms (depressive/manic), and work hours at baseline, 6-, 12- and 24-months after initiation of LG-CC. Frequency of LG-CC sessions and number of care-manager contacts also were ascertained. Results At baseline, 21% were employed, 29.5% were unemployed, and 49.6% were on disability. Improvement in affective symptoms was seen over the 24-month period, but not in HRQoL. Lower depression symptoms, but not mania, at baseline predicted greater likelihood of employment status in 24-months. Degree of LG-CC participation was associated with a reduced likelihood of becoming disabled/unemployed and increased number of hours worked in 24-months. Limitations The study was originally designed to compare implementation strategies and not the effectiveness of LG-CC on employment outcomes. Further, it was unclear whether improvement in work functioning were personal goals of the participants of this study. Conclusions Fewer depressive symptoms were associated with positive employment outcomes over time. Collaborative Care Models that are already implemented by existing providers that focus on management of affective symptoms show promise in positively impacting employment outcomes.

Menopausal lipid profile changes may increase cardiovascular risk. The effects of conjugated estrogens (CE)/bazedoxifene (BZA), an approved menopausal therapy, on lipids have not been fully characterized.The purpose of this study was to determine the effects of CE/BZA on lipids in the Selective estrogens, Menopause, And Response to Therapy (SMART) trials for ≥ 1 year.This was a pooled analysis of 3 randomized, double-blind, placebo (PBO)-controlled phase 3 trials (SMART-1, -4, and -5).The study was conducted in North America, Europe, Asia-Pacific Region, and Latin America.Participants were nonhysterectomized postmenopausal women aged 40 to 75 years, not taking lipid-lowering medications (N = 2796).Treatments were CE 0.45 mg/BZA 20 mg, CE 0.625 mg/BZA 20 mg, and PBO.The adjusted mean percentage changes from baseline in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, and the LDL-C/HDL-C ratio at 12 and 24 months were measured.At 12 months, CE 0.45 mg/BZA 20 mg and CE 0.625 mg/BZA 20 mg produced significant (P.001) improvements vs PBO in TC (-4.20% and -4.37% vs -0.88%), LDL-C (-9.33% and -10.78% vs -1.08%), HDL-C (4.59% and 6.21% vs 1.30%), and the LDL-C/HDL-C ratio (-11.59% and -14.00% vs -0.84%). Triglycerides were significantly (P.001) increased from baseline with both doses vs PBO (15.13% and 15.74% vs 4.43%). Similar trends (all P.001) were seen at 24 months when SMART-1 and SMART-4 were pooled (TC: -3.25% and -3.13% vs 0.95%; LDL-C: -7.47% and -8.08% vs 2.95%; HDL-C: 5.91% and 7.19% vs 1.72%; triglycerides: 18.87% and 18.82% vs 6.49%; and the LDL-C/HDL-C ratio: -10.05% and -12.82% vs 2.56%).CE/BZA was associated with mostly favorable changes in lipid parameters for up to 2 years in nonhysterectomized postmenopausal women.

Impairment in neuropsychological functioning is common in major depressive disorder (MDD), but it is not clear to what degree these deficits are related to risk (e.g. trait), scar, burden or state effects of MDD. The objective of this study was to use neuropsychological measures, with factor scores in verbal fluency, processing speed, attention, set-shifting and cognitive control in a unique population of young, remitted, unmedicated, early course individuals with a history of MDD in hopes of identifying putative trait markers of MDD.Youth aged 18-23 in remission from MDD (rMDD; n = 62) and healthy controls (HC; n = 43) were assessed with neuropsychological tests at two time points. These were from four domains of executive functioning, consistent with previous literature as impaired in MDD: verbal fluency and processing speed, conceptual reasoning and set-shifting, processing speed with interference resolution, and cognitive control.rMDD youth performed comparably to HCs on verbal fluency and processing speed, processing speed with interference resolution, and conceptual reasoning and set-shifting, reliably over time. Individuals with rMDD demonstrated relative decrements in cognitive control at Time 1, with greater stability than HC participants.MDD may be characterized by regulatory difficulties that do not pertain specifically to active mood state or fluctuations in symptoms. Deficient cognitive control may represent a trait vulnerability or early course scar of MDD that may prove a viable target for secondary prevention or early remediation.

Summary Establishing disaster preparedness is an urgent matter, particularly with regard to mental health. This article examines the challenges of mental health disaster planning in the context of an urban setting, which may differ from those pertaining to rural areas. The need to better integrate public health disaster planning and mental health disaster planning is critical. This document particularly focuses on the challenges involved in leading, coordinating, and convening an urban mental health disaster response. With time, dedication, resources, and creation of effective policy, successful mental health response capability will evolve and endure.

