Assessing postoperative cognitive change after cardiopulmonary bypass surgery.

Cognitive decline after cardiopulmonary bypass (CPB) surgery has been a concern since the advent of CPB procedures. A primary focus of many studies on this topic has been to quantify the incidence of post-CPB cognitive impairment. However, studies that have used traditional parametric statistics have generally failed to confirm that long-lasting (–- I month) cognitive declines occur reliably after CPB surgery. For the present study, the authors used a split-plot analysis of variance model that revealed preoperative memory impairments in the CPB patients and new postoperative impairments of attention. The authors discuss the assumptions of, and problems associated with, analysis methods that are often used to quantify the incidence of cognitive impairment following CPB surgery. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cognitive functioning ten years following traumatic brain injury and rehabilitation.

Many previous studies investigating long-term cognitive impairments following traumatic brain injury (TBI) have focused on extremely severely injured patients, relied on subjective reports of change and failed to use demographically relevant control data. The aim of this study was to investigate cognitive impairments 10 years following TBI and their association with injury severity. Sixty TBI and 43 control participants were assessed on tests of attention, processing speed, memory, and executive function. The TBI group demonstrated significant cognitive impairment on measures of processing speed (Symbol Digit Modalities Test [SDMT], Smith, 1973; Digit Symbol Coding, Wechsler, 1997), memory (Rey Auditory Verbal Learning Test [RAVLT]; Rey, 1958; Lezak, 1976), Doors and People tests; Baddeley, Emslie & Nimmo-Smith, 1994) and executive function (Hayling C [Burgess & Shallice, 1997] and SART errors, Robertson, Manly, Andrade, Baddeley & Yiend, 1997). Logistic Regression analyses indicated that the SDMT, Rey AVLT and Hayling C and SART errors most strongly differentiated the groups in the domains of attention/processing speed, memory and executive function, respectively. Greater injury severity was significantly correlated with poorer test performances across all domains. This study shows that cognitive impairments are present many years following TBI and are associated with injury severity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

M1 muscarinic agonist treatment reverses cognitive and cholinergic impairments of apolipoprotein E-deficient mice

Recent studies suggest that apolipoprotein E (apoE) plays a specific role in brain cholinergic function and that the E4 allele of apoE (apoE4), a major risk factor for Alzheimer's disease (AD), may predict the extent of cholinergic dysfunction and the efficacy of cholinergic therapy in this disease. Animal model studies relevant to this hypothesis revealed that apoE-deficient (knockout) mice have working memory impairments that are associated with distinct dysfunction of basal forebrain cholinergic neurons. Cholinergic replacement therapy utilizing M1-selective muscarinic agonists has been proposed as effective treatment for AD patients. In the present study, we examined whether the memory deficits and brain cholinergic deficiency of apoE-deficient mice can be ameliorated by the M1-selective agonist 1-methylpiperidine-4-spiro-(2'-methylthiazoline), [AF150(S)]. Treatment of apoE-deficient mice with AF150(S) for 3 weeks completely abolished their working memory impairments. Furthermore, this reversal of cognitive deficit was associated with a parallel increase of histochemically determined brain choline acetyltransferase and acetylcholinesterase levels and with the recovery of these cholinergic markers back to control levels. These findings show that apoE deficiency-related cognitive and cholinergic deficits can be ameliorated by M1-selective muscarinic treatment. They also provide a novel model system for development and evaluation of therapeutic strategies directed specifically at the AD patients whose condition is attributed to the apoE genotype.     

Apolipoprotein E and Cognitive Performance: A Meta-Analysis.

The ε4 allele of the apolipoprotein E (APOE) gene is a known risk factor for Alzheimer's disease and may also affect cognitive performance in normal aging. Evidence of the presence and magnitude of ε4-related cognitive deficits was examined with a meta-analysis of the available literature. Thirty-eight studies were included, and cognitive performance was collapsed into 8 domains. Results indicated significant APOE-ε4 group differences for global cognitive functioning, episodic memory, and executive functioning, in favor of non-ε4 carriers. In addition, older age and APOE-ε4 heterozygosity was associated with smaller ε4-related impairments. The meta-analysis results suggest that APOE-ε4 genotype does affect cognitive performance in healthy aging, although the influence is relatively small and specific to certain domains of cognitive performance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Brief Treatments for Cannabis Dependence: Findings From a Randomized Multisite Trial.

