Short-term prospective memory deficits in chronic back pain patients

Objective: Chronic pain, particularly low back pain, is widespread. Although a great deal is known about the impact that this has on quality of life and physical activity, relatively little has been established regarding the more cognitive effects of pain. This study aims to find out whether individuals with chronic pain experience memory deficits in prospective memory (PM), the process of remembering to do things at some future point in time. Examples of PM include remembering to keep an appointment, such as a visit to a clinic, or to perform a particular task, such as paying a bill on time. Methods: The PM of 50 participants with chronic pain was compared with 50 pain-free participants. Each participant completed the Prospective Memory Questionnaire, which assesses three aspects of prospective memory (short-term habitual, long-term episodic, and internally cued), and records the use of strategies to aid remembering. Results: In comparison to those not in pain, participants with chronic pain had significantly impaired short-term prospective memory, an effect which was evident even after co-varying use of analgesics and other drugs. Conclusions: These findings provide new insights into prospective memory dysfunction in people with chronic pain. Possible mechanisms for this dysfunction are discussed and suggestions for future research given

What is the therapeutic value of antidepressants in dementia? A narrative review

Objectives: Antidepressants are commonly used in dementia. Depression is a frequent and important co-morbidity in dementia and antidepressants are often used to treat depression and more widely. However there are questions about their utility in depression in dementia and other behavioural and psychological symptoms of dementia (BPSD). The aim of this narrative review is to summarise the evidence on whether there is therapeutic value in prescribing antidepressants to people with dementia. Methods: A PubMed search was performed to identify RCTs that prescribed antidepressants to people with dementia, either in the treatment of BPSD (depression, anxiety, agitation/aggression, psychosis, apathy) or for secondary outcomes (quality of life, carer burden, activities of daily living, cognition, clinical severity, adverse events). Results: Thirty-six RCTs were identified (participant n=3,386). A consistent finding in well-designed blinded placebo controlled trials in dementia is the lack of positive effect of antidepressants on outcomes of interest including depression. One large well-designed study has reported a significant reduction in agitation in people with dementia, but at the expense of clinically significant adverse events. Otherwise change observed in open trials is also seen in the placebo group, suggesting any effect is not attributable to the prescription of antidepressants. Conclusions: It is striking how few data there are on indications other than depression. We should question the use of antidepressants in dementia. Definitive trials of clinical effectiveness of specific indications such as anxiety and agitation in dementia and discontinuation of antidepressants in dementia are needed

NETosis in Alzheimer's Disease

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the progressive deterioration of cognitive functions. Its neuropathological features include amyloid-\u3b2 (A\u3b2) accumulation, the formation of neurofibrillary tangles, and the loss of neurons and synapses. Neuroinflammation is a well-established feature of AD pathogenesis, and a better understanding of its mechanisms could facilitate the development of new therapeutic approaches. Recent studies in transgenic mouse models of AD have shown that neutrophils adhere to blood vessels and migrate inside the parenchyma. Moreover, studies in human AD subjects have also shown that neutrophils adhere and spread inside brain vessels and invade the parenchyma, suggesting these cells play a role in AD pathogenesis. Indeed, neutrophil depletion and the therapeutic inhibition of neutrophil trafficking, achieved by blocking LFA-1 integrin in AD mouse models, significantly reduced memory loss and the neuropathological features of AD. We observed that neutrophils release neutrophil extracellular traps (NETs) inside blood vessels and in the parenchyma of AD mice, potentially harming the blood-brain barrier and neural cells. Furthermore, confocal microscopy confirmed the presence of NETs inside the cortical vessels and parenchyma of subjects with AD, providing more evidence that neutrophils and NETs play a role in AD-related tissue destruction. The discovery of NETs inside the AD brain suggests that these formations may exacerbate neuro-inflammatory processes, promoting vascular and parenchymal damage during AD. The inhibition of NET formation has achieved therapeutic benefits in several models of chronic inflammatory diseases, including autoimmune diseases affecting the brain. Therefore, the targeting of NETs may delay AD pathogenesis and offer a novel approach for the treatment of this increasingly prevalent disease

Single-Neuron Theory of Consciousness

By most accounts, the mind arises from the integrated activity of large populations of neurons distributed across multiple brain regions. A contrasting model is presented in the present paper that places the mind/brain interface not at the whole brain level but at the level of single neurons. Specifically, it is proposed that each neuron in the nervous system is independently conscious, with conscious content corresponding to the spatial pattern of a portion of that neuron's dendritic electrical activity. For most neurons, such as those in the hypothalamus or posterior sensory cortices, the conscious activity would be assumed to be simple and unable to directly affect the organism's macroscopic conscious behavior. For a subpopulation of layer 5 pyramidal neurons in the lateral prefrontal cortices, however, an arrangement is proposed to be present such that, at any given moment: i) the spatial pattern of electrical activity in a portion of the dendritic tree of each neuron in the subpopulation individually manifests a complexity and diversity sufficient to account for the complexity and diversity of conscious experience; ii) the dendritic trees of the neurons in the subpopulation all contain similar spatial electrical patterns; iii) the spatial electrical pattern in the dendritic tree of each neuron interacts nonlinearly with the remaining ambient dendritic electrical activity to determine the neuron's overall axonal response; iv) the dendritic spatial pattern is reexpressed at the population level by the spatial pattern exhibited by a synchronously firing subgroup of the conscious neurons, thereby providing a mechanism by which conscious activity at the neuronal level can influence overall behavior. The resulting scheme is one in which conscious behavior appears to be the product of a single macroscopic mind, but is actually the integrated output of a chorus of minds, each associated with a different neuron