Performance-based and subjective measures of functioning in middle-aged and older adults with bipolar disorder.

Performance-based measures may be useful in quantifying functional impairment associated with bipolar disorder, particularly among older adults. Among 30 outpatients with bipolar disorder and 31 normal comparison subjects (NCs), we administered the UCSD Performance-Based Skills Assessment (UPSA) and 2 subjective measures of functioning. The UPSA simulates real-world everyday tasks, such as financial management. We compared UPSA scores between groups and, within the bipolar group, examined associations between UPSA scores and subjective functioning, cognitive functioning, and depressive, and manic symptoms. By large effect sizes, the bipolar disorder group had lower scores on the UPSA and its subscales compared with NCs. Within the bipolar group, UPSA scores correlated strongly with Quality of Well-Being Scale but not SF-36 scores, and the UPSA was not related to depressive or manic symptoms, but was associated with cognitive functioning. Given its relative independence from symptoms, the UPSA may be useful in gauging the effectiveness of rehabilitation for bipolar disorder.

Ecological momentary assessment in aging research: a critical review.

Ecological momentary assessment (EMA) gathers respondent data on affective, behavioral, and contextual experiences as close in time to those experiences as possible. Potential advantages of EMA in aging research include reducing memory biases and gathering intra-individual data, yet there is little understanding about implementation. The goal of this critical review was to assess the feasibility and applications of EMA in psychological and behavioral research on aging. Through a comprehensive search of the online electronic databases, Psycinfo and Pubmed, for English-language peer-reviewed journals published between 1990 and 2007, we identified 40 articles using EMA methods in older adults. Studies sampled participants between five times per day over one day to once a week for 210 days. Samples were generally not cognitively impaired, evenly split between healthy and clinical populations, and only 6 of 40 studies focused on psychiatric diagnoses. The most common assessment content solicited ratings on affect (n=15), activities of daily living (n=12), physical activities (n=10), and social exchanges (n=8). A total of 90% of the studies that reported compliance reported rates over 80%. Uses of EMA varied widely, with research goals including validation of global measures, detection of subtle treatment effects, and for testing hypotheses about causal intra-individual relationships. Although these measures appear feasible and useful in aging research, recommendations for future studies include adapting measures to enable data collection among older participants with cognitive impairments and/or psychopathology, along with greater use of electronic data capture to improve compliance and increase ease of implementation.

Assessment of medication management ability in middle-aged and older adults with bipolar disorder.

Medication nonadherence is a key clinical concern in bipolar disorder (BD) across the life span. Cognitive deficits in older adults with BD may hinder medication management ability, which, in turn, may lead to nonadherence. Using an innovative performance-based measure of medication management ability, the Medication Management Ability Assessment (MMAA), we compared performance of 29 middle-aged older community-dwelling outpatients with BD who were clinically stable (mean age, 61 years; SD, 11 years; range, 45-86 years) with those of 59 normal control subjects (NCs) and 219 outpatients with schizophrenia. The MMAA is a role-play task that simulates a medication regimen likely to be encountered by older adults. Within the BD group, we examined the relationships of MMAA scores to demographic, psychiatric symptoms severity, and the Mattis Dementia Rating Scale (DRS) scores. The BD group made 2.8 times the errors on the MMAA than NCs (BD group, 6.2; SD, 5.5 vs NCs, 2.2; SD, 2.5) and did not significantly differ from the Schizophrenia group in errors on the MMAA. Errors in the BD group were more likely to be taking in too few medications as taking in too many. Within the BD group, a significant correlation was seen between MMAA scores and the DRS Total score, but not with age, education, Brief Psychiatric Rating Scale, Hamilton Depression Rating Scale, number of psychiatric medications, or medical conditions. Among DRS subscales, the Memory Subscale correlated most strongly with MMAA errors. This small cross-sectional study suggests that deficits in medication management ability may be present in later-life BD. Neurocognitive deficits may be important in understanding problems with unintentional nonadherence.

