Treatment of dementia with neurotransmission modulation

The prevalence of dementia is growing in developed countries where elderly patients are increasing in numbers. Neurotransmission modulation is one approach to the treatment of dementia. Cholinergic precursors, anticholinesterases, nicotine receptor agonists and muscarinic M-2 receptor antagonists are agents that enhance cholinergic neurotransmission and that depend on having some intact cholinergic innervation to be effective in the treatment of dementia. The cholinergic precursor choline alfoscerate may be emerging as a potential useful drug in the treatment of dementia, with few adverse effects. Of the anticholinesterases, donepezil, in addition to having a similar efficacy to tacrine in mild-to-moderate Alzheimer's disease (AD), appears to have major advantages; its use is associated with lower drop-out rates in clinical trials, a lower incidence of cholinergic-like side effects and no liver toxicity. Rivastigmine is efficacious in the treatment in dementia with Lewy bodies, a condition in which the other anticholinesterases have not been tested extensively to date. Galantamine is an anticholinesterase and also acts as an allosteric potentiating modulator at nicotinic receptors to increase the release of acetylcholine. Pooled data from clinical trials of patients with mild-to-moderate AD suggest that the benefits and safety profile of galantamine are similar to those of the anticholinesterases. Selective nicotine receptor agonists are being developed that enhance cognitive performance without influencing autonomic and skeletal muscle function, but these have not yet entered clinical trial for dementia. Unlike the cholinergic enhancers, the M, receptor agonists do not depend upon intact cholinergic nerves but on intact M, receptors for their action, which are mainly preserved in AD and dementia with Lewy bodies. The M, receptor-selective agonists developed to date have shown limited efficacy in clinical trials and have a high incidence of side effects. A major recent advancement in the treatment of dementia is memantine, a non-competitive antagonist at NMDA receptors. Memantine is beneficial in the treatment of severe and moderate to-severe AD and may also be of some benefit in the treatment of mild-to-moderate vascular dementia. Drugs that modulate 5-HT, somatostatin and noradrenergic neurotransmission are also being considered for the treatment of dementia.

Prospective study of physical activity and depressive symptoms in middle-aged women

Background: Although many studies support an inverse association between physical activity (PA) and depressive symptoms, prospective relationships between these variables have been confounded by pre-existing psychological and physical health problems. Methods: This study examined the dose-response relationships between self-reported PA and depressive symptoms, using cross-sectional and prospective data from a population-based cohort of middle-aged women who participated in the Australian Longitudinal Study on Women's Health (ALSWH) between 1996 and 2001. Participants completed three mailed surveys (SI, 1996; S2, 1998; S3, 2001), which included questions about time spent in walking, moderate- and vigorous-intensity PA, and measures of psychological health (Center for Epidemiologic Studies Depression scale [CESD-10], and Mental health [MH] subscale of the Short Form 36 survey). Relationships between previous (SI, S2), current (S3), and habitual (S1, S2, S3) PA and depressive symptoms were examined, adjusting for sociodemographic and health-related variables (n = 9207). Results: Mean CESD-10 scores decreased, and MH scores increased with increasing levels of previous, current, and habitual activity. Odds ratios for CESD-10 scores >= 10 or MH scores = 60 minutes of moderate-intensity PA per week, compared with those who reported less PA than this. Women who were in the lowest PA category at SI, but who subsequently reported >= 240 metabolic equivalent minutes (MET.mins) per week had lower odds of CESD-10 scores of >= 10 or MH scores

Can parents and teachers provide a reliable and valid report of behavioral inhibition?

Reliability and validity of parent and teacher report of behavioral inhibition (BI) was examined among children aged 3 to 5 years. Confirmatory factor analysis supported 6 correlated factors reflecting specific BI contexts, each loading on a single, higher order factor of BI. Internal consistency was acceptable, with moderate stability over 1 year and strong correlation with a brief inhibition subscale from a temperament questionnaire. Children who were rated by mothers and teachers as high BI took longer to initiate contact with a stranger, spoke less often and for shorter periods, and required more prompting to elicit speech compared with low-BI peers in a simulated stranger interaction task. Father report of BI was significantly associated with mean duration of speech and eye gaze.

