Does antiretroviral therapy improve HIV-associated cognitive impairment? A quantitative review of the literature.

The development of antiretroviral therapy (ART) has dramatically improved survival for those living with human immunodeficiency virus (HIV), but whether ART improves cognitive functioning remains unclear. The aim of the present review was to examine systematically the extent to which ART improves cognition among individuals with HIV using meta-analytic methods. Twenty-three studies were included in the quantitative review. ART was associated with modest improvements in attention (mean d = .17; p < .001; 95% confidence interval [CI], .09/.25), executive function (mean d = .18; p < .001; 95% CI, .10/.26), and motor function (mean d = .24; p < .001; 95% CI, .16/.32). ART did not improve language, verbal memory, visual memory or visuospatial function. The extent to which cognition improved was correlated with the change in CD4 cell count following ART, suggesting a link between cognitive outcome and immune system integrity. Together, the present findings indicate that the neuropsychological test performance of most HIV patients taking ART is comparable to those not taking ART. Development of pharmaceutical treatments and rehabilitation strategies that target the cognitive effects of HIV infection is needed.

Specificity of verbal learning impairment and recovery in a marijuana-dependent male: the effects of sustained marijuana abstinence.

INTRODUCTION: We present the case of a young adult in treatment for marijuana dependence, with recurrent depression and a history of possible traumatic brain injury, complaining of concentration, memory, and initiation problems. METHODS: The patient was assessed longitudinally during treatment with a brief neuropsychological battery, as well as measures of marijuana use and mood. RESULTS: Testing at treatment baseline revealed performance that was generally in the high average range or higher on measures of reaction time and attention, with a selective impairment in verbal learning (borderline to extremely low range). Following 8 weeks of abstinence from marijuana, his verbal learning recovered to expected levels (high average range), with signs of improved learning strategy, efficiency, rate, and capacity. However, his reaction time and attention showed minimal evidence of change. CONCLUSIONS: This finding is consistent with the literature that demonstrates that marijuana-associated neurocognitive impairments may be most pronounced in the domain of verbal learning and may remit with abstinence. The clinical implications of these case findings and recommendations for neuropsychological assessment of marijuana abusers are discussed.

Functional consequences of HIV-associated neuropsychological impairment.

This review focuses on the "real world" implications of infection with HIV/AIDS from a neuropsychological perspective. Relevant literature is reviewed which examines the relationships between HIV-associated neuropsychological impairment and employment, driving, medication adherence, mood, fatigue, and interpersonal functioning. Specifically, the relative contributions of medical, cognitive, psychosocial, and psychiatric issues on whether someone with HIV/AIDS will be able to return to work, adhere to a complicated medication regimen, or safely drive a vehicle will be discussed. Methodological issues that arise in the context of measuring medication adherence or driving capacity are also explored. Finally, the impact of HIV/AIDS on mood state, fatigue, and interpersonal relationships are addressed, with particular emphasis on how these variables interact with cognition and independent functioning. The purpose of this review is to integrate neuropsychological findings with their real world correlates of functional behavior in the HIV/AIDS population.

Cognitive function of older patients receiving adjuvant chemotherapy for breast cancer: a pilot prospective longitudinal study.

OBJECTIVES: To report on the longitudinal cognitive functioning of older women receiving adjuvant chemotherapy for breast cancer. DESIGN: Neuropsychological and functional status testing were performed before chemotherapy and 6 months after chemotherapy. SETTING: Cancer center. PARTICIPANTS: Thirty-one patients aged 65 and older with Stage I to III breast cancer. Of the 31 patients enrolled, three refused post-testing, and 28 were evaluable. MEASUREMENTS: The following domains of cognitive function were examined: attention; verbal memory; visual memory; and verbal, spatial, psychomotor, and executive functions. RESULTS: Participants had a mean age of 71 (range 65-84): 39% Stage I, 50% Stage II, and 11% Stage III. The number of scores 2 standard deviations (SDs) below the norm were calculated for each patient before and 6 months after chemotherapy; 14 (50%) had no change, 11 (39%) worsened, and three (11%) improved (P=.05). Seven patients (25%) experienced a decline in cognitive function, defined as a 1-SD decline from pre- to post-testing in two or more neuropsychological domains. Exploratory analyses revealed no significant difference between functional status, comorbidity, and depression scale scores and change in overall quality-of-life scores before and after chemotherapy. CONCLUSION: In this cohort of older women receiving adjuvant chemotherapy, a subset experienced a decline in cognitive function from before chemotherapy to 6 months after chemotherapy. Further prospective study is needed to confirm these observations and to identify the subgroup at special risk.

