BACKGROUND: The misuse of prescription psychostimulants (PPs) is growing among medical students, who are subject to high levels of stress, not least because of a demanding and competitive educational environment.
OBJECTIVE: To investigate this phenomenon among medical students in Belgium to identify misuse risk factors.
METHODS: We conducted a cross-sectional study using an online questionnaire from 7 march 2023 to 3 April 2023. A semi-quantitative questionnaire based on a literature review and consultation with experts was drawn up, including the Perceived Stress Scale (PSS-10) and the Big Five Inventory (BFI-10). The questionnaire was administered to 323 final-year medical students (61.9% of whom responded) and comparatively to 325 second-to-last-year students and 205 first-year students (response rate was 36.9% and 18.5%, respectively). Descriptive and bivariate analyses were performed with Jamovi (version 2.3.21).
RESULTS: Use of PPs increased over the years. In the final year, 12.6% reported that they had already used PPs to improve their cognitive performance, and 3.6% were currently using them. Various risk factors were associated with the misuse of PPs, including lack of consciousness, sensation-seeking, other substances use, high stress levels, social influence, curriculum high standards perception, and lack of ethical concern regarding the substance use.
CONCLUSIONS: This study showed that more than one in ten final-year students have used PPs at least once during their studies, which can be explained mainly by challenging medical education context and personality traits. Tailored preventive strategies should be implemented.

BACKGROUND: Choline alfoscerate (alpha-glycerylphosphorylcholine) is a phospholipid that includes choline, which increases the release of acetylcholine. The ASCOMALVA trial, a combination of donepezil and choline alfoscerate, slowed cognitive decline in Alzheimer disease. This study aims to replicate the effect by combining donepezil with other nootropics currently used in South Korea.
METHODS: The 119 patients with cognitive decline who were eligible to use donepezil, with an mini-mental state examination (MMSE) score of 26 or less, were assigned to: donepezil alone (DO); donepezil and choline alfoscerate (DN); donepezil and acetyl-l-carnitine (DA); or donepezil and ginkgo biloba extract (DG). Cognitive evaluations such as MMSE, clinical dementia rating, Alzheimer disease assessment scale-cognitive subscale (ADAS-Cog), and Alzheimer disease assessment scale-noncognitive subscale were performed at the 12th and 24th weeks from the baseline time point.
RESULTS: At the 12th week, the MMSE score increased 3.52% in the DN group, whereas it increased by 1.36% in the DO group. In the DA + DG group, it decreased by 2.17%. At the 24th week, the MMSE score showed an increase of 1.07% in the DO group and 1.61% in the DN group, but decreased by 5.71% in the DA + DG group. ADAS-Cog decreased by 0.9% in the DO group, while it improved by 13.9% in the DN group at the 12th week. At the 24th week, ADAS-Cog showed improvement in the DN group by 18.5%, whereas it improved by 9.4% in the DO group. Alzheimer disease assessment scale-noncognitive subscale also revealed better performance in the DN group than in the DO group at the 12th and 24th weeks.
CONCLUSIONS: Choline alfoscerate exhibits additional cognitive improvement in both cognitive and noncognitive domains, supporting the findings of the ASCOMALVA trial.

An updated time-trend analysis of anti-dementia drugs (ADDs) is lacking. The aim of this study is to assess the incident rate (IR) of ADD in individuals with dementia using real-world data.
Primary care data (country/database) from the UK/CPRD-GOLD (2007-20), Spain/SIDIAP (2010-20) and the Netherlands/IPCI (2008-20), standardised to a common data model.
Cohort study. Participants: dementia patients ≥40 years old with ≥1 year of previous data. Follow-up: until the end of the study period, transfer out of the catchment area, death or incident prescription of rivastigmine, galantamine, donepezil or memantine. Other variables: age/sex, type of dementia, comorbidities. Statistics: overall and yearly age/sex IR, with 95% confidence interval, per 100,000 person-years (IR per 105 PY (95%CI)).
We identified a total of (incident anti-dementia users/dementia patients) 41,024/110,642 in UK/CPRD-GOLD, 51,667/134,927 in Spain/SIDIAP and 2,088/17,559 in the Netherlands/IPCI.In the UK, IR (per 105 PY (95%CI)) of ADD decreased from 2007 (30,829 (28,891-32,862)) to 2010 (17,793 (17,083-18,524)), then increased up to 2019 (31,601 (30,483 to 32,749)) and decrease in 2020 (24,067 (23,021-25,148)). In Spain, IR (per 105 PY (95%CI)) of ADD decreased by 72% from 2010 (51,003 (49,199-52,855)) to 2020 (14,571 (14,109-15,043)). In the Netherlands, IR (per 105 PY (95%CI)) of ADD decreased by 77% from 2009 (21,151 (14,967-29,031)) to 2020 (4763 (4176-5409)). Subjects aged ≥65-79 years and men (in the UK and the Netherlands) initiated more frequently an ADD.
Treatment of dementia remains highly heterogeneous. Further consensus in the pharmacological management of patients living with dementia is urgently needed.