Objectives Openness to experience (O) is a well-established personality factor and is associated with cognitive performance. Little is known about the personality-cognitive relationship in bipolar disorder, an illness with significant variability in mood. Cognitive evaluation is essential in psychopathology assessment as it may reflect underlying disease processes and psychosocial functional capacity. Screening using a proxy personality variable may identify those in need of comprehensive cognitive testing. We hypothesized that O and measures of cognition would associate in both the Bipolar Disorder (BD) and healthy control (HC) samples, whereas neuroticism and extraversion would correlate with cognition only in the BD sample. Methods Data from a longitudinal study of BD were used to study the association between personality factors and cognitive measures of attention, executive functioning, memory and fine motor skills. Regression analyses were used to determine the variables that account for the association between personality and cognition. Results Aspects of O explained significant cognitive variance (~5%) in both groups; this persisted when demographic variables (including BD versus HC status) were considered. Neuroticism and extraversion did not consistently correlate with cognitive performance in either group. Limitations There were more females in the HC group who were slightly younger compared to the BD group. We lack direct measures of positive affect, and there is a reliance on a single measure of personality. Conclusions BD Individuals scoring low on self-reported Openness are potential candidates for more comprehensive cognitive assessments (which represent a limited resource).

Objective Functional connectivity MRI (fcMRI) studies of individuals currently diagnosed with major depressive disorder (MDD) document hyperconnectivities within the default mode network (DMN) and between the DMN and salience networks (SN) with regions of the cognitive control network (CCN). Studies of individuals in the remitted state are needed to address whether effects derive from trait, and not state or chronic burden features of MDD. Method fcMRI data from two 3.0 Tesla GE scanners were collected from 30 unmedicated (47% medication naïve) youth (aged 18–23, modal depressive episodes = 1, mean age of onset = 16.2, SD = 2.6) with remitted MDD (rMDD; modal years well = 4) and compared with data from 23 healthy controls (HCs) using four bilateral seeds in the DMN and SN (posterior cingulate cortex (PCC), subgenual anterior cingulate (sgACC), and amygdala), followed by voxel-based comparisons of the whole brain. Results Compared to HCs, rMDD youth exhibited hyperconnectivities from both PCC and sgACC seeds with lateral, parietal, and frontal regions of the CCN, extending to the dorsal medial wall. A factor analysis reduced extracted data and a PCC factor was inversely correlated with rumination among rMDD youth. Two factors from the sgACC hyperconnectivity clusters were related to performance in cognitive control on a Go/NoGo task, one positively and one inversely. Conclusions Findings document hyperconnectivities of the DMN and SN with the CCN (BA 8/10), which were related to rumination and sustained attention. Given these cognitive markers are known predictors of response and relapse, hyperconnectivities may increase relapse risk or represent compensatory mechanisms.

To determine the effect of continuous-volume scanning (CVS) on z-axis resolution, section sensitivity profiles were measured on an electron beam computed tomography (CT) scanner and compared with those obtained using the step-volume scanning (SVS) mode. A steel bead was imaged using different scan parameters, and the mean CT number over the bead was plotted against the z-axis position to determine section sensitivity profiles. From these profiles, full width at half maximum (FWHM), full width at tenth maximum (FWTM), and full width at tenth area (FWTA) were calculated. A uniform water phantom was imaged to measure noise. To determine the visual significance of changes in the section sensitivity profile, a section thickness and contiguity phantom was imaged. All section sensitivity profiles measured had an FWHM value within 0.5 mm of the nominal scan width. The FWTM and FWTA values increased with the CVS mode compared with the SVS mode. This broadening of the section sensitivity profiles was most significant with larger collimator widths. However, use of smaller collimator widths increased image noise. When all other parameters remained constant, increasing the exposure time to reduce image noise did not affect the section sensitivity profile. The CVS mode produced wider section sensitivity profiles than the SVS mode. This effect was minimized when the smallest collimator width was used, but at the expense of increased image noise.

