A randomized evaluation of on-site monitoring nested in a multinational randomized trial.

BACKGROUND: Evidence from prospectively designed studies to guide on-site monitoring practices for randomized trials is limited. A cluster randomized study, nested within the Strategic Timing of AntiRetroviral Treatment (START) trial, was conducted to evaluate on-site monitoring. METHODS: Sites were randomized to either annual on-site monitoring or no on-site monitoring. All sites were centrally monitored, and local monitoring was carried out twice each year. Randomization was stratified by country and projected enrollment in START. The primary outcome was a participant-level composite outcome including components for eligibility errors, consent violations, use of antiretroviral treatment not recommended by protocol, late reporting of START primary and secondary clinical endpoints (defined as the event being reported more than 6 months from occurrence), and data alteration and fraud. Logistic regression fixed effect hierarchical models were used to compare on-site versus no on-site monitoring for the primary composite outcome and its components. Odds ratios and 95% confidence intervals comparing on-site monitoring versus no on-site monitoring are cited. RESULTS: In total, 99 sites (2107 participants) were randomized to receive annual on-site monitoring and 97 sites (2264 participants) were randomized to be monitored only centrally and locally. The two monitoring groups were well balanced at entry. In the on-site monitoring group, 469 annual on-site monitoring visits were conducted, and 134 participants (6.4%) in 56 of 99 sites (57%) had a primary monitoring outcome. In the no on-site monitoring group, 85 participants (3.8%) in 34 of 97 sites (35%) had a primary monitoring outcome (odds ratio = 1.7; 95% confidence interval: 1.1-2.7; p = 0.03). Informed consent violations accounted for most outcomes in each group (56 vs 41 participants). The largest odds ratio was for eligibility violations (odds ratio = 12.2; 95% confidence interval: 1.8-85.2; p = 0.01). The number of participants with a late START primary endpoint was similar for each monitoring group (23 vs 16 participants). Late START grade 4 and unscheduled hospitalization events were found for 34 participants in the on-site monitoring group and 19 participants in the no on-site monitoring group (odds ratio = 2.0; 95% confidence interval: 1.1-3.7; p = 0.02). There were no cases of data alteration or fraud. Based on the travel budget for on-site monitoring and the hours spent conducting on-site monitoring, the estimated cost of on-site monitoring was over US$2 million. CONCLUSION: On-site monitoring led to the identification of more eligibility and consent violations and START clinical events being reported more than 6 months from occurrence as compared to no on-site monitoring. Considering the nature of the excess monitoring outcomes identified at sites receiving on-site monitoring, as well as the cost of on-site monitoring, the value to the START study was limited.

Changes in state legislation and the impacts on elder financial fraud and exploitation.

OBJECTIVES: The purpose of this paper is to summarize how state legislators are responding to the increasing incidence of elder financial fraud and exploitation (EFFE) and investigate the impact of new state legislation. METHODS: Our empirical model investigates the impact of recent changes in state legislation, after controlling for relevant state demographics, on the prevalence of EFFE claims reported in the Consumer Sentinel Network database. We use panel data in a fixed effects model with and without time dummy variables. RESULTS: States with additional penalties targeting EFFE have a significantly lower percentage of complaints from elders, whereas the impact of mandatory and protected voluntary reporting laws is not significant in this sample. DISCUSSION: State legislators have increased their awareness of and are acting to produce legislation protecting the elderly from EFFE. Increased information, training and data sharing across states can go a long way to detecting and prosecuting EFFE cases.

Key Features of a Multi-Disciplinary Hospital-Based Rehabilitation Program for Children and Adolescents with Moderate to Severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome ME/CFS.

PURPOSE OF THE STUDY: There is limited published data on treatment or outcomes of children and young people (CYP) with moderate or severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Here, we describe outcomes of moderate and severe ME/CFS in CYP treated in a tertiary adolescent service. This information is useful when planning services for CYP and families affected by moderate/severe ME/CFS and to guide future management trials and commissioning decisions. STUDY DESIGN: A retrospective review was conducted of medical records of the 27 CYP who received ward-based treatment in 2015. Notes were retrospectively reviewed to assess progress in four markers of wellbeing over the period of treatment: (i) mobility, (ii) education, (iii) sleep and (iv) involvement in social/recreational activities. RESULTS: A total of 23/27 (85%) showed improvement in one or more domains over their period of ward-based therapy. 19/27 (70%) of patients showed improvement in physical ability. In 15/23 patients (65%), there was an improvement in ability to access education, in 12/24 (50%) sleep improved, and 16/27 (59%) demonstrated an improvement in socialising/ability perform recreational activities. CONCLUSION/IMPLICATIONS: A multidisciplinary hospital-based rehabilitation programme for moderate and severe ME/CFS was associated with improvement in at least one area of wellbeing in 85% of the CYP we reviewed. These data may be used as a baseline to evaluate the impact of other models of delivering care for this patient group. It may be useful when considering other groups such as those affected by Post-COVID Syndrome.