Levodopa slows prosaccades and improves antisaccades: an eye movement study in Parkinson's disease.

BACKGROUND: The integrity of frontal systems responsible for voluntary control and their interaction with subcortical regions involved in reflexive responses were studied in patients with Parkinson's disease (PD). Previous studies have shown that patients with PD have impaired executive function, including deficits in attention, motor planning and decision making. METHODS: Executive function was measured through eye movements: reflexive (stimulus driven) prosaccades and voluntary (internally guided) antisaccades. Patients with advanced idiopathic PD, off and on their optimal levodopa therapy, were tested on a prosaccade and an antisaccade task and compared with matched controls. RESULTS: Levodopa significantly increased response time for reflexive prosaccades and reduced error rate for voluntary antisaccades. CONCLUSIONS: Consistent with our proposed model, patients with PD in the medicated state are better able to plan and execute voluntary eye movements. These findings suggest levodopa improves function of the voluntary frontostriatal system, which is deficient in PD.

Age-related reduction in estrogen receptor-mediated mechanisms of vascular relaxation in female spontaneously hypertensive rats.

Hypertension increases with aging, and changes in vascular estrogen receptors (ERs) may play a role in age-related hypertension in women. We tested whether age-related increases in blood pressure in female spontaneously hypertensive rats (SHRs) are associated with reduction in amount and/or vascular relaxation effects of estrogen and ER. Arterial pressure and plasma estradiol were measured in adult (12 weeks) and aging (16 months) female SHRs, and thoracic aorta was isolated for measurement of active stress, 45Ca2+ influx, and ERs. Arterial pressure was greater and plasma estradiol was less in aging females than in adult females. In aorta of adult females, Western blots revealed alpha- and beta-ERs that were slightly reduced in aging rats. In endothelium-intact vascular strips, phenylephrine (Phe; 10(-5) mol/L) caused greater active stress in aging rats (9.3+/-0.2) than in adult rats (6.2+/-0.3x10(4) N/m2). 17beta-estradiol (E2) caused relaxation of Phe contraction and stimulation of vascular nitrite/nitrate production, which was reduced in aging rats. In endothelium-denuded strips, E2 still caused relaxation of Phe contraction, which was smaller in aging rats than adult rats. KCl (51 mmol/L), which stimulates Ca2+ influx, produced greater active stress in aging rats (9.1+/-0.3) than in adult rats (5.9+/-0.2x10(4) N/m2). E2 caused relaxation of KCl contraction and inhibition of Phe- and KCl-induced 45Ca2+ influx, which were reduced in aging rats. Thus, aging in female SHR is associated with reduction in ER-mediated NO production from endothelial cells and decrease in inhibitory effects of estrogen on Ca2+ entry mechanisms of smooth muscle contraction. The age-related decrease in ER-mediated vascular relaxation may explain the increased vascular contraction and arterial pressure associated with aging in females.

Endothelin-1--induced enhancement of coronary smooth muscle contraction via MAPK-dependent and MAPK-independent [Ca(2+)](i) sensitization pathways.

