The effects of atorvastatin on emotional processing, reward learning, verbal memory and inflammation in healthy volunteers: An experimental medicine study.

BACKGROUND: Growing evidence from clinical trials and epidemiological studies suggests that statins can have clinically significant antidepressant effects, potentially related to anti-inflammatory action on several neurobiological structures. However, the underlying neuropsychological mechanisms of these effects remain unexplored. AIMS: In this experimental medicine trial, we investigated the 7-day effects of the lipophilic statin, atorvastatin on a battery of neuropsychological tests and inflammation in healthy volunteers. METHODS: Fifty healthy volunteers were randomised to either 7 days of atorvastatin 20 mg or placebo in a double-blind design. Participants were assessed with psychological questionnaires and a battery of well-validated behavioural tasks assessing emotional processing, which is sensitive to putative antidepressant effects, reward learning and verbal memory, as well as the inflammatory marker, C-reactive protein. RESULTS: Compared to placebo, 7-day atorvastatin increased the recognition (p = 0.006), discriminability (p = 0.03) and misclassifications (p = 0.04) of fearful facial expression, independently from subjective states of mood and anxiety, and C-reactive protein levels. Otherwise, atorvastatin did not significantly affect any other psychological and behavioural measure, nor peripheral C-reactive protein. CONCLUSIONS: Our results reveal for the first time the early influence of atorvastatin on emotional cognition by increasing the processing of anxiety-related stimuli (i.e. increased recognition, discriminability and misclassifications of fearful facial expression) in healthy volunteers, in the absence of more general effects on negative affective bias. Further studies exploring the effects of statins in depressed patients, especially with raised inflammatory markers, may clarify this finding and inform future clinical trials.

Smoking is associated with impaired verbal learning and memory performance in women more than men.

Vascular contributions to cognitive impairment and dementia (VCID) include structural and functional blood vessel injuries linked to poor neurocognitive outcomes. Smoking might indirectly increase the likelihood of cognitive impairment by exacerbating vascular disease risks. Sex disparities in VCID have been reported, however, few studies have assessed the sex-specific relationships between smoking and memory performance and with contradictory results. We investigated the associations between sex, smoking, and cardiovascular disease with verbal learning and memory function. Using MindCrowd, an observational web-based cohort of ~ 70,000 people aged 18-85, we investigated whether sex modifies the relationship between smoking and cardiovascular disease with verbal memory performance. We found significant interactions in that smoking is associated with verbal learning performance more in women and cardiovascular disease more in men across a wide age range. These results suggest that smoking and cardiovascular disease may impact verbal learning and memory throughout adulthood differently for men and women.

Association of Naturalistic Administration of Cannabis Flower and Concentrates With Intoxication and Impairment.

Importance: The rapidly growing legal cannabis market includes new and highly potent products, the effects of which, to our knowledge, have not previously been examined in biobehavioral research studies because of federal restrictions on cannabis research. Objective: To use federally compatible, observational methods to study high-∆9-tetrahydrocannabinol (THC) legal market forms of cannabis. Design, Setting, and Participants: In this cohort study with a between-groups design that was conducted in a community and university setting, cannabis flower users and concentrate users were randomly assigned to higher- vs lower-THC products within user groups. Participants completed a baseline and an experimental mobile laboratory assessment that included 3 points: before, immediately after, and 1 hour after ad libitum legal market flower and concentrate use. Of the 133 individuals enrolled and assessed, 55 regular flower cannabis users (41.4%) and 66 regular concentrate cannabis users (49.6%) complied with the study's cannabis use instructions and had complete data across primary outcomes. Exposures: Flower users were randomly assigned to use either 16% or 24% THC flower and concentrate users were randomly assigned to use either 70% or 90% THC concentrate that they purchased from a dispensary. Main Outcomes and Measures: Primary outcome measures included plasma cannabinoids, subjective drug intoxication, and neurobehavioral tasks testing attention, memory, inhibitory control, and balance. Results: A total of 121 participants completed the study for analysis: 55 flower users (mean [SD] age, 28.8 [8.1] years; 25 women [46%]) and 66 concentrate users (mean [SD] age, 28.3 [10.4] years; 30 women [45%]). Concentrate users compared with flower users exhibited higher plasma THC levels and 11-hydroxyΔ9-THC (THC's active metabolite) across all points. After ad libitum cannabis administration, mean plasma THC levels were 0.32 (SE = 0.43) µg/mL in concentrate users (to convert to millimoles per liter, multiply by 3.18) and 0.14 (SE = 0.16) µg/mL in flower users. Most neurobehavioral measures were not altered by short-term cannabis consumption. However, delayed verbal memory (F1,203 = 32.31; P < .001) and balance function (F1,203 = 18.88; P < .001) were impaired after use. Differing outcomes for the type of product (flower vs concentrate) or potency within products were not observed. Conclusions and Relevance: This study provides information about the association of pharmacological and neurobehavioral outcomes with legal market cannabis. Short-term use of concentrates was associated with higher levels of THC exposure. Across forms of cannabis and potencies, users' domains of verbal memory and proprioception-focused postural stability were primarily associated with THC administration.

