Medial temporal lobe atrophy relates more strongly to sleep-wake rhythm fragmentation than to age or any other known risk.

Atrophy of the medial temporal lobe of the brain is key to memory function and memory complaints in old age. While age and some morbidities are major risk factors for medial temporal lobe atrophy, individual differences remain, and mechanisms are insufficiently known. The largest combined neuroimaging and whole genome study to date indicates that medial temporal lobe volume is most associated with common polymorphisms in the GRIN2B gene that encodes for the 2B subunit (NR2B) of the NMDA receptor. Because sleep disruption induces a selective loss of NR2B from hippocampal synaptic membranes in rodents, and because of several other reports on medial temporal lobe sensitivity to sleep disruption, we hypothesized a contribution of the typical age-related increase in sleep-wake rhythm fragmentation to medial temporal lobe atrophy. Magnetic resonance imaging and actigraphy in 138 aged individuals showed that individual differences in sleep-wake rhythm fragmentation accounted for more (19%) of the variance in medial temporal lobe atrophy than age did (15%), or any of a list of health and brain structural indicators. The findings suggest a role of sleep-wake rhythm fragmentation in age-related medial temporal lobe atrophy, that might in part be prevented or reversible.

EEG-neurofeedback training and quality of life of institutionalized elderly women (a pilot study).

This pilot study attempted to study the applicability of neurofeedback for elderly persons living in nursing homes. We hypothesized an improve of cognitive functioning and the independence in daily life (IDL) of elderly people by using low beta (12-15HZ) EEG neurofeedback training (E-NFT). The participants (active E-NFT group, n=10; control group, n=6) were community living elderly women without dementia. Neurofeedback training was adjusted ten times within 9 weeks, with a training duration of 21 minutes by use of a single electrode, which was centrally placed on the skull surface. Executive functioning (measured with the Rey and fluency tasks), memory capacity (measured with the 15 words test), and IDL (measured with the Groningen Activity Restriction Scale) were measured before and after ten E-NFT sessions in nine weeks. No effects were found for IDL nor executive functioning. Interestingly, performance on the memory test improved in the experimental group, indicating a possible positive effect of E-NFT on memory in elderly women. This study demonstrates that E-NFT is applicable to older institutionalized women. The outcome of this pilot-study justifies the investigation of possible memory effects in future studies.

Unpacking the relationship between Big Five personality traits and experimental pain: A systematic review and meta-analysis.

Pain is essential for survival, but individual responses to painful stimuli vary, representing a complex interplay between sensory, cognitive, and affective factors. Individual differences in personality traits and in pain perception covary but it is unclear which traits play the most significant role in understanding the pain experience and whether this depends on pain modality. A systematic search identified 1534 records (CINAHL, MEDLINE, PsycInfo, PubMed and Web of Science), of which 22 were retained and included in a systematic review. Only studies from the pressure pain domain (n=6) could be compared in a formal meta-analysis to evaluate the relationship between Big Five traits and experimental pain. Pressure pain tolerance correlated positively with Extraversion and negatively with Neuroticism with a trivial effect size (<0.1). While these findings suggest personality might be only weakly related to pain in healthy individuals, we emphasize the need to consider standardization, biases, and adequate sample sizes in future research, as well as additional factors that might affect experimental pain sensitivity.

The effect of Virtual Reality on evoked potentials following painful electrical stimuli and subjective pain.

BACKGROUND: Virtual reality (VR) has been shown to reduce pain, however outcome parameters of previous studies have primarily been of a subjective nature and susceptible to bias. This study investigated the effect of VR on cortical processing of evoked potentials (EPs) and subjectively reported pain. Additionally, we explored whether subjects' demographic and personal characteristics modulated the effect of VR analgesia. METHODS: Three VR conditions were compared in a randomized cross-over study of 30 healthy volunteers: Passive VR (i.e. no interaction possible with the virtual world), active VR (interactive virtual environment) and no VR (black screen). Subjects received noxious electrical stimuli at random intervals during all conditions. EPs, recorded at Cz, were extracted time locked to stimuli. Pain scores were reported after each condition. RESULTS: Active VR significantly decreased pain scores and amplitudes of N1 and P3. Passive VR had no analgesic effect. Age was significantly correlated to pain scores, with older subjects demonstrating larger effects of VR. Gender, game experience, and susceptibility for immersion, did not influence VR analgesia. CONCLUSION: Active VR decreases pre-perceptual and perceptual brain activity following painful electrical stimuli, corresponding with reduced pain experience. VR has potential to serve as a non-pharmacologic treatment for pain, particularly in elderly patients.

