Postoperative neurocognitive disorder is a disease that frequently develops in older patients during the perioperative period. Postoperative neurological disorders neurological most severe complications include as delirium, cognitive dysfunction, acute cerebral ischemic stroke, and hemorrhagic stroke. Milder complications are anxiety, personality changes and impaired memory.

Alterations in cognitive functions are common in the perioperative course. Although often unnoticed by physicians, these alterations have gained increased interest, both by clinicians and scientists, and knowledge of the preventive measures of postoperative cognitive decline has become mandatory for anesthetists and surgeons.

Despite advancements in understanding postoperative neurocognitive disorder, this disorder's mechanisms remain unclear, including pathophysiological processes such as central synaptic plasticity and function, neuroinflammation, excitotoxicity, and neurotrophic support.

Growing evidence suggests that microenvironmental changes in exosomes and microRNAs are major factors for postoperative neurocognitive disorder induction in older individuals.

Exosomes are carriers for transporting different bioactive molecules between nerve cells in the microenvironment and maintaining intercellular communication and tissue homeostasis.

This article reviews the effects of exosomes and miRNAs on the brain microenvironment in postoperative neurocognitive disorder and has important implications to improve postoperative neurocognitive disorder diagnosis, as well as to develop targeted therapy of this disorder.

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Oxidative stress is a major factor in aging and is implicated in the pathogenesis of tumors, diabetes mellitus, cardiovascular and neurodegenerative diseases, including Alzheimer Disease (AD).

Epidemiological evidence indicates a consistent association between the intake of tomatoes and reduced cardiovascular and neoplastic risk. Limited evidence from human intervention trials suggests that increasing tomato intake, besides improving CV markers, enhances cognitive performances.

Reports on a significant positive correlation between consumption of carotenoid-rich food and prevention of Alzheimer's disease led to the investigation of carotenoids for the treatment and prevention of Alzheimer's disease. More than 1100 types of carotenoids are found naturally, out of which only around 50 are absorbed and metabolized in human body.

Lycopene is one of the most commonly ingested members of fat-soluble carotenoid family that gives vegetables and fruits their red, yellow, or orange color. Dietary intake of tomatoes seems to be more effective than tomato/lycopene supplementation.

In this review, the authors highlight the various in vitro and preclinical studies demonstrating the neuroprotective effect of lycopene. Also, some epidemiological and interventional studies investigating the protective effect of lycopene in Alzheimer's disease are discussed.

The authors also discuss various significant mechanisms, through which lycopene might exert its remissive effects in Alzheimer's disease. Finally, to overcome the issue of poor chemical stability and bioavailability of lycopene, some of the novel delivery systems developed for lycopene are also been briefly highlighted.

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There is a bit weird observation about drugs that had a successful phase II in ALS: On third of those drugs can counter HIV.

Human Endogenous retroviruses (ERVs) are elements in the genome that closely resemble retroviruses. They comprise up to 5–8% of the human genome. They have repeatedly been implicated in the aetiology and pathophysiology of numerous human disorders, particularly in those that affect the central nervous system.

There is evidence that HERVs can be reactivated by viral infections, such as: 1) retroviruses – human immunodeficiency virus type-1 (HIV-1), human T-lymphotropic virus 1 (HTLV-1);

2) RNA viruses – influenza A virus, hepatitis C virus (HCV), severe acute respiratory syndrome coronavirus-2 (SARSCoV-2);

3) DNA viruses – herpes simplex virus type-1 (HSV-1), Epstein-Barr virus (EBV), human cytomegalovirus (CMV), Kaposi’s sarcoma-associated herpesvirus (KSHV) [66]

A growing number of studies links the induction and expression of these retroviral elements with the onset and severity of neurodevelopmental and psychiatric disorders.

Although these disorders differ in terms of overall disease pathology and causalities, a certain degree of chronic inflammation can be identified in all of them.

Based on these commonalities, the authors discuss in this new publication of the bidirectional relationship between ERV expression and inflammation and highlight that numerous entry points to this reciprocal sequence of events exist, including initial infections with ERV-activating pathogens, exposure to non-infectious inflammatory stimuli, and conditions in which epigenetic silencing of ERV elements are disrupted.

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Exercise has systemic health benefits in people, in part, through improving whole-body insulin sensitivity. The brain is an insulin sensitive organ that is often underdiscussed relative to skeletal muscle, liver, and adipose tissue. While brain insulin action may have only subtle impacts on peripheral regulation of systemic glucose homeostasis, it is important for weight regulation as well as mental health. In fact, brain insulin signaling is also involved in processes that support healthy cognition.

Furthermore, brain insulin resistance has been associated with age-related declines in memory and executive function as well as Alzheimer's disease pathology. Herein, the authors provide an overview of brain insulin sensitivity in relation to cognitive function from animal and human studies, with particular emphasis placed on the impact exercise may have on brain insulin sensitivity. Mechanisms discussed include mitochondrial function, brain growth factors, and neurogenesis, which collectively help combat obesity-related metabolic disease and Alzheimer's dementia.

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Beta blockers, also spelled β-blockers, are a class of medications that are used to manage abnormal heart rhythms, and to protect the heart from a second heart attack after a first heart attack. They are also widely used to treat high blood pressure.

Patients aged ≥ 75 years who receive a beta-blocker after heart failure with reduced ejection fraction (HFrEF) hospitalization have significantly lower 90-day mortality and readmission rates.

Several studies have shown it may also be useful to diminish the risk of Alzheimer disease.

This study aimed to determine the association between beta-blocker use and outcomes among patients with reduced ejection fraction and Alzheimer's disease and related dementias.

Using a random 40% sample of Medicare Parts A, B, and D data the authors identified 357,030 patients with ≥1 hospitalization for reduced ejection fraction between 2008 and 2018. 12.7% of those patients had dementia.