Impact of 2 Weeks of Monitored Abstinence on Cognition in Adolescent and Young Adult Cannabis Users.

OBJECTIVES: Previous research suggests recovery from cannabis-related deficits in verbal learning and memory functioning after periods of cannabis abstinence in adolescents. Here, we examine how cannabis cessation affects cognitive performance over 2 weeks of monitored abstinence compared to controls in adolescents and young adults. METHODS: Seventy-four participants (35 cannabis users) aged 16-26 ceased all cannabis, alcohol, and other illicit substance consumption for a 2-week period; abstinence was monitored via weekly urinalysis, breath, and sweat patch testing. Starting at baseline, participants completed weekly abbreviated neuropsychological batteries. Measures included tests of attention, inhibition, verbal working memory, and learning. Repeated measures assessed within and between subject effects for time and group status, while controlling for past year alcohol and nicotine use. RESULTS: Cannabis users showed increased performance compared to controls on sustained attention tasks after 2 weeks of cannabis use. CONCLUSIONS: Deficits in attention, but not verbal learning and memory, recovered after 2 weeks of monitored abstinence. This differs from previous literature, suggesting that other cognitive domains may show signs of recovery after periods of cannabis cessation in adolescents and young adults.

Prevalence and factors of verbal learning and memory dysfunction in patients with epilepsy - A single centre study.

The objective of this study is to determine prevalence and factors leading to verbal learning and memory dysfunction among patients with epilepsy. A total of 211 subjects were recruited. Their verbal memory was assessed by Rey's Auditory Verbal Learning Test (RAVLT). This test was further subdivided into four major spheres for analysis, namely the verbal learning, interference list, immediate memory and delayed memory. All data collected were analyzed using Statistical Package for Social Sciences. Among the 211 patients, 55% (n = 116) had focal seizures and the remaining 45% (n = 95) had generalized seizures. Prevalence of verbal learning and memory impairment was high at 39.97% overall, and found most commonly in patients with focal impaired awareness seizures. Verbal learning and immediate memory dysfunction were significantly lower in focal impaired awareness group compared to others. Age more than 50 years, exposure to three or more antiepileptic drugs and use of carbamazepine more than 1000 mg a day were the predictors in poor verbal memory outcome. No statistical difference was observed in the mean RAVLT scores among the gender and hand dominance groups. Between patients with and without electroencephalogram changes as well as brain magnetic resonance imaging changes, the mean RAVLT scores showed no statistically significant difference. Verbal learning and memory impairment is prevalent among the epilepsy patients. The consequences of the memory impairment can be as debilitating as the seizure control. RAVLT is a reliable and practical test in the clinical setting.

Improvement in verbal learning over the first year of antipsychotic treatment is associated with serum HDL levels in a cohort of first episode psychosis patients.

