Can placebo or nocebo pills improve or impair cognition performance?

OBJECTIVE: Although the placebo effect is well known to affect many behaviors, the effects on cognitive performance are less well investigated. METHODS: In this study, the effects of a placebo and a nocebo manipulation on cognitive performance was investigated in healthy young participants in an unblinded between-subjects study. In addition, the participants were asked about their subjective experience in the placebo and nocebo condition. RESULTS: The data suggested that the placebo condition induced the feeling of being more attentive and more motivated and the nocebo condition induced a feeling of being less attentive and alert and that they performed less well than normal. However, no placebo or nocebo effects were found on the actual performance on word learning, working memory, Tower of London task, or spatial pattern separation. CONCLUSIONS: These findings further support the notion that placebo or nocebo effects are not likely to occur in young healthy volunteers. However, other studies suggest that placebo effects can be found in implicit memory tasks and in participants with memory problems. Further placebo/nocebo studies are indicated using different experimental designs and different populations in order to better understand the placebo effect on cognitive performance.

Cannabis increases susceptibility to false memory.

With the growing global acceptance of cannabis and its widespread use by eyewitnesses and suspects in legal cases, understanding the popular drug's ramifications for memory is a pressing need. In a double-blind, randomized, placebo-controlled trial, we examined the acute and delayed effects of Δ9-tetrahydrocannabinol (THC) intoxication on susceptibility to false memory in 64 healthy volunteers. Memory was tested immediately (encoding and retrieval under drug influence) and 1 wk later (retrieval sober). We used three different methods (associative word lists and two misinformation tasks using virtual reality). Across all methods, we found evidence for enhanced false-memory effects in intoxicated participants. Specifically, intoxicated participants showed higher false recognition in the associative word-list task both at immediate and delayed test than controls. This yes bias became increasingly strong with decreasing levels of association between studied and test items. In a misinformation task, intoxicated participants were more susceptible to false-memory creation using a virtual-reality eyewitness scenario and virtual-reality perpetrator scenario. False-memory effects were mostly restricted to the acute-intoxication phase. Cannabis seems to increase false-memory proneness, with decreasing strength of association between an event and a test item, as assessed by different false-memory paradigms. Our findings have implications for how and when the police should interview suspects and eyewitnesses.

The value of maintaining cognition in patients with mild cognitive impairment: The innovation headroom and potential cost-effectiveness of roflumilast.

INTRODUCTION: Early health-technology assessment can support discussing scarce resource allocation among stakeholders. We explored the value of maintaining cognition in patients with mild cognitive impairment (MCI) by estimating: (1) the innovation headroom and (2) the potential cost effectiveness of roflumilast treatment in this population. METHODS: The innovation headroom was operationalized by a fictive 100% efficacious treatment effect, and the roflumilast effect on memory word learning test was assumed to be associated with 7% relative risk reduction of dementia onset. Both were compared to Dutch setting usual care using the adapted International Pharmaco-Economic Collaboration on Alzheimer's Disease (IPECAD) open-source model. RESULTS: The total innovation headroom expressed as net health benefit was 4.2 (95% bootstrap interval: 2.9-5.7) quality-adjusted life years (QALYs). The potential cost effectiveness of roflumilast was k€34 per QALY. DISCUSSION: The innovation headroom in MCI is substantial. Although the potential cost effectiveness of roflumilast treatment is uncertain, further research on its effect on dementia onset is likely valuable.

Cholinergic models of memory impairment in animals and man: scopolamine vs. biperiden.

Scopolamine has been used as a pharmacologic model for cognitive impairments in dementia and Alzheimer's disease. The validity of this model seems to be limited because findings in animals do not readily translate to novel treatments in humans. Biperiden is also a cholinergic deficit model for cognitive impairments but specifically blocks muscarinic M1 receptors. The effects of scopolamine and biperiden (and pirenzepine) are compared in animal studies and related to findings in humans. It is concluded that the effects on cognitive functions are different for scopolamine and biperiden, and they should be considered as different cognitive deficit models. Scopolamine may model more advanced stages of Alzheimer's disease whereas biperiden may model the early deficits in declarative memory in aging and mild cognitive impairment.