Patients with reduced ejection fraction and dementia had higher 90-day and 1-year mortality compared to patients with reduced ejection fraction-only.

Discontinuing beta-blocker was associated with a 2.2-fold higher risk of 90-day mortality among patients with HF-only and a 2.- fold higher risk of 90-day mortality among patients with reduced ejection fraction + dementia.

Not starting a beta-blocker was associated with a 1.8-fold higher risk of 90-day mortality among patients with reduced ejection fraction-only and a 1.7-fold higher risk of 90-day mortality among patients with reduced ejection fraction + dementia. Similar risks were seen at 1 year.

In conclusion beta-blocker therapy was found to be associated with significantly lower short and long-term mortality rates among all patients with reduced ejection fraction.

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The Parkinson Associated Risk Syndrome study was designed to evaluate whether screening with olfactory testing and dopamine transporter imaging could identify participants at risk for developing Parkinson's disease.

Hyposmia, a reduced ability to smell odors, has been associated with increased risk of Parkinson disease, but, taken alone, lacks specificity. The scientists in a new publication evaluated whether repeating olfactory testing improves the diagnostic characteristics of this screening approach.

The participants that they included in their study completed up to 10 years of clinical and imaging evaluations in the PARS cohort. Olfaction was assessed with the University of Pennsylvania Smell Identification Test at baseline and on average 1.4 years later. Multiple logistic regression and Cox proportional hazards regression were used to estimate the hazard of development of clinical Parkinson disease or abnormal DAT imaging.

DAT scan (Dopamine Transporter Scan) commonly refers to a diagnostic method to investigate if there is a loss of dopaminergic neurons in striatum.

Of 186 studied patients who were initially hyposmic, 28% reverted to normosmia on repeat testing. No initially normosmic subjects and only 2% of reverters developed DAT imaging progression or clinical Parkinson disease, compared to 29% of subjects with persistent hyposmia who developed abnormal DAT and 20% who developed clinical Parkinson disease. The relative risk of clinical conversion to Parkinson disease was 8.3 and of abnormal DAT scan was 12.5 for persistent hyposmia, compared to reversion.

Persistent hyposmia on serial olfactory testing significantly increases the risk of developing clinical Parkinson disease and abnormal DAT imaging, compared to hyposmia on a single test. Repeat olfactory testing may be an efficient and cost-effective strategy to improve identification of at-risk patients for early diagnosis and disease modification studies.

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The predominantly pre-synaptic intrinsically disordered protein α-synuclein is prone to misfolding and aggregation in synucleinopathies, such as Parkinson's disease and Dementia with Lewy bodies. For example molecules of the chaperone machinery are often deposited in Lewy bodies.

A new publication describes a vicious cycle in which parts of a chaperone facilitate the accumulation of toxic α-synuclein, which induces proteostatic stress that itself leads to an increase in insoluble fragments of the chaperone.

Molecular chaperones (proteins that assist the conformational folding or unfolding of large proteins) play important roles in protein misfolding diseases. Heat shock proteins are chaperones that protect cells when stressed by elevated temperatures. Heat shock protein 90 (Hsp90) is one of the most common of those chaperone proteins.

In this new publication, authors from Canada, Brazil and Israel show that STI1, the Hsp90 co-chaperone (proteins that assist chaperones ) co-immunoprecipitated α-synuclein, and co-deposited with Hsp90 and Hsp70 in phosphorylated α-synuclein in ubiquitin-positive inclusions in two mouse models of α-synuclein misfolding.

In Parkinson disease human brains, STI1 was increased, and in neurologically healthy brains, STI1 and α-synuclein location correlated. Nuclear Magnetic Resonance analyses revealed direct interaction of α-synuclein with STI1 and indicated that the STI1 domain ( a region of a protein's polypeptide chain that is self-stabilizing and that folds independently from the rest) TPR2A, but not TPR1 or TPR2B domains, interacted with the C-terminal domain of α-synuclein.

Mice over-expressing STI1 and Hsp90ß presented elevated α-synuclein S129 phosphorylation accompanied by inclusions when injected with α-synuclein pre-formed fibrils.

In contrast, reduced STI1 function decreased protein inclusion formation, S129 α-synuclein phosphorylation, while mitigating motor and cognitive deficits as well as mesoscopic brain atrophy in α-synuclein-over-expressing mice.

In conclusion the authors' findings reveal a vicious cycle in which STI1 facilitates the generation and accumulation of toxic α-synuclein conformers, while α-synuclein-induced proteostatic stress increased insoluble STI1 and Hsp90.

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Resting motor threshold is the minimum intensity that evoked a visible contralateral involuntary finger twitch.

Resting motor threshold asymmetry is the absolute difference between the left and right RMT measurements.

Conflicting results have emerged from studies examining the potential of resting motor threshold as a neurophysiological marker for Alzheimer's disease diagnosis and progression.

In this study, the authors estimated the strength of the association between Resting motor threshold measurements and severity of cognitive impairment in a relatively large sample of clinical trial participants with mild to moderate Alzheimer's disease.

Resting motor threshold for each participant was determined by applying single-pulse transcranial magnetic stimulation repeated at varying intensities over left and right sides of the primary motor cortex.

Cognitive impairment was measured with the Montreal Cognitive Assessment and the Alzheimer Disease Assessment Scale - Cognitive scores.

Although the left and right resting motor threshold was lower in CDR 2 than in CDR 1 participants, neither RMT nor RMT asymmetry correlated significantly with cognitive test scores.

In conclusion, authors' study in a large sample size does not support the idea that resting motor threshold is a sensitive marker of cognitive decline/severity in Alzheimer's disease.

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