To investigate whether changes in serum lipids are associated with cognitive performance in first episode psychosis (FEP) patients during their first year of antipsychotic drug treatment. One hundred and thirty-two antipsychotic-treated FEP patients were included through the TOP study along with 83 age- and gender-matched healthy controls (HC). Information regarding cognitive performance, psychotic symptoms, lifestyle, body mass index, serum lipids [total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, and triglycerides] and antipsychotic treatment was obtained at baseline and after 1 year. The cognitive test battery is comprised of assessments for verbal learning, processing speed, working memory, verbal fluency, and inhibition. Mixed-effects models were used to study the relationship between changes over time in serum lipids and cognitive domains, controlling for potential confounders. There was a significant group by HDL interaction effect for verbal learning (F = 11.12, p = 0.001), where an increase in HDL levels was associated with improvement in verbal learning in FEP patients but not in HC. Practice effects, lifestyle, and psychotic symptoms did not significantly affect this relationship. Antipsychotic-treated FEP patients who increased in HDL levels during the first year of follow-up exhibited better verbal learning capacity. Further investigations are needed to clarify the underlying mechanisms.

Acute and Long-term Memantine Add-on Treatment to Risperidone Improves Cognitive Dysfunction in Patients with Acute and Chronic Schizophrenia.

INTRODUCTION: Patients with schizophrenia are mainly characterized by negative symptoms and cognitive dysfunction. In this proof-of-concept study we tested effects on cognition and negative symptoms of a 6- or 24-week memantine add-on treatment to risperidone in patients with acute or chronic schizophrenia. MATERIALS AND METHODS: Patients with an acute episode of schizophrenia (n=11) and predominating positive symptoms were randomized to a 6-week add-on treatment with memantine (10 mg twice a day) versus placebo and patients with chronic schizophrenia (n=13) and negative symptoms were randomized to a 24-week add-on treatment with memantine (10 mg twice a day) versus placebo. All patients received antipsychotic medication with risperidone (2-8 mg/day). Psychopathological changes were assessed with the Positive and Negative Syndrome Scale (PANSS) at baseline and after 2, 4, 6, 12, and 24 weeks. Cognitive function was measured at baseline, after 6 weeks, and 24 weeks. RESULTS: Patients with acute schizophrenia who received add-on treatment with memantine showed a significantly higher performance in attention intensity (p=0.043), problem-solving (p=0.043), verbal learning (p=0.050), and flexibility (p=0.049). Patients with chronic schizophrenia showed a significantly higher immediate memory in the memantine group compared to the placebo group (p=0.033) and a significantly greater reduction of the PANSS sum score if compared to the placebo group. DISCUSSIONS: Our study gives further evidence that memantine add-on treatment to risperidone may have neuroprotective effects and improve cognitive function in patients with schizophrenia. ClinicalTrials.gov Number: NCT00148590 and NCT00148616.

Biperiden Selectively Impairs Verbal Episodic Memory in a Dose- and Time-Dependent Manner in Healthy Subjects.

PURPOSE/BACKGROUND: Biperiden is a muscarinic antagonist that produces memory impairments without impairing attention or motor functions in healthy subjects. It has been suggested that a biperiden-induced memory deficit could model age- and dementia-related memory impairments. The goal of the current study was to determine the dose- and time-dependent effects of biperiden on cognition in healthy volunteers. METHODS/PROCEDURES: Twenty-one healthy volunteers participated in a placebo-controlled, 3-way, crossover study. After a baseline test, cognitive performance was tested at 3 time points after a single dose of biperiden 2 or 4 mg, or placebo. Episodic memory was measured using a 15-word verbal learning task (VLT). Furthermore, n-back tasks, a sustained attention to response task and a reaction time task were used, as well as subjective alertness and a side effects questionnaire. In addition, blood serum values and physiological measures were taken. FINDINGS/RESULTS: Biperiden decreased the number of words recalled in immediate and delayed recall of the VLT 90 minutes after drug intake. A dose-dependent impairment was found for the delayed recall, whereas the immediate recall was equally impaired by the 2 doses. Biperiden did not affect the performance on the VLT 4 hours after administration. Performance in the n-back task and the sustained attention to response task were not affected by biperiden at any time point. Both doses were well tolerated as reported side effects were mild at Tmax and were minimal at the other time points. IMPLICATIONS/CONCLUSIONS: Biperiden exerts effects on episodic memory without negatively affecting other cognitive performance and behavioral measures that were assessed in this study. The data provide further evidence that biperiden has selective effects on cognition, even after a high dose.

A role for 5-HT4 receptors in human learning and memory.

