The increasing prevalence of Alzheimer's disease (AD) emphasizes the need for sensitive biomarkers. Memory, a core deficit in AD, involves the interaction of distributed brain networks. We propose ...that biomarkers should be sought at the level of disease-specific disturbances in large-scale neural networks instead of alterations in a single brain region. This is the first voxel-level quantitative meta-analysis of default mode connectivity and task-related activation in 1196 patients and 1255 controls to detect robust changes in components of large-scale neural networks. We show that with disease progression, specific components of networks are widespread altered. The medial parietal regions and the subcortical areas are differentially affected depending on the disease stage. Specific compensatory mechanisms are only seen in the earliest stages, before symptoms are evident, and could become a functional network biomarker or target for interventions. These results underline the need to further fine-grain these networks spatially and temporally across disease stages. To conclude, AD should indeed be considered as a syndrome involving neural network disruption before cognitive deficits are detectable.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
BACKGROUND:In this article, the authors explore functional connectivity and network topology in electroencephalography recordings of patients with delirium after cardiac surgery, aiming to improve ...the understanding of the pathophysiology and phenomenology of delirium. The authors hypothesize that disturbances in attention and consciousness in delirium may be related to alterations in functional neural interactions.
METHODS:Electroencephalography recordings were obtained in postcardiac surgery patients with delirium (N = 25) and without delirium (N = 24). The authors analyzed unbiased functional connectivity of electroencephalography time series using the phase lag index, directed phase lag index, and functional brain network topology using graph analysis.
RESULTS:The mean phase lag index was lower in the α band (8 to 13 Hz) in patients with delirium (median, 0.120; interquartile range, 0.113 to 0.138) than in patients without delirium (median, 0.140; interquartile range, 0.129 to 0.168; P < 0.01). Network topology in delirium patients was characterized by lower normalized weighted shortest path lengths in the α band (t = −2.65; P = 0.01). δ Band–directed phase lag index was lower in anterior regions and higher in central regions in delirium patients than in nondelirium patients (F = 4.53; P = 0.04, and F = 7.65; P < 0.01, respectively).
CONCLUSIONS:Loss of α band functional connectivity, decreased path length, and increased δ band connectivity directed to frontal regions characterize the electroencephalography during delirium after cardiac surgery. These findings may explain why information processing is disturbed in delirium.
OBJECTIVES:Accurate prognostic information in patients with severe traumatic brain injury remains limited, but mortality following the withdrawal of life-sustaining therapies is high and variable ...across centers. We designed a survey to understand attitudes of physicians caring for patients with severe traumatic brain injury toward the determination of prognosis and clinical decision making on the level of care.
DESIGN, SETTING, AND PARTICIPANTS:We conducted a cross-sectional study of intensivists, neurosurgeons, and neurologists that participate in the care of patients with severe traumatic brain injury at all Canadian level 1 and level 2 trauma centers.
INTERVENTION:None.
MEASUREMENTS:The main outcome measure was physicians’ perceptions of prognosis and recommendations on the level of care.
MAIN RESULTS:Our response rate was 64% (455/712). Most respondents (65%) reported that an accurate prediction of prognosis would be most helpful during the first 7 days. Most respondents (>80%) identified bedside monitoring, clinical exam, and imaging to be useful for evaluating prognosis, whereas fewer considered electrophysiology tests (<60%) and biomarkers (<15%). In a case-based scenario, approximately one-third of respondents agreed, one-third were neutral, and one-third disagreed that the patient prognosis would be unfavorable at one year. About 10% were comfortable recommending withdrawal of life-sustaining therapies.
CONCLUSIONS:A significant variation in perceptions of neurologic prognosis and in clinical decision making on the level of care was found among Canadian intensivists, neurosurgeons, and neurologists. Improved understanding of the factors that can accurately predict prognosis for patients with traumatic brain injury is urgently needed.
