Severe Memory Loss Research Articles

Deciphering the Role of Adrenergic Receptors in Alzheimer's Disease: Paving the Way for Innovative Therapies.

Neurodegenerative diseases are currently among the most devastating diseases with no effective disease-modifying drugs in the market, with Alzheimer's disease (AD) being the most prevalent. AD is a complex multifactorial neurodegenerative disorder characterized by progressive and severe cognitive impairment and memory loss. It is the most common cause of progressive memory loss (dementia) in the elderly, and to date, there is no effective treatment to cure or slow disease progression substantially. The role of adrenergic receptors in the pathogenesis of Alzheimer's disease and other tauopathies is poorly understood or investigated. Recently, some studies indicated a potential benefit of drugs acting on the adrenergic receptors for AD and dementias, although due to the heterogeneity of the drug classes used, the results on the whole remain inconclusive. The scope of this review article is to comprehensively review the literature on the possible role of adrenergic receptors in neurodegenerative diseases, stemming from the use of agonists and antagonists including antihypertensive and asthma drugs acting on the adrenergic receptors, but also from animal models and in vitro models where these receptors have been studied. Ultimately, we hope to obtain a better understanding of the role of these receptors, identify the gaps in knowledge, and explore the possibility of repurposing such drugs for AD, given their long history of use and safety.

Paraneoplastic limbic encephalitis in a patient with small cell lung cancer. Case report

Paraneoplastic limbic encephalitis (PLE) is a rare autoimmune neurological syndrome caused by selective involvement of the limbic system with the development of neuropsychiatric symptoms and cognitive impairment. PLE is associated with malignancies. We observed PLE in a patient with small cell lung cancer (SCLC). Patient B. complained of severe weakness, headache attacks, irritability, memory loss, and cramps in the muscles of the limbs for 2 months. Contrast-enhanced magnetic resonance imaging of the brain showed signs of PLE. Anti-neuronal antibodies were detected in the blood serum: anti-Hu, anti-CV2 and anti-Ma2, anti-amphiphysin. In the cerebrospinal fluid, anti-Hu antibodies, lymphocytosis of 88%, and increased protein of 0.6 g/L were found. The patient was consulted by a neurologist and diagnosed with PLE. No treatment was administered. After 2 months, the patient reported a significant deterioration. Memory impairment progressed, convulsive seizures with short-term loss of consciousness became more frequent, and the patient became aggressive and withdrawn. Positron emission tomography combined with computed tomography with 18F-fluorodeoxyglucose was performed. There was an excessive radiopharmaceutical uptake in a limited area of the medial parts of the left temporal lobe. A tumor was detected in the upper lobe of the right lung. A bronchoscopy with biopsy was performed. Histological examination showed SCLC. Clinical diagnosis: SCLC of the right lung, stage IIb cT2bN1M0; PLE. Cytotoxic and immunotherapy were administered. The case shows that PLE is a rare neurological syndrome associated in most cases with SCLC, usually in the early stages of the malignancy. Neuropsychiatric and cognitive disorders and seizures are predominant in clinical presentation. PLE neuroimaging is performed using contrast-enhanced magnetic resonance imaging and positron emission tomography combined with computed tomography with 18F-fluorodeoxyglucose, the latter being the method of choice. The presence of antineuronal antibodies in serum and cerebrospinal fluid confirms the autoimmune (paraneoplastic) nature of the process.

Memory problems in elderly people with traumatic brain injury

AbstractThe aim of this study is to assess the effectiveness of various therapy methods in elderly individuals with traumatic brain injury (TBI), taking into account the degree of memory loss and the severity of the injury. The study was conducted in 2022 in Moscow, Russia, and Sofia, Bulgaria, involving six clinics. A total of 200 elderly patients with TBI participated in the study, with a mean age of 72 years. Patients were categorized into groups based on the degree of memory loss and severity of the injury. Standardized tests, including the Mini‐Mental State Examination (MMSE), Clock Drawing Test, Digit Symbol Substitution Test, and Free, and Cued Selective Reminding Test, were used to assess cognitive functions. The Progressive Learning Test evaluated patients' ability to memorize and reproduce information over time. Groups receiving physical therapy and cognitive rehabilitation showed statistically significant improvement in cognitive functions compared to other therapy methods. Specifically, the mean score of the MMSE in these groups increased by 7 points (p < .001). Patients with more severe memory loss demonstrated more pronounced improvement in cognitive functions following the integrated therapy approach. The mean MMSE score increased by 10 points (p < .001), whereas in patients with milder memory loss, the growth was less significant (mean increase of 5 points, p < .05). Groups receiving physical therapy and cognitive rehabilitation consistently demonstrated significantly better results compared to speech therapy and psychological support throughout the study period.