Neurocognitive consequences of HIV infection in older adults: an evaluation of the "cortical" hypothesis.

The incidence and prevalence of older adults living with HIV infection is increasing. Recent reports of increased neuropathologic and metabolic alterations in older HIV+ samples, including increased cortical beta-amyloid, have led some researchers to suggest that aging with HIV may produce a neuropsychological profile akin to that which is observed in "cortical" dementias (e.g., impairment in memory consolidation). To evaluate this possibility, we examined four groups classified by HIV serostatus and age (i.e., younger ≤40 years and older ≥50 years): (1) Younger HIV- (n = 24); (2) Younger HIV+ (n = 24); (3) Older HIV- (n = 20); and (4) Older HIV+ (n = 48). Main effects of aging were observed on episodic learning and memory, executive functions, and visuoconstruction, and main effects of HIV were observed on measures of verbal learning and memory. The interaction of age and HIV was observed on a measure of verbal recognition memory, which post hoc analyses showed to be exclusively attributed to the superior performance of the younger HIV seronegative group. Thus, in this sample of older HIV-infected individuals, the combined effects of HIV and aging do not appear to result in a "cortical" pattern of cognitive deficits.

HIV-associated episodic memory impairment: evidence of a possible differential deficit in source memory for complex visual stimuli.

HIV infection is often associated with frontal systems pathology and related deficits in the strategic encoding and retrieval aspects of episodic memory. However, no prior HIV studies have explicitly examined source memory, which refers to recall of information regarding the context in which a declarative memory was formed. Source memory is heavily reliant on frontal systems and strategic cognitive processes and is singly dissociable from the content of the memory (i.e., item memory), which is more dependent on medial temporal systems and automatic processes. The present study examined item and source memory in 60 individuals with HIV infection and 35 demographically similar seronegative participants. The primary finding of interest was a significant HIV effect on source (but not item) memory for complex visual stimuli. Follow-up correlational analyses showed a significant association between visual source memory errors and impairment on measures of executive functions, working memory, and higher-level list learning encoding strategies. These findings extend the hypothesized profile of strategic encoding and retrieval deficits in HIV to the construct of source memory, which may be differentially affected relative to item memory for complex visual stimuli.

Subcortical lacunes are associated with executive dysfunction in cognitively normal elderly.

BACKGROUND AND PURPOSE: The relationship between subcortical ischemic vascular disease (SIVD) and cognition in normal elderly is unclear, in part because of methodological inconsistencies across studies. To clarify this relationship, the current study investigated a well characterized cognitively normal elderly sample (>or=55 years) with quantitative MRI and psychometrically robust neuropsychological measures within a multivariate model. Converging evidence suggests that SIVD selectively impairs frontal-executive tasks by disrupting frontal-subcortical circuits. We therefore hypothesized that MRI markers of SIVD would be selectively associated with worse executive functioning. METHODS: We studied 94 participants who were cognitively and functionally normal. Volumetric measures of white matter signal hyperintensity (WMH), subcortical lacunes, hippocampal volume, and cortical gray matter were obtained to predict performance on composite measures of executive functioning and episodic memory. RESULTS: Hierarchical regression demonstrated that after controlling for demographic variables, MMSE, and total intracranial volume, the total number of subcortical lacunes was the only significant predictor, with a greater number of lacunes associated with poorer executive performance. Hippocampal volume best predicted episodic memory performance. CONCLUSIONS: Results suggest that SIVD in the form of silent lacunes corresponds to poorer executive functioning even in otherwise normal elderly, which is consistent with the hypothesis that SIVD preferentially disrupts frontal-subcortical circuits. The clinical importance of these findings is highlighted by the fact that 33% of the normal elderly participants in this study had lacunar infarcts.

Discriminant validity and neuroanatomical correlates of rule monitoring in frontotemporal dementia and Alzheimer's disease.