BACKGROUND: 5-HT4 receptor stimulation has pro-cognitive and antidepressant-like effects in animal experimental studies; however, this pharmacological approach has not yet been tested in humans. Here we used the 5-HT4 receptor partial agonist prucalopride to assess the translatability of these effects and characterise, for the first time, the consequences of 5-HT4 receptor activation on human cognition and emotion. METHODS: Forty one healthy volunteers were randomised, double-blind, to a single dose of prucalopride (1 mg) or placebo in a parallel group design. They completed a battery of cognitive tests measuring learning and memory, emotional processing and reward sensitivity. RESULTS: Prucalopride increased recall of words in a verbal learning task, increased the accuracy of recall and recognition of words in an incidental emotional memory task and increased the probability of choosing a symbol associated with a high likelihood of reward or absence of loss in a probabilistic instrumental learning task. Thus acute prucalopride produced pro-cognitive effects in healthy volunteers across three separate tasks. CONCLUSIONS: These findings are a translation of the memory enhancing effects of 5-HT4 receptor agonism seen in animal studies, and lend weight to the idea that the 5-HT4 receptor could be an innovative target for the treatment of cognitive deficits associated with depression and other neuropsychiatric disorders. Contrary to the effects reported in animal models, prucalopride did not reveal an antidepressant profile in human measures of emotional processing.

Verbal memory predicts treatment outcome in syndromal anxious depression: An iSPOT-D report.

BACKGROUND: Major Depressive Disorder (MDD), anxiety disorders, and high levels of anxious symptoms are associated with impaired cognitive functioning. However, little is known of how cognitive functioning is impaired in people with anxious depression. Here, we compared cognitive functioning between people with anxious depression, non-anxious depression, and healthy controls. We also tested whether anxious depression moderated the relationship between cognitive functioning and treatment outcome. METHODS: 1008 adults with MDD and 336 healthy controls completed IntegNeuro: a computerized cognitive functioning test battery. Participants were then randomised to one of three antidepressants and reassessed at 8 weeks using the 17-item Hamilton Depression Rating Scale (HRSD17) and the 16-Item Quick Inventory of Depressive Symptomatology-Self-Rated for remission and response. Syndromal anxious depression was defined as MDD with a comorbid anxiety disorder. HRSD anxious depression was defined as MDD with a comorbid HRSD17 anxiety/somatisation factor score ≥ 7. RESULTS: Syndromal anxious depression was associated with better psychomotor functioning and poorer working memory, cognitive flexibility and information processing speed compared to their non-anxious counterparts. HRSD anxious depression was associated with better psychomotor functioning compared to their non-anxious counterparts. Syndromal anxious depression moderated the relationship between verbal memory and treatment outcome. In people with syndromal anxious depression, poorer baseline verbal memory predicted poorer treatment outcome. LIMITATIONS: As DSM-IV criteria was used, the DSM-5 anxious distress specifier characterisation of anxious depression could not be assessed CONCLUSIONS: Syndromal anxious depression is characterised by impaired executive functions and moderates the relationship between verbal memory functioning and treatment outcome.

Working Memory Capacity Is Negatively Associated with Memory Load Modulation of Alpha Oscillations in Retention of Verbal Working Memory.

Working memory capacity (WMC) measures the amount of information that can be maintained online in the face of distraction. Past work has shown that the efficiency with which the frontostriatal circuit filters out task-irrelevant distracting information is positively correlated with WMC. Recent work has demonstrated a role of posterior alpha oscillations (8-13 Hz) in providing a sensory gating mechanism. We investigated the relationship between memory load modulation of alpha power and WMC in two verbal working memory experiments. In both experiments, we found that posterior alpha power increased with memory load during memory, in agreement with previous reports. Across individuals, the degree of alpha power modulation by memory load was negatively associated with WMC, namely, the higher the WMC, the less alpha power was modulated by memory load. After the administration of topiramate, a drug known to affect alpha oscillations and have a negative impact on working memory function, the negative correlation between memory load modulation of alpha power and WMC was no longer statistically significant but still somewhat detectable. These results suggest that (1) individuals with low WMC demonstrate stronger alpha power modulation by memory load, reflecting possibly an increased reliance on sensory gating to suppress task-irrelevant information in these individuals, in contrast to their high WMC counterparts who rely more on frontal areas to perform this function and (2) this negative association between memory load modulation of alpha oscillations and WMC is vulnerable to drug-related cognitive disruption.

