Effect of Treatment of the Cholinergic Precursor Choline Alphoscerate in Mild Cognitive Dysfunction: A Randomized Controlled Trial.

Background and Objectives: The focus on mild cognitive dysfunction in adults is of great interest, given the risk of worsening and conversion to dementia. Cognitive dysfunctions are characterized by a decrease in the weight and volume of the brain, due to cortical atrophy, with a widening of the grooves and flattening of the convolutions. Brain atrophy that mainly involves the hippocampus is related to the progression of cognitive impairment and the conversion from mild cognitive dysfunction to dementia. Currently, there is no treatment for MCI. Results from a trial on Alzheimer's disease (ASCOMALVA trial) suggest that a sustained cholinergic challenge can slow the progression of brain atrophy typical of Alzheimer's disease associated with vascular damage. This study intends to evaluate the efficacy of choline alphoscerate in patients with mild cognitive impairment (MCI) and associated vascular damage, in stabilizing and/or slowing brain atrophy typical of adult-onset cognitive dysfunction, and in improving and/or slowing the progression of cognitive and behavioral symptoms associated with MCI. Materials and Methods: This randomized controlled trial will recruit 60 patients that will be evaluated and randomized in a 1:1 ratio to receive choline alphoscerate (1200 mg/day) or placebo, for 12 months. Analyses will be carried out using SPSS vesion No 26 the Statistician in charge of this study, with the statistical significance level chosen as 0.05. Discussion: This trial may provide evidence about the efficacy of treatment with the cholinergic precursor choline alphoscerate in patients with mild cognitive dysfunction. The results of this study will be published in peer-reviewed journals. Registration: EudraCT number: 2020-000576-38.

Efficacy and impact on cognitive functions and quality of life of perampanel as first add-on therapy in patients with epilepsy: A retrospective study.

Cognitive dysfunctions are frequent in patients with epilepsy. This comorbidity significantly alters their quality of life and plays an important role in their therapeutic management. Perampanel is a noncompetitive antagonist of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors and is considered a new generation AED (antiepileptic drug) with limited impact on cognitive functions.The aims of this study were to evaluate the efficacy of perampanel as first add-on therapy and its impact on cognitive functions and quality of life in patients with epilepsy followed for 6 months at the Neurology Division of "A. Cardarelli" Hospital in Naples (Italy).

Overweight among seafarers working on board merchant ships.

BACKGROUND: Obesity and overweight represent a relevant risk factor for seafarer's health. The frequency and distribution of overweight and obesity among seafarers working on board of Italian flag ships were studied. Analysis was made on occupational medicine files collected, in the frame of health surveillance inspections, between 2013 and 2016 from Centro Internazionale Radio Medico (CIRM). METHODS: The data of nationality, age, weight, height, blood glucose and blood pressure values obtained from 1155 seafarers were analyzed. Body mass index (BMI) values were calculated and compared with data reported for the general population of the same nationality of seafarers examined. RESULTS: BMI values revealed a tendency to overweight, whereas blood glucose and systolic blood pressure values were in general in the normal range. Approximtely 40% of subjects investigated were overweight, and more than the 10% of them were obese. Underweight was noticeable only in 1.22% of crew members and 0.34% of officers. The 0.52% of subjects investigated was diabetic, and 2.68% were hypertensive. Seafarers, regardless their nationality and rank, showed a greater tendency to overweight and obesity compared with general population of the same ethnicity. CONCLUSIONS: Due to the occurrence of overweight and obesity among seafarers, campaigns for promoting awareness of the phenomenon and on the danger of these conditions for health should be promoted. Specific initiatives to avoid the assumption of junk food and the organization of adequate spaces, times and programs for physical exercise sessions on board should be offered for keeping seafarers healthier.

A Clinical Evidence of a Correlation Between Insulin Resistance and the ALCAT Food Intolerance Test.