The antimuscarinic agent biperiden selectively impairs recognition of abstract figures without affecting the processing of non-words.

OBJECTIVES: The present study investigated the effects of biperiden, a muscarinic type 1 antagonist, on the recognition performance of pre-experimentally unfamiliar abstract figures and non-words in healthy young volunteers. The aim was to examine whether 4 mg biperiden could model the recognition memory impairment seen in healthy aging. METHODS: A double-blind, placebo-controlled, two-way crossover study was conducted. We used a three-phase (deep memorization, shallow memorization, and recognition) old/new discrimination paradigm in which memory strength was manipulated. Strong memories were induced by deep encoding and repetition. Deep encoding was encouraged by redrawing the abstract figures and mentioning existing rhyme words for the non-words (semantic processing). Weak memories were created by merely instructing the participants to study the stimuli (shallow memorization). RESULTS: Biperiden impaired recognition accuracy and prolonged reaction times of the drawn and the studied abstract figures. However, participants were biased towards "old" responses in the placebo condition. The recognition of the new abstract figures was unaffected by the drug. Biperiden did not affect the recognition of the non-words. CONCLUSIONS: Although biperiden may model age-related deficits in episodic memory, the current findings indicate that biperiden does not mimic age-related deficits in recognition performance.

A Crime Script Analysis of Child Sexual Exploitation Material Fora on the Darkweb.

This study's aim is to contribute to the knowledge on the steps involved in child sexual exploitation material (CSEM) crimes committed in Darkweb CSEM communities. Due to the anonymous and illegal nature of these communities, academic research is scarce. This study provides a crime script analysis of member communication data from four CSEM Darkweb fora obtained by law enforcement. For cross-validation, suspect interviews from a relevant case file were analyzed. A step-by-step description of the crime process, starting with the preparations necessary to access Darkweb CSEM fora and ending with the postactivity behaviors of exiting the crime scene and preventing detection, is given, focusing on the casts, activities, probs, and personal and contextual requirements at each stage. The findings highlight the scope of the CSEM problem, as well as the influence the Darkweb has on the way the crime is committed. Suitable targets for law enforcement intervention are discussed.

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.

Differentiating Individuals Convicted of Sexual Offenses: A Two-Country Latent Class Analysis.

Sexual offenses are often part of a larger criminal career also encompassing nonsexual crimes. However, most sexual offending typologies focus on an individual's most recent sexual offense. We compare data from Belgian and Dutch national conviction cohorts and use latent class analysis to distinguish groups of individuals based on their history of sexual and nonsexual offenses, considering continuity and variety. The resulting classification is compared between individuals convicted of sexual offenses and individuals convicted of nonsexual offenses. Results show that four latent classes can be distinguished based on continuity and variety in criminal histories of individuals convicted of sexual offenses, and that some of these classes resemble those distinguished among individuals convicted of nonsexual offenses. We find limited overlap between these latent classes and typologies based solely on the index offense. Results show marked similarities across countries. These results challenge theories of sexual offending to incorporate patterns of nonsexual offending.

Possible overlapping time frames of acquisition and consolidation phases in object memory processes: a pharmacological approach.

In previous studies, we have shown that acetylcholinesterase inhibitors and phosphodiesterase inhibitors (PDE-Is) are able to improve object memory by enhancing acquisition processes. On the other hand, only PDE-Is improve consolidation processes. Here we show that the cholinesterase inhibitor donepezil also improves memory performance when administered within 2 min after the acquisition trial. Likewise, both PDE5-I and PDE4-I reversed the scopolamine deficit model when administered within 2 min after the learning trial. PDE5-I was effective up to 45 min after the acquisition trial and PDE4-I was effective when administered between 3 and 5.5 h after the acquisition trial. Taken together, our study suggests that acetylcholine, cGMP, and cAMP are all involved in acquisition processes and that cGMP and cAMP are also involved in early and late consolidation processes, respectively. Most important, these pharmacological studies suggest that acquisition processes continue for some time after the learning trial where they share a short common time frame with early consolidation processes. Additional brain concentration measurements of the drugs suggest that these acquisition processes can continue up to 4-6 min after learning.

