Erik Oudman

Effects of Δ9-tetrahydrocannabinol on human working memory function

BACKGROUND Evidence indicates involvement of the endocannabinoid (eCB) system in both the pathophysiology of schizophrenia and working memory (WM) function. Additionally, schizophrenia patients exhibit relatively strong WM deficits. These findings suggest the possibility that the eCB system is also involved in WM deficits in schizophrenia. In the present study, we examined if perturbation of the eCB system can induce abnormal WM activity in healthy subjects. METHODS A pharmacological functional magnetic resonance imaging study was conducted with a placebo-controlled, cross-over design, investigating effects of the eCB agonist Δ9-tetrahydrocannabinol on WM function in 17 healthy volunteers, by means of a parametric Sternberg item-recognition paradigm with five difficulty levels. RESULTS Performance accuracy was significantly reduced after Δ9-tetrahydrocannabinol. In the placebo condition, brain activity increased linearly with rising WM load. Δ9-Tetrahydrocannabinol administration enhanced activity for low WM loads and reduced the linear relationship between WM load and activity in the WM system as a whole and in left dorsolateral prefrontal cortex, inferior temporal gyrus, inferior parietal gyrus, and cerebellum in particular. CONCLUSIONS Δ9-Tetrahydrocannabinol enhanced WM activity network-wide for low loads, while reducing the load-dependent response for increasing WM loads. These results indicate that a challenged eCB system can induce both abnormal WM activity and WM performance deficits and provide an argument for the possibility of eCB involvement in WM deficits in schizophrenia.

Is Electroconvulsive Therapy (ect) Effective and Safe for Treatment of Depression in Dementia?: A Short Review

Depression is one of the most frequently diagnosed psychiatric disorders in patients with dementia with a prevalence of up to 50%. The detrimental effects of depression in dementia include disability in daily living, worse quality of life, and faster cognitive decline. Although electroconvulsive therapy (ECT) is a well-established and effective treatment for depression in the elderly, it is currently an overlooked treatment option in the elderly with dementia and depression. The aim of this review was to provide a critical analysis of the efficacy and safety of ECT in depression superimposed on dementia by reviewing the current literature on this topic. Current evidence suggests that ECT is an effective treatment for depression in dementia, although the relatively small number of controlled studies hampers the comparison of effectiveness between healthy nongeriatric patients and those with dementia. Moreover, the systematic reports on cognitive side effects are very limited in number and currently only apply to moderately mild or mild dementia of nonvascular origin. Some studies do suggest that cognitive side effects are likely in later stages of dementia and in patients with vascular dementia. It is therefore of crucial relevance to prospectively study effects of ECT in different types and phases of dementia in controlled trials. From a clinical perspective, it is essential to inform and educate patients and family about the possible risks and benefits of ECT treatment for depression in dementia.

Intact memory for implicit contextual information in Korsakoff's amnesia.

Implicit contextual learning is the ability to acquire contextual information from our surroundings without conscious awareness. Such contextual information facilitates the localization of objects in space. In a typical implicit contextual learning paradigm, subjects need to find a target among a number of distractors during visual search. Some of the configurations of stimuli are repeated during the experiment resulting in faster responses than for novel configurations, without subjects being aware of their repetition. Patients with Korsakoffs syndrome (KS) have been found to show devastating explicit spatial amnesia. Less is know about their implicit spatial memory abilities. The aim of the present research was to examine whether implicit contextual learning is intact in KS. Therefore, eighteen KS patients and twenty-two age-IQ- and education-matched controls performed the Implicit Contextual Learning task and a paradigm intended to assess explicit, spatial working memory, i.e. the Box task. Intact implicit contextual learning was observed in both the control group and the KS patients. In turn KS patients did have markedly lower explicit spatial working memory scores. The implicit learning effect was not related to the spatial working memory scores. Together these results clearly suggest that implicit and explicit spatial memory have a different neurocognitive basis.

Biomarkers of delirium as a clue to diagnosis and pathogenesis of Wernicke-Korsakoff syndrome.

Wernickes encephalopathy (WE) and Korsakoffs syndrome are considered to be different stages of the same disorder due to thiamine deficiency, which is called Wernicke−Korsakoff syndrome (WKS). The earliest biochemical change is the decrease of α‐ketoglutarate‐dehydrogenase activity in astrocytes. According to autopsy‐based series, mental status changes are present in 82% of WE cases. The objective of the present review is to identify possible underlying mechanisms relating the occurrence of delirium to WKS.

The Montreal Cognitive Assessment (MoCA) is Superior to the Mini Mental State Examination (MMSE) in Detection of Korsakoff’s Syndrome

The Montreal Cognitive Assessment (MoCA) and Mini Mental State Examination (MMSE) are brief screening instruments for cognitive disorders. Although these instruments have frequently been used in the detection of dementia, there is currently little knowledge on the validity to detect Korsakoff’s syndrome (KS) with both screening instruments. KS is a chronic neuropsychiatric disorder associated with profound declarative amnesia after thiamine deficiency. A representative sample of 30 patients with KS and 30 age-, education-, gender- and premorbid-IQ-matched controls was administered the MoCA and MMSE. The area under the receiver operating characteristic curve (AUC) was calculated in addition to the sensitivity, specificity, positive predictive value, and negative predictive value for various cut-off points on the MoCA and MMSE. Compared with the MMSE, the MoCA demonstrated consistently superior psychometric properties and discriminant validity—AUC: MoCA (1.00 SE .003) and MMSE (0.92 SE .033). When applying a cut-off value as suggested in the manuals of both instruments, the MMSE (< 24) misdiagnosed 46.7% of the patients, while the MoCA (< 26) diagnosed all patients correctly. As a screening instrument with the most optimal cut-offs, the MoCA (optimal cutoff point 22/23, 98.3% correctly diagnosed) was superior to the MMSE (optimal cutoff point 26/27, 83.3% correctly diagnosed). We conclude that both tests have adequate psychometric properties as a screening instrument for the detection of KS, but the MoCA is superior to the MMSE for this specific patient population.