Investigating the Impact of IL-6 and CXCL8 on Neurodegeneration and Cognitive Decline in Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder primarily affecting the elderly, characterized by severe cognitive impairment and memory loss. Emerging evidence suggests that neuroinflammation plays a significant role in AD pathogenesis, with cytokines like interleukin-6 (IL-6) and C-X-C motif chemokine ligand 8 (CXCL8) contributing to the disease progression. We utilized GEO datasets to identify IL-6 and CXCL8 as pivotal inflammatory markers in AD. In vitro experiments were conducted using SK-N-BE(2)-M17 and THP-1 cell lines treated with IL-6 and CXCL8 to model AD. Additionally, in vivo tests on Amyloid Precursor Protein/Presenilin 1 (APP/PS1) AD mouse models were performed to assess the impact of these cytokines on cognitive functions and brain pathology. The results indicated a significant decrease in cell viability, increased apoptosis, and elevated inflammatory factor secretion following IL-6 and CXCL8 treatment in vitro. In vivo, AD mouse models treated with these cytokines exhibited exacerbated emotional distress, decreased social interaction, impaired cognitive functions, and increased amyloid protein deposition in neural tissues. The study highlights the detrimental effects of IL-6 and CXCL8 on neuronal health and cognitive functions in AD. These findings suggest that targeting these cytokines could offer potential therapeutic interventions for improving patient outcomes in Alzheimer's disease.

Brain-targeted Tet-1 peptide-PLGA nanoparticles for berberine delivery against STZ-induced Alzheimer’s disease in a rat model: Alleviation of hippocampal synaptic dysfunction, Tau pathology, and amyloidogenesis

Alzheimer’s disease (AD) is an age-related neurodegenerative disorder that causes severe dementia and memory loss. Surface functionalized poly(lactic-co-glycolic acid) nanoparticles have been reported for better transport through the blood–brain barrier for AD therapy. This study investigated the improved therapeutic potential of berberine-loaded poly(lactic-co-glycolic acid)/Tet-1 peptide nanoparticles (BBR/PLGA-Tet NPs) in a rat model of sporadic AD. BBR was loaded into the PLGA-Tet conjugate. BBR/PLGA-Tet NPs were physicochemically and morphologically characterized. AD was achieved by bilateral intracerebroventricular (ICV) injection of streptozotocin (STZ). Cognitively impaired rats were divided into STZ, STZ + BBR, STZ + BBR/PLGA-Tet NPs, and STZ + PLGA-Tet NPs groups. Cognitive improvement was assessed using the Morris Water Maze. Brain acetylcholinesterase and monoamine oxidase activities, amyloid β42 (Aβ42), and brain glycemic markers were estimated. Further, hippocampal neuroplasticity (BDNF, pCREB, and pERK/ERK), Tau pathogenesis (pGSK3β/GSK3β, Cdk5, and pTau), inflammatory, and apoptotic markers were evaluated. Finally, histopathological changes were monitored. ICV-STZ injection produces AD-like pathologies evidenced by Aβ42 deposition, Tau hyperphosphorylation, impaired insulin signaling and neuroplasticity, and neuroinflammation. BBR and BBR/PLGA-Tet NPs attenuated STZ-induced hippocampal damage, enhanced cognitive performance, and reduced Aβ42, Tau phosphorylation, and proinflammatory responses. BBR/PLGA-Tet NPs restored neuroplasticity, cholinergic, and monoaminergic function, which are critical for cognition and brain function. BBR/PLGA-Tet NPs may have superior therapeutic potential in alleviating sporadic AD than free BBR due to their bioavailability, absorption, and brain uptake.

Novel insights on the probable mechanism associated with histamine oral model-inducing neuropathological and behavioral toxicity in rats.