Repeated intravenous infusions of ketamine: Neurocognition in patients with anxious and nonanxious treatment-resistant depression.

BACKGROUND: Recent studies have suggested that neurocognition is changed after repeated infusions of ketamine in patients with treatment-resistant depression (TRD). The objective of this study was to investigate whether differences existed in the neurocognitive effect of six ketamine infusions in patients with anxious and nonanxious TRD and to determine the association between baseline neurocognition and changes in symptoms after the infusions. METHOD: Patients with anxious (n = 30) and nonanxious TRD (n = 20) received six intravenous infusions of ketamine (0.5 mg/kg over 40 min) over 12 days. Speed of processing (SOP), working memory (WM), verbal learning and memory (VBM), visual learning and memory (VSM) and the severity of depressive and anxious symptoms were assessed at baseline, one day after the last infusion (day 13) and two weeks after the completion of the serial infusions (day 26). A linear mixed model was used to determine whether the neurocognitive changes differed between the two groups. Pearson correlation analysis was used to determine the relationship between baseline neurocognition and the changes in the symptomatic scores. RESULTS: Patients with anxious TRD had significant increases in SOP on day 13 and day 26 (both p < 0.001), and in VBM on day 13 (p = 0.028). However, no significant increase in any neurocognitive domain was found in patients with nonanxious TRD. Faster SOP at baseline was associated with greater improvement of anxious symptoms in patients with anxious TRD, and better VSM at baseline was associated with greater improvement of depressive symptoms in patients with nonanxious TRD. LIMITATION: The major limitation of this study is the open-label design. CONCLUSION: After six ketamine infusions, neurocognitive improvement was observed in patients with anxious TRD but not in patients with nonanxious TRD.

False memory formation in cannabis users: a field study.

RATIONALE: Cannabis use is widespread and has previously been associated with memory impairments. However, the role of cannabis in relation to false memory production, i.e., memories of events that were not experienced, is less well-understood. OBJECTIVE: The aim of the current field study was to examine the impact of cannabis use on false memory production. METHODS: The Deese/Roediger-McDermott (DRM) paradigm was used to induce false memories. In this paradigm, participants study word lists that are associatively related to a non-presented word, termed the critical lure. In a later memory test, true recognition rates and false alarm rates toward critical lures and unrelated items are assessed. Memory performance was compared between three groups: regular cannabis consumers who were acutely intoxicated (n = 53), regular cannabis consumers who were sober (n = 50), and cannabis-naïve controls (n = 53). The participants were approached in Dutch coffee shops (cannabis outlets) and cafes and asked to participate in our study. After collecting general information on their cannabis use, they were subjected to the DRM procedure. RESULTS: Although false memory rates for critical lures did not statistically differ between groups, both intoxicated and sober cannabis consumers falsely recognized more unrelated items than control participants. Also, individuals without a history of cannabis use demonstrated higher memory accuracy compared with the intoxicated group. CONCLUSION: It is concluded that cannabis intoxication and history of cannabis use induce a liberal response criterion for newly presented words for which the level of association with previously learned words is low and uncertainty is high.

Cognitive function in aging cocaine smokers.

BACKGROUND: Little is known about the functional status of older drug users, who may pose challenges to public health systems in coming years. Here, we assessed cognitive function in aging cocaine smokers compared to demographically matched controls. METHODS: A total of 22 non-treatment-seeking aging (50-60 years old) cocaine smokers (⩾twice/week; ⩾15 years of weekly use) and 19 controls completed a comprehensive cognitive battery. Controls with cannabis, tobacco, and alcohol use were included to better match the cocaine users. All cocaine users, and current cannabis- or alcohol-using controls, completed testing after 4 drug-free inpatient days to better control for acute and residual drug effects. RESULTS: Cocaine users (52.9 ± 2.5 years old, four female; cocaine use 3.9 ± 1.4 days/week) and controls (52.7 ± 2.6 years old, four female) were well matched demographically, but cocaine users reported a more extensive substance use profile. Cocaine users showed marginally worse verbal learning than controls, recalling on average one word fewer across immediate and delayed word recall trials. Their performance was intact relative to controls across all other measures of cognitive function. Bayesian analysis indicated the absence of group differences was not due to power limitations. CONCLUSION: These data suggest that aging, long-term cocaine users have similar cognitive functioning to appropriately matched controls when tested under drug-free conditions, with only marginal decreases in verbal learning. Findings, although reassuring with regard to broad cognitive capacities in aging cocaine smokers, suggest that future investigations of cognitive function in aging drug users are warranted.