The bothersome vasomotor and vaginal symptoms and bone loss that accompany the menopausal transition are associated with significant direct costs due to physician visits and medication, as well as indirect costs from reduced health-related quality of life (HRQoL) and work productivity. With life expectancies increasing, the number of postmenopausal women is also increasing, and more women are remaining in the workforce. These factors have led to an increased burden of menopausal symptoms on healthcare systems. Hormone therapy (HT) has been shown to effectively reduce menopausal symptoms and significantly increase quality-adjusted life years in postmenopausal women, particularly in women experiencing severe symptoms. However, many women discontinue use of HT before their symptoms have dissipated due to safety and tolerability concerns. The tissue selective estrogen complex (TSEC) that pairs bazedoxifene (BZA) with conjugated estrogens (CE) has been developed to provide relief of menopausal symptoms and prevent bone loss without stimulating the breast or endometrium, and to have improved tolerability compared with HT. In this context, BZA 20 mg/CE 0.45 and 0.625 mg were shown to prevent bone loss and effectively treat menopausal symptoms in postmenopausal women with an intact uterus, while also demonstrating a favorable safety/tolerability profile. BZA 20 mg/CE 0.45 and 0.625 mg were further associated with clinically significant improvements in HRQoL, sleep, and treatment satisfaction. Taken together, the reduction in menopausal symptoms, improvement in HRQoL, and favorable safety/tolerability profile associated with BZA/CE suggest that it is a cost-effective alternative to HT for managing the burden of menopausal symptoms.

The effects of bazedoxifene (BZA)/conjugated estrogens (CE) on sleep and health-related quality of life (HRQoL) were evaluated in nonhysterectomized postmenopausal women who were enrolled in a randomized, double-blind, placebo- and active-controlled phase 3 trial.The sleep/HRQoL substudy enrolled 459 women with bothersome moderate to severe vasomotor symptoms who were randomized to BZA 20 mg/CE 0.45 mg, BZA 20 mg/CE 0.625 mg, BZA 20 mg, CE 0.45 mg/medroxyprogesterone acetate (MPA) 1.5 mg, or placebo for 1 year. On months 3 and 12, sleep parameters were evaluated using the Medical Outcomes Study sleep scale, and HRQoL was assessed using the Menopause-Specific Quality of Life (MENQOL) questionnaire.BZA/CE and CE/MPA significantly improved sleep and HRQoL compared with placebo. On month 3, most Medical Outcomes Study sleep parameter improvements with BZA/CE and CE/MPA versus placebo were not significant. On month 12, both BZA/CE doses and CE/MPA significantly improved time to fall asleep and sleep disturbance (P0.05 vs. placebo); BZA 20 mg/CE 0.625 mg and CE/MPA also showed significant improvements in sleep adequacy and sleep problem indices I and II (P0.01 vs placebo). Both BZA/CE doses and CE/MPA significantly improved MENQOL vasomotor function score versus placebo at 3 and 12 months (P0.001). At 3 months, total MENQOL score was significantly improved with BZA 20 mg/CE 0.625 mg and CE/MPA versus placebo (P0.05); at 12 months, both BZA/CE doses and CE/MPA showed significant improvements (P0.001).Symptomatic postmenopausal women who are treated with BZA/CE for 1 year demonstrate significant improvements in sleep and HRQoL, similar to women treated with CE/MPA.

Bipolar disorder (BPD) and normal aging are known to impact cognitive skills and health-related quality of life (HRQOL). This study investigated how aging and disease interact in predicting cognitive and psychosocial outcomes.Eight cognitive and ten subjective HRQOL domain ratings were measured. Subjects included 80 young (18-29 years) and late middle-aged (50-65 years) BPD patients in the euthymic phase and 70 age-equivalent healthy comparison participants.An age X disease interaction was detected in three domains of cognitive functioning that reflect emotion processing, processing speed, and executive functioning skills, with BPD patients in the older group performing most poorly. There was a double burden of aging and disease on reported ability to perform physical tasks. However, regardless of age, disease status was associated with lower ratings of HRQOL in the psychosocial/affective sphere and the majority of cognitive domains. Post hoc analyses revealed that number of years ill was positively associated with select HRQOL ratings in older, but not younger BPD adults.These findings may stimulate future longitudinal study of cognition and quality of life in BPD patients across the life span, focusing on additive and interactive effects of aging and disease burden, which could culminate in developing more effective treatment and rehabilitation strategies for this traditionally challenging to treat population.