Procedural Learning and Memory Rehabilitation in Korsakoff's Syndrome - a Review of the Literature

Korsakoff’s syndrome (KS) is a chronic neuropsychiatric disorder caused by alcohol abuse and thiamine deficiency. Patients with KS show restricted autonomy due to their severe declarative amnesia and executive disorders. Recently, it has been suggested that procedural learning and memory are relatively preserved in KS and can effectively support autonomy in KS. In the present review we describe the available evidence on procedural learning and memory in KS and highlight advances in memory rehabilitation that have been demonstrated to support procedural memory. The specific purpose of this review was to increase insights in the available tools for successful memory rehabilitation and give suggestions how to apply these tools in clinical practice to increase procedural learning in KS. Current evidence suggests that when memory rehabilitation is adjusted to the specific needs of KS patients, this will increase their ability to learn procedures and their typically compromised autonomy gets enhanced.

Acquisition of an instrumental activity of daily living in patients with Korsakoff's syndrome: A comparison of trial and error and errorless learning

Patients with Korsakoffs syndrome show devastating amnesia and executive deficits. Consequently, the ability to perform instrumental activities such as making coffee is frequently diminished. It is currently unknown whether patients with Korsakoffs syndrome are able to (re)learn instrumental activities. A good candidate for an effective teaching technique in Korsakoffs syndrome is errorless learning as it is based on intact implicit memory functioning. Therefore, the aim of the current study was two-fold: to investigate whether patients with Korsakoffs syndrome are able to (re)learn instrumental activities, and to compare the effectiveness of errorless learning with trial and error learning in the acquisition and maintenance of an instrumental activity, namely using a washing machine to do the laundry. Whereas initial learning performance in the errorless learning condition was superior, both intervention techniques resulted in similar improvement over eight learning sessions. Moreover, performance in a different spatial layout showed a comparable improvement. Notably, in follow-up sessions starting after four weeks without practice, performance was still elevated in the errorless learning condition, but not in the trial and error condition. The current study demonstrates that (re)learning and maintenance of an instrumental activity is possible in patients with Korsakoffs syndrome.

Quality of life in nursing home residents with advanced dementia: a 2‐year follow‐up

Quality of life (QOL) in dementia has become increasingly recognized as an important clinical and policy concern, but little is known about the progression of QOL in patients with advanced dementia on psychogeriatric units of nursing homes. Therefore, the primary goal of the current study was to assess the evolution of QOL in advanced dementia patients on a psychogeriatric unit.

Route learning in Korsakoff's syndrome: Residual acquisition of spatial memory despite profound amnesia.

Korsakoffs syndrome (KS) is characterized by explicit amnesia, but relatively spared implicit memory. The aim of this study was to assess to what extent KS patients can acquire spatial information while performing a spatial navigation task. Furthermore, we examined whether residual spatial acquisition in KS was based on automatic or effortful coding processes. Therefore, 20 KS patients and 20 matched healthy controls performed six tasks on spatial navigation after they navigated through a residential area. Ten participants per group were instructed to pay close attention (intentional condition), while 10 received mock instructions (incidental condition). KS patients showed hampered performance on a majority of tasks, yet their performance was superior to chance level on a route time and distance estimation tasks, a map drawing task and a route walking task. Performance was relatively spared on the route distance estimation task, but there were large variations between participants. Acquisition in KS was automatic rather than effortful, since no significant differences were obtained between the intentional and incidental condition on any task, whereas for the healthy controls, the intention to learn was beneficial for the map drawing task and the route walking task. The results of this study suggest that KS patients are still able to acquire spatial information during navigation on multiple domains despite the presence of the explicit amnesia. Residual acquisition is most likely based on automatic coding processes.

A case of chronic Wernicke's encephalopathy: A neuropsychological study

A 54-year-old woman was referred to our Korsakoff Center because of extensive cognitive problems following acute Wernicke’s encephalopathy (WE). She had a relatively short history of alcohol abuse and was found lying on the floor in her home by her son. After 5 days without treatment, she was diagnosed with WE in a general hospital. During the course of the disease, minimal change to the acute situation occurred, with chronic confusion, attention deficits, and incoherent behavior symptoms most notable unlike classical Korsakoff’s syndrome. Neuropsychological assessment after 4 and 16 months after admission to the hospital revealed global cognitive decline, with striking impairments in attentional, executive, and memory functions. The present case study suggests that the state of confusion and the neuropsychological symptoms in WE can become chronic in case of very late treatment. We therefore recommend that confused alcoholics should receive appropriate parenteral thiamine according to the current clinical standards.