Modulation of tactile perception by Virtual Reality distraction: The role of individual and VR-related factors.

BACKGROUND: Virtual reality (VR) has shown to be an effective distraction method in health care. However, questions remain regarding individual and VR-related factors that may modulate the effect of VR. PURPOSE: To explore the effect of VR distraction on tactile perception thresholds in healthy volunteers, in relation to personal characteristics and interactivity of VR applications. METHODS: A randomized three way cross-over study was conducted to investigate the effects of active and passive VR applications in 50 healthy participants. Main outcome measures were monofilament detection thresholds (MDT) and electrical detection thresholds (EDT). Personal characteristics (e.g. age, gender, susceptibility for immersion) and immersion in the VR conditions were analyzed for their effect on VR induced threshold differences. RESULTS: The use of VR caused a significant increase in both MDT and EDT compared to the control condition (MDT: F (2, 76) = 20.174, p < 0.001; EDT F (2, 76) = 6.907, p = 0.002). Furthermore, a significant difference in favour of active VR compared to passive VR was found in MDT (p = 0.012), but not in EDT. No significant gender effect was found. There was a significant positive correlation between age and active VR distraction (r = 0.333, p = 0.018). Immersion in the VR world was positively correlated with the effect of VR, whereas visualization and daydreaming were negatively correlated with VR effects. CONCLUSION: VR increased tactile perception thresholds, with active VR having the largest effect. Results indicate that the efficacy of VR may increase with increasing age. Gender did not affect VR susceptibility.

Effects of meal composition and meal timing on the expression of genes involved in hepatic drug metabolism in rats.

INTRODUCTION: With chronotherapy, drug administration is synchronized with daily rhythms in drug clearance and pharmacokinetics. Daily rhythms in gene expression are centrally mastered by the suprachiasmatic nucleus of the hypothalamus as well as by tissue clocks containing similar molecular mechanisms in peripheral organs. The central timing system is sensitive to changes in the external environment such as those of the light-dark cycle, meal timing and meal composition. We investigated how changes in diet composition and meal timing would affect the daily hepatic expression rhythms of the nuclear receptors PXR and CAR and of enzymes involved in P450 mediated drug metabolism, as such changes could have consequences for the practice of chronotherapy. MATERIALS AND METHODS: Rats were subjected to either a regular chow or a free choice high-fat-high-sugar (fcHFHS) diet. These diets were provided ad libitum, or restricted to either the light phase or the dark phase. In a second experiment, rats had access to chow either ad libitum or in 6 meals equally distributed over 24 hours. RESULTS: Pxr, Alas1 and Por displayed significant day-night rhythms under ad libitum chow fed conditions, which for Pxr was disrupted under fcHFHS diet conditions. Although no daily rhythms were detected in expression of CAR, Cyp2b2 and Cyp3a2, the fcHFHS diet did affect basal expression of these genes. In chow fed rats, dark phase feeding induced a diurnal rhythm in Cyp2b2 expression while light phase feeding induced a diurnal rhythm in Car expression and completely shifted the peak expression of Pxr, Car, Cyp2b2, Alas1 and Por. The 6-meals-a-day feeding only abolished the Pxr rhythm but not the rhythms of the other genes. CONCLUSION: We conclude that although nuclear receptors and enzymes involved in the regulation of hepatic drug metabolism are sensitive to meal composition, changes in meal timing are mainly effectuated via changes in the molecular clock.

[Chronic pain in dementia and in disorders with a high risk for congnitive impairment]. / Chronische pijn bij dementie en bij aandoeningen met een verhoogd risico op cognitieve achteruitgang.

Ageing increases the risk for the etiology of chronic pain and dementia. hence, the increase in the number of elderly people implies that the number of elderly with dementia suffering from chronic pain will increase as well. A key question relates to if and how patients with dementia perceive pain. the inadequateness of pain assessment, particularly in a more advanced stage, is also reflected in a decreased use of analgesics by elderly people with dementia. Insight into possible changes in pain experience as have been observed in the few available clinical studies, could be enhanced by knowledge about the neuropathology which may differ per subtype of dementia. It is striking that pain has not been examined in degenerative diseases of the central nervous system with a high risk for cognitive impairment such as Parkinson's disease and multiple sclerosis. In these disorders, pain is a prominent clinical symptom and to date it is not known whether the experience of pain will change in a stage in which patients become cognitively impaired. Finally, a number of instruments which are most appropriate to assess pain in communicative and non-communicative patients are discussed.