Histamine (HIS) is an important chemical mediator that causes vasodilation and contributes to anaphylactic reactions. Recently, HIS is an understudied neurotransmitter in the central nervous system, and its potential role in neuroinflammation and neurodegeneration is a critical area of research. So, the study's goal is to investigate the consequences of repeated oral intake of HISon the rat's brain and explore the mechanistic way of its neurotoxicity. Thirty male rats were divided into three groups (n = 10). The following treatments were administered orally to all rats every day for 14 days. Group (1) was given distilled water, whereas groups (2 & 3) were given HIS at dosage levels 250and 500 mg/kg body weight (BWT), respectively. Brain tissue samples were collected at 7- and 14-days from the beginning of the experiment. Our results revealed that continuous oral administration of HIS at both doses for 14 days significantly reduced the BWT and induced severe neurobehavioral changes, including depression, dullness, lethargy, tremors, abnormal walking, and loss of spatial learning and memory in rats. In all HIS receiving groups, HPLC data showed a considerable raise in the HIS contents of the brain. Additionally, the daily consumption of HIS causes oxidative stress that is dose- and time-dependent which is characterized by elevation of malondialdehyde levels along with reduction of catalase activity and reduced glutathione levels. The neuropathological lesions were commonly observed in the cerebrum, striatum, and cerebellum and confirmed by the immunohistochemistry staining that demonstrating moderate to strong caspase-3 and inducible nitric oxide synthaseexpressions in all HIS receiving groups, mainly those receiving 500 mg/kg HIS. NF-κB, TNF-α, and IL-1β gene levels were also upregulated at 7- and 14-days in all HIS groups, particularly in those getting 500 mg/kg. We concluded that ROS-induced apoptosis and inflammation was the essential mechanism involved in HIS-mediated neurobehavioral toxicity and histopathology.

Palliative Care Knowledge and Attitudes Among Patients With Neuroinflammatory Diseases.

Background: Neuroinflammatory diseases are progressive leading to loss of function and disability. Although palliative care (PC) utilization has increased globally, it has scarcely increased in neurology. Objectives: To explore PC attitudes and knowledge among patients with neuroinflammatory diseases, such as multiple sclerosis, neuromyelitis optica spectrum disorder, and myelin oligodendrocyte glycoprotein antibody-associated disease. Methods: A cross-sectional 1-year study was conducted using the Palliative Care Knowledge Scale (PaCKS) and the PC Health Information National Trends Survey (HINTS). Murray's transition theory guided this study, which integrates palliative services including decision making, communication, and coordinated care. Results: The majority of study patients were female (69%) (N = 86) and White (79%). Forty-two percent indicated that they had never heard about PC, 46% said that they knew a little bit about PC, and 12% said that they knew a lot about PC. Fifty percent of patients knew the goals of PC and had knowledge about PC services. Forty-four percent to 60% agreed that PC goals include helping friends and family to cope with a patient's illness, offering social and emotional support, and managing pain and other symptoms. Patients who self-reported being familiar with PC performed significantly better on the PaCKS than those unfamiliar with PC (p < 0.001), and those who self-reported moderate or severe memory loss performed significantly worse on the PaCKS than those with mild memory loss (p = 0.027). There was an association between higher education and PC knowledge and between patients' PaCKS scores and their self-reported HINTS PC knowledge. Conclusions: Patients have partial PC knowledge. Patients require education about PC early in their disease along their illness trajectory.

Implication of tau propagation on neurodegeneration in Alzheimer's disease.

Propagation of tau fibrils correlate closely with neurodegeneration and memory deficits seen during the progression of Alzheimer's disease (AD). Although it is not well-established what drives or attenuates tau spreading, new studies on human brain using positron emission tomography (PET) have shed light on how tau phosphorylation, genetic factors, and the initial epicenter of tau accumulation influence tau accumulation and propagation throughout the brain. Here, we review the latest PET studies performed across the entire AD continuum looking at the impact of amyloid load on tau pathology. We also explore the effects of structural, functional, and proximity connectivity on tau spreading in a stereotypical manner in the brain of AD patients. Since tau propagation can be quite heterogenous between individuals, we then consider how the speed and pattern of propagation are influenced by the starting localization of tau accumulation in connected brain regions. We provide an overview of some genetic variants that were shown to accelerate or slow down tau spreading. Finally, we discuss how phosphorylation of certain tau epitopes affect the spreading of tau fibrils. Since tau pathology is an early event in AD pathogenesis and is one of the best predictors of neurodegeneration and memory impairments, understanding the process by which tau spread from one brain region to another could pave the way to novel therapeutic avenues that are efficient during the early stages of the disease, before neurodegeneration induces permanent brain damage and severe memory loss.