Objective Migraine is a common comorbidity of bipolar disorder and is more prevalent in women than men. We hypothesized comorbid migraine would be associated with features of illness and psychosocial risk factors that would differ by gender and impact outcome. Method A retrospective analysis was conducted to assess association between self-reported, physician-diagnosed migraine, clinical variables of interest, and mood outcome in subjects with DSM-IV bipolar disorder (N = 412) and healthy controls (N = 157) from the Prechter Longitudinal Study of Bipolar Disorder, 2005-2010. Informed consent was obtained from all participants. Results Migraine was more common in subjects with bipolar disorder (31%) than in healthy controls (6%) and had elevated risk in bipolar disorder women compared to men (OR = 3.5; 95% CI, 2.1-5.8). In men, migraine was associated with bipolar II disorder (OR = 9.9; 95% CI, 2.3-41.9) and mixed symptoms (OR = 3.5; 95% CI, 1.0-11.9). In comparison to absence of migraine, presence of migraine was associated with an earlier age at onset of bipolar disorder by 2 years, more severe depression (β = .13, P = .03), and more frequent depression longitudinally (β = .13, P = .03). Migraine was correlated with childhood emotional abuse (P = .01), sexual abuse (P = 4 × 10⁻³), emotional neglect (P = .01), and high neuroticism (P = 2 × 10⁻³). Protective factors included high extraversion (P = .02) and high family adaptability at the trend level (P = .08). Conclusions Migraine is a common comorbidity with bipolar disorder and may impact long-term outcome of bipolar disorder, particularly depression. Clinicians should be alert for migraine comorbidity in women and in men with bipolar II disorder. Effective treatment of migraine may impact mood outcome in bipolar disorder as well as headache outcome. Joint pathophysiologic mechanisms between migraine and bipolar disorder may be important pathways for future study of treatments for both disorders.

While preliminary evidence supports the criterion validity of the CogState computerized brief battery in mild cognitive impairment (MCI) and Alzheimer disease (AD), definitive validation studies examining a wider range of dementia-related disorders relative to conventional neuropsychological techniques are necessary.Participants satisfying clinical consensus criteria for dementia (AD, n = 37; frontotemporal dementia, n = 7; and dementia with Lewy bodies, n = 5), MCI (n = 16), and the healthy controls (n = 22) were administered a battery of brief neuropsychological and select computerized (CogState) cognitive tests. The battery, administered through the University of Michigan Alzheimer's Disease Research Center, included measures of processing speed, attention, working memory, and learning.CogState and standard neuropsychological task scores were significantly lower for dementia participants than that of the nondementia groups (P.05), with a single CogState test distinguishing control from MCI participants, but minimal differentiation existing between dementias using the CogState. Correlations were modest between conventional and computerized test scores, covering matching domains and mostly reflecting the multidimensional nature of cognitive paradigms.Results support the clinical validity of this brief computerized screening battery when used in established dementias, but not to differentiate between various dementias, and suggest that the select CogState battery's effectiveness in identifying MCI from controls was not as strong as identifying specific dementias.

Measures of cognitive dysfunction in Bipolar Disorder (BD) have identified state and trait dependent metrics. An influence of substance abuse (SUD) on BD has been suggested. This study investigates potential differential, additive, or interactive cognitive dysfunction in bipolar patients with or without a history of SUD. Two hundred fifty-six individuals with BD, 98 without SUD and 158 with SUD, and 97 Healthy Controls (HC) completed diagnostic interviews, neuropsychological testing, and symptom severity scales. The BD groups exhibited poorer performance than the HC group on most cognitive factors. The BD with SUD exhibited significantly poorer performance than BD without SUD in visual memory and conceptual reasoning/set-shifting. In addition, a significant interaction effect between substance use and depressive symptoms was found for auditory memory and emotion processing. BD patients with a history of SUD demonstrated worse visual memory and conceptual reasoning skills above and beyond the dysfunction observed in these domains among individuals with BD without SUD, suggesting greater impact on integrative, gestalt-driven processing domains. Future research might address longitudinal outcome as a function of BD, SUD, and combined BD/SUD to evaluate neural systems involved in risk for, and effects of, these illnesses.

The key factors for the success of the World Wide Web are its large size and the lack of a centralized control over its contents. In recent years, many advances have been made in preserving web content but much of this content (namely, social media content) was not archived, or still to this day is not being archived,for various reasons. Tools built to accomplish this frequently break because of the dynamic structure of social media websites. Because many social media websites exhibit a commonality in hierarchy of the content, it would be worthwhile to setup a means to reference this hierarchy for tools to leverage and become adaptive as the target websites evolve. As relying on the service to provide this means is problematic in the context of archiving, we can surmise that the only way to assure that all of these shortcomings are not experienced is to rely on the original context in which the user views the content, i.e. the webbrowser. In this thesis I will describe an abstract specification and concrete implementations of the specification that allow tools to leverage the context of theweb browser to capture content into personal web archives. These tools will then be able to accomplish personal web archiving in a way that makes them more robust. As evaluation, I will make a change in the hierarchy of a synthetic social media website and its respective specification. Then, I will show that anadapted tool, using the specification, continues to function and is able to archive the social media website.

This thesis consists of seven original compositions written and performed during graduate study. These pieces were performed or read on June 19, 2011; November 28, 2011; February 9, 2012; March 28, 2012; April 10, 2012 and April 14, 2012. Their combined duration is approximately 47 minutes.