Objective: Difficulties in communication and social relationships present a formidable challenge for many people after traumatic brain injury (TBI). These difficulties are likely to be partially ...attributable to problems with emotion perception. Mounting evidence shows facial affect recognition to be particularly difficult after TBI. However, no attempt has been made to systematically estimate the magnitude of this problem or the frequency with which it occurs. Method: A meta-analysis is presented examining the magnitude of facial affect recognition difficulties after TBI. From this, the frequency of these impairments in the TBI population is estimated. Effect sizes were calculated from 13 studies that compared adults with moderate to severe TBI to matched healthy controls on static measures of facial affect recognition. Results: The studies collectively presented data from 296 adults with TBI and 296 matched controls. The overall weighted mean effect size for the 13 studies was −1.11, indicating people with TBI on average perform about 1.1 SD below healthy peers on measures of facial affect recognition. Based on estimation of the TBI population standard deviation and modeling of likely distribution shape, it is estimated that between 13% and 39% of people with moderate to severe TBI may have significant difficulties with facial affect recognition, depending on the cut-off criterion used. Conclusion: This is clearly an area that warrants attention, particularly examining techniques for the rehabilitation of these deficits.
Full text
Available for:
CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK
Individuals with Parkinson's disease (PD) have shown deficits in the ability to recognize emotion. However, these results have been inconsistent. In addition, questions remain about whether any ...deficit in PD is secondary to depression and broader cognitive impairments, and the effects of stimulus modality, task type, and specific emotion remain unclear. A meta-analysis of 34 comparisons, using data from 1,295 individual participants, was conducted to (a) provide a reliable estimate of the magnitude of the purported deficit in emotion recognition and (b) examine the influence of several potential moderators of emotion recognition abilities in PD. Results show a robust link between PD and specific deficits in recognizing emotion, from both the face and the voice (overall effect size
g
= 0.52). The deficit extends across stimulus modalities and task types and is particularly acute with respect to negative emotions. Although this deficit does not appear to be secondary to comorbid depression or visuospatial impairments, the potential role of working memory constraints warrants further investigation. We highlight the potential implications of these findings for communication abilities in PD.
Full text
Available for:
CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK
Rationale
Caffeine is widely consumed in foods and beverages and is also used for a variety of medical purposes. Despite its widespread use, relatively little is understood regarding how genetics ...affects consumption, acute response, or the long-term effects of caffeine.
Objective
This paper reviews the literature on the genetics of caffeine from the following: (1) twin studies comparing heritability of consumption and of caffeine-related traits, including withdrawal symptoms, caffeine-induced insomnia, and anxiety, (2) association studies linking genetic polymorphisms of metabolic enzymes and target receptors to variations in caffeine response, and (3) case-control and prospective studies examining relationship between polymorphisms associated with variations in caffeine response to risks of Parkinson’s and cardiovascular diseases in habitual caffeine consumers.
Results
Twin studies find the heritability of caffeine-related traits to range between 0.36 and 0.58. Analysis of polysubstance use shows that predisposition to caffeine use is highly specific to caffeine itself and shares little common disposition to use of other substances. Genome association studies link variations in adenosine and dopamine receptors to caffeine-induced anxiety and sleep disturbances. Polymorphism in the metabolic enzyme cytochrome P-450 is associated with risk of myocardial infarction in caffeine users.
Conclusion
Modeling based on twin studies reveals that genetics plays a role in individual variability in caffeine consumption and in the direct effects of caffeine. Both pharmacodynamic and pharmacokinetic polymorphisms have been linked to variation in response to caffeine. These studies may help guide future research in the role of genetics in modulating the acute and chronic effects of caffeine.
Full text
Available for:
DOBA, EMUNI, FIS, FSPLJ, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
The meta-analytic findings of Binder et al. (1997) and Frencham et al. (2005) showed that the neuropsychological effect of mild traumatic brain injury (mTBI) was negligible in adults by 3 months post ...injury. Pertab et al. (2009) reported that verbal paired associates, coding tasks, and digit span yielded significant differences between mTBI and control groups. We re-analyzed data from the 25 studies used in the prior meta-analyses, correcting statistical and methodological limitations of previous efforts, and analyzed the chronicity data by discrete epochs. Three months post injury the effect size of −0.07 was not statistically different from zero and similar to that which has been found in several other meta-analyses (Belanger et al., 2005; Schretlen & Shapiro, 2003). The effect size 7 days post injury was −0.39. The effect of mTBI immediately post injury was largest on Verbal and Visual Memory domains. However, 3 months post injury all domains improved to show non-significant effect sizes. These findings indicate that mTBI has an initial small effect on neuropsychological functioning that dissipates quickly. The evidence of recovery in the present meta-analysis is consistent with previous conclusions of both Binder et al. and Frencham et al. Our findings may not apply to people with a history of multiple concussions or complicated mTBIs.