Insulin resistance (IR) is defined as the inability of a known quantity of exogenous or endogenous insulin to increase glucose uptake and utilization. Several mechanisms have been proposed as possible causes underlying the development of IR and the IR syndrome. IR occurs as part of a cluster of cardiovascular-metabolic abnormalities commonly referred to as "The Metabolic Syndrome." This may lead to the development of type 2 diabetes, accelerated atherosclerosis, hypertension, dysmenorrhea, hirsutism, and polycystic ovarian syndrome, depending on the genetic background of the individual developing IR. The aim of this study was to assess, in 123 female and 35 male (mean age, 42 y ± 10.3; range 19-75 y) volunteers) whether IR could be partly related to a dietary sugar intolerance and whether there could be a correlation between the ALCAT intolerance test and a mutation of the TCFTL2 gene (it promotes the trascription of the proglucagone and plays a key role in the development of the Langherans islands). Results evidenced that subjects with an intolerance to sugar, also showed a statistically significant complete or incomplete alteration of the TCFTL2 genetic test. Based upon these findings, our study demonstrated that there is a clinical correlation between the ALCAT food intolerance test and the IR. The positivity to the ALCAT test of one of the sugars tested (fructose, sugar cane, and sugar beet) indicates, in the majority of the subjects, the presence of a mutation of the gene TCF7L2 and could contribute to the prevention and treatment of the IR.

Diagnosis of polymyalgia rheumatica in primary health care: favoring and confounding factors - a cohort study.

OBJECTIVES: To evaluate in a primary care setting the favoring and confounding factors for the diagnosis of polymyalgia rheumatica (PMR). MATERIAL AND METHODS: Among 303 patients consecutively referred by their general practitioners (GPs) to our rheumatologic outpatient clinic, we identified three groups: group A - patients with confirmed diagnosis of PMR, group B - patients with unconfirmed diagnosis, group C - patients with unrecognized PMR. All the diagnostic confounding and favoring factors were discussed with GPs using an e-mail questionnaire. Participation in rheumatology training courses represented the final question. The collected data were statistically assessed in a blind way. In Fisher's exact test and ANOVA test, a p-value was significant if < 0.05. The study was carried out in compliance with the Helsinki Declaration and approved by the Ethics Committee of Mariano Lauro Hospital. Every patient signed an informed consent form at the time of the first visit. RESULTS: All patients were Caucasian; 24.1% were male; mean age was 72.3 ±8.6 years (min. - 51, max. - 94). There were 41 patients in group A, 93 in group B and 169 in group C. The percentage of misdiagnoses was very high (87.1%): among 134 patients diagnosed with PMR by their GPs (group A + group B) confirmation was made in 41, and in 169 unrecognized PMR was found. Participation in training courses was very significant compared to the diagnostic accuracy (p < 0.0001 in χ2 test) and to the diagnosis timing (24.3 days ±12.5 vs. 42.9 ±15.5 with p-value < 0.05 in the ANOVA test). When the percentages were assessed according to participation, an inadequate evaluation of some clinical manifestations favored over-diagnosis among the trained GPs. CONCLUSIONS: The level of diagnostic accuracy for PMR must be improved in primary care. Participation in rheumatology training courses can be an important step.

Dopamine, vesicular transporters, and dopamine receptor expression in rat major salivary glands.

The localization of dopamine stores and the expression and localization of dopamine (DAT) and vesicular monoamine transporters (VMAT) type-1 and -2 and of dopamine D1-like and D2-like receptor subtypes were investigated in rat submandibular, sublingual, and parotid salivary glands by HPLC with electrochemical detection, as well as immunochemical and immunohistochemical techniques. Male Wistar rats of 2 mo of age were used. The highest dopamine levels were measured in the parotid gland, followed by the submandibular and sublingual glands. Western blot analysis revealed DAT, VMAT-1, VMAT-2, and dopamine receptors immunoreactivity in membrane preparations obtained from the three glands investigated. Immunostaining for dopamine and transporters was developed within striated ducts. Salivary glands processed for dopamine receptors immunohistochemistry developed an immunoreaction primarily in striated and excretory ducts. In the submandibular gland, acinar cells displayed strong immunoreactivity for the D2 receptor, while cells of the convoluted granular tubules were negative for both D1-like and D2-like receptors. Parotid glands acinar cells displayed the highest immunoreactivity for both D1 and D2 receptors compared with other salivary glands. The above localization of dopamine and dopaminergic markers investigated did not correspond closely with neuron-specific enolase (NSE) localization. This indicates that at least in part, catecholamine stores and dopaminergic markers are independent from glandular innervation. These findings suggest that rat major salivary glands express a dopaminergic system probably involved in salivary secretion. The stronger immunoreactivity for dopamine transporters and receptors in striated duct cells suggests that the dopaminergic system could regulate not only quality, but also volume and ionic concentration of saliva.