Marijuana use associated with worse verbal learning and delayed recall in a sample of young adults.

BACKGROUND: There is concern about the cognitive consequences of marijuana consumption. AIM: To assess the influence of current and past marijuana use and frequency on verbal learning and memory in a sample of adults aged 21 years old. MATERIAL AND METHODS: Marijuana use was assessed using a clinician administered interview in 654 participants (56% females), who reported frequency of use, age of first use and whether its use led to problems in their lives. The CogState International Shopping List was administered to assess learning and memory. RESULTS: Seventy percent reported ever using marijuana, 46% consuming during the past year and 27% during the past 30 days. The latter scored significantly lower on delayed recall. Current and frequent use were significantly associated with lower accuracy in verbal learning and memory. CONCLUSIONS: In this cohort of adults aged 21 years old, marijuana use was prevalent and related to worse verbal memory.

Verbal learning deficits associated with increased anticholinergic burden are attenuated with targeted cognitive training in treatment refractory schizophrenia patients.

Targeted cognitive training (TCT) has been reported to improve verbal learning deficits in patients with schizophrenia (SZ). Despite positive findings, it is not clear whether demographic factors and clinical characteristics contribute to the success of TCT on an individual basis. Medication-associated anticholinergic burden has been shown to impact TCT-associated verbal learning gains in SZ outpatients, but the role of anticholinergic medication burden on TCT gains in treatment refractory SZ patients has not been described. In this study, SZ patients mandated to a locked residential rehabilitation center were randomized to treatment as usual (TAU; n=22) or a course of TAU augmented with TCT (n=24). Anticholinergic medication burden was calculated from medication data at baseline and follow-up using the Anticholinergic Cognitive Burden (ACB) Scale. MATRICS Consensus Cognitive Battery Verbal Learning domain scores were used as the primary outcome variable. The TAU and TCT groups were matched in ACB at baseline and follow-up. While baseline ACB was not associated with verbal learning in either group, increases in ACB over the course of the study were significantly associated with deterioration of verbal learning in the TAU group (r=-0.51, p=0.02). This was not seen in subjects randomized to TCT (r=-0.13, p=0.62). Our results suggest that TCT may blunt anticholinergic medication burden associated reduction in verbal learning in severely disabled SZ inpatients.

Marijuana use associated with worse verbal learning and delayed recall in a sample of young adults / El consumo de marihuana se asocia a una menor capacidad de aprendizaje verbal y memoria tardía en adultos jóvenes

ABSTRACT Background: There is concern about the cognitive consequences of marijuana consumption. Aim: To assess the influence of current and past marijuana use and frequency on verbal learning and memory in a sample of adults aged 21 years old. Material and Methods: Marijuana use was assessed using a clinician administered interview in 654 participants (56% females), who reported frequency of use, age of first use and whether its use led to problems in their lives. The CogState International Shopping List was administered to assess learning and memory. Results: Seventy percent reported ever using marijuana, 46% consuming during the past year and 27% during the past 30 days. The latter scored significantly lower on delayed recall. Current and frequent use were significantly associated with lower accuracy in verbal learning and memory. Conclusions: In this cohort of adults aged 21 years old, marijuana use was prevalent and related to worse verbal memory.

Antecedentes: Existe preocupación acerca de los efectos cognitivos del consumo de marihuana. Objetivo: Estudiar el efecto de consumo de marihuana presente o pasado en la capacidad de aprendizaje verbal y memoria en una muestra de adultos de 21 años. Material y Métodos: El consumo de marihuana fue evaluado mediante una entrevista médica en 654 adultos de 21 años (56% mujeres), quienes informaron acerca de la frecuencia de consumo, edad de comienzo y si el consumo les ha causado problemas en sus vidas. Se les administró el Cogstate International Shopping List para evaluar aprendizaje y memoria. Resultados: El 70% informó haber consumido marihuana alguna vez, 46% la usó durante el último año y el 27% en los últimos 30 días. Estos últimos tuvieron un menor puntaje en memoria tardía. El consumo actual y frecuente se asoció a una menor precisión en la capacidad de aprendizaje verbal y memoria. Conclusiones: En esta cohorte de adultos de 21 años, el consumo de marihuana fue prevalente y relacionado a una menor memoria verbal.

