Ari D. Kalechstein

MDMA use and neurocognition: a meta-analytic review.

RationaleTo determine the association between MDMA misuse and neurocognition using meta-analysis.ObjectiveSeparate analyses were conducted based on two sets of inclusion/exclusion criteria. A relatively stringent set required that the subjects be matched on important moderator variables, whereas the other did not. The study participants’ performance in the following neurocognitive domains was reviewed: attention/concentration, verbal and nonverbal learning and memory, psychomotor speed and executive systems functioning.ResultsIn the 11 studies meeting the relatively stringent inclusion/exclusion criteria for this review, MDMA use was associated with neurocognitive deficits in each domain. Similarly, in the 23 studies meeting the relatively lenient inclusion/exclusion criteria for this review, MDMA use was associated with neurocognitive deficits in each domain. Small to medium effect sizes were generally observed. A comparison of the effect sizes across the two sets of analyses did not reveal significant differences.ConclusionsThe findings from this review reveal that MDMA use is associated with neurocognitive deficits. The implications of these findings are discussed.

Neurocognitive functioning is associated with employment status: a quantitative review.

Neurocognitive assessment is frequently used as a basis for making determinations regarding a person’s ability to work; yet, to our knowledge, a review of the association between neurocognition and employment status has not been conducted. For this review, we utilized meta-analysis to quantify objectively the association between eight neurocognitive domains and employment status. The meta-analysis revealed that performance in each domain was significantly associated with employment status, and that the associations were greatest for the following domains: intellectual functioning, executive functioning, and memory. These findings support the ecological validity of neurocognitive assessment.

Presence and persistence of psychotic symptoms in cocaine- versus methamphetamine-dependent participants.

The primary objective of this study was to compare and contrast psychotic symptoms reported by cocaine- and methamphetamine-dependent individuals. Participants included 27 cocaine-dependent and 25 methamphetamine-dependent males, as well as 15 cocaine-dependent and 18 methamphetamine-dependent females. After screening, participants were excluded if they met criteria for any Axis I diagnosis other than nicotine dependence, or methamphetamine or cocaine dependence (ie, participants had to use either methamphetamine or cocaine but were excluded if they met dependence criteria for both). The participants were administered the newly developed Psychotic Symptom Assessment Scale (PSAS), which assesses psychotic symptoms. A high proportion of both cocaine- and methamphetamine-dependent men and women reported delusions of paranoia and auditory hallucinations. However, during the abstinent and intoxicated conditions, methamphetamine-dependent men and women were more likely than cocaine-dependent men and women to report psychotic symptoms. Future studies will compare psychotic symptoms reported by non-dependent recreational stimulant users to stimulant-dependent individuals.

Relationship of iq to verbal learning and memory: Test and retest

The relationship between Wechsler Adult Intelligence Scale-Revised (WAIS-R) IQ and performance on measures of memory was examined in 64 adults tested twice at a 2-week interval. Repeated measures analyses of variance revealed that individuals with Low-Average WAIS-R Full Scale IQ scores performed significantly more poorly than did individuals with Average and High-Average Full Scale IQs on memory measures including the Wechsler Memory Scale-Revised (WMS-R) General Memory and Delayed Recall indices, as well as California Verbal Learning Test (CVLT) Total Words. Learning Slope, and Discriminability. Although all three groups demonstrated significant practice effects on each memory measure, group differences in performance persisted at retest. Multiple regression analyses revealed that WAIS-R factor scores Verbal Comprehension and Freedom from Distractibility accounted for up to 42% of the variance in WMS-R and CVLT indices. Moreover, WAIS-R performance at initial testing accounted for 22-41% of the variance in memory performance at retest. These results are discussed in the context of the construct stabilities of intelligence and memory, as well as the psychometric precision of the tests used to measure these constructs.

Modafinil administration improves working memory in methamphetamine-dependent individuals who demonstrate baseline impairment.

Modafinil improves working memory in healthy subjects and individuals diagnosed with schizophrenia and Attention Deficit/Hyperactivity Disorder, though the effects of modafinil have not been evaluated on working memory in methamphetamine-dependent subjects. This double-blind, placebo-controlled study evaluated whether a daily dose of 400 mg of modafinil, administered over three consecutive days, would enhance performance on a measure of working memory relative to test performance at baseline and following 3 days of placebo administration in 11 methamphetamine addicted, nontreatment-seeking volunteers. The results revealed that participants demonstrating relatively poor performance on the third day of a 3-day washout period (ie, at baseline), showed significant improvement on measures of working memory, but not on measures of episodic memory or information processing speed. In contrast, for participants demonstrating relatively high performance at baseline, modafinil administration did not affect test scores. The findings provide an initial indication that modafinil can reverse methamphetamine-associated impairments in working memory.

The effect of alcohol and tobacco consumption, and apolipoprotein E genotype, on the age of onset in Alzheimer's disease

This study examined the association between a history of heavy alcohol use and smoking, presence of the apolipoprotein‐E epsilon 4 allele (APOE ε4), and age of disease onset in a community dwelling sample of 685 Alzheimers disease (AD) patients spanning three ethnic groups.