Apathy in Alzheimer's disease: any effective treatment?

OBJECTIVE: This review has evaluated the effectiveness of pharmacological treatment of apathy in patients with Alzheimer's disease (AD). METHODS: A systematic literature search was conducted on published clinical trials assessing the effects of pharmacological treatment on apathy in AD over the last 10 years. RESULTS: Fourteen studies considered of good quality were included in the analysis (4 randomized controlled trials, 9 open-label studies, and 1 retrospective analysis). Cholinesterase inhibitors were investigated in 9 studies, monoaminergic compounds such as methylphenidate and modafinil in two trials and one trial, respectively, and Ginkgo biloba (EGb 761 extract) and citalopram in one study each. Cholinesterase inhibitors did not show statistical significant effect in 1 RCT study but were associated to improvement in 3 open-label studies. Methylphenidate elicited a small but significant activity accompanied by relevant side effects such as high blood pressure, cough, and osteoarticular pain. EGb 761 was well tolerated and countered apathy. Other treatments induced modest improvements or were ineffective. CONCLUSIONS: Apathy treatment remains a challenge and there is no evident advantage of any specific pharmacotherapy tested so far. The development of controlled studies according to updated guidelines for the diagnosis of apathy in patients with AD is desirable.

Efficacy of memantine, donepezil, or their association in moderate-severe Alzheimer's disease: a review of clinical trials.

BACKGROUND: Acetylcholinesterase (AChE)/cholinesterase (ChE) inhibitors (Is) and memantine are licensed for symptomatic treatment of mild-moderate and moderate-severe forms of Alzheimer's disease (AD), respectively. High doses of the AChE-I donepezil were licensed in the USA for moderate-severe AD, and the association AChE/ChE-Is plus memantine was proposed for AD at this stage. OBJECTIVES: This paper has reviewed evidence from clinical trials of the effectiveness of memantine, donepezil, or the two drugs in association in managing moderate-severe AD. METHOD: Double-blind, placebo-controlled randomized trials (RCTs) using memantine or donepezil alone or in association versus placebo in moderate-severe AD were reviewed. Analysis done in January 2013 considered the years 2007-2012. RESULTS AND CONCLUSION: Only 83 of the 941 papers selected were considered relevant, and only 13 met the criterion of "adequacy and representativeness." Memantine and donepezil lead to improvements in moderate-to-severe AD and the choice between the compounds should be based on their contraindications more than on disease severity. No evidence was found of advantages of the association of memantine-donepezil. The heterogeneity of conditions explored by RCTs, the relatively short time of observation (24-52 weeks), and the different cognitive assessment tools used did not allow comparing properly different trials.

Activity of Choline Alphoscerate on Adult-Onset Cognitive Dysfunctions: A Systematic Review and Meta-Analysis.

BACKGROUND: Choline alphoscerate (alpha glyceryl phosphorylcholine, α-GPC) is a choline-containing phospholipid used as a medicine or nutraceutical to improve cognitive function impairment occurring in neurological conditions including adult-onset dementia disorders. Despite its 1985 marketing authorization, there are still discrepancies between countries regarding its approval as a prescription medicine and discussions about its effectiveness. OBJECTIVE: This study aimed to evaluate the efficacy of the α-GPC compound for treating cognitive impairment in patients with adult-onset neurological disorders. METHODS: Relevant studies were identified by searching PubMed, Web of Science, and Embase. Studies that evaluated the effects of α-GPC alone or in combination with other compounds on adult-onset cognitive impairment reporting cognition, function, and behavior were considered. We assessed the risk of bias of selected studies using the Cochrane risk of bias tool. RESULTS: A total of 1,326 studies and 300 full-text articles were screened. We included seven randomized controlled trials (RCTs) and one prospective cohort study that met our eligibility criteria. We found significant effects of α-GPC in combination with donepezil on cognition [4 RCTs, mean difference (MD):1.72, 95% confidence interval (CI): 0.20 to 3.25], functional outcomes [3 RCTs, MD:0.79, 95% CI: 0.34 to 1.23], and behavioral outcomes [4 RCTs; MD: -7.61, 95% CI: -10.31 to -4.91]. We also observed that patients who received α-GPC had significantly better cognition than those who received either placebo or other medications [MD: 3.50, 95% CI: 0.36 to 6.63]. CONCLUSION: α-GPC alone or in combination with donepezil improved cognition, behavior, and functional outcomes among patients with neurological conditions associated with cerebrovascular injury.