Psychological ownership: Towards a theoretical and empirical understanding of causes and consequences

In much the same way we consider our house or car 'mine', we may also consider facets of employment as a possession. Psychological ownership is the state ascribed to such feelings of possession in the absence of any formal or legal claims of ownership. In the present context, the target of such feelings of ownership is directed towards the employing organisation, or individual employee's specific job. TJie aim of this research is to extend previous propositions of ownership feelings to encompass related work attitudes and behavioural outcomes of psychological ownership in an organisational context. As a result, a theory of psychological ownership in organisations is presented encompassing antecedents, consequences, and the related work attitudes of job satisfaction and organisational commitment. Questionnaire data from 68 employees and their managers was used to test hypotheses derived from the proposed theory. Results revealed that psychological ownership predicted the work attitudes of job satisfaction and organisational commitment, and mediated the relationship between autonomy and these work attitudes. Both organisation- based and job-based psychological ownership were found to be distinct work attitudes, distinguishable from job satisfaction and organisational commitment. There was no support, however, for a direct or mediated relationship between psychological ownership and behavioural outcomes, including in-role behaviour, and helping and voice extra-role behaviours. These findings have considerable theoretical and empirical implications for the field of psychological ownership, and offer support for psychological ownership as a real and important work attitude.

Genetic and environmental sources of covariance between reading tests used in neuropsychological assessment and IQ subtests

In this study, we examined genetic and environmental influences on covariation among two reading tests used in neuropsychological assessment (Cambridge Contextual Reading Test [CCRT], [Beardsall, L., and Huppert, F. A. ( 1994). J. Clin. Exp. Neuropsychol. 16: 232 - 242], Schonell Graded Word Reading Test [SGWRT], [ Schonell, F. J., and Schonell, P. E. ( 1960). Diagnostic and attainment testing. Edinburgh: Oliver and Boyd.]) and among a selection of IQ subtests from the Multidimensional Aptitude Battery (MAB), [Jackson, D. N. (1984). Multidimensional aptitude battery, Ontario: Research Psychologists Press.] and the Wechsler Adult Intelligence Scale-Revised (WAIS-R) [Wechsler, D. (1981). Manual for the Wechsler Adult Intelligence Scale-Revised (WAIS-R). San Antonio: The Psychological Corporation]. Participants were 225 monozygotic and 275 dizygotic twin pairs aged from 15 years to 18 years ( mean, 16 years). For Verbal IQ subtests, phenotypic correlations with the reading tests ranged from 0.44 to 0.65. For Performance IQ subtests, phenotypic correlations with the reading tests ranged from 0.23 to 0.34. Results of Structural Equation Modeling (SEM) supported a model with one genetic General factor and three genetic group factors ( Verbal, Performance, Reading). Reading performance was influenced by the genetic General factor ( accounting for 13% and 20% of the variance for the CCRT and SGWRT, respectively), the genetic Verbal factor ( explaining 17% and 19% of variance for the CCRT and SGWRT), and the genetic Reading factor ( explaining 21% of the variance for both the CCRT and SGWRT). A common environment factor accounted for 25% and 14% of the CCRT and SGWRT variance, respectively. Genetic influences accounted for more than half of the phenotypic covariance between the reading tests and each of the IQ subtests. The heritabilities of the CCRT and SGWRT were 0.54 and 0.65, respectively. Observable covariance between reading assessments used by neuropsychologists to estimate IQ and IQ subtests appears to be largely due to genetic effects.

Association between apolipoprotein E epsilon 4 and neuropsychiatric symptoms during interferon alpha treatment for chronic hepatitis C

Neuropsychiatric complications are common in patients with chronic hepatitis C undergoing treatment with interferon alpha. These side effects include alterations of mood, cognition, and neuroendocrine function and are unpredictable. In a number of neurological disorders characterized by neuropsychiatric symptoms and cognitive dysfunction, inheritance of an apolipoprotein E (APOE) epsilon4 allele is associated with adverse neuropsychiatric outcomes. The authors present evidence that the APOE genotype may influence a patient's neuropsychiatric response to interferon alpha treatment. The inheritance of APOE genotypes was examined in 110 patients with chronic hepatitis C treated with interferon alpha. A retrospective investigation was conducted by assessing the rates of psychiatric referral and neuropsychiatric symptoms experienced during treatment along with other complaints indicating psychological distress. A highly statistically significant association was seen between APOE genotypes and interferon-induced neuropsychiatric symptoms. Patients with an epsilon4 allele were more likely to be referred to a psychiatrist and had more neuropsychiatric symptoms during antiviral treatment than those without an epsilon4 allele. Additionally, patients with an epsilon4 allele were more likely to experience irritability or anger and anxiety or other mood symptoms. These data demonstrate that an individual's APOE genotype may influence the neuropsychiatric response to antiviral therapy with interferon alpha. Prospective studies evaluating the importance of APOE in susceptibility to interferon alpha-induced neuropsychiatric complications are needed. Moreover, pathways involving APOE should be considered in understanding the pathophysiology of interferon alpha-induced neuropsychiatric complications.