This study evaluated the efficacy of 2 brief interventions for cannabis-dependent adults. A multisite randomized controlled trial compared cannabis use outcomes across 3 study conditions: (a) 2 sessions of motivational enhancement therapy (MET); (b) 9 sessions of multicomponent therapy that included MET, cognitive-behavioral therapy, and case management; and (c) a delayed treatment control (DTC) condition. Participants were 450 adult marijuana smokers with a Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994) diagnosis of cannabis dependence. Assessments were conducted at baseline, and at 4, 9, and 15 months postrandomization. The 9-session treatment reduced marijuana smoking and associated consequences significantly more than the 2-session treatment, which also reduced marijuana use relative to the DTC condition. Most differences between treatments were maintained over the follow-up period. Discussion focuses on the relative efficacy of these brief treatments and the clinical significance of the observed changes in marijuana use. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cognitive impairment in chronic alcoholics: Some cause for optimism.

Even after they cease drinking, many alcoholics show continued impairment of cognitive functioning on both intelligence and neuropsychological tests, with deficits being apparent in visual perception, learning and memory, and the use of problem-solving strategies. Neuropsychological investigations have suggested that these deficits reflect premature aging, a direct dose response relationship, or localized brain damage. However, studies have shown that a considerable recovery of cognitive functioning occurs, most dramatically after drinking cessation and more slowly thereafter. Tasks that require novel, complex, and rapid information processing require longer to recover, and persistent impairments in visual-spatial abilities, abstraction and problem solving, and short-term memory are common, particularly in older alcoholics. Practical applications of this research are discussed in terms of the possibility of reducing cognitive dysfunction and improving treatment outcome in alcoholics. (72 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neuropsychological impairment in patients with schizophrenia and evidence of hyponatremia and polydipsia.

Patients with schizophrenia and water imbalance may represent a subset of patients with distinct pathophysiological abnormalities and susceptibility to cognitive impairment. Specifically, patients with polydipsia and hyponatremia have been shown to have smaller anterior hippocampal volumes, which are also associated with various impairments in neuroendocrine function. To determine whether abnormalities in patients with water imbalance extend to the cognitive realm, the present study evaluated neuropsychological functioning in three groups of patients with schizophrenia: polydipsic hyponatremic, polydipsic normonatremic, and nonpolydipsic normonatremic. Participants were administered cognitive tests assessing intelligence, attention, learning/memory (verbal, nonverbal, emotional), and facial discrimination. Hyponatremic patients showed poorer overall neuropsychological functioning relative to all other patients, and polydipsic normonatremic patients performed intermediate to the other two groups. Results indicate that patients with schizophrenia and polydipsia, and particularly those with hyponatremia, show prominent cognitive deficits relative to patients without water imbalance. The clinical, neuroendocrine, and cognitive abnormalities in these patients may arise from pathology within the anterior hippocampus and associated prefrontal/limbic brain regions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparative data on child and adolescent cognitive measures associated with depression.

As a way to better understand the effects of treatment for depression, comparative data on measures of cognition have been compiled previously for adults. Such data should be able to aid the evaluation of cognition and cognitive change, and may provide valuable information for clinicians and researchers alike. In this article, analogous comparative data on cognitive measures associated with depression in children and adolescents are presented. The reviewed instruments assess cognitive errors, attributional style, dysfunctional attitudes, hopelessness, negative self-statements, and Beck's negative cognitive triad. As with adults, these data may have implications for enhancing understanding of empirically supported treatments for children and adolescents, may be useful in vulnerability research, and may be useful to clinicians seeking to develop treatment strategies and to gauge treatment effectiveness. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Recent developments in the pharmacotherapy of substance abuse

Modern concepts of addictive disorders emphasize the compulsive and relapsing drug-taking behaviors rather than tolerance and physical dependence. As with any chronic disorder, long-term treatment is necessary and medications may aid in the rehabilitative process. Specific medications have been demonstrated to be helpful for psychiatric disorders coexisting with addiction. Medications have also been demonstrated in controlled studies to aid in the rehabilitation of patients dependent on nicotine, alcohol, or opiates. Thus far, no medication has been clearly demonstrated to benefit patients suffering from abuse or dependence on cocaine, cannabinoids, nonalcohol sedatives, or hallucinogens.     

Marijuana use and treatment outcome in cocaine-dependent patients.

Marijuana use was assessed in 186 people seeking treatment for cocaine dependence. Comparisons were made between clients who did and did not report using marijuana and between marijuana users who did and did not meet diagnostic criteria for marijuana dependence. The relationship between marijuana use and treatment outcome was also explored. A high rate of current marijuana use (59%) was observed at intake, and the majority of the marijuana users (74%) used marijuana at some point during treatment. Marijuana use at intake was associated with increased psychosocial impairment and substance-use severity. However, no significant adverse relations were observed between marijuana use at intake or during treatment and treatment outcome. Such functional independence may have important implications for addressing marijuana use during treatment for cocaine dependence. These findings should be interpreted with caution pending replication in prospective studies and with other treatment approaches. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cognitive impairment influences drinking outcome by altering therapeutic mechanisms of change.