Neurocognitive function in clinically stable men with bipolar I disorder or schizophrenia and normal control subjects.

BACKGROUND: Patients with bipolar disorder and schizophrenia have been shown to have neurocognitive deficits when compared with control subjects. The degree and pattern of impairment between psychiatric groups have rarely been compared, especially when subjects are psychiatrically stable. METHODS: Using a standard neurocognitive battery, we compared euthymic outpatients with bipolar disorder (n = 40), stable patients with schizophrenia (n = 20), and subjects with no psychiatric disorder (n = 22). The neurocognitive domains assessed included executive functioning, verbal memory, visual memory, procedural learning, visuoconstructive ability, and language functions. Effect sizes were calculated for each cognitive domain across groups. RESULTS: Stable schizophrenic subjects demonstrated a generalized cognitive impairment across most domains compared with control subjects, with average effect sizes of .9. Euthymic bipolar subjects were significantly impaired compared with control subjects only in executive functioning (Wisconsin Card Sorting Task) and verbal memory (California Verbal Learning Test) domains (effect sizes in the .8-.9 range). Performance on the executive function measures was bimodal among bipolar subjects, suggesting two subgroups: one with relatively normal and one with impaired executive functioning. No significant differences between the bipolar patient group and control subjects were observed in visuoconstructive ability, procedural learning, or language function. CONCLUSIONS: Both euthymic bipolar subjects and relatively stable schizophrenic subjects differed from control subjects in neurocognitive function. Among schizophrenic subjects, a generalized cognitive impairment was observed, and the degree of impairment was greater in the schizophrenic compared with the bipolar subjects. Subjects with bipolar disorder were impaired in two specific domains (verbal memory and executive function). Furthermore, within the bipolar group there was a subset with relatively normal executive functioning and a subset with significant impairment. Possible reasons for the persistence of these neurocognitive deficits in some subjects with bipolar disorder during periods of euthymia are reviewed.

Executive dysfunction in geriatric depression.

OBJECTIVE: The purpose of this study was to characterize the neuropsychological presentation of geriatric depression and to determine whether depression-related executive dysfunction is more pronounced during advanced age. METHOD: The attention and executive functioning of 40 adults with major depression were compared with those of 40 healthy comparison subjects; 20 subjects were 20-60 years old, and 20 were > or =61 years. It was hypothesized that depressed subjects, regardless of age, would perform more poorly than comparison subjects on both attention and executive tasks but that the older depressed adults would evidence significantly greater impairment on executive measures. RESULTS: A significant interaction between age and depressive status was noted for tasks of executive functioning, while no age-depression interaction was found for tasks of selective or sustained attention. Older depressed adults demonstrated the slowest psychomotor speed and the poorest performance on tasks requiring set shifting, problem solving, and initiation of novel responses. CONCLUSIONS: Patients with late-life depression have significant impairment in executive functioning. These findings can guide the development of stimulated functional neuroimaging paradigms that may clarify the pathophysiology of geriatric depression. Timely identification of attentional and executive processes fundamental to the daily functioning of depressed older adults may lead to compensatory strategies that will improve the outcomes of late-life depression.

Forensic evaluation of trauma syndromes in children.

There are significant differences between a clinical evaluation and a forensic evaluation [289-291]. These differences must be kept solidly in mind in performing the evaluation. The forensic evaluator needs to assess the validity of complaints, including the possibility of malingering and the child's ability to describe symptoms accurately, the connection between the symptoms and a given incident, and the potential long-term sequelae of a trauma. The goal of the interview is not to treat, but to obtain information. Assessing the validity of complaints is perhaps the greatest challenge. This requires obtaining and reconciling data from numerous sources, including interviews with the child and parents, and information from other sources, as well as rating scales and validity testing. One must be very cautious in asking leading questions and using standardized PTSD protocols, lest they teach the parents and child about the symptoms of PTSD and thereby distort the information they provide as a result. The forensic interviewer should consider what will be needed when called to testify in court. What data will convince the jury? How might the opposing attorney challenge the assessment? What scientific studies support the findings and conclusions concerning the diagnosis, functional impairment, and validity. The precise DSM-IV-TR diagnosis is not always key in a forensic evaluation. What is essential is establishing the connection between the trauma and ensuing emotional problems. All of the symptoms the individual has as a result of the trauma become important, whether or not they contribute to fulfillment of DSM-IV-TR criteria. This contrasts with a clinical evaluation in which one needs to demonstrate the existence of a DSM-IV-TR diagnosis for reimbursement purposes. Finally, the forensic evaluator should be familiar with current practice guidelines for examination of children with PTSD. Any deviation may need to be explained in court [264,292].