Rodent Models of Huntington's Disease: An Overview.

Huntington's disease (HD) is an autosomal-dominant inherited neurological disorder caused by a genetic mutation in the IT15 gene. This neurodegenerative disorder is caused by a polyglutamine repeat expansion mutation in the widely expressed huntingtin (HTT) protein. HD is characterized by the degeneration of basal ganglia neurons and progressive cell death in intrinsic neurons of the striatum, accompanied by dementia and involuntary abnormal choreiform movements. Animal models have been extensively studied and have proven to be extremely valuable for therapeutic target evaluations. They reveal the hallmark of the age-dependent formation of aggregates or inclusions consisting of misfolded proteins. Animal models of HD have provided a therapeutic strategy to treat HD by suppressing mutant HTT (mHTT). Transgenic animal models have significantly increased our understanding of the molecular processes and pathophysiological mechanisms underlying the HD behavioral phenotype. Since effective therapies to cure or interrupt the course of the disease are not yet available, clinical research will have to make use of reliable animal models. This paper reviews the main studies of rodents as HD animal models, highlighting the neurological and behavioral differences between them. The choice of an animal model depends on the specific aspect of the disease to be investigated. Toxin-based models can still be useful, but most experimental hypotheses depend on success in a genetic model, whose choice is determined by the experimental question. There are many animal models showing similar HD symptoms or pathologies. They include chemical-induced HDs and genetic HDs, where cell-free and cell culture, lower organisms (such as yeast, Drosophila, C. elegans, zebrafish), rodents (mice, rats), and non-human primates are involved. These models provide accessible systems to study molecular pathogenesis and test potential treatments. For developing more effective pharmacological treatments, better animal models must be available and used to evaluate the efficacy of drugs.

Association Between the Cholinesterase Inhibitor Donepezil and the Cholinergic Precursor Choline Alphoscerate in the Treatment of Depression in Patients with Alzheimer's Disease.

Background: Depressive symptoms are common in Alzheimer's disease (AD) patients and are associated with an increased functional decline. Selective serotonin reuptake inhibitor antidepressants showed a limited efficacy. Objective: The purpose of this work was to evaluate if a higher brain cholinergic stimulation induced by the association between the acetylcholinesterase inhibitor donepezil and the cholinergic precursor choline alphoscerate has any effect on depression in AD patients. Methods: Patients were selected among those recruited in the ASCOMALVA (association between the cholinesterase inhibitor donepezil and the cholinergic precursor choline alphoscerate in AD) trial. Depressive symptoms were investigated in 90 AD patients through the neuropsychiatric inventory at baseline and after 3, 6, 9, 12, 18, and 24 months of treatment. Patients were randomized in a group association therapy (45 subjects) receiving donepezil 10 mg plus choline alphoscerate 1,200 mg/day, and a group monotherapy (45 subjects) receiving donepezil 10 mg/day plus placebo. Based on the results of the MMSE at the recruitment patients were divided into 3 groups: severely impaired (score < 15); moderately impaired (score 19-16); mild-moderately impaired (score 24-20). Results: Depression symptoms were significantly lower (p < 0.05) in patients treated with donepezil plus choline alphoscerate compared to patients treated with donepezil alone. Subjects of the group having mild to moderate cognitive impairment were those more sensitive to the association treatment. Conclusion: Depression symptoms of AD patients in the mild to moderate stage probably could to benefit of a stronger cholinergic stimulation induced by associating donepezil with the cholinergic precursor choline alphoscerate.

Effects of choline containing phospholipids on the neurovascular unit: A review.