Full text
Available for:
BFBNIB, NUK, PILJ, SAZU, UL, UM, UPUK
Xenon, the inert anesthetic gas, is neuroprotective in models of brain injury. The authors investigate the neuroprotective mechanisms of the inert gases such as xenon, argon, krypton, neon, and ...helium in an in vitro model of traumatic brain injury.
The authors use an in vitro model using mouse organotypic hippocampal brain slices, subjected to a focal mechanical trauma, with injury quantified by propidium iodide fluorescence. Patch clamp electrophysiology is used to investigate the effect of the inert gases on N-methyl-D-aspartate receptors and TREK-1 channels, two molecular targets likely to play a role in neuroprotection.
Xenon (50%) and, to a lesser extent, argon (50%) are neuroprotective against traumatic injury when applied after injury (xenon 43±1% protection at 72 h after injury N=104; argon 30±6% protection N=44; mean±SEM). Helium, neon, and krypton are devoid of neuroprotective effect. Xenon (50%) prevents development of secondary injury up to 48 h after trauma. Argon (50%) attenuates secondary injury, but is less effective than xenon (xenon 50±5% reduction in secondary injury at 72 h after injury N=104; argon 34±8% reduction N=44; mean±SEM). Glycine reverses the neuroprotective effect of xenon, but not argon, consistent with competitive inhibition at the N-methyl-D-aspartate receptor glycine site mediating xenon neuroprotection against traumatic brain injury. Xenon inhibits N-methyl-D-aspartate receptors and activates TREK-1 channels, whereas argon, krypton, neon, and helium have no effect on these ion channels.
Xenon neuroprotection against traumatic brain injury can be reversed by increasing the glycine concentration, consistent with inhibition at the N-methyl-D-aspartate receptor glycine site playing a significant role in xenon neuroprotection. Argon and xenon do not act via the same mechanism.
Abstract We examined the effects of ibuprofen on cognitive deficits, Aβ and tau accumulation in young triple transgenic (3xTg-AD) mice. 3xTg-AD mice were fed ibuprofen-supplemented chow between 1 and ...6 months. Untreated 3xTg-AD mice showed significant impairment in the ability to learn the Morris water maze (MWM) task compared to age-matched wild-type (WT) mice. The performance of 3xTg-AD mice was significantly improved with ibuprofen treatment compared to untreated 3xTg-AD mice. Ibuprofen-treated transgenic mice showed a significant decrease in intraneuronal oligomeric Aβ and hyperphosphorylated tau (AT8) immunoreactivity in the hippocampus. Confocal microscopy demonstrated co-localization of conformationally altered (MC1) and early phosphorylated tau (CP-13) with oligomeric Aβ, and less co-localization of oligomeric Aβ and later forms of phosphorylated tau (AT8 and PHF-1) in untreated 3xTg-AD mice. Our findings show that prophylactic treatment of young 3xTg-AD mice with ibuprofen reduces intraneuronal oligomeric Aβ, reduces cognitive deficits, and prevents hyperphosphorylated tau immunoreactivity. These findings provide further support for intraneuronal Aβ as a cause of cognitive impairment, and suggest that pathological alterations of tau are associated with intraneuronal oligomeric Aβ accumulation.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
BACKGROUND: Regular consumption of fruit and vegetables has been considered to be associated with a reduced risk of dementia and age-associated cognitive decline, although the association is ...currently unsupported by a systematic review of the literature. METHODS: We searched Medline, Embase, Biosis, ALOIS, the Cochrane library, different publisher databases as well as bibliographies of retrieved articles. All cohort studies with a follow-up of 6 months or longer were included if they reported an association of Alzheimer’s disease or cognitive decline in regard to the frequency of fruit and vegetables consumption. FINDINGS: Nine studies with a total of 44 004 participants met the inclusion criteria. Six studies analyzed fruit and vegetables separately and five of them found that higher consumption of vegetables, but not fruit is associated with a decreased risk of dementia or cognitive decline. The same association was found by three further studies for fruit and vegetable consumption analytically combined. CONCLUSION: Increased intake of vegetables is associated with a lower risk of dementia and slower rates of cognitive decline in older age. Yet, evidence that this association is also valid for high fruit consumption is lacking.
PDF
