- Memory Complaints, Dementia, and Neuropathology in Older Blacks and Whites. [Journal Article]
- ANAnn Neurol 2018 Feb 21
- CONCLUSIONS: Memory complaints are common in older black and white persons, and relate to cognitive decline, dementia risk, and neurodegenerative pathologies. This article is protected by copyright. All rights reserved.
- Phenotypic Variability in Autosomal Dominant Familial Alzheimer Disease due to the S170F Mutation of Presenilin-1. [Journal Article]
- NDNeurodegener Dis 2018 Feb 22; 18(2-3):57-68
- CONCLUSIONS: The variable clinical findings associated with the S170F mutation highlight the relevance of atypical phenotypes in the context of research and under a clinical perspective. CSF sampling and detection of Aβ species may be essential to indicate AD pathology in unclear cases presenting with cognitive and motor symptoms at a younger age.
- Pharmacological Inhibition of Necroptosis Protects from Dopaminergic Neuronal Cell Death in Parkinson's Disease Models. [Journal Article]
- CRCell Rep 2018 Feb 20; 22(8):2066-2079
- Dysfunctions in mitochondrial dynamics and metabolism are common pathological processes associated with Parkinson's disease (PD). It was recently shown that an inherited form of PD and dementia is ca...
Dysfunctions in mitochondrial dynamics and metabolism are common pathological processes associated with Parkinson's disease (PD). It was recently shown that an inherited form of PD and dementia is caused by mutations in the OPA1 gene, which encodes for a key player in mitochondrial fusion and structure. iPSC-derived neural cells from these patients exhibited severe mitochondrial fragmentation, respiration impairment, ATP deficits, and heightened oxidative stress. Reconstitution of normal levels of OPA1 in PD-derived neural cells normalized mitochondria morphology and function. OPA1-mutated neuronal cultures showed reduced survival in vitro. Intriguingly, selective inhibition of necroptosis effectively rescued this survival deficit. Additionally, dampening necroptosis in MPTP-treated mice protected from DA neuronal cell loss. This human iPSC-based model captures both early pathological events in OPA1 mutant neural cells and the beneficial effects of blocking necroptosis, highlighting this cell death process as a potential therapeutic target for PD.
- sAPPβ and sAPPα increase structural complexity and E/I input ratio in primary hippocampal neurons and alter Ca2+homeostasis and CREB1-signaling. [Journal Article]
- ENExp Neurol 2018 Feb 18
- One major pathophysiological hallmark of Alzheimer's disease (AD) is senile plaques composed of amyloid β (Aβ). In the amyloidogenic pathway, cleavage of the amyloid precursor protein (APP) is shifte...
One major pathophysiological hallmark of Alzheimer's disease (AD) is senile plaques composed of amyloid β (Aβ). In the amyloidogenic pathway, cleavage of the amyloid precursor protein (APP) is shifted towards Aβ production and soluble APPβ (sAPPβ) levels. Aβ is known to impair synaptic function; however, much less is known about the physiological functions of sAPPβ. The neurotrophic properties of sAPPα, derived from the non-amyloidogenic pathway of APP cleavage, are well-established, whereas only a few, conflicting studies on sAPPβ exist. The intracellular pathways of sAPPβ are largely unknown. Since sAPPβ is generated alongside Aβ by β-secretase (BACE1) cleavage, we tested the hypothesis that sAPPβ effects differ from sAPPα effects as a neurotrophic factor. We therefore performed a head-to-head comparison of both mammalian recombinant peptides in developing primary hippocampal neurons (PHN). We found that sAPPα significantly increases axon length (p = 0.0002) and that both sAPPα and sAPPβ increase neurite number (p < 0.0001) of PHN at 7 days in culture (DIV7) but not at DIV4. Moreover, both sAPPα- and sAPPβ-treated neurons showed a higher neuritic complexity in Sholl analysis. The number of glutamatergic synapses (p < 0.0001), as well as layer thickness of postsynaptic densities (PSDs), were significantly increased, and GABAergic synapses decreased upon sAPP overexpression in PHN. Furthermore, we showed that sAPPα enhances ERK and CREB1 phosphorylation upon glutamate stimulation at DIV7, but not DIV4 or DIV14. These neurotrophic effects are further associated with increased glutamate sensitivity and CREB1-signaling. Finally, we found that sAPPα levels are significantly reduced in brain homogenates of AD patients compared to control subjects. Taken together, our data indicate critical stage-dependent roles of sAPPs in the developing glutamatergic system in vitro, which might help to understand deleterious consequences of altered APP shedding in AD patients, beyond Aβ pathophysiology.
- Blood pressure variability and neurocognitive functioning. [Journal Article]
- JCJ Clin Hypertens (Greenwich) 2018 Feb 21
- Biomarkers for detection, prognosis and therapeutic assessment of neurological disorders. [Journal Article]
- RNRev Neurosci 2018 Feb 21
- Neurological disorders have aroused a significant concern among the health scientists globally, as diseases such as Parkinson's, Alzheimer's and dementia lead to disability and people have to live wi...