Hem coagulase induced cerebral venous sinus thrombosis in patients with uterine fibroids surgery.

Cerebral venous sinus thrombosis (CVST) is a rare, high-risk, and easily misdiagnosed disease. Currently, there are case reports of hem coagulase-induced thrombotic events, but no reports of CVST being associated with hem coagulase. A 35-years-old woman presented to the outpatient clinic with a severe headache and sudden memory loss with intravenous hem coagulase for postoperative bleeding after uterine fibroids surgery. Abnormal neurological signs included slowed reactions, poor memory, and decreased numeracy. Magnetic resonance imaging and computed tomography scan showed multiple cerebral infarcts, and the infarct area was non-arterial. Brain magnetic resonance venography showed obstruction of the left sigmoid sinus. High-resolution magnetic resonance imaging of the left sigmoid sinus showed abnormally high signal. The patient was treated with a subcutaneous Low-Molecular-Weight Heparin Sodium injection 0.4 ml, twice a day (7 days), and oral Warfarin Sodium 3 mg, once a day, while monitoring the international normalized ratio, adjust the warfarin sodium dosage according to the international normalized ratio level. One month later, the patient had no neurological symptoms and her cognitive function returned to normal. hem coagulase may be a contributing factor to CVST in patients undergoing uterine fibroids surgery and should be administered intravenously with caution.

Review and analysis of deep neural network models for Alzheimer's disease classification using brain medical resonance imaging

AbstractAlzheimer's disease is a type of progressive neurological disorder which is irreversible and the patient suffers from severe memory loss. This disease is the seventh largest cause of death across the globe. As yet there is no cure for this disease, the only way to control it is its early diagnosis. Deep Learning techniques are mostly preferred in classification tasks because of their high accuracy over a large dataset. The main focus of this paper is on fine‐tuning and evaluating the Deep Convolutional Networks for Alzheimer's disease classification. An empirical analysis of various deep learning‐based neural network models has been done. The architectures evaluation includes InceptionV3, ResNet with 50 layers and 101 layers and DenseNet with 169 layers. The dataset has been taken from Kaggle which is publicly available and comprises of four classes which represents the various stages of Alzheimer's disease. In our experiment, the accuracy of DenseNet consistently improved with the increase in the number of epochs resulting in a 99.94% testing accuracy score better than the rest of the architectures. Although the results obtained are satisfactory, but for future research, we can apply transfer learning on other deep models like Inception V4, AlexNet etc., to increase accuracy and decrease computational time. Also, in future we can work on other datasets like ADNI or OASIS and use Positron emitted tomography, diffusion tensor imaging neuroimages and their combinations for better result.

Alzheimer\'s disease and traditional medicinal plants: A review

Alzheimer's disease (AD) is characterized by severe memory loss that affects one's ability to operate in social and professional contexts. More than 20 million individuals worldwide are affected by it, making it the most prevalent type of dementia. An elusive memory loss, corresponding functional deterioration, and behavioral abnormalities are hallmarks of AD. AD is the most common cause of disability in the elderly and patients may survive for more than ten years after receiving their diagnosis. From its lowest level at ages 65 to 70 to rates that may approach 6 percent for those over the age of 85, the incidence of AD ranges from 1 to 4 percent of the population per year. Over a hundred novel products are currently undergoing clinical trials thanks to ayurvedic medicinal plants, which have shown to be the most fruitful source of leads or medication development. Indeed, the use of several Ayurvedic medicinal plants and their ingredients for treating Alzheimer's disease has been detailed in a number of scientific research. Phytochemical analyses of the various plant parts have revealed the presence of numerous valuable compounds, including lignans, flavonoids, tannins, polyphenols, triterpenes, sterols, and alkaloids, that exhibit a wide range of pharmacological activities, including anti-inflammatory, anti-amyloidogenic, anticholinesterase, hypolipidemic, and antioxidant effects. However, the precise mechanism of their action is still unclear. This study compiles studies on several medicinal plants that have demonstrated potential for correcting the pathology of Alzheimer's disease. The report provides sufficient baseline data that could be used in drug discovery campaigns and development processes, thereby providing new functional leads for Alzheimer's disease. It does this by summarizing information regarding the phytochemistry, biological, and cellular activities, as well as the clinical applications, of these various plants.