Despite the predominant frontal neuropathology of frontotemporal dementia (FTD), traditional measures of executive functioning do not reliably distinguish FTD from Alzheimer's disease (AD). Performance monitoring is an executive function that is associated with frontal lobe integrity and may be disrupted in FTD. The current study adopted a component process approach to evaluate the discriminant validity and neuroanatomical correlates of performance monitoring (i.e., rule monitoring) during an executive spatial planning task. Forty-four participants with FTD, 30 with AD, and 27 healthy comparison (HC) subjects completed the Delis-Kaplan Executive Function System (D-KEFS) Tower task. A subset of patients underwent structural magnetic resonance imaging to obtain regional measures of cortical volumes. FTD and AD groups demonstrated significantly poorer overall achievement scores on the Tower test relative to the HC sample, but did not differ from one another. In contrast, the FTD group committed significantly more rule violation errors than both HC and AD groups, indicating poorer performance monitoring. In addition, poorer overall achievement correlated with smaller brain volumes in several regions, including bilateral frontal and parietal regions, whereas an increased number of rule violations correlated specifically with decreased bilateral frontal volume. Both left and right frontal volumes remained significant predictors of rule violation errors after controlling for the contribution of overall achievement on the task and all other brain regions. Findings are consistent with literature implicating the frontal lobes in performance monitoring and highlight the importance of characterizing the component processes of performance failures in the cognitive assessment of FTD and AD.

HIV-associated prospective memory impairment increases risk of dependence in everyday functioning.

HIV infection is associated with impairments in prospective memory (ProM), an aspect of episodic memory that refers to the ability to execute a future intention, such as remembering to take a medication at a specific time. The current study sought to examine the relationship between HIV-associated ProM impairment and the successful management of instrumental activities of daily living (IADLs). In a cohort of 66 HIV-infected individuals, ProM accounted for a significant proportion of variance in self-reported IADL dependence, over and above that which was explained by retrospective memory and by current affective distress. Analysis of component cognitive processes revealed that the relationship between HIV-associated ProM deficits and IADL dependence was driven by impaired cue detection and by deficits in self-initiated intention retrieval. Results were not better explained by demographic factors, HIV disease severity, psychiatric comorbidity, or substance use. Collectively, these data support the potential incremental ecological validity of ProM as a predictor of dependence in IADLs among persons living with HIV infection.

Frequency and predictors of self-reported prospective memory complaints in individuals infected with HIV.

Failures of episodic retrospective memory (RetM) are among the most frequently reported cognitive complaints endorsed by individuals living with HIV infection. The present study sought to examine the nature, frequency, and determinants of self-reported complaints of prospective memory (ProM) in HIV, which is a singly dissociable and ecologically relevant aspect of episodic memory involving the execution of future intentions. Seventy-five HIV seropositive individuals and 60 seronegative volunteers were administered the Prospective and Retrospective Memory Questionnaire (PMRQ) as part of extensive neuropsychological, psychiatric, and medical research assessments. The HIV sample endorsed more frequent ProM complaints in daily life than the seronegative group, particularly on items requiring self-initiated cue detection and retrieval. Within both study groups, ProM complaints were significantly more frequent than RetM complaints. Although the HIV sample was impaired relative to the seronegative group on an objective, performance-based ProM test, self-reported ProM complaints did not correspond to actual ProM abilities. However, greater frequency of self-reported ProM complaints was moderately associated with increased fatigue, as well as with symptoms of anxiety and depression. Consistent with prior research on RetM in HIV, results indicate that affective distress contributes to a metamemory deficit for HIV-associated ProM impairment, which highlights the potential importance of assessing both self-reported and performance-based ProM in clinical and research neuroAIDS evaluations.

Improved quality of life with immediate versus deferred initiation of antiretroviral therapy in early asymptomatic HIV infection.