BACKGROUND: Donepezil has been approved in Japan for the treatment of dementia with Lewy bodies (DLB) based on clinical trials showing its beneficial effects on cognitive impairment. This phase IV study evaluated the efficacy of donepezil by focusing on global clinical status during a 12-week double-blind phase.
METHODS: Patients with probable DLB were randomly assigned to the placebo (n = 79) or 10 mg donepezil (n = 81) groups. The primary endpoint was changes in global clinical status, assessed using the Clinician\'s Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus). We also assessed four CIBIC-plus domains (general condition, cognitive function, behaviour, and activities of daily living) and changes in cognitive impairment and behavioural and neuropsychiatric symptoms measured using the Mini-Mental State Examination (MMSE) and the Neuropsychiatric Inventory (NPI), respectively.
RESULTS: Although donepezil\'s superiority was not shown in the global clinical status, a significant favourable effect was detected in the cognitive domain (P = 0.006). MMSE scores improved in the donepezil group after adjustments in post hoc analysis (MMSE mean difference, 1.4 (95% confidence interval (CI), 0.42-2.30), P = 0.004). Improvements in NPIs were similar between the groups (NPI-2: -0.2 (95% CI, -1.48 to 1.01), P = 0.710; NPI-10: 0.1 (95% CI, -3.28 to 3.55), P = 0.937).
CONCLUSIONS: The results support the observation that the efficacy of 10 mg donepezil in improving cognitive function is clinically meaningful in DLB patients. The evaluation of global clinical status might be affected by mild to moderate DLB patients enrolled in this study. No new safety concerns were detected.

There is media concern over students using prescription stimulants as \"cognitive enhancers\" to try and improve their academic performance. However, there is limited evidence about the prevalence of this behaviour in the United Kingdom, or whether it has increased in recent years.
We review survey studies on students\' use of cognitive enhancers.
Overall reported use is low, with some inconclusive evidence that it is increasing. Use of modafinil appears to be higher than that of methylphenidate or dexamphetamine.
There is a clear need for large-scale research in this area, using representative sampling and survey methods that protect student anonymity.

OBJECTIVE: The use of prescription stimulants for cognitive enhancement by healthy university students, identified as the largest cohort of cognitive enhancer (CE) users, is of growing interest. The purpose of this study was to look at the understanding, perception, experience, and level of access of CEs among healthy university students in the United Arab Emirates (UAE).
METHODS: The study was conducted in six highly competitive university programmes. Semi-structured interviews were conducted with 18 university students to discuss their own experiences and those of their friends and peers regarding the use of prescription stimulants. In addition, semi-structured interviews were conducted with seven teaching faculty staff members (registered pharmacists and medical doctors) to explore their views on the use of CEs in their university.
RESULTS: Data were analysed thematically for the identification of themes and subthemes within the data using coding. It was found that, \'Adderall\' was the most common prescribed CE drug and caffeine super strength pills were the most common non-prescribed CE drug, both reported to enhance concentration, motivation, and meet academic deadlines.
CONCLUSIONS: It is expected that the findings of this study will be of interest to a wide range of services in UAE universities. This will enable them to raise awareness about the use of CEs among students.

Bacosides are the main biologically active components derived from the plant bacopa monnieri (Bacopa monnieri (L.) Wettst.), which has been used as a nootropic in Indian medicine for many centuries. In recent years, these compounds have attracted attention because of their wide range of neurobiological effects. The neuroprotective effects of bacosides on brain neurons under the influence of various damaging factors (neurotoxins, oxidative stress, beta-amyloid deposition, cigarette smoke, etc.) have been established. It was shown that these substances reduce the levels of inflammatory cytokines and inhibit the processes of demyelination of neurons. The anticonvulsant effect of bacosides has been established. These compounds also improve cognitive functions, including memory and learning abilities. The effects associated with the influence on the dopaminergic and serotonergic systems of the striatum are of interest for the therapy of morphine addiction. The theoretical justifications for the future use of bacosides as a multipurpose means of complex therapy of individual diseases in neurological and psychiatric practice are presented.
Бакозиды — главные биологически активные компоненты растения бакопа Монье (Bacopa monnieri (L.) Wettst.), которое в индийской медицине многие столетия используется в качестве ноотропного средства. В последние годы эти соединения привлекают внимание из-за широкого спектра нейробиологических эффектов. Установлено нейропротективное действие бакозидов при воздействии различных повреждающих факторов (нейротоксинов, окислительного стресса, отложения бета-амилоида и др.). Было показано, что данные вещества снижают уровни воспалительных цитокинов и ингибируют процессы демиелинизации нейронов. Установлено противосудорожное действие бакозидов. Данные соединения также улучшают когнитивные функции, включая память и способности к обучению. Эффекты, связанные с влиянием на дофаминергическую и серотонинергическую системы стриатума, представляют интерес для терапии морфиновой зависимости. Приведены теоретические обоснования применения бакозидов в будущем в качестве многоцелевого средства комплексной терапии отдельных заболеваний в неврологической и психиатрической практике.