The roles of choline and of choline-containing phospholipids (CCPLs) on the maintenance and progress of neurovascular unit (NVU) integrity are analyzed. NVU is composed of neurons, glial and vascular cells ensuring the correct homeostasis of the blood-brain barrier (BBB) and indirectly the function of the central nervous system. The CCPLs phosphatidylcholine (lecithin), cytidine 5'-diphosphocholine (CDP-choline), choline alphoscerate or α-glyceryl-phosphorylcholine (α-GPC) contribute to the modulation of the physiology of the NVU cells. A loss of CCPLs contributes to the development of neurodegenerative diseases such as Alzheimer's disease, multiple sclerosis, Parkinson's disease. Our study has characterized the cellular components of the NVU and has reviewed the effect of lecithin, of CDP-choline and α-GPC documented in preclinical studies and in limited clinical trials on these compounds. The interesting results obtained with some CCPLs, in particular with α-GPC, probably would justify reconsideration of the most promising molecules in larger attentively controlled studies. This can also contribute to better define the role of the NVU in the pathophysiology of brain disorders characterized by vascular impairment.

Artificial Intelligence Models in the Diagnosis of Adult-Onset Dementia Disorders: A Review.

Background: The progressive aging of populations, primarily in the industrialized western world, is accompanied by the increased incidence of several non-transmittable diseases, including neurodegenerative diseases and adult-onset dementia disorders. To stimulate adequate interventions, including treatment and preventive measures, an early, accurate diagnosis is necessary. Conventional magnetic resonance imaging (MRI) represents a technique quite common for the diagnosis of neurological disorders. Increasing evidence indicates that the association of artificial intelligence (AI) approaches with MRI is particularly useful for improving the diagnostic accuracy of different dementia types. Objectives: In this work, we have systematically reviewed the characteristics of AI algorithms in the early detection of adult-onset dementia disorders, and also discussed its performance metrics. Methods: A document search was conducted with three databases, namely PubMed (Medline), Web of Science, and Scopus. The search was limited to the articles published after 2006 and in English only. The screening of the articles was performed using quality criteria based on the Newcastle-Ottawa Scale (NOS) rating. Only papers with an NOS score ≥ 7 were considered for further review. Results: The document search produced a count of 1876 articles and, because of duplication, 1195 papers were not considered. Multiple screenings were performed to assess quality criteria, which yielded 29 studies. All the selected articles were further grouped based on different attributes, including study type, type of AI model used in the identification of dementia, performance metrics, and data type. Conclusions: The most common adult-onset dementia disorders occurring were Alzheimer's disease and vascular dementia. AI techniques associated with MRI resulted in increased diagnostic accuracy ranging from 73.3% to 99%. These findings suggest that AI should be associated with conventional MRI techniques to obtain a precise and early diagnosis of dementia disorders occurring in old age.

An Optimized Decision Tree with Genetic Algorithm Rule-Based Approach to Reveal the Brain's Changes During Alzheimer's Disease Dementia.

BACKGROUND: It is desirable to achieve acceptable accuracy for computer aided diagnosis system (CADS) to disclose the dementia-related consequences on the brain. Therefore, assessing and measuring these impacts is fundamental in the diagnosis of dementia. OBJECTIVE: This study introduces a new CADS for deep learning of magnetic resonance image (MRI) data to identify changes in the brain during Alzheimer's disease (AD) dementia. METHODS: The proposed algorithm employed a decision tree with genetic algorithm rule-based optimization to classify input data which were extracted from MRI. This pipeline is applied to the healthy and AD subjects of the Open Access Series of Imaging Studies (OASIS). RESULTS: Final evaluation of the CADS and its comparison with other systems supported the potential of the proposed model as a novel tool for investigating the progression of AD and its great ability as an innovative computerized help to facilitate the decision-making procedure for the diagnosis of AD. CONCLUSION: The one-second time response, together with the identified high accurate performance, suggests that this system could be useful in future cognitive and computational neuroscience studies.

Tele-Neuropsychological Assessment of Alzheimer's Disease.