“Hablemos de Alzheimer”: Words Mexican Americans use to talk about Alzheimer’s disease genetic testing. Implications for precision medicine education.

AbstractBackgroundEffective Alzheimer’s disease (AD) diagnosis and therapy will require a tailored approach to each person’s unique AD manifestation, known as AD precision medicine (PM). PM‐associated comprehensive genetic testing is currently restricted to the research domain and not readily available to minoritized Hispanics/Latinos (H/L). Successful AD precision medicine programs benefitting everyone require culturally appropriate patient outreach/education materials. We investigated the words H/L use to talk about AD genetic testing.MethodWe conducted freelisting interviews with 14 Spanish‐preferring Mexican American adults (female, 85.7%; mean age, 49.3±16.8 years, range = 19‐73; completed less than or at most a high school education, 35.7%). Participants were presented with vignettes about a H/L father of varied ages (5th‐7th decade) and degrees of cognitive impairment (no memory deficits to severe memory loss) who received genome sequencing results. During freelisting, participants were given prompts about the vignettes, and were asked to list all words that came to mind when they thought about the prompts. Responses were reviewed for semantically related words. Discrepancies were resolved by consensus agreement. Among sociodemographic data collected, familism and perceived social status were measured by the Pan‐Hispanic Familism Scale and scored (1‐strongly disagree to 5‐strongly agree, max score 25), and the MacArthur Scale of Subjective Social Status (SSS; each item: 1‐lowest to 10‐highest), respectively.ResultsHighest frequency unique word/word clusters (n = 151) for one vignette (father: age 70 with cognitive slowing, prompt: father’s reaction to his own moderate risk result) included worry (17.2%), age/aging/older (15.9%), family (12.6%), high/medium/low chance (12.6%), Alzheimer’s (10.6%), and normal/well/healthy (7.9%). High frequency of family‐related worry aligned with high familism scores (M = 23.2±2.6, range = 15‐25). Moderate frequency words of participants, 78.6% of whom perceived they held social standing in the top half of the community (SSS&gt;5), reflected action orientation: do (6.6%), seek (1.7%), inform (1.5%), and manage (1.1%).ConclusionSpanish‐preferring Mexican Americans respond robustly to information about family. Family‐centered educational materials about AD precision medicine, including information about healthy aging versus neurodegeneration, risk magnitude categories, and action words, could have high impact. Additional research to learn words used by diverse Spanish‐preferring H/L is needed.

A network pharmacology approach to identify the mechanisms and molecular targets of curcumin against Alzheimer disease.

Background:Alzheimer disease (AD) is a degenerative brain disease, which may lead to severe memory loss and other cognitive disorders. However, few effective drugs are available in the clinic at present. Curcumin, a major ingredient of traditional Chinese medicine, Curcuma Longa, has various pharmacological activities. Therefore, exploring clinical drugs based on the inhibition of AD pathological features is imperative.Methods:First, we utilized the HERB database and Swisstarget Prediction database to get the related targets of curcumin and intersected with the AD targets. The intersection targets were used to construct the protein-protein interaction network and performed gene ontology and kyoto encyclopedia of genes and genomes analyses. Further, we obtained targets of curcumin against AD-related tau and aβ pathology via the AlzData database. These targets were applied to perform GEO and receiver operating characteristic analyses. Finally, the reliability of the core targets was evaluated using molecular docking technology.Results:We identified 49 targets of curcumin against AD, and kyoto encyclopedia of genes and genomes pathway enrichment analysis demonstrated that the Alzheimer disease pathway (has05010) was significantly enriched. Even more, we obtained 16 targets of curcumin-related Aβ and tau pathology. Among these targets, 8 targets involved the Alzheimer disease pathway and the biological process analyses showed that positive regulation of cytokine production (GO:0001819) was significantly enriched. Bioinformatic analyses indicated that HMOX1, CSF1R, NFKB1, GSK3B, BACE1, AR, or PTGS1 expression was significantly different compared to the control group in the AD patients. Finally, molecular docking studies suggested these genes have a good binding force with curcumin.Conclusions:In this study, we identified curcumin exerted the effect of treating AD by regulating multitargets and multichannels through the method of network pharmacology.