Association between quantitative EEG and neurocognition in methamphetamine-dependent volunteers

OBJECTIVE Exposure to methamphetamine is associated with long-lasting reductions in markers for dopaminergic neurons in preclinical models and in humans. These changes may be associated with alterations in brain electrical activity and in cognition. METHODS The sample included 9 methamphetamine-dependent subjects and 10 non-drug-using volunteers. Methamphetamine-dependent subjects were hospitalized for 4 days to document abstinence; non-drug-using volunteers were studied as outpatients. EEGs were recorded in the eyes-closed resting state, and absolute EEG power in each frequency band (0.5-4 Hz, 4-8 Hz, 8-12 Hz, and 12-20 Hz) was measured using a fast Fourier transform. EEG power was log-transformed prior to analysis. Cognition was measured using computerized reaction time tasks. RESULTS Within the methamphetamine-dependent group only, increased theta quantitative EEG (QEEG) power correlated significantly with reaction time on tasks that were more difficult or that were degraded by fatigue. Increased theta QEEG power also correlated with reduced accuracy on a working memory task. CONCLUSIONS Increased QEEG power in the theta band is associated with worse performance on reaction time tasks in the methamphetamine-dependent sample but not in the non-drug-using volunteers. SIGNIFICANCE Methamphetamine dependence is associated with pathological alterations in brain electrical activity and in cognitive performance. QEEG appears to provide a sensitive measure of methamphetamine-associated alterations in brain function.

Acute, low-dose methamphetamine administration improves attention/information processing speed and working memory in methamphetamine-dependent individuals displaying poorer cognitive performance at baseline

Abstinent methamphetamine (Meth) dependent individuals demonstrate poorer performance on tests sensitive to attention/information processing speed, learning and memory, and working memory when compared to non-Meth dependent individuals. The poorer performance on these tests may contribute to the morbidity associated with Meth-dependence. In light of this, we sought to determine the effects of acute, low-dose Meth administration on attention, working memory, and verbal learning and memory in 19 non-treatment seeking, Meth-dependent individuals. Participants were predominantly male (89%), Caucasian (63%), and cigarette smokers (63%). Following a four day, drug-free washout period, participants were given a single-blind intravenous infusion of saline, followed the next day by 30 mg of Meth. A battery of neurocognitive tasks was administered before and after each infusion, and performance on measures of accuracy and reaction time were compared between conditions. While acute Meth exposure did not affect test performance for the entire sample, participants who demonstrated relatively poor performance on these tests at baseline, identified using a median split on each test, showed significant improvement on measures of attention/information processing speed and working memory when administered Meth. Improved performance was seen on the following measures of working memory: choice reaction time task (p≤0.04), a 1-back task (p≤0.01), and a 2-back task (p≤0.04). In addition, those participants demonstrating high neurocognitive performance at baseline experienced similar or decreased performance following Meth exposure. These findings suggest that acute administration of Meth may temporarily improve Meth-associated neurocognitive performance in those individuals experiencing lower cognitive performance at baseline. As a result, stimulants may serve as a successful treatment for improving cognitive functioning in those Meth-dependent individuals experiencing neurocognitive impairment.

A clinical comparison of two forms of the card sorting test

Abstract This study examined 67 older adults with dementia and 157 predominantly younger individuals with HIV-1 infection to determine the comparability of two commonly used forms of the Card Sorting Test: the traditional Wisconsin Card Sorting Test (WCST) and Nelsons Modified Card Sorting Test (MCST). Three frequently used clinical outcome measures were examined: the total number of categories achieved; the ratio of perseverative errors to total trials; and the number of failures to maintain set exhibited in the protocol. Our results indicated that when the number of perseverative errors relative to total trials is used as a clinical indicator, the WCST and MCST appear to be comparable. For the number of categories achieved, the forms appear comparable only in the non-elderly, non-demented sample. Finally, we did not find comparable results between the two forms for the number of failures to maintain set.

Short-term, low-dose varenicline administration enhances information processing speed in methamphetamine-dependent users

UNLABELLED Long-term, high-dose methamphetamine (METH) use is associated with decrements in neurocognition and, given the association between impaired neurocognition and poorer treatment outcomes in individuals dependent on alcohol and drugs, it is considered to be a neglected area of critical concern. The objective of this study was to determine whether varenicline, a partial agonist at α4β2- and a full agonist at α7-nicotinic acetylcholine receptors, enhances attention/information processing speed, episodic memory, and working memory in non-treatment seeking METH-dependent participants. Twenty-six participants were randomly assigned to receive oral placebo or oral varenicline (titrated up to 1 mg) over 5 days during three separate inpatient phases, and 17 completed each inpatient phase. Participants were predominately male (71%) and Caucasian (71%). Varenicline significantly improved reaction time on the n-back for visual stimuli (F(1,47)=5.369, p=0.025, η2=0.103), and a trend was observed for improvement in reaction time for auditory stimuli (F(1,47)=3.141, p=0.083, η2=0.063). For those study participants whose reaction time was in the lower half of the distribution at baseline, the effect was even more pronounced for auditory (F(1,22)=5.287, p=0.031, η2=0.194) and visual (F(1,22)=11.981, p=0.002, η2=0.353) stimuli relative to placebo. In contrast, varenicline did not modulate mean or maximum span of working memory or performance on tests of episodic memory or attention (ps>0.05). Given the potential importance of this finding, it should be replicated in a larger sample over a longer treatment period with a higher dose of varenicline (2 mg). TRIAL REGISTRATION clinicalTrials.gov Identifier NCT01571167.