BACKGROUND: Because of the new pandemic caused by the novel coronavirus disease (COVID-19), the demand for telemedicine and telemonitoring solutions has been exponentially raised. Because of its special advantage to treat patients in an emergency without physical presence at a hospital via video conferencing, telemedicine has been used to overcome distance barriers and to improve access to special domains like neurology. In these pandemic times, telemedicine has been also employed as a support for the diagnosis and treatment of adult-onset dementia disorders including Alzheimer's disease. OBJECTIVE: In this study, we carried out a systematic literature analysis to clarify if the neuropsychological tests traditionally employed in face-to-face (FTF) contexts are reliable via telemedicine. METHODS: A systematic literature search for the past 20 years (2001-2020) was carried out through the medical databases PubMed (Medline) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL). The quality assessment was conducted by adopting the Newcastle Ottawa Scale (NOS) and only studies with a NOS ≥ 7 were included in this review. RESULTS: The Mini-Mental State Examination (MMSE) results do not differ when tests are administered in the traditional FTF modality or by videoconference, and only negligible minor changes in the scoring system were noticeable. Other neuropsychological tests used to support the diagnosis of AD and dementia such as the Token Test, the Comprehension of Words and Phrases (ACWP), the Controlled Oral Word Association Test showed high reliability between the two modalities considered. No differences in the reliability concerning the living setting or education of the subjects were reported. CONCLUSIONS: The MMSE, which is the main screening test for dementia, can be administered via telemedicine with minor adaptation in the scoring system. Telemedicine use for other neuropsychological tests also resulted in general reliability and enough accuracy. Cognitive assessment by videoconference is accepted and appreciated and therefore can be used for dementia diagnosis in case of difficulties to performing FTF assessments. This approach can be useful given a personalized medicine approach for the treatment of adult-onset dementia disorders.

Improved Alzheimer's Disease Detection by MRI Using Multimodal Machine Learning Algorithms.

Adult-onset dementia disorders represent a challenge for modern medicine. Alzheimer's disease (AD) represents the most diffused form of adult-onset dementias. For half a century, the diagnosis of AD was based on clinical and exclusion criteria, with an accuracy of 85%, which did not allow for a definitive diagnosis, which could only be confirmed by post-mortem evaluation. Machine learning research applied to Magnetic Resonance Imaging (MRI) techniques can contribute to a faster diagnosis of AD and may contribute to predicting the evolution of the disease. It was also possible to predict individual dementia of older adults with AD screening data and ML classifiers. To predict the AD subject status, the MRI demographic information and pre-existing conditions of the patient can help to enhance the classifier performance. In this work, we proposed a framework based on supervised learning classifiers in the dementia subject categorization as either AD or non-AD based on longitudinal brain MRI features. Six different supervised classifiers are incorporated for the classification of AD subjects and results mentioned that the gradient boosting algorithm outperforms other models with 97.58% of accuracy.

Natural Antioxidant Application on Fat Accumulation: Preclinical Evidence.

Obesity represents one of the most important challenges in the contemporary world that must be overcome. Different pathological consequences of these physical conditions have been studied for more than 30 years. The most nagging effects were found early in the cardiovascular system. However, later, its negative impact was also investigated in several other organs. Damage at cellular structures due to overexpression of reactive oxygen species together with mechanisms that cause under-production of antioxidants leads to the development of obesity-related complications. In this view, the negative results of oxidant molecules due to obesity were studied in various districts of the body. In the last ten years, scientific literature has reported reasonable evidence regarding natural and synthetic compounds' supplementation, which showed benefits in reducing oxidative stress and inflammatory processes in animal models of obesity. This article attempts to clarify the role of oxidative stress due to obesity and the opposing role of antioxidants to counter it, reported in preclinical studies. This analysis aims to clear-up different mechanisms that lead to the build-up of pro-oxidants during obesity and how various molecules of different origins hinder this phenomenon, behaving as antioxidants.

Comparative Assessment of the Activity of Racemic and Dextrorotatory Forms of Thioctic (Alpha-Lipoic) Acid in Low Back Pain: Preclinical Results and Clinical Evidences From an Open Randomized Trial.