OBJECTIVE: To determine if immediate compared to deferred initiation of antiretroviral therapy (ART) in healthy persons living with HIV had a more favorable impact on health-related quality of life (QOL), or self-assessed physical, mental, and overall health status. DESIGN: QOL was measured in the Strategic Timing of Antiretroviral Therapy study, which randomized healthy ART-naive persons living with HIV with CD4 cell counts above 500 cells/µl from 35 countries to immediate versus deferred ART. METHODS: At baseline, months 4 and 12, then annually, participants completed a visual analog scale (VAS) for 'perceived current health' and the Short-Form 12-Item Health Survey version 2 from which the following were computed: general health perception; physical component summary (PCS); and mental component summary (MCS); the VAS and general health were rated from 0 (lowest) to 100 (highest). RESULTS: QOL at study entry was high (mean scores: VAS = 80.9, general health = 72.5, PCS = 53.7, MCS = 48.2). Over a mean follow-up of 3 years, changes in all QOL measures favored the immediate group (P < 0.001); estimated differences were as follows: VAS = 1.9, general health = 3.6, PCS = 0.8, MCS = 0.9. When QOL changes were assessed across various demographic and clinical subgroups, treatment differences continued to favor the immediate group. QOL was poorer in those experiencing primary outcomes; however, when excluding those with primary events, results remained favorable for immediate ART recipients. CONCLUSION: In an international randomized trial in ART-naive participants with above 500 CD4 cells/µl, there were modest but significant improvements in self-assessed QOL among those initiating ART immediately compared to deferring treatment, supporting patient-perceived health benefits of initiating ART as soon as possible after an HIV diagnosis.

Cortical and subcortical neurodegeneration is associated with HIV neurocognitive impairment.

OBJECTIVE: To determine the association of markers of regional neurodegeneration (ND) at autopsy to degree of neurocognitive impairment in persons with HIV. DESIGN: In a prospectively followed cohort of HIV-infected individuals we examined the relationship between antemortem neuropsychological (NP) abilities and postmortem neuropathological data. METHODS: Twenty-seven HIV-infected individuals with both neuropsychological and neuropathological data were identified. Laser confocal scanning microscopy was used to determine the degree of ND based on: (1) microtubule-associated protein (MAP2; reflecting neuronal cell bodies and dendrites) and (2) synaptophysin (SYN; a measure of presynaptic terminals). A regional combined score, based on the distribution of percentage neuropil occupied by MAP2 and SYN and emphasizing severity of ND, was created for each brain region: midfrontal cortex, hippocampus, and putamen. RESULTS: The regional combined scores from each brain region studied were better correlated with level of global NP impairment than measures of SYN and MAP2 individually. In a regression, hippocampal and putamen regional combined scores were independent predictors of degree of antemortem NP impairment (F(3,23) = 6.17; P < 0.01; R2 = 0.45). The correlations among regional ND measures demonstrated that ND is unevenly distributed across multiple brain regions. CONCLUSIONS: As the anatomic distribution and temporal progression of neuropathologic changes appears to differ across individuals, it is important to consider both cortical and subcortical brain regions in studies of neuropathogenesis and treatment of HIV-related brain disease. Furthermore, combining information from several markers of neural injury provided the strongest association with degree of neurocognitive impairment during life.

New Alström syndrome phenotypes based on the evaluation of 182 cases.

BACKGROUND: Alström syndrome is a recessively inherited genetic disorder characterized by congenital retinal dystrophy that leads to blindness, hearing impairment, childhood obesity, insulin resistance, and type 2 diabetes mellitus. We provide new details on cardiologic, hepatic, gastrointestinal, urologic, pulmonary, and neurobehavioral phenotypes in Alström syndrome and describe the histopathologic findings in 5 individuals. METHODS: We obtained data on 182 patients from clinical examinations, medical record reviews, standardized questionnaires, and personal interviews with physicians and parents. RESULTS: Dilated cardiomyopathy occurred in 60% of patients. Age at onset was either during infancy, often before vision disturbances were noted, or in adolescence or adulthood. There is a risk of recurrence of infantile cardiomyopathy. Hyperinsulinemia (92%) developed in early childhood and progressed to type 2 diabetes mellitus in 82% of those older than 16 years. Hypertriglyceridemia (54%) precipitated pancreatitis in 8 patients. Urologic dysfunction and gastrointestinal disturbances occurred in 48% and 35% of patients, respectively. Fifty-three percent of patients had persistent pulmonary symptoms. Neurologic symptoms in 20% of patients included clonic tic and absence seizures. Developmental motor or language delays were observed in 46% of patients. Fibrotic infiltrations of multiple organs, that is, kidney, heart, liver, lung, urinary bladder, gonads, and pancreas, were observed. CONCLUSIONS: The wide-ranging and complex spectrum of phenotypes reported herein broadens those previously described for Alström syndrome. These findings will aid physicians in making an early and accurate diagnosis and will help effect appropriate monitoring and treatment.