Activated microglia by 18F-DPA714 PET in a case of anti-LGI1 autoimmune encephalitis

We reported a female patient with severe memory loss and faciobrachial dystonic seizures. Anti-LGI1 antibodies were detected in both serum and cerebrospinal fluid. Brain MRI only showed subtle abnormality. She received immunotherapy but unfortunately underwent two relapses after the first attack, resulting in gradual memory decline. Intriguingly, we found higher distribution of 18F-DPA714 in her left medial temporal lobe by PET/CT scan. A novel non-invasive molecular imaging technology indicated potential microglial activation, which might be a promising biomarker for diagnosing and monitoring anti-LGI1 autoimmune encephalitis.

MiRNA sensing hydrogels capable of self-signal amplification for early diagnosis of Alzheimer's disease

Alzheimer's disease (AD), one of the leading senile disorders in the world, causes severe memory loss and cognitive impairment. To date, there is no clear cure for AD. However, early diagnosis and monitoring can help mitigate the effects of this disease. In this study, we reported a platform for diagnosing early-stage AD using microRNAs (miRNAs) in the blood as biomarkers. First, we selected an appropriate target miRNA (miR-574-5p) using AD model mice (4-month-old 5XFAD mice) and developed a hydrogel-based sensor that enabled high-sensitivity detection of the target miRNA. This hydrogel contained catalytic hairpin assembly (CHA) reaction-based probes, leading to fluorescence signal amplification without enzymes and temperature changes, at room temperature. This sensor exhibited high sensitivity and selectivity, as evidenced by its picomolar-level detection limit (limit of detection: 1.29 pM). Additionally, this sensor was evaluated using the plasma of AD patients and non-AD control to validate its clinical applicability. Finally, to use this sensor as a point-of-care-testing (POCT) diagnostic system, a portable fluorometer was developed and verified for feasibility of application.

Concurrent suppression of Aβ aggregation and NLRP3 inflammasome activation for treating Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative illness accompanied by severe memory loss, cognitive disorders and impaired behavioral ability. Amyloid β-peptide (Aβ) aggregation and nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome play crucial roles in the pathogenesis of AD. Aβ plaques not only induce oxidative stress and impair neurons, but also activate the NLRP3 inflammasome, which releases inflammatory cytokine IL-1β to trigger neuroinflammation. A bifunctional molecule, 2-[2-(benzo[d]thiazol-2-yl)phenylamino]benzoic acid (BPBA), with both Aβ-targeting and inflammasome-inhibiting capabilities was designed and synthesized. BPBA inhibited self- and Cu2+- or Zn2+-induced Aβ aggregation, disaggregated the already formed Aβ aggregates, and reduced the neurotoxicity of Aβ aggregates; it also inhibited the activation of the NLRP3 inflammasome and reduced the release of IL-1β in vitro and vivo. Moreover, BPBA decreased the production of reactive oxygen species (ROS) and alleviated Aβ-induced paralysis in transgenic C. elegans with the human Aβ42 gene. BPBA exerts an anti-AD effect mainly through dissolving Aβ aggregates and inhibiting NLRP3 inflammasome activation synergistically.

Estimating Prognosis and Frailty in Persons Aged ≥75Years in the Emergency Department: Further Validation of Dynamic Silver Code.

To assess concurrent validity of the Dynamic Silver Code (DSC), a tool based on administrative data that predicts prognosis in older adults accessing the emergency department (ED), in terms of association with markers of poor functional and cognitive status. Cross-sectional. Data were obtained in the AIDEA study, which enrolled a cohort of ≥75-year-old patients, accessing the ED of 2 hospitals in Florence, Italy. The DSC score and classes (I to IV, corresponding to an increasing risk of death) were obtained from administrative data. Information on health and functional status prior to ED access were collected from face-to-face, direct, or proxy interviews. The 4AT test was administered to screen for possible delirium. Bivariate comparisons of the prevalence of each functional and cognitive marker across 4 DSC classes were performed. Multinomial logistic regression was used to assess the multivariable risk of being in II, III, or IV DSC class vs I. Among 3358 participants (mean age 83years, men 44%), 32.9%, 30.3%, 19.5%, and 17.2% were in DSC class I, II, III, and IV. Preadmission abnormal functional and cognitive conditions, and delirium in the ED, were increasingly more common from DSC class I through IV (P < .001). In particular, the prevalence of total inability to walk increased from 2.9% (class I) to 23.4% (class IV). In multivariable analyses, this was the strongest predictor of being in progressively worse DSC classes, whereas feeling of exhaustion, reporting of serious falls, weight loss, and severe memory loss or diagnosis of dementia gave some contribution. The ability of the DSC to predict survival in older persons appears to rely on its prevailing association with markers of functional impairment. These results may support clinical use of the tool.