Decision-making in long-term cocaine users: Effects of a cash monetary contingency on Gambling task performance.

BACKGROUND: The Iowa Gambling task, which typically incorporates hypothetical monetary earnings and losses for performance, has been widely used to measure decision-making in substance abusers. We examined the effects of a cash monetary contingency on Gambling task performance in cocaine abusers and control participants. METHODS: Twenty-two long-term cocaine smokers who met DSM-IV criteria for cocaine dependence and 24 non-cocaine-using control participants completed this study. Both groups were similar in terms of age, executive function, and self-reported alcohol and marijuana use. All participants performed the Gambling task under two counterbalanced conditions: under one condition, earnings and losses were hypothetical, and under the other condition, earnings and losses were in cash. RESULTS: Condition x group interactions on card selection and task completion time were noted (p<0.05). Under the hypothetical payment condition, cocaine abusers selected a greater proportion of cards from disadvantageous decks than advantageous decks (p<0.05), but took a similar amount of time to complete the task, relative to control participants. However, under the cash payment condition, no group differences were seen for card selection and cocaine abusers took more time than controls to complete the task (p<0.05). CONCLUSIONS: The application of tangible consequences improved the decision-making and effort of cocaine abusers on the Gambling task, relative to control participants. These findings underscore the importance of considering population-specific factors (e.g., sensitivity to instructional vs. consequential control) when conducting neuropsychological research in substance abusers.

On becoming a peer reviewer for a neuropsychology journal.

The peer-review process is an invaluable service provided by the professional community, and it provides the critical foundation for the advancement of science. However, there is remarkably little systematic guidance for individuals who wish to become part of this process. This paper, written from the perspective of reviewers and editors with varying levels of experience, provides general guidelines and advice for new reviewers in neuropsychology, as well as outlining benefits of participation in this process. It is hoped that the current information will encourage individuals at all levels to become involved in peer-reviewing for neuropsychology journals.

Acute effects of smoked marijuana on decision making, as assessed by a modified gambling task, in experienced marijuana users.

The impact of regular marijuana use on executive cognitive abilities, including decision making, is not well understood. While cross-sectional studies have suggested that substance abusers exhibit impaired decision making, as assessed by the Iowa Gambling Task, the direct role of marijuana use in the Gambling Task performance of marijuana smokers has not been well defined. In this report, we present data on performance on a modified Gambling Task in experienced marijuana users after they had smoked marijuana under controlled laboratory conditions. A total of 36 marijuana users, who reported smoking approximately 24 marijuana cigarettes per week, completed this 3-session outpatient study. During each session, these volunteers completed the Gambling Task once at baseline and 3 times after smoking a single marijuana cigarette (0.0, 1.8, or 3.9% Delta9-THC). Marijuana cigarettes were administered in a double-blind fashion, and the sequence of Delta9-THC concentration was balanced across volunteers. Marijuana increased the time required to complete the task. However, advantageous card selection and money earned on the task were not disrupted by marijuana. These data are consistent with previous findings that indicated that speed of performance on tests of executive function, but not accuracy, is disrupted in experienced marijuana users during marijuana intoxication.

Neuropsychiatric predictors of return to work in HIV/AIDS.

This study followed 118 HIV+ individuals who had taken steps to return to work to determine facilitators or barriers in returning to work. Over the two-year study period, 52% of the participants obtained employment. Memory function served as the most potent predictor of obtaining employment. Persons who were younger, did not have a diagnosis of AIDS and who had shorter periods of unemployment prior to entering the study also had better chances of finding employment during the study. After finding employment, participants reported lower levels of depression as well, an apparent result of their obtaining employment. These findings indicate that memory is a key neuropsychiatric variable that is perhaps most relevant to HIV+ persons' quest to return to work.

Functional ("psychogenic") amnesia.

Patients who present with severely impaired memory functioning without a discernable neurological cause typically have experienced one or more severely stressful life events. These patients, who are described as having "psychogenic" or "dissociative" amnesia, typically differ from patients with the neurologic amnestic syndrome in that memory for their personal life histories is much more severely affected than is their ability to learn and retain new information; that is, they have isolated retrograde amnesia. Recent cognitive and brain imaging research has begun to reveal some of the cerebral mechanisms underlying functional amnesia, but this disorder remains best conceptualized as a relatively rare form of illness-simulating behavior rather than a disease. Neuropsychological assessment is often useful in revealing the circumscribed nature of the patient's performance deficits, the spared functions that can be brought to bear in rehabilitation, and the emotional disorders requiring psychiatric treatment. Controlled treatment trials are nonexistent, but case reports suggest that supportive psychotherapy, systematic relaxation training, hypnosis, and sedative/anxiolytic medications are useful in facilitating recovery. These treatments are often combined with a psychoeducational approach that essentially reteaches the patient his or her life story.