Role of catecholaminergic inputs to the medial prefrontal cortex in local and subcortical expression of Fos after psychological stress

A wide variety of stressors elicit Fos expression in the medial prefrontal cortex (mPFC). No direct attempts, however, have been made to determine the role of the inputs that drive this response. We examined the effects of lesions of mPFC catecholamine terminals on local expression of Fos after exposure to air puff, a stimulus that in the rat acts as an acute psychological stressor. We also examined the effects of these lesions on Fos expression in a variety of subcortical neuronal populations implicated in the control of adrenocortical activation, one classic hallmark of the stress response. Lesions of the mPFC that were restricted to dopaminergic terminals significantly reduced numbers of Fos-immunoreactive (Fos-IR) cells seen in the mPFC after air puff, but had no significant effect on stress-induced Fos expression in the subcortical structures examined. Lesions of the mPFC that affected both dopaminergic and noradrenergic terminals also reduced numbers of Fos-IR cells observed in the mPFC after air puff. Additionally, these lesions resulted in a significant reduction in stress-induced Fos-IR in the ventral bed nucleus of the stria terminalis. These results demonstrate a role for catecholaminergic inputs to the mPFC, in the generation of both local and subcortical responses to psychological stress. (C) 2004 Wiley-Liss, Inc.

Physical and psychological factors predict outcome following whiplash injury

Predictors of outcome following whiplash injury are limited to socio-demographic and symptomatic factors, which are not readily amenable to secondary and tertiary intervention. This prospective study investigated the predictive capacity of early measures of physical and psychological impairment on pain and disability 6 months following whiplash injury. Motor function (ROM; kinaesthetic sense; activity of the superficial neck flexors (EMG) during cranio-cervical flexion), quantitative sensory testing (pressure, thermal pain thresholds, brachial plexus provocation test), sympathetic vasoconstrictor responses and psychological distress (GHQ-28, TSK, IES) were measured in 76 acute whiplash participants. The outcome measure was Neck Disability Index scores at 6 months. Stepwise regression analysis was used to predict the final NDI score. Logistic regression analyses predicted membership to one of the three groups based on final NDI scores (< 8 recovered, 10-28 mild pain and disability, > 30 moderate/severe pain and disability). Higher initial NDI score (1.007-1.12), older age (1.03-1.23), cold hyperalgesia (1.05-1.58), and acute post-traumatic stress (1.03-1.2) predicted membership to the moderate/severe group. Additional variables associated with higher NDI scores at 6 months on stepwise regression analysis were: ROM loss and diminished sympathetic reactivity. Higher initial NDI score (1.03-1.28), greater psychological distress (GHQ-28) (1.04-1.28) and decreased ROM (1.03-1.25) predicted subjects with persistent milder symptoms from those who fully recovered. These results demonstrate that both physical and psychological factors play a role in recovery or non-recovery from whiplash injury. This may assist in the development of more relevant treatment methods for acute whiplash. (c) 2004 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Interactions among smoking, obesity, and symptoms of acid reflux in Barrett's esophagus