Phosphodiesterase Inhibition and Regulation of Dopaminergic Frontal and Striatal Functioning: Clinical Implications.

BACKGROUND: The fronto-striatal circuits are the common neurobiological basis for neuropsychiatric disorders, including schizophrenia, Parkinson's disease, Huntington's disease, attention deficit hyperactivity disorder, obsessive-compulsive disorder, and Tourette's syndrome. Fronto-striatal circuits consist of motor circuits, associative circuits, and limbic circuits. All circuits share 2 common features. First, all fronto-striatal circuits consist of hyper direct, direct, and indirect pathways. Second, all fronto-striatal circuits are modulated by dopamine. Intracellularly, the effect of dopamine is largely mediated through the cyclic adenosine monophosphate/protein kinase A signaling cascade with an additional role for the cyclic guanosine monophosphate/protein kinase G pathway, both of which can be regulated by phosphodiesterases. Phosphodiesterases are thus a potential target for pharmacological intervention in neuropsychiatric disorders related to dopaminergic regulation of fronto-striatal circuits. METHODS: Clinical studies of the effects of different phosphodiesterase inhibitors on cognition, affect, and motor function in relation to the fronto-striatal circuits are reviewed. RESULTS: Several selective phosphodiesterase inhibitors have positive effects on cognition, affect, and motor function in relation to the fronto-striatal circuits. CONCLUSION: Increased understanding of the subcellular localization and unraveling of the signalosome concept of phosphodiesterases including its function and dysfunction in the fronto-striatal circuits will contribute to the design of new specific inhibitors and enhance the potential of phosphodiesterase inhibitors as therapeutics in fronto-striatal circuits.

Accelerated cognitive decline in a rodent model for temporal lobe epilepsy.

OBJECTIVE: Cognitive impairment is frequently observed in patients with temporal lobe epilepsy. It is hypothesized that cumulative seizure exposure causes accelerated cognitive decline in patients with epilepsy. We investigated the influence of seizure frequency on cognitive decline in a rodent model for temporal lobe epilepsy. METHODS: Neurobehavioral assessment was performed before and after surgery, after the induction of self-sustaining limbic status epilepticus (SSLSE), and in the chronic phase in which rats experienced recurrent seizures. Furthermore, we assessed potential confounders of memory performance. RESULTS: Rats showed a deficit in spatial working memory after the induction of the SSLSE, which endured in the chronic phase. A progressive decline in recognition memory developed in SSLSE rats. Confounding factors were absent. Seizure frequency and also the severity of the status epilepticus were not correlated with the severity of cognitive deficits. SIGNIFICANCE: The effect of the seizure frequency on cognitive comorbidity in epilepsy has long been debated, possibly because of confounders such as antiepileptic medication and the heterogeneity of epileptic etiologies. In an animal model of temporal lobe epilepsy, we showed that a decrease in spatial working memory does not relate to the seizure frequency. This suggests for other mechanisms are responsible for memory decline and potentially a common pathophysiology of cognitive deterioration and the occurrence and development of epileptic seizures. Identifying this common denominator will allow development of more targeted interventions treating cognitive decline in patients with epilepsy. The treatment of interictal symptoms will increase the quality of life of many patients with epilepsy.

Girls' childhood trajectories of disruptive behavior predict adjustment problems in early adolescence.

BACKGROUND: It is widely recognized that early onset of disruptive behavior is linked to a variety of detrimental outcomes in males, later in life. In contrast, little is known about the association between girls' childhood trajectories of disruptive behavior and adjustment problems in early adolescence. METHODS: This study used nine waves of data from the ongoing Pittsburgh Girls Study. A semiparametric group-based model was used to identify trajectories of disruptive behavior in 1,513 girls from age 6 to 12 years. Adjustment problems were characterized by depression, self-harm, Post Traumatic Stress Disorder (PTSD), substance use, interpersonal aggression, sexual behavior, affiliation with delinquent peers, and academic achievement at ages 13 and 14. RESULTS: Three trajectories of childhood disruptive behavior were identified: low, medium, and high. Girls in the high group were at increased risk for depression, self-harm, PTSD, illegal substance use, interpersonal aggression, early and risky sexual behavior, and lower academic achievement. The likelihood of multiple adjustment problems increased with trajectories reflecting higher levels of disruptive behavior. CONCLUSION: Girls following the high childhood trajectory of disruptive behavior require early intervention programs to prevent multiple, adverse outcomes in adolescence and further escalation in adulthood.