Endothelin-1 (ET-1) has been implicated in coronary vasospasm by enhancing coronary vasoconstriction to vasoactive eicosanoids, and a role for protein kinase C (PKC) activation has been suggested. However, the cellular mechanisms downstream from PKC activation are unclear. We investigated whether physiological concentrations of ET-1 enhance coronary smooth muscle contraction by activating a PKC-mediated signaling pathway involving tyrosine phosphorylation and activation of mitogen-activated protein kinase (MAPK). Cell contraction was measured in smooth muscle cells isolated from porcine coronary artery, [Ca(2+)](i) was measured in fura-2 loaded cells, and tissue fractions were examined for reactivity with anti-phosphotyrosine (P-Tyr) and anti-MAPK antibodies using immunoprecipitation and immunoblot analysis. In Hanks' solution (1 mmol/L Ca(2+)), ET-1 (10 pmol/L) did not increase basal [Ca(2+)](i) (81 +/- 2 nmol/L) but caused cell contraction (10%) that was inhibited by calphostin C (10(-6) mol/L), inhibitor of PKC, tyrphostin (10(-6) mol/L), inhibitor of tyrosine kinase, and PD098059 (10(-6) mol/L), inhibitor of MAPK kinase. The vasoactive eicosanoid prostaglandin F(2alpha) (PGF(2alpha); 10(-7) mol/L) caused increases in cell contraction (11%) and [Ca(2+)](i) (122 +/- 9 nmol/L) that were inhibited by the Ca(2+) channel blocker verapamil (10(-6) mol/L) but not by calphostin C, tyrphostin, or PD098059. Pretreatment with ET-1 for 10 minutes enhanced cell contraction to PGF(2alpha) (33%) with no additional increase in [Ca(2+)](i) (124 +/- 10 nmol/L). Activation of PKC by phorbol 12-myristate 13-acetate (PMA; 10(-7) mol/L) caused cell contraction and enhanced PGF(2alpha) contraction (32%) with no additional increase in [Ca(2+)](i) (126 +/- 9 nmol/L). The ET-1-- and PMA-induced enhancement of PGF(2alpha) contraction was abolished by verapamil or calphostin C but not by tyrphostin or PD098059. ET-1 and PMA caused significant increases in tyrosine phosphorylation of MAPK that were inhibited by calphostin C, tyrphostin, and PD098059. PGF(2alpha) did not cause any additional increases in tyrosine phosphorylation of MAPK in tissues untreated or pretreated with ET-1 or PMA. Thus, physiological concentrations of ET-1 activate a Ca(2+)-independent PKC-mediated signaling pathway that involves tyrosine phosphorylation and activation of MAPK. The enhancement of PGF(2alpha)-induced coronary smooth muscle contraction by ET-1 involves additional activation of a Ca(2+)-sensitive PKC-mediated pathway but not tyrosine phosphorylation or activation of MAPK. The MAPK-dependent and MAPK-independent signaling pathways represent possible cellular mechanisms by which ET-1 could enhance coronary vasoconstriction to vasoactive eicosanoids in coronary vasospasm.

Pathophysiology of essential hypertension: role of the pump, the vessel, and the kidney.

Essential hypertension is characterized by significant and persistent elevations in arterial pressure. Hypertension is a multifactorial disorder that may involve abnormalities in the functions of the heart pump, the blood vessels, and the kidneys. Short-term and long-term regulation of arterial pressure is influenced by changes in cardiac function, the peripheral vascular resistance, and the renal control mechanisms of plasma electrolytes and volume. Increases in the heart rate and stroke volume lead to increases in the cardiac output and could contribute to increases in arterial pressure particularly in relatively young individuals. Vascular endothelial cell dysfunction could lead to reduction in endothelium-derived relaxing factors such as nitric oxide, prostacyclin, and endothelium-derived hyperpolarizing factor, or increased production of contracting factors such as endothelin-1 and thromboxane A2. Also, increased activity of signaling pathways of vascular smooth muscle contraction such as [Ca(2+)]i, protein kinase C, mitogen-activated protein kinase, and Rho kinase could enhance vasoconstriction. The decreased vascular relaxation and excessive vasoconstriction lead to significant increases in the peripheral vascular resistance and arterial pressure over time, particularly with aging. Alterations in body fluid regulation by the kidneys could lead to salt and water retention, increased plasma volume, and cardiac output. Also, activation of the renin-angiotensin system increases the levels of angiotensin II in the plasma, leading to generalized vasoconstriction, or locally in the kidneys, leading to salt and water retention. Individual changes in cardiac, vascular, or renal function seldom occur separately, and, if so, they may lead to mild or moderate increases in arterial pressure. Combined alterations in cardiac, vascular, and renal functions are more common and are often associated with pathologic increases in arterial pressure and established hypertension.