Association between dyads and correct responses on the Paced Auditory Serial Addition Task (PASAT).

The sensitivity of the Paced Auditory Serial Addition Task (PASAT) to working memory deficits may be enhanced by examining "dyads" (i.e., correct responses immediately preceded by a correct response) as a complement to the traditional total correct summary score. In a sample of 397 mostly African American (79%) healthy adults, total dyad and total correct scores were highly correlated (r = .96, p < .001); however, the magnitude of this association diminished in faster stimulus presentation trials, particularly among participants with impaired working memory abilities.

Action (verb) generation in HIV-1 infection.

It has been proposed that verb generation is primarily associated with left fronto-basal ganglia circuits, whereas the generation of nouns is principally mediated by dominant left temporo-parietal networks. Consistent with this premise, action (verb) fluency - a verbal fluency task requiring the spontaneous generation of verbs - has shown greater sensitivity to frontal-basal ganglia pathophysiology (e.g., dementia in Parkinson's disease (PDD)) than noun fluency. The present study examined action and noun fluency in persons with HIV-1 infection-a disease known to be associated with a frontal-basal ganglia circuit neuropathogenesis. Action and noun ("animals") verbal fluency protocols were administered to 97 persons with HIV-1 infection and 20 demographically comparable healthy comparison (HC) subjects. A significant interaction emerged between verbal fluency task and HIV-1 serostatus such that the HIV+ group generated significantly fewer actions (verbs) relative to the HC sample. Findings indicate that persons infected with HIV-1 experience difficulty rapidly generating verbs, but not nouns from semantic memory. Considering the prominent frontal-basal ganglia circuit neuropathophysiology of HIV-1 infection, these data are consistent with the hypothesized dissociation between noun and verb generation as pertains to generative fluency.

Deficient strategic control of verbal encoding and retrieval in individuals with methamphetamine dependence.

Methamphetamine (MA) dependence is associated with deficits in episodic verbal memory, but the cognitive mechanisms underlying such impairments are not known. The authors evaluated a component process model of episodic verbal memory in 87 persons with MA dependence (MA+) and 71 demographically similar non-MA-using controls (MA-). Compared with MA- controls, MA+ participants demonstrated deficient overall learning, free recall, and utilization of semantic clustering, as well as higher rates of repetitions and intrusions. No between-groups differences were evident on measures of serial clustering, retention, or recognition discrimination. Taken together, these findings indicate that MA dependence is associated with deficient strategic (i.e., executive) control of verbal encoding and retrieval, which is consistent with the sequelae of MA-related prefronto-striatal circuit neurotoxicity.

Construct validity of Hopkins Verbal Learning Test-Revised component process measures in an HIV-1 sample.

Executive dyscontrol of episodic verbal learning and memory secondary to prefrontostriatal circuit neuropathophysiology is a common feature of HIV-1 infection. Prior research indicates that standard clinical learning and recall indexes from Hopkins Verbal Learning Test-Revised (HVLT-R) are among the most sensitive indicators of HIV-associated neurocognitive disorders. Emerging data support the validity of qualitative component process measures derived from the HVLT-R (e.g., Semantic Clustering); however, no prior studies have examined these particular indices of performance in an HIV-1-infected population. In the present study, we examined the construct validity of HVLT-R component process indices in a sample of 42 persons with HIV-1 infection and 29 demographically similar seronegative comparison participants. The HIV-1 sample performed significantly below the seronegative group on Total and Delayed Recall, Semantic Clustering, and the Retrieval Index. No between-group differences were observed on Serial Clustering, Pair Frequency, Learning, Repetitions, Semantic False Positive Recognition Errors, or the Recognition Discrimination Index. In addition, the HVLT-R component process measures demonstrated evidence of convergent and divergent validity with standard clinical tests in the HIV-1 sample. Findings support the construct validity of HVLT-R component process measures and are commensurate with prior literature indicating that HIV-1 disease is associated with deficient executive control of encoding and retrieval within verbal episodic memory.

Duration of Diabetes Predicts Aortic Pulse Wave Velocity and Vascular Events in Alström Syndrome.