Serious neuropsychological impairments are seen in a minority of addiction treatment clients, and, theoretically, these impairments should undermine behavioral changes targeted by treatment; however, little evidence supports a direct influence of impairment on treatment response. To address this paradox, the authors used structural equation modeling and Project MATCH data (N=1,726) to examine direct, mediated, and moderated paths between cognitive impairment, therapeutic processes, and treatment outcome. Mediated relations were found, wherein impairment led to less treatment compliance, lower self-efficacy, and greater Alcoholics Anonymous Involvement, which, in turn, more proximally predicted drinking. Impairment further moderated the effect of self-efficacy, making it a poor predictor of drinking outcomes in impaired clients, thereby suggesting that impaired and unimpaired clients traverse different pathways to addiction recovery. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

(+)-Eburnamenine-14-carboxylic acid (2-nitroxyethyl) ester (VA-045), a putative cognitive enhancer, facilitates recovery from concussive brain injury-induced learning and memory impairments in mice

We characterized alterations in the ability of concussive brain injury (CBI) models to perform a water-finding task and examined effects of (+)-eburnamenine-14-carboxylic acid (2-nitroxyethyl) ester (VA-045), a novel apovincaminic acid derivative, on post-traumatic impairments in latent learning and memory processes. Two types of CBI-induced amnesia (retrograde and anterograde) were produced by means of post- or preacquisition head impact using a simple weight-drop device. Profound impairments of latent learning and memory processes related to retention and retrieval were observed in the CBI mice. In the CBI-induced retrograde amnesia model, VA-045 (0.5-4.0 mg/kg) significantly ameliorated impairments of latent learning and retention in both the retention test and the retest. In the CBI-induced anterograde amnesia model, the protective effects of the compound on impairments in latent learning and retention or retrieval were significant in both the retention test and the retest. These results suggested that VA-045 may be a novel cognitive enhancer for attenuating or protecting against the learning and memory dysfunction associated with CBI.     

Use of IQ-Adjusted Norms to Predict Progressive Cognitive Decline in Highly Intelligent Older Individuals.

Identifying high-functioning older individuals in preclinical phases of Alzheimer's disease (AD) may require more sensitive methods than the standard approach. The authors explored the utility of adjusting for premorbid intelligence to predict progressive cognitive decline or Mild Cognitive Impairment (MCI) in 42 highly intelligent older individuals. When scores were adjusted for baseline IQ, 9 participants had executive impairments, 11 had memory impairments, and 22 scored in the normal range. None were impaired according to standard age norms. Three and a half years later, 9 participants with IQ-adjusted memory impairment declined in naming, visuospatial functioning, and memory; 6 convened to MCI. Three participants with normal memory declined. Implications for using IQ-adjusted norms to predict preclinical AD are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Item and associative memory in amnestic mild cognitive impairment: Performance on standardized memory tests.

The earliest neuroanatomical changes in amnestic mild cognitive impairment (aMCI) involve the hippocampus and entorhinal cortex, structures implicated in the integration and learning of associative information. The authors hypothesized that individuals with aMCI would have impairments in associative memory above and beyond the known impairments in item memory. A group of 29 individuals with aMCI and 30 matched control participants were administered standardized tests of object-location recall and symbol-symbol recall, from which both item and associative recall scores were derived. As expected, item recall was impaired in the aMCI group relative to controls. Associative recall in the aMCI group was even more impaired than was item recall. The best group discriminators were measures of associative recall, with which the sensitivity and specificity for detecting aMCI were 76% and 90% for symbol-symbol recall and were 86% and 97% for object-location recall. Associative recall may be particularly sensitive to early cognitive change in aMCI, because this ability relies heavily on the medial temporal lobe structures that are affected earliest in aMCI. Incorporating measures of associative recall into clinical evaluations of individuals with memory change may be useful for detecting aMCI. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cue reactivity in young marijuana smokers: A preliminary investigation.

To develop and evaluate the feasibility of a cue reactivity paradigm for young marijuana smokers, the authors set up a laboratory procedure involving neutral and marijuana-related imagery, video, and in vivo cues. Fifteen adolescents and young adults with cannabis use disorders completed the procedure, which included continuous measurement of skin conductance and heart rate. Participants also completed questionnaires regarding marijuana craving before, during, and after cue presentations. Higher levels of craving and skin conductance were observed during marijuana cue presentations. The procedure appears to elicit cue reactivity among adolescents and young adults with cannabis use disorders and should be further evaluated and refined with a larger sample. Implications for future studies are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Biological and Psychological Factors Associated With Memory Function in Fibromyalgia Syndrome.