Detection of inadequate effort on the California Verbal Learning Test-Second edition: forced choice recognition and critical item analysis.

The Forced Choice Recognition (FCR) and the Critical Item Analysis (CIA) indices of the California Verbal Learning Test-II (CVLT-II) have been identified by the CVLT-II test developers as potentially useful, brief screening indicators of effort in neuropsychological assessment. This retrospective study analyzes performance on these measures in three groups: (1) clinically referred individuals; (2) forensically referred individuals not suspected of inadequate effort; and (3) forensically referred individuals whose performance on freestanding tests of effort suggested inadequate effort. Performances on FCR were analyzed for their relation to actual memory impairment and with regard to concrete and abstract distractor endorsement. FCR and CIA performances were analyzed for agreement with formal tests of inadequate effort and their test characteristics. Incremental validity was assessed by hierarchical logistic regression with previously identified indices for detection of inadequate effort on the CVLT. Results indicate that (1) FCR and CIA performances are not related to decreased memory performance; (2) FCR and CIA indices exhibit higher specificity and lower sensitivity, with higher positive predictive value than negative predictive value; and (3) FCR and CIA indices exhibit modest incremental validity with previously identified indices. Implications for use of FCR and CIA indices in inadequate effort detection are discussed

Components of depression in HIV-1 infection: their differential relationship to neurocognitive performance.

Both depression and neurocognitive compromise are commonly observed among persons infected with the Human Immunodeficiency Virus (HIV). To date, the majority of studies have failed to find a consistent relationship between mood and cognition among HIV-seropositive (HIV+) individuals, suggesting that these constructs are independent of one another. However, depression is a multi-dimensional syndrome and its measurement often utilizes multi-factorial instruments containing cognitive, affective, somatic, and motivational components. The degree to which various symptoms or dimensions of depression might be related to neuropsychological performance in HIV-1 infection is not typically explored and was a main objective of the current study. A sample of 247 HIV+ persons completed both a comprehensive neurocognitive battery and the Beck Depression Inventory (BDI) as part of a standard clinical evaluation at a major community hospital. To examine the dimensionality of the BDI, a principal components analysis was conducted which suggested a three-factor solution comprised of factors representing Self-Reproach (SR), Mood-Motivation Disturbance (MM), and Somatic Disturbance (SOM). The relationship between each of these three factors and neurocognitive performance was examined using both regression and analysis of variance techniques. These analyses showed the MM factor, more so than either the SR or SOM factors, to be associated with several aspects of neurocognitive performance, including verbal memory, executive functioning, and motor speed. These findings suggest that certain items on depression rating scales may be more indicative of central nervous system (CNS) involvement than others. The association between disturbance in mood and motivation and neurocognitive compromise may suggest that each are sequelae of disease specific mechanisms.

Effect of adjuvant breast cancer chemotherapy on cognitive function from the older patient's perspective.

PURPOSE: This longitudinal prospective study describes the older breast cancer patient's perception of the cognitive impact of adjuvant chemotherapy. METHODS: A total of 50 patients > or =age 65 with stage I to III breast cancer enrolled in this IRB-approved prospective study. Of the 50, 3 refused postchemotherapy testing and 2 had a cerebrovascular accident (CVA) during therapy, leaving 45 evaluable patients. The Squire Memory Self-Rating Questionnaire, given before and 6 months after chemotherapy, measured patients' perceptions of the ability to learn new information, of working memory, and of remote learning capabilities. RESULTS: Mean age was 70 years (range 65-84). Breast cancer stages were: I (33%), II (64%), III (2%). A 51% (23/45) of study participants perceived a decline in memory from before to 6 months after completion of chemotherapy. Patients who perceived a poorer memory than average before chemotherapy were more likely to report further memory deterioration after chemotherapy (19/30, 63%) than patients who perceived that their memory was average or better than average prior to chemotherapy (4/15, 27%). The memory domain most likely to be perceived as affected was the ability to learn new information (22/45, 49%) compared to remote memory (9/45, 20%) or working memory (13/45, 29%) capabilities. CONCLUSION: Approximately half of these older women perceived a decline in cognitive function from before to 6 months after chemotherapy. This perceived decline in cognitive function was most pronounced in patients with preexisting memory complaints. Further prospective study is needed to confirm these observations, correlate perceived memory changes with objective findings, and identify subgroups at special risk.