Declarative memory.

Declarative Memory consists of memory for events (episodic memory) and facts (semantic memory). Methods to test declarative memory are key in investigating effects of potential cognition-enhancing substances--medicinal drugs or nutrients. A number of cognitive performance tests assessing declarative episodic memory tapping verbal learning, logical memory, pattern recognition memory, and paired associates learning are described. These tests have been used as outcome variables in 34 studies in humans that have been described in the literature in the past 10 years. Also, the use of episodic tests in animal research is discussed also in relation to the drug effects in these tasks. The results show that nutritional supplementation of polyunsaturated fatty acids has been investigated most abundantly and, in a number of cases, but not all, show indications of positive effects on declarative memory, more so in elderly than in young subjects. Studies investigating effects of registered anti-Alzheimer drugs, cholinesterase inhibitors in mild cognitive impairment, show positive and negative effects on declarative memory. Studies mainly carried out in healthy volunteers investigating the effects of acute dopamine stimulation indicate enhanced memory consolidation as manifested specifically by better delayed recall, especially at time points long after learning and more so when drug is administered after learning and if word lists are longer. The animal studies reveal a different picture with respect to the effects of different drugs on memory performance. This suggests that at least for episodic memory tasks, the translational value is rather poor. For the human studies, detailed parameters of the compositions of word lists for declarative memory tests are discussed and it is concluded that tailored adaptations of tests to fit the hypothesis under study, rather than "off-the-shelf" use of existing tests, are recommended.

Purinergic signaling and hippocampal long-term potentiation.

The purines ATP and adenosine are widely recognized for their neuromodulatory effects. They have been shown to have effects on neurons via various receptors and interactions with glial cells. In particular, long-term potentiation (LTP) in hippocampal slice preparations has been found to be modulated by ATP and adenosine. This review gives an overview of purinergic signaling in relation to hippocampal LTP and memory formation. The data supports the hypothesis that adenosine mediates a tonic suppression of synaptic transmission. Thus, low adenosine levels appear to increase basal synaptic activity via a decreased activation of the inhibitor A1 receptor, consequently making it more difficult to induce LTP because of lower contrast. During high stimulation, the inhibition of neighboring pathways by adenosine, in combination with an A2a receptor activation, appears to increase contrast of excited pathways against a nonexcited background. This would enable amplification of specific signaling while suppressing non-specific events. Although a clear role for purinergic signaling in LTP is evident, more studies are needed to scrutinize the modulatory role of ATP and adenosine and their receptors in synaptic plasticity and memory.

Treatment with the selective PDE4B inhibitor A-33 or PDE4D inhibitor zatolmilast prevents sleep deprivation-induced deficits in spatial pattern separation.

Sleep deprivation (SD) disrupts hippocampus-dependent memory, particularly in the dentate gyrus (DG) region, an area crucial for pattern separation. Previous research showed that non-selective phosphodiesterase type 4 (PDE4) inhibitors like roflumilast can alleviate these deficits. However, it remains unclear whether these outcomes are specific to a particular subfamily of PDE4. Hence, this study examined the specific impact of PDE4B inhibitor (A-33) and PDE4D inhibitor (zatolmilast) on spatial pattern separation in sleep deprived mice. Results demonstrated that SD impairs pattern separation, but both zatolmilast and A-33 alleviate these effects. However, A-33 impaired pattern separation in non-sleep deprived animals. The cognitive benefits of these inhibitors after SD may arise from alterations in relevant signaling pathways in the DG. This study provides initial evidence that inhibiting PDE4B or PDE4D holds promise for mitigating memory deficits due to SD.