CONTEXT: Alström syndrome is characterized by increased risk of cardiovascular disease from childhood. OBJECTIVE: To explore the association between risk factors for cardiovascular disease, aortic pulse wave velocity, and vascular events in Alström syndrome. DESIGN: Cross-sectional analyses with 5-year follow-up. SETTING: The UK NHS nationally commissioned specialist clinics for Alström syndrome. PATIENTS: Thirty-one Alström patients undertook vascular risk assessment, cardiac studies, and aortic pulse wave velocity measurement. Subsequent clinical outcomes were recorded. INTERVENTIONS: Insulin resistance was treated with lifestyle intervention and metformin, and diabetes with the addition of glitazones, glucagon-like peptide 1 agonists, and/or insulin. Thyroid and T deficiencies were corrected. Dyslipidemia was treated with statins and nicotinic acid derivatives. Cardiomyopathy was treated with standard therapy as required. MAIN OUTCOME MEASURES: The associations of age, gender, and risk factors for cardiovascular disease with aortic pulse wave velocity were assessed and correlated with the effects of reduction in left ventricular function. Vascular events were monitored for 5 years. RESULTS: Aortic pulse wave velocity was positively associated with the duration of diabetes (P = .001) and inversely with left ventricular ejection fraction (P = .036). Five of the cohort with cardiovascular events had higher aortic pulse wave velocity (P = .0247), and all had long duration of diabetes. CONCLUSIONS: Duration of diabetes predicted aortic pulse wave velocity in Alström syndrome, which in turn predicted cardiovascular events. This offers hope of secondary prevention because type 2 diabetes can be delayed or reversed by lifestyle interventions.

INVESTIGATING THE EFFICACY OF CLINICAL TRIAL MONITORING STRATEGIES: Design and Implementation of the Cluster Randomized START Monitoring Substudy.

BACKGROUND: Trial monitoring protects participant safety and study integrity. While monitors commonly go on-site to verify source data, there is little evidence that this practice is efficient or effective. An ongoing international HIV treatment trial (START) provides an opportunity to explore the usefulness of different monitoring approaches. METHODS: All START sites are centrally monitored and required to follow a local monitoring plan requiring specific quality assurance activities. Additionally, sites were randomized (1:1) to receive, or not receive, annual on-site monitoring. The study will determine if on-site monitoring increases the identification of major protocol deviations (eligibility or consent violations, improper study drug use, primary or serious event underreporting, data alteration or fraud). RESULTS: The START study completed enrollment in December 2013, with planned follow-up through December 2016. The monitoring study is ongoing at 196 sites in 34 countries. Results are expected when the START study concludes in December 2016.

Qualitative aspects of verbal fluency in HIV-associated dementia: a deficit in rule-guided lexical-semantic search processes?

HIV-associated dementia (HAD) is widely considered a "subcortical" dementia that involves a disruption of frontal-basal ganglia circuits. Deficits in verbal fluency are common in HAD; however, the cognitive underpinnings of these deficits are not well understood. To elucidate the cognitive mechanisms underlying the diminished verbal fluency output in HAD, we examined several qualitative aspects of letter fluency in 21 individuals with HAD, 51 nondemented persons with HIV infection (HIV+), and 30 healthy controls (HC) who were comparable for age, education, sex, ethnicity, and estimated premorbid verbal intelligence. The verbal fluency protocols were scored to obtain the total number of correct words, average phonemic cluster size, total number of switches between phonemic clusters, and the proportion of error responses (i.e., intrusions, perseverations, and variants). Consistent with prior research, HAD participants produced significantly fewer total correct words relative to the HC and nondemented HIV+ groups. The HAD group also demonstrated fewer switches and a higher proportion of response errors (especially intrusion errors), but no differences were observed in average cluster size. Findings are interpreted as reflecting a disruption of rule-guided lexical-semantic search strategies in HAD, perhaps mediated by prefrontal-striatal circuit dysfunction, rather than depleted lexical-semantic memory stores.

Nonacute (residual) neuropsychological effects of cannabis use: a qualitative analysis and systematic review.

Because there is a possibility that cannabis or cannabis-like molecules might be used as treatments for certain conditions in the future, it becomes important to consider the possible adverse effects of these compounds. In this paper, the authors review the evidence for persisting effects of nonacute cannabis use on the central nervous system, as reflected by alteration in neuropsychological performance. From the 40 articles that met criteria for inclusion in this review, the authors could not detect consistent evidence for persisting neuropsychological deficits in cannabis users; however, 22 of the 40 studies reported at least some subtle impairments. The inability to reach a firm conclusion results largely from methodological limitations inherent in most studies. These are considered in detail to inform future studies on (nonacute) consequences of cannabis consumption on cognitive abilities.