Background: Barrett's esophagus, a metaplastic precursor to esophageal adenocarcinoma, is becoming increasingly prevalent in many populations. Clinical studies suggest acid reflux causes Barrett's esophagus; however, no population-based estimates of risk have been reported, and the role of other health factors in modifying risk is unclear. Methods: We conducted a population-based case-control study in Brisbane, Australia. Cases were 167 patients with histologically confirmed Barrett's esophagus diagnosed between February and December 2003. Age-matched and sex-matched controls (n = 261) were randomly selected from a population register. Data on exposure to self-reported symptoms of acid reflux, smoking, obesity, and other factors were collected through self-completed questionnaires followed by telephone interview. Risks of Barrett's esophagus and Barrett's esophagus with dysplasia associated with these exposures were estimated by the odds ratio (OR) and 95% confidence interval (95% Cl), both crude and adjusted for other factors. Results: Self-reported weekly episodes of acid reflux were associated with greatly increased risks of Barrett's esophagus (adjusted OR, 29.7; 95% CI, 12.2-72.6) and Barrett's esophagus with dysplasia (OR, 59.7; 95% CI, 18.5-193). Smoking was also associated with risk of Barrett's esophagus. We found evidence of interactions between symptoms of acid reflux and smoking and obesity. Obese people with self-reported symptoms of acid reflux had markedly higher risks of Barrett's esophagus (OR, 34.4; 95% CI, 6.3-188) than people with reflux alone (OR, 9.3; 95% CI, 1.4-62.2) or obesity alone (OR, 0.7,95% CI, 0.2-2.4). Similarly, those reporting both acid reflux symptoms and smoking were at substantially higher risks of Barrett's esophagus (OR, 51.4; 95% CI, 14.1-188) than those reporting acid reflux or smoking alone. Conclusions: Although history of symptoms of acid reflux is the principle factor associated with Barrett's esophagus, risks are substantially increased by obesity and smoking.

Physical and psychological factors maintain long-term predictive capacity post-whiplash injury

Higher initial levels of pain and disability, older age, cold hyperalgesia, impaired sympathetic vasoconstriction and moderate post-traumatic stress symptoms have been shown to be associated with poor outcome 6 months following whiplash injury. This study prospectively investigated the predictive capacity of these variables at a long-term follow-up. Sixty-five of an initial cohort of 76 acutely injured whiplash participants were followed to 2-3 years post-accident. Motor function (ROM; kinaesthetic sense; activity of the superficial neck flexors (EMG) during cranio-cervical flexion), quantitative sensory testing (pressure, thermal pain thresholds and brachial plexus provocation test), sympathetic vasoconstrictor responses and psychological distress (GHQ-28, TSK and IES) were measured. The outcome measure was Neck Disability Index (NDI) scores. Participants with ongoing moderate/severe symptoms at 2-3 years continued to manifest decreased ROM, increased EMG during cranio-cervical flexion, sensory hypersensitivity and elevated levels of psychological distress when compared to recovered participants and those with milder symptoms. The latter two groups showed only persistent deficits in cervical muscle recruitment patterns. Higher initial NDI scores (OR 1.00-1.1), older age (OR 1.00-1.13), cold hyperalgesia (OR 1.1-1.13) and post-traumatic stress symptoms (OR 1.03-1.2) remained significant predictors of poor outcome at long-term follow-up (r(2) = 0.56). The robustness of these physical and psychological factors suggests that their assessment in the acute stage following whiplash injury will be important. (c) 2006 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Disrupted cortical proprioceptive representation evokes symptoms of peculiarity, foreignness and swelling, but not pain

Objectives. It has been proposed that disruption of the internal proprioceptive representation, via incongruent sensory input, may underpin pathological pain states, but experimental evidence relies on conflicting visual input, which is not clinically relevant. We aimed to determine the symptomatic effect of incongruent proprioceptive input, imparted by vibration of the wrist tendons, which evokes the illusion of perpetual wrist flexion and disrupts cortical proprioceptive representation. Methods. Twenty-nine healthy and naive volunteers reported symptoms during five conditions: control, active and passive wrist flexion, extensor carpi radialis tendon vibration to evoke illusion of perpetual wrist flexion, and ulnar styloid (sham) vibration. No advice was given about possible illusions. Results. Twenty-one subjects reported the illusion of perpetual wrist flexion during tendon vibration. There was no effect of condition or of whether or not subjects reported an illusion on discomfort/pain (P > 0.28). Peculiarity, swelling and foreignness were greater during tendon vibration than during the other conditions, and greater during tendon vibration in those who reported an illusion of wrist flexion than in those who did not (P < 0.05 for all). Symptoms were reported by at least two subjects in each condition and four subjects reported systemic symptoms (e.g. nausea). Conclusions. In healthy volunteers, incongruent proprioceptive input does not cause discomfort or pain but does evoke feelings of peculiarity, swelling and foreignness in the limb.