Peripheral neuropathies, characterized by altered nociceptive and muscular functions, are related to oxidative stress. Thioctic acid is a natural antioxidant existing as two optical isomers, but most clinically used as racemic mixture. The present study investigated the central nervous system's changes which followed loose-ligation-derived compression of sciatic nerve, the putative neuroprotective role of thioctic acid and the pain-alleviating effect on low-back pain suffering patients. Loose ligation of the right sciatic nerve was performed in spontaneously hypertensive rats (SHR), a model of increased oxidative stress, and in normotensive Wistar-Kyoto rats (WKY). Animals with sciatic nerve ligation were left untreated or were treated intraperitoneally for 15 days with 250 µmol·kg-1·die-1 of (+/-)-thioctic acid; 125 µmol·kg-1·die-1 of (+/-)-thioctic acid; 125 µmol·kg-1·die-1 of (+)-thioctic acid lysine salt; 125 µmol·kg-1·die-1 of (-)-thioctic acid; 300 µmol·kg-1·die-1 pregabalin. Control SHR and WKY rats received the same amounts of vehicle. The clinical trial NESTIORADE (Sensory-Motor Neuropathies of the Sciatic Nerve: Comparative evaluation of the effect of racemic and dextro-rotatory forms of thioctic acid) examined 100 patients (49 males and 51 females aged 53 ± 11 years) dividing them into two equal-numbered groups, each treated daily for 60 days with 600 mg of (+/-)-thioctic acid or (+)-thioctic acid, respectively. The trial was registered prior to patient enrollment at EudraCT website (OSSC Number: 2011-000964-81). In the preclinical study, (+)-thioctic acid was more active than (+/-)- or (-)-enantiomers in relieving pain and protecting peripheral nerve as well as in reducing oxidative stress and astrogliosis in the spinal cord. Main findings of NESTIORADE clinical trial showed a greater influence on painful symptomatology, a quicker recovery and a better impact on quality of life of (+)-thioctic acid vs. (+/-)-thioctic acid. These data may have a pharmacological and pharmacoeconomical relevance and suggest that thioctic acid, above all (+)-enantiomer, could be considered for treatment of low-back pain involving neuropathy.

A Comprehensive Machine-Learning Model Applied to Magnetic Resonance Imaging (MRI) to Predict Alzheimer's Disease (AD) in Older Subjects.

Increasing evidence suggests the utility of magnetic resonance imaging (MRI) as an important technique for the diagnosis of Alzheimer's disease (AD) and for predicting the onset of this neurodegenerative disorder. In this study, we present a sophisticated machine learning (ML) model of great accuracy to diagnose the early stages of AD. A total of 373 MRI tests belonging to 150 subjects (age ≥ 60) were examined and analyzed in parallel with fourteen distinct features related to standard AD diagnosis. Four ML models, such as naive Bayes (NB), artificial neural networks (ANN), K-nearest neighbor (KNN), and support-vector machines (SVM), and the receiver operating characteristic (ROC) curve metric were used to validate the model performance. Each model evaluation was done in three independent experiments. In the first experiment, a manual feature selection was used for model training, and ANN generated the highest accuracy in terms of ROC (0.812). In the second experiment, automatic feature selection was conducted by wrapping methods, and the NB achieved the highest ROC of 0.942. The last experiment consisted of an ensemble or hybrid modeling developed to combine the four models. This approach resulted in an improved accuracy ROC of 0.991. We conclude that the involvement of ensemble modeling, coupled with selective features, can predict with better accuracy the development of AD at an early stage.

Volume Analysis of Brain Cognitive Areas in Alzheimer's Disease: Interim 3-Year Results from the ASCOMALVA Trial.

BACKGROUND: Cerebral atrophy is a common feature of several neurodegenerative disorders, including Alzheimer's disease (AD). In AD, brain atrophy is associated with loss of gyri and sulci in the temporal and parietal lobes, and in parts of the frontal cortex and cingulate gyrus. OBJECTIVE: The ASCOMALVA trial has assessed, in addition to neuropsychological analysis, whether the addition of the cholinergic precursor choline alphoscerate to treatment with donepezil has an effect on brain volume loss in patients affected by AD associated with cerebrovascular injury. METHODS: 56 participants to the randomized, placebo-controlled, double-blind ASCOMALVA trial were assigned to donepezil + placebo (D + P) or donepezil + choline alphoscerate (D + CA) treatments and underwent brain magnetic resonance imaging and neuropsychological tests every year for 4 years. An interim analysis of 3-year MRI data was performed by voxel morphometry techniques. RESULTS: The D + P group (n = 27) developed atrophy of the gray and white matter with concomitant increase in ventricular space volume. In the D + CA group (n = 29) the gray matter atrophy was less pronounced compared to the D + P group in frontal and temporal lobes, hippocampus, and amygdala. These morphological data are consistent with the results of the neuropsychological tests. CONCLUSION: Our findings indicate that the addition of choline alphoscerate to standard treatment with the cholinesterase inhibitor donepezil counters to some extent the loss in volume occurring in some brain areas of AD patients. The observation of parallel less pronounced decrease in cognitive and functional tests in patients with the same treatment suggests that the morphological changes observed may have functional relevance.