Neurological disorders have aroused a significant concern among the health scientists globally, as diseases such as Parkinson's, Alzheimer's and dementia lead to disability and people have to live with them throughout the life. Recent evidence suggests that a number of environmental chemicals such as pesticides (paraquat) and metals (lead and aluminum) are also the cause of these diseases and other neurological disorders. Biomarkers can help in detecting the disorder at the preclinical stage, progression of the disease and key metabolomic alterations permitting identification of potential targets for intervention. A number of biomarkers have been proposed for some neurological disorders based on laboratory and clinical studies. In silico approaches have also been used by some investigators. Yet the ideal biomarker, which can help in early detection and follow-up on treatment and identifying the susceptible populations, is not available. An attempt has therefore been made to review the recent advancements of in silico approaches for discovery of biomarkers and their validation. In silico techniques implemented with multi-omics approaches have potential to provide a fast and accurate approach to identify novel biomarkers.
- Mindfulness and meditation: treating cognitive impairment and reducing stress in dementia. [Journal Article]
- RNRev Neurosci 2018 Feb 21
- This study investigates the relationship between mindfulness, meditation, cognition and stress in people with Alzheimer's disease (AD), dementia, mild cognitive impairment and subjective cognitive de...
This study investigates the relationship between mindfulness, meditation, cognition and stress in people with Alzheimer's disease (AD), dementia, mild cognitive impairment and subjective cognitive decline. Accordingly, we explore how the use of meditation as a behavioural intervention can reduce stress and enhance cognition, which in turn ameliorates some dementia symptoms. A narrative review of the literature was conducted with any studies using meditation as an intervention for dementia or dementia-related memory conditions meeting inclusion criteria. Studies where moving meditation was the main intervention were excluded due to the possible confounding of exercise. Ten papers were identified and reviewed. There was a broad use of measures across all studies, with cognitive assessment, quality of life and perceived stress being the most common. Three studies used functional magnetic resonance imaging to measure functional changes to brain regions during meditation. The interventions fell into the following three categories: mindfulness, most commonly mindfulness-based stress reduction (six studies); Kirtan Kriya meditation (three studies); and mindfulness-based Alzheimer's stimulation (one study). Three of these studies were randomised controlled trials. All studies reported significant findings or trends towards significance in a broad range of measures, including a reduction of cognitive decline, reduction in perceived stress, increase in quality of life, as well as increases in functional connectivity, percent volume brain change and cerebral blood flow in areas of the cortex. Limitations and directions for future studies on meditation-based treatment for AD and stress management are suggested.
- The economic burden of overactive bladder (OAB) and its effects on the costs associated with other chronic, age-related comorbidities in the United States. [Journal Article]
- NUNeurourol Urodyn 2018 Feb 21
- CONCLUSIONS: Within this US-based population, the healthcare costs of OAB patients were more than 2.5 times those of similar patients without OAB. Additionally, patients with OAB and chronic, age-related comorbidities incurred higher healthcare costs than non-OAB controls with the same comorbidities.
- Dressing disrupted: negotiating care through the materiality of dress in the context of dementia. [Journal Article]
- SHSociol Health Illn 2018; 40(2):340-352
- This paper explores how the materiality of dress mediates and shapes practices of care in the context of dementia. Earlier research called for an approach to conceptualising care that recognised the ...
This paper explores how the materiality of dress mediates and shapes practices of care in the context of dementia. Earlier research called for an approach to conceptualising care that recognised the role played by everyday artefacts. We extend this to a consideration of dress and dressing the body in relation to people with dementia that involves the direct manipulation of material objects, as well as the materiality of bodies. The paper draws on an ESRC funded study Dementia and Dress, which examined experiences of dress for people with dementia, families and care-workers using ethnographic and qualitative methods. Our analysis explores the process of dressing the body, the physicality of guiding and manipulating bodies into clothing, dealing with fabrics and bodies which 'act back' and are resistant to the process of dressing. We consider how the materiality of clothing can constrain or enable practices of care, exploring tensions between garments that support ease of dressing and those that sustain identity. Examining negotiations around dress also reveals tensions between competing 'logics' of care (Mol ).
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- The relationship between voxel-based metrics of resting state functional connectivity and cognitive performance in cognitively healthy elderly adults. [Journal Article]
- BIBrain Imaging Behav 2018 Feb 20
- In previous studies, resting-state functional connectivity (FC) metrics of specific brain regions or networks based on prior hypotheses have been correlated with cognitive performance. Without constr...
In previous studies, resting-state functional connectivity (FC) metrics of specific brain regions or networks based on prior hypotheses have been correlated with cognitive performance. Without constraining our analyses to specific regions or networks, we employed whole-brain voxel-based weighted degree (WD), a measure of local FC strength, to be correlated with three commonly used neuropsychological assessments of language, executive function and memory retrieval in both positive and negative directions in 67 cognitively healthy elderly adults. We also divided voxel-based WD into short-ranged and long-ranged WDs to evaluate the influence of FC distance on the WD-cognition relationship, and performed three validation tests. Our results showed that for language and executive function tests, positive WD correlates were located in the frontal and temporal cortices, and negative WD correlates in the precuneus and occipital cortices; for memory retrieval, positive WD correlates were located in the inferior temporal cortices, and negative WD correlates in the anterior cingulate cortices and supplementary motor areas. An FC-distance-dependent effect was also observed, with the short-ranged WD correlates of language and executive function tests located in the medial brain regions and the long-ranged WD correlates in the lateral regions. Our findings suggest that inter-individual differences in FC at rest are predictive of cognitive ability in the elderly adults. Moreover, the distinct patterns of positive and negative WD correlates of cognitive performance recapitulate the dichotomy between task-activated and task-deactivated neural systems, implying that a competition between distinct neural systems on functional network topology may have cognitive relevance.