Phenolic phytochemicals for treatment of Alzheimer’s condition - a review

The progressive neurodegenerative disease, Alzheimer's disease, affects daily life due to severe memory loss and declining cognitive function. Alzheimer's disease has several hypotheses for its pathophysiology, and on the basis of those hypotheses, researchers are exploring a variety of pathologic targets to find a cure or symptomatic treatment. It has long been known that plants are effective in treating dementia, amnesia, and Alzheimer's disease. A lot of preclinical and clinical studies on plant-based drugs have shown promising results in treating the disease. In this review, we will focus on plants rich in phenolic phytochemicals and the benefit of those phytochemicals in Alzheimer’s disease treatment. Keywords: Alzheimer's disease, phenolic phytochemicals, neurodegenerative disease

Design of Customized Virtual Reality Serious Games for the Cognitive Rehabilitation of Retrograde Amnesia After Brain Stroke

Abstract This article presents a software platform to design serious games for the rehabilitation of severe memory loss by means of virtual reality (VR). In particular, the focus is on retrograde amnesia, a condition affecting patient's quality of life usually after brain stroke. Currently, the standard rehabilitation process includes showing pictures of familiar environments to help memory recover, while the proposed rehabilitation solution aims at developing patient-specific serious games for memory loss starting from 3D scanning of familiar environments. The Occipital Structure sensor and the Skanect application have been used for the virtualization of the real objects and the environment. Instead of following the traditional approach to design a video game during which the game logic is specifically developed for a virtual scene and the software code is not meant to be recombined, a modular procedure has been designed using Unity to interface the virtual objects of each acquired environment without modifying the game logic. In addition, the developed solution makes available a set of software modules for patient's monitoring and data management to automatically generate medical reports, which can be easily connected to each new serious game. A test has been performed to assess the main features of the VR platform and its usability recruiting ten testers. Medical personnel evaluated positively the platform, and they highlighted the importance of objective data to improve the ecological validity of the cognitive rehabilitation for retrograde amnesia.

Outpatient cognitive therapy can change the course of dementia irrespective of etiology

AbstractIntroductionNeuroplasticity can only occur in an ideal body condition and establish a new synaptic connection with repeated stimulations in weak cognitive domains or circuits.MethodA Two‐phase study was planned as a course of memory loss treatment in an outpatient clinic for a period of 3 years. 49 of 72 acquired brain injury and dementia patients completed X≥14 sessions of cognitive therapy intervention within the period of 2‐4 months. Patients selected for intervention had mild severe memory loss on MoCA Score [(9‐24)/30]. The first phase of intervention was the correction of nutraceutical status and sleep optimization. The second phase of the intervention was individualized cognitive therapy (CT) by trained cognitive therapists after the Digital Mobile Assessment of Cognitive test (DMAC) was given before and after an intervention. The domains included visual, auditory, delayed recall, attention, executive, number recall, disinhibition, language, and working memory.ResultsStatistical analysis of n‐49 with confidence interval 95%, series paired t‐tests showed in the post‐intervention group, on average, scores were higher as follows: Visual domain 4.89% to 13.74% (p &lt; 0.001), Auditory domain 8.35% to 19.72% (p &lt; 0.001), Delayed recall 21.34% to 33.95% (p &lt; 0.001), Disinhibition Frontal domain 6.89% to 21.80% (p &lt; 0.001), Attention domain 9.33%, 26.12% (p &lt; 0.001 ), Executive domain 9.81%, 23.06% ( p &lt; 0.001), Number domain 5.22% to 17.91% (p &lt; 0.001), and Working memory 2.96%, 29.85% (p = 0.01).DiscussionDr. Eric Kandel, Nobel Laureate, showed that damaged neurons can synapse after repeated neuron stimulation. Physical therapy is a standard of practice after acquired brain injury, but cognitive impairment evaluation is often ignored. The systematic approach to body optimization for learning and cognitive therapy can change the course of cognitive decline in dementia or acquired brain injury.ConclusionThe significant improvement in mild to severe dementia in short‐term memory or patients’ ability of memory retention improved 22% to 34% in the intervention group provides statistically significant evidence that a systematic approach to cognitive therapy can reverse the course of cognitive decline.