Early warning signals for predicting cryptomarket vendor success using dark net forum networks.

In this work we focus on identifying key players in dark net cryptomarkets that facilitate online trade of illegal goods. Law enforcement aims to disrupt criminal activity conducted through these markets by targeting key players vital to the market's existence and success. We particularly focus on detecting successful vendors responsible for the majority of illegal trade. Our methodology aims to uncover whether the task of key player identification should center around plainly measuring user and forum activity, or that it requires leveraging specific patterns of user communication. We focus on a large-scale dataset from the Evolution cryptomarket, which we model as an evolving communication network. Results indicate that user and forum activity, measured through topic engagement, is best able to identify successful vendors. Interestingly, considering users with higher betweenness centrality in the communication network further improves performance, also identifying successful vendors with moderate activity on the forum. But more importantly, analyzing the forum data over time, we find evidence that attaining a high betweenness score comes before vendor success. This suggests that the proposed network-driven approach of modelling user communication might prove useful as an early warning signal for key player identification.

A proof of concept phase II study with the PDE-4 inhibitor roflumilast in patients with mild cognitive impairment or mild Alzheimer's disease dementia (ROMEMA): study protocol of a double-blind, randomized, placebo-controlled, between-subjects trial.

BACKGROUND: Research into the neurobiological underpinnings of learning and memory has demonstrated the cognitive-enhancing effects associated with diverse classes of phosphodiesterase (PDE) inhibitors. Specific PDE inhibitors have been identified to improve neuronal communication through selective inhibition of PDE activity. Roflumilast, a PDE4 inhibitor, has demonstrated efficacy in enhancing episodic memory in healthy adults and elderly participants with pronounced memory impairment, indicative of amnestic mild cognitive impairment (aMCI). In alignment with these findings, the present protocol aims to provide a proof of concept phase II of the potential of roflumilast to aid patients diagnosed with (a)MCI or mild Alzheimer's disease (AD) dementia. METHODS: The study will be conducted according to a double-blind, randomized placebo-controlled, between-subjects design. Participants with (a)MCI and mild AD dementia will be recruited through the Memory Clinic at the Maastricht University Medical Centre + (MUMC +) in Maastricht, the Netherlands, alongside outreach through regional hospitals, and social media. The study will have three arms: placebo, 50 µg roflumilast, and 100 µg roflumilast, with a treatment duration of 24 weeks. The primary outcome measure will focus on the assessment of episodic memory, as evaluated through participants' performance on the 15-word Verbal Learning Task (VLT). Our secondary objectives are multifaceted, including an exploration of various cognitive domains. In addition, insights into the well-being and daily functioning of participants will be investigated through interviews with both the participants and their (informal) caregivers, we are interested in the well-being and daily functioning of the participants. DISCUSSION: The outcomes of the present study aim to elucidate the significance of the PDE4 inhibition mechanism as a prospective therapeutic target for enhancing cognitive function in individuals with (a)MCI and mild AD dementia. Identifying positive effects within these patient cohorts could extend the relevance of this treatment to encompass a broader spectrum of neurological disorders. TRIAL REGISTRATION: The Medical Ethics Committee of MUMC + granted ethics approval for the 4th version of the protocol on September 10th, 2020. The trial was registered at the European Drug Regulatory Affairs Clinical Trials (EudraCT) registered on the 19th of December 2019 ( https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-004959-36/NL ) and ClinicalTrial.gov (NCT04658654, https://clinicaltrials.gov/study/NCT04658654?intr=roflumilast&cond=mci&rank=1 ) on the 8th of December 2020. The Central Committee on Research Involving Human Subjects (CCMO) granted approval on the 30th of September 2020.

Objectifying subjective memory complaints: VR-based Verbal Word Learning Test in chronic stroke patients.