No interaction between rivastigmine and citalopram on memory and novelty processing in healthy human volunteers.

BACKGROUND: Animal literature suggests an interaction between acetylcholine and serotonin on cognitive functions. AIMS: The aim of the current study was to assess whether both neurotransmitters interact during memory and novelty processing in humans. METHODS: We tested the interaction between acetylcholine and serotonin on cognitive functions in healthy volunteers by means of treatment with rivastigmine and citalopram, respectively. RESULTS: The main result of the study showed that during the verbal learning task participants significantly recalled fewer words after citalopram treatment than after rivastigmine or placebo during both the immediate and delayed recall tasks. Rivastigmine was not able to reverse the impairing effect of citalopram. CONCLUSIONS: This finding is in line with previous studies in which we manipulated acetylcholine and serotonin in different manners. Taken together, these studies in humans do not support the notion from animal studies that these two neurotransmitters interact on cognitive functions.

Production Effect in Adults With ADHD With and Without Methylphenidate (MPH): Vocalization Improves Verbal Learning.

OBJECTIVES: Reading aloud (vocal production) enhances memory relative to reading silently, the Production Effect (PE) in memory. Thus, vocalization has been suggested as a mnemonic device. The current study tested the PE in a sample of adults with ADHD and in a control sample, evaluating verbal learning. METHODS: Twenty adults with ADHD and 21 controls learned a list of words, half by reading aloud and half by reading silently. Free recall test followed. The participants with ADHD performed the task twice (in two different sessions in a counterbalanced order), before self-administration of a single dose of methylphenidate (MPH) and 60-min after dosage. RESULTS: PEs were found for all groups. Memory was better for the controls than for the ADHD group (with or without MPH). In the ADHD group, recall rates and the PE were higher with than without MPH. CONCLUSIONS: These results suggest that vocalization yields a larger memory gain with MPH. Possibly, MPH enables the ADHD participants to better shift their attention to the aloud words, enhancing their retrieval rates. Theoretically, these findings stress the role of attention in the PE. (JINS, 2019, 25, 230-235).

Benzodiazepine Use Disorder and Cognitive Impairment in Older Patients: A Six-Month-Follow-Up Study in an Outpatient Unit in Barcelona.

OBJECTIVE: Adverse health effects including cognitive impairment have been described in older adults with benzodiazepine misuse, although the literature about this issue is scarce. The present study aimed to assess cognitive decline in older adults with benzodiazepine use disorder and changes in cognitive state at the 6-month follow-up, as well as whether patients achieved abstinence. METHOD: A 6-month follow-up longitudinal study was conducted in an outpatient drug center in Barcelona in a sample of older adults (≥65 years old) who had benzodiazepine use disorder. The sample was compared with an equivalent control group. A neuropsychological protocol was performed at baseline and after 6-month follow-up covering the most important cognitive domains. RESULTS: The final sample comprised 33 patients with an average age of 73.5 years. At baseline, patients presented impairment in several domains compared with the control group: visual immediate recall (p < .001), visual delayed recall (p < .001), copy (p < .001), working memory (p < .003), immediate verbal learning (p < .002), total words learned (p < .009), set switching (p < .001), verbal fluency (p < .007), speed processing (p < .002), solving problems (p < .006), nonverbal fluency (p < .004), and sustained attention in all three areas omissions (p < .001), variability (p < .001), and perseverance (p < .005). At 6-month follow-up, patients achieving abstinence showed improvement compared with patients in active consumption in visual delayed recall (p < .006), total words learned (p < .010), and verbal fluency (p < .013). CONCLUSIONS: Benzodiazepine misuse in older adults may produce negative effects on cognitive skills. Recovery of some of these cognitive deficits may be possible with benzodiazepine abstinence.