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Context: Ecstasy (street name for [±]-3,4-methylenedioxymethamphetamine [MDMA]) use has been associated with cognitive deficits, especially in verbal memory. However, owing to the cross-sectional and retrospective nature of currently available studies, questions remain regarding the causal direction and clinical relevance of these findings.Objective: To examine the relationship between Ecstasy use and subsequent cognitive performance.

Although 3,4-methylenedioxymethamphetamine (MDMA or ecstasy) has been shown to damage brain serotonin (5-HT) neurons in animals and possibly humans, little is known about the long-term consequences of MDMA-induced 5-HT neurotoxic lesions on functions in which 5-HT is involved, such as cognitive function. Because 5-HT transporters play a key element in the regulation of synaptic 5-HT transmission it may be important to control for the potential covariance effect of a polymorphism in the 5-HT transporter promoter gene region (5-HTTLPR) when studying the effects of MDMA as well as cognitive functioning. The aim of the study was to investigate the effects of moderate and heavy MDMA use on cognitive function, as well as the effects of long-term abstention from MDMA, in subjects genotyped for 5-HTTLPR. A second aim of the study was to determine whether these effects differ for females and males. Fifteen moderate MDMA users (<55 lifetime tablets), 22 heavy MDMA+ users (>55 lifetime tablets), 16 ex-MDMA+ users (last tablet > 1 year ago) and 13 controls were compared on a battery of neuropsychological tests. DNA from peripheral nuclear blood cells was genotyped for 5-HTTLPR using standard polymerase chain reaction methods.A significant group effect was observed only on memory function tasks (p = 0.04) but not on reaction times (p = 0.61) or attention/executive functioning (p = 0.59). Heavy and ex-MDMA+ users performed significantly poorer on memory tasks than controls. In contrast, no evidence of memory impairment was observed in moderate MDMA users. No significant effect of 5-HTTLPR or gender was observed. While the use of MDMA in quantities that may be considered "moderate" is not associated with impaired memory functioning, heavy use of MDMA use may lead to long lasting memory impairments. No effect of 5-HTTLPR or gender on memory function or MDMA use was observed.

Previous studies have suggested toxic effects of recreational ecstasy use on the serotonin system of the brain. However, it cannot be excluded that observed differences between users and non-users are the cause rather than the consequence of ecstasy use. As part of the Netherlands XTC Toxicity (NeXT) study, we prospectively assessed sustained effects of ecstasy use on the brain in novel ecstasy users using repeated measurements with a combination of different neuroimaging parameters of neurotoxicity. At baseline, 188 ecstasy-naive volunteers with high probability of first ecstasy use were examined. After a mean period of 17 months follow-up, neuroimaging was repeated in 59 incident ecstasy users and 56 matched persistent ecstasy-naives and their outcomes were compared. Neuroimaging included [(123)I]beta-carbomethoxy-3beta-(4-iodophenyl)tropane (CIT) SPECT to measure serotonin transporter densities as indicators of serotonergic function; (1)H-MR spectroscopy ((1)H-MRS) to measure brain metabolites as indicators of neuronal damage; diffusion tensor imaging (DTI) to measure the apparent diffusion coefficient and fractional anisotropy (FA) of the diffusional motion of water molecules in the brain as indicators of axonal integrity; and perfusion weighted imaging (PWI) to measure regional relative cerebral blood volume (rrCBV) which indicates brain perfusion. With this approach, both structural ((1)H-MRS and DTI) and functional ([(123)I]beta-CIT SPECT and PWI) aspects of neurotoxicity were combined. Compared to persistent ecstasy-naives, novel low-dose ecstasy users (mean 6.0, median 2.0 tablets) showed decreased rrCBV in the globus pallidus and putamen; decreased FA in thalamus and frontoparietal white matter; increased FA in globus pallidus; and increased apparent diffusion coefficient in the thalamus. No changes in serotonin transporter densities and brain metabolites were observed. These findings suggest sustained effects of ecstasy on brain microvasculature, white matter maturation and possibly axonal damage due to low dosages of ecstasy. Although we do not know yet whether these effects are reversible or not, we cannot exclude that ecstasy even in low doses is neurotoxic to the brain.

These findings strongly suggest a specific sustained negative effect of ecstasy use on verbal memory. The clinical relevance is not immediately clear, because test performance generally remained within the normal range. However the magnitude of the effect is substantial (d>0.5) and long-term consequences cannot be excluded.

Although there are indications that ecstasy users have higher levels of depression, impulsivity, and sensation seeking, it is unknown whether these are consequences of ecstasy use or predisposing factors for starting ecstasy use. We prospectively assessed the predictive value of depression, impulsivity, and sensation seeking on future first time ecstasy use. We also assessed whether depression, impulsivity, and sensation seeking had changed after first ecstasy use. Depression, impulsivity, and sensation seeking were assessed using self-report questionnaires in 188 ecstasy-naive volunteers with high probability for future ecstasy use. After a mean follow-up of 17 months, measurements were repeated in 59 incident ecstasy users (mean 6.0 tablets) and 61 matched persistent ecstasy-naive volunteers. Only experience seeking (subscale of the sensation seeking scale) predicted future ecstasy use (OR -- 1.05, 95% CI 1.00 to 1.10), but after adjustment for potential confounders this was not significant anymore. At follow-up, significant effects of ecstasy use on the general and the disinhibition subscale of the sensation seeking scale were observed (after adjustment for potential confounders: regression coefficient B 0.51, 95% CI 0.20 to 0.83 and B -- 3.25, 95% CI 1.74 to 4.76, respectively). These data indicate that depression, impulsivity, and sensation seeking do not predict first time ecstasy use in a population of young adults with the intention to start using ecstasy and that low level ecstasy use does not seem to cause depression or impulsivity. However, low level ecstasy use may increase (certain aspects of) sensation seeking.

Background: Diagnosing dementia in elderly immigrants is often difficult due to language and cultural barriers, low education, and illiteracy. We compared the diagnostic accuracy of the Rowland Universal Dementia Assessment Scale (RUDAS) to that of the Mini Mental State Examination (MMSE). Methods: A total of 144 patients (42 with intact cognition, 44 with mild cognitive impairment [MCI], and 58 with dementia) were administered both instruments and were diagnosed by specialists blinded for MMSE and RUDAS results. Results: Areas under the curve for discriminating intact cognition from MCI and dementia were comparable for RUDAS (0.81; 95% confidence interval 0.74–0.88) and MMSE (0.75; 95% confidence interval 0.69–0.85). Education and literacy were not correlated with the RUDAS but had a medium-large correlation with the MMSE (rho = 0.39). Conclusions: The study provides additional evidence for the usefulness of the RUDAS in a highly illiterate, culturally diverse geriatric outpatient population.