Chronische pijn bij dementie en bij aandoeningen met een verhoogd risico op cognitieve achteruitgang.

Chronic pain in dementia and in disorders with a high risk for cognitive impairment. Ageing increases the risk for the etiology of chronic pain ánd dementia. Hence, the increase in the number of elderly people implies that the number of elderly with dementia suffering from chronic pain will increase as well. A key question relates to if and how patients with dementia perceive pain. The inadequateness of pain assessment, particularly in a more advanced stage, is also reflected in a decreased use of analgesics by elderly people with dementia. Insight into possible changes in pain experience as have been observed in the few available clinical studies, could be enhanced by knowledge about the neuropathology which may differ per subtype of dementia. It is striking that pain has not been examined in degenerative diseases of the central nervous system with a high risk for cognitive impairment such as Parkinson's disease and multiple sclerosis. In these disorders, pain is a prominent clinical symptom and to date it is not known whether the experience of pain will change in a stage in which patients become cognitively impaired. Finally, a number of instruments which are most appropriate to assess pain in communicative and non-communicative patients are discussed.

Negative expectations facilitate mechanical hyperalgesia after high-frequency electrical stimulation of human skin.

BACKGROUND: High-frequency electrical stimulation (HFS) of human skin induces not only an increased pain sensitivity in the conditioning area but also an increased pain sensitivity to mechanical punctate stimuli in the non-conditioned surrounding skin area. The aim of the present study was to investigate whether this heterotopically increased mechanical pain sensitivity can be facilitated through the induction of negative expectations. METHODS: In two independent conditions [a nocebo (n = 15) and control condition (n = 15)], we applied mechanical pain stimuli before, directly after, 10 min and 20 min after HFS in the skin area surrounding the conditioning area, and measured the reported pain intensity [visual analogue scale (VAS)]. All subjects (of both conditions) received a written instruction about the HFS protocol, but only the instruction in the nocebo condition was extended by the following text (in Dutch): 'After the HFS, your skin will become more sensitive to the pinprick stimulation'. RESULTS: Our results clearly show that induced expectations of increased mechanical pain sensitivity after HFS facilitates the reported pain intensity after HFS more than when no information is given. CONCLUSIONS: This study shows for the first time that brain mechanisms, via the induction of negative expectations, can facilitate heterotopic mechanical hyperalgesia after HFS of human skin.

On the moderating role of age in the relationship between pain and cognition.

BACKGROUND: A relationship between pain perception and cognitive function is evident. However, the directionality of this association is unclear and may be influenced by age. That is, inverse associations between pain and cognition have been reported in young and middle-aged chronic pain patients, whereas higher clinical pain ratings have been associated with better cognitive performance in older chronic pain patients. Therefore, this study examined the possible moderating role of age in the pain-cognition relationship. METHOD: Twenty-two younger and 24 older chronic pain participants completed neuropsychological tests of psychomotor speed, memory and executive function. They also completed the McGill Pain Questionnaire to evaluate clinical pain. RESULTS: Interaction analyses revealed that age indeed moderates the relationship between clinical pain ratings and cognitive functions. In the younger age group, pain ratings were inversely related to memory and executive function. In the older age group, a positive relationship was found between pain ratings and executive function, whereas the inverse association of clinical pain with memory was no longer present. CONCLUSIONS: This study was the first to confirm the hypothesis that age is an important moderator of the relationship between pain and cognition. An important finding is that in older adults, most inverse effects of pain on cognition are either no longer present or may even be reversed. The positive relationship between pain and executive function may indicate age-related reduced integrity of a shared underlying neural substrate.

Distortions in rest-activity rhythm in aging relate to white matter hyperintensities.

Distortions in the rest-activity rhythm in aging are commonly observed. Neurodegenerative changes of the suprachiasmatic nucleus have been proposed to underlie this disrupted rhythm. However, based on previous studies, it can be proposed that white matter hyperintensities (WMH) may also play a role in the altered rest-activity rhythm in aging. The present study focused on the rest-activity rhythm, as assessed with actigraphy, and WMH in nondemented aging. With regard to the rest-activity rhythm, the interdaily stability (IS), intradaily variability (IV) and the amplitude (AMP) of the rhythm were of interest. The white matter hyperintensities were examined separately for the periventricular (PVH) and deep white matter (DWMH) regions, while distinguishing between the various locations within these regions (e.g. occipital PVH). The results indicated that frontal DWMH related to both IS and AMP. A reduction in the most active 10-h period mediated the relationship between frontal DWMH and AMP. Possible underlying mechanisms of these associations are discussed.