Memory impairment imposes a great burden on stroke patients and can be divided into Objective Memory Problems (OMPs) and Subjective Memory Complaints (SMCs). Studies have shown that these do not always co-occur. Possibly, the gap between SMCs and OMPs can be bridged when using a more ecologically valid memory test and considering the impact of other common stroke symptoms such as sensory hypersensitivity (SHS) and fatigue. In the present study, we applied Virtual Reality (VR) to create a sensory-rich environment with real-life stimuli. Memory performance was tested with the 15-Verbal Word Learning Test (VLT). Furthermore, we assessed SMCs (Everyday Memory Questionnaire), and the levels of SHS (Multi-Modal Evaluation of Sensory Sensitivity) and fatigue in the previous month. 31 chronic stroke patients and 32 healthy controls participated. The results showed that participants' memory performance decreased in a sensory-rich compared to a neutral environment. This decrease did not significantly differ between the groups. Interestingly, fatigue and SHS are related to the level of SMC in stroke patients but no such evidence was found in healthy controls. Last, for stroke patients, we found a significant negative correlation between SMCs and memory performance in a sensory-rich environment, but not in a neutral environment. In conclusion, our study implicates that in stroke patients, fatigue and SHS are related to SMCs and that using a sensory-rich VR environment might be a more ecologically valid way to objectify SMCs. However, interpretative caution is warranted due to the absence of sex and age-matched controls and potential selection bias.

Why do users continue to contribute to darknet Child Sexual Abuse Material forums? Examining social exchange, social capital, and social learning explanations using digital forensic artifacts.

BACKGROUND: The darknet hosts an increasing number of hidden services dedicated to the distribution of child sexual abuse material (CSAM). Given that by contributing CSAM to the forum members subject themselves to criminal prosecution, questions regarding the motivation for members contributing to darknet CSAM forums arise. OBJECTIVE: Building on insights gained from research into clearnet communities, here we examine the extent to which social incentives generated by the online CSAM community may explain members' posting behavior on darknet CSAM forums. PARTICIPANTS AND SETTING: We analyze digital forensic artifacts on the online behavior of members of a darknet CSAM forum that was shut down by law enforcement agencies in July 2015. METHODS: We apply group-based trajectory modelling (GBTM), social network analysis, and mixed-effect survival models. RESULTS: Applying GBTM three posting trajectories can be distinguished. Social network analyses finds the reply network to be more centralized than predicted by chance. Mixed-effect survival models show positive associations between the length of members' first post and the time since members' first registration on the forum and subsequent posting. Contrarily, the number of replies received appears to mitigate subsequent posting. CONCLUSIONS: Findings show posting activity on the forum to be concentrated in a minority of forum members who show posting trajectories that are both frequent and persistent. Results further suggest persistence in posting is motivated by social identity and, to a lesser extent, differential association processes.

The Reliability and Clinical Validation of Automatically-Derived Verbal Memory Features of the Verbal Learning Test in Early Diagnostics of Cognitive Impairment.

BACKGROUND: Previous research has shown that verbal memory accurately measures cognitive decline in the early phases of neurocognitive impairment. Automatic speech recognition from the verbal learning task (VLT) can potentially be used to differentiate between people with and without cognitive impairment. OBJECTIVE: Investigate whether automatic speech recognition (ASR) of the VLT is reliable and able to differentiate between subjective cognitive decline (SCD) and mild cognitive impairment (MCI). METHODS: The VLT was recorded and processed via a mobile application. Following, verbal memory features were automatically extracted. The diagnostic performance of the automatically derived features was investigated by training machine learning classifiers to distinguish between participants with SCD versus MCI/dementia. RESULTS: The ICC for inter-rater reliability between the clinical and automatically derived features was 0.87 for the total immediate recall and 0.94 for the delayed recall. The full model including the total immediate recall, delayed recall, recognition count, and the novel verbal memory features had an AUC of 0.79 for distinguishing between participants with SCD versus MCI/dementia. The ten best differentiating VLT features correlated low to moderate with other cognitive tests such as logical memory tasks, semantic verbal fluency, and executive functioning. CONCLUSIONS: The VLT with automatically derived verbal memory features showed in general high agreement with the clinical scoring and distinguished well between SCD and MCI/dementia participants. This might be of added value in screening for cognitive impairment.