OBJECTIVE: (S)-oxiracetam is the major active enantiomer of oxiracetam, which is being developed for dementia. This trial was designed to evaluate the safety, tolerability, and pharmacokinetics of oral (S)-oxiracetam in healthy Chinese volunteers.
METHODS: A randomized, controlled, double-blind and dose-escalation design was used in this Phase I trial, which consisted of a single-ascending-dose (SAD) study (400-2000 mg) and a multiple-ascending-dose (MAD) study (400-1600 mg). Blood, urine and feces samples were collected for pharmacokinetic analysis. Safety was evaluated by monitoring adverse events (AEs).
RESULTS: AEs in both studies were mild or moderate in severity and dose-independent. In the SAD study, no chiral transformation was observed. 55.03% and 36.16% of (S)-oxiracetam was excreted unchanged in urine and feces, respectively. Exposures exhibited dose-proportional increases over the range of 400 to 1600 mg but almost unchanged from 1600 to 2000 mg. (S)-oxiracetam was absorbed rapidly, reaching a peak at 0.75-1.00 h, and t1/2 was 6.12-6.60 h. Food had no effect on AUC, but prolonged Tmax to 3.00 h. In the MAD study, steady-state was observed on day 5. Mild accumulations were observed after 7 days of repeated dosing.
CONCLUSIONS: (S)-oxiracetam was safe and tolerated with favorable pharmacokinetic profiles at all study doses, providing dosing evidence for further efficacy evaluation.

OBJECTIVE: This study aimed to investigate the efficacy of taking Mind Lab Pro, a plant-based nootropic on memory in a group of healthy adults. Auditory, visual, visual working memory, immediate and delayed recall (DR) were assessed.
METHODS: The study employed a pseudo randomised, double blinded, placebo-controlled design. A total of 49 healthy individuals completed the study with 36 in the experimental group and 13 in the control group. Participants ranged between 20 and 68 years with a mean age of 31.4 ± 14.4 years. Pre and post taking either the Mind Lab Pro supplement or placebo for 30 days. All participants completed the Wechsler Memory Scale Fourth UK Edition (WSM-IV UK).
RESULTS: We found that the experimental group significantly improved in all memory subtests assessed (p < 0.05) whilst the control group only significantly improved in auditory memory and immediate recall (p = 0.004 and p = 0.014 respectively). A significant difference in immediate and DR was also found between the control and experimental group (p = 0.005 and 0.034 respectively).
CONCLUSIONS: The use of Mind Lab Pro for 4 weeks improves memory with the experimental group significantly improving in all sub areas of memory as assessed by the WSM-IV UK.

Cognitive operations including pre-attentive sensory processing are markedly impaired in patients with schizophrenia (SCZ) but evidence significant interindividual heterogeneity, which moderates treatment response with nicotinic acetylcholine receptor (nAChR) agonists. Previous studies in healthy volunteers have shown baseline-dependency effects of the α7 nAChR agonist cytidine 5\'-diphosphocholine (CDP-choline) administered alone and in combination with a nicotinic allosteric modulator (galantamine) on auditory deviance detection measured with the mismatch negativity (MMN) event-related potential (ERP).
The objective of this pilot study was to assess the acute effect of this combined α7 nAChR-targeted treatment (CDP-choline/galantamine) on speech MMN in patients with SCZ (N = 24) stratified by baseline MMN responses into low, medium, and high baseline auditory deviance detection subgroups.
Patients with a stable diagnosis of SCZ attended two randomized, double-blind, placebo-controlled and counter-balanced testing sessions where they received a placebo or a CDP-choline (500 mg) and galantamine (16 mg) treatment. MMN ERPs were recorded during the presentation of a fast multi-feature speech MMN paradigm including five speech deviants. Clinical measures were acquired before and after treatment administration.
While no main treatment effect was observed, CDP-choline/galantamine significantly increased MMN amplitudes to frequency, duration, and vowel speech deviants in low group individuals. Individuals with higher positive and negative symptom scale negative, general, and total scores expressed the greatest MMN amplitude improvement following CDP-choline/galantamine.
These baseline-dependent nicotinic effects on early auditory information processing warrant different dosage and repeated administration assessments in patients with low baseline deviance detection levels.