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

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 bett

Benzodiazepine prescriptions on merchant ships without a doctor on board: analysis from medical records of Centro Internazionale Radio Medico (CIRM)

Background: Benzodiazepines are drugs widely used for the treatment of anxiety and insomnia. The present study has analysed the prescriptions of this class of drugs among sailing seafarers, to evaluate the appropriateness of prescribed therapies. Materials and methods: This study assessed the benzodiazepine prescriptions made by Centro Internazionale Radio Medico (CIRM) doctors from 2011 to 2015. A total of 17,844 medical records were examined. Analysis considered the prescriptions of benzodiazepines in monotherapy, or in association with other drugs. Diagnoses of pathologies for which benzodiazepines were prescribed were made according to the ICD-10 classification system proposed by the World Health Organisation. Results: Among medical records analysed, benzodiazepines were prescribed in 765 cases (3.29% of total cases assisted by CIRM). Benzodiazepines were prescribed as a single-drug treatment in 626 (81.83%) cases, whereas in 139 cases they were associated with other classes of drugs. In case of opioids prescribed in association with benzodiazepines, the drug used was codeine. This therapeutic association was prescribed in cases of severe pain. Conclusions: Although the “off label” use of benzodiazepines is not uncommon in medical practice, clear evidence indicates their potential side effects for human health. In this respect, medical professionals should comply with international guidelines on the use of benzodiazepines, both when prescribed as a single drug or in combination with other classes of drugs. These recommendations should be considered seriously in case of limited medical facilities such as on board of sailing ships.

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

Arylsulphatase A activity and sulphatide concentration in placenta, membranes and cord after delivery

Aim: We evaluated variations in behavior of arylsulphatase A activity (an enzyme that catabolizes sulphatides) and of sulphatide concentration in the placenta, cord and membranes of healthy gravidas at term pregnancy, following spontaneous birth. Methods: We extracted and biochemically determined arylsulphatase A and sulphatide concentration in placenta, cord and membranes (far from and close to internal uterine os) in 14 patients. Results: Activity of arylsulphatase A decreased in the cord, in membranes far from the internal uterine os, in membranes close to the internal uterine os and in the placenta. Sulphatide concentration was minimal in the cord and maximal in placenta, with intermediate values in the membranes. No correlation was found between arylsulphatase A activity and sulphatide concentration, nor among arylsulphatase A activities, nor among sulphatide concentrations among the different tissues. It seems that multiparity may increase and the duration of active labor may decrease arylsulphatase A activity in membranes far from the internal uterine os, while active labor duration does not appear to have any implication on sulphatide concentration in membranes close to the internal uterine os. Conclusions: Arylsulphatase A activities and sulphatide concentrations in fetal adnexa show significant differences.Peer Reviewe

The Effect of the Association between Donepezil and Choline Alphoscerate on Behavioral Disturbances in Alzheimer's Disease: Interim Results of the ASCOMALVA Trial

BACKGROUND: Behavioral and psychological symptoms of dementia (BPSD) are a group of psychological reactions, psychiatric symptoms, and behaviors commonly found in Alzheimer's disease (AD). Four clusters of BPSD have been described: mood disorders (depression, anxiety, and apathy), psychotic symptoms (delusions and hallucinations), aberrant motor behaviors (pacing, wandering, and other purposeless behaviors), and inappropriate behaviors (agitation, disinhibition, and euphoria). Most of them are attributed to acetylcholine deficiency. OBJECTIVE: To evaluate if a higher amount of acetylcholine obtained by associating donepezil and choline alphoscerate might have a favorable effect on BPSD. METHODS: BPSD were measured at baseline and after 24 months in 113 mild/moderate AD patients, included in the double-blind randomized trial ASCOMALVA, by the Neuropsychiatric Inventory (NPI). Two matched groups were compared: group A treated with donepezil (10 mg/day) plus choline alphoscerate (1200 mg/day), and group B treated with donepezil (10 mg/day) plus placebo. RESULTS: Data of NPI revealed a significant decrease of BPSD severity and distress of the caregiver in patients of group A compared with group B. Mood disorders (depression, anxiety and apathy) were significantly decreased in subjects treated with donepezil and choline alphoscerate, while their severity and frequency was increased in the other group. CONCLUSIONS: Patients treated with donepezil plus choline alphoscerate showed a lower level of behavioral disturbances than subjects treated with donepezil only, suggesting that the association can have beneficial effect

The Psychological General Well-Being Index (PGWBI) for assessing stress of seafarers on board merchant ships

Background: In their working activity, seafarers are exposed to high levels of stress that should be accuratelyinvestigated, measured, followed up and, if possible, countered. This is also required by regulations recently entered into force such as the Maritime Labour Convention 2006, recommending to consider special physiological or psychological problems created by the shipboard environment. The choice of the tools for this evaluation is challenging, and a common basic standard usable in a large scale should be identified.Aim: The aim of this study was to evaluate: 1) the suitability of the Psychological General Well-Being Index (PGWBI) questionnaire conducted on board for assessing stress in the sailing seafarers, 2) The presenceof stress in seafarers of different categories (deck officers, engine officers, deck crew, engine crew, chiefstewards/catering staff) monitored by the PGWBI.Materials and methods: 162 male seafarers on board of 7 tankers belonging to the same shipping companywere evaluated through the PGWB questionnaire. Analysis of variance (ANOVA) was used to analyse thedifferences in the scores of the questionnaire.Results: Engine officers exhibited significantly higher anxiety levels than the deck or engine crew, andshowed lower satisfaction than the deck crew. Deck and engine officers revealed higher self-control levelsthan the engine crew. Chief stewards/catering staff showed lower vitality levels than the deck crew.Conclusions: Deck or engine officers should achieve a greater self-control than the crew and this is documentedby the present study. Our findings support the view that management responsibility is more often associated with higher levels of stress. In our opinion, the PGWB questionnaire is a reasonable compromise forobtaining a global evaluation of psychological conditions, including stress of seafarers. It should be therefore considered as a large scale tool for assessing the well-being and eventual stress levels of sailing seafarers

Immunological pattern alteration in shoe, hide, and leather industry workers exposed to exavalent chromium

The aim of this work was to assess the effects of hexavalent chromium [Cr(VI)] on shoe, leather, and hide industry workers, based on the assumption that Cr(VI) can behave as an environmental immunological "stressor." The immunological patterns of 84 male subjects were studied in relation to Cr(VI) hematic and urinary levels. Cr(VI) was measured through atomic absorption. Lymphocyte subsets, mitogen-mediated lymphocyte-proliferation, cytokine levels, and natural killer (NK) cytotoxic activity were also assayed. RESULTS: The urinary levels of the total amount of Cr(VI) were significantly higher in a subgroup of exposed subjects (group B) than in the control or in the lower exposed (group A). In group B, Cr(VI) caused a decrease in the density of glucocorticoid receptors (GR) on peripheral blood mononuclear cells (PBMC) and a increase of IL-6. Cr(VI) did not modify NK-mediated cytotoxicity, the plasmatic levels of inflammatory cytokines and related soluble receptors, and prostaglandin levels, while it tended to increase lymphocyte sensitivity to mitogens and