Fibromyalgia is a stress-related disorder characterized by chronic pain, memory impairment, and neuroendocrine aberrations. With the hypothesis that biological and psychological symptoms may underlie the cognitive problems, the relative influences of neuroendocrine function and psychological factors on declarative memory were examined among 50 women with fibromyalgia. This within-group analysis controlled for age, education, pain, and relevant medications. Neuroendocrine function and depression had significant independent associations with memory function. Higher log-transformed mean salivary cortisol levels were associated with better performance on both immediate and delayed visual recall and with delayed verbal recall. Depressive symptoms were negatively associated with verbal recall. These findings suggest that a basic disorder of endocrine stress responses may contribute to the cognitive symptoms experienced by fibromyalgia patients. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A twin study of cognitive function in chronic fatigue syndrome: The effects of sudden illness onset.

Variable reports of neuropsychological deficits in individuals with chronic fatigue syndrome (CFS) may, in part, be attributable to methodological limitations. In this study, these limitations were addressed by controlling for genetic and environmental influences and by assessing the effects of comorbid depression and mode of illness onset. Specifically, the researchers conducted a co-twin control study of 22 pairs of monozygotic twins, in which 1 twin met strict criteria for CFS and the co-twin was healthy. Twins underwent a structured psychiatric interview and comprehensive neuropsychological assessment evaluating 6 cognitive domains. Results indicated that twin groups had similar intellectual and visual memory functioning, but fatigued twins exhibited decreases in motor functions (p = .05), speed of information processing (p = .02), verbal memory (p = .02), and executive functioning (p = .01). Major depression did not affect neuropsychological functioning among fatigued twins, although twins with sudden illness onset demonstrated slowed information processing compared with those with gradual onset (p = .01). Sudden onset CFS was associated with reduced speed of information processing. If confirmed, these findings suggest the need to distinguish illness onset in future CFS studies and may have implications for treatment, cognitive rehabilitation, and disability determination. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Addiction is a brain disease, and it matters

Scientific advances over the past 20 years have shown that drug addiction is a chronic, relapsing disease that results from the prolonged effects of drugs on the brain. As with many other brain diseases, addiction has embedded behavioral and social-context aspects that are important parts of the disorder itself. Therefore, the most effective treatment approaches will include biological, behavioral, and social-context components. Recognizing addiction as a chronic, relapsing brain disorder characterized by compulsive drug seeking and use can impact society's overall health and social policy strategies and help diminish the health and social costs associated with drug abuse and addiction.     

Quantitation of cannabinoids in biological fluids by radioimmunoassay

A tritium based radioimmunoassay for delta9THC and its metabolites has been developed for the use of investigators studying the epidemiological, medical, clinical, and research aspects of cannabis use. The assay is sufficiently sensitive to detect cannabinoids in the urine of marijuana smokers for several days after their last exposure to the drug. The results obtained from a 28 day study indicate that the assay reflects the administration and removal of oral doses of THC. The specificity of the antisera, as determined in cross reactivity studies, allows not only the assay of metabolites in biological samples without interference from other drugs, but also the evaluation of extracts of other kinds of samples which may contain unmetabolized delta9THC. The technique of radioimmunoassay has many advantages over other methods of analysis. It is simple to perform and can be readily applied to the rapid analysis of large numbers of samples. It can be used in the direct analysis of physiological fluids and other biological samples which ordinarily have to be processed before other techniques can be applied. The method is non-destructive abd obviates the need to use radiolabelled drugs in man during metabolic and other studies. This radioimmunoassay has been designed with particular emphasis on ease of use by other investigators. We anticipate that it will prove useful to investigators and scientists for determining the absence, or presence and amount, of THC metabolite in a biological specimen, for epidemiologists in determining the full extent of cannabis use and to the medical/clinical community for establishing the minimum effective dose of delta9THC for each patient. The widespread application of a single method of analysis should also remove a great deal of the controversy surrounding marijuana studies performed to date.     

Daily stressors and memory failures in a naturalistic setting: Findings from the va normative aging study.

Laboratory studies of stress and memory have generally found that people with more stress tend to have poorer cognitive performance. The present investigation examined the relationship between stressors and memory failures in a naturalistic setting via a daily diary study of 333 older adults in the VA Normative Aging Study. Multilevel models indicated that on days when people experienced stressors, particularly interpersonal stressors, they were more likely to report memory failures. These stressors were also associated with an increase in memory failures from one day to the next. The findings may be important for preventions to mitigate age-related cognitive decline. (PsycINFO Database Record (c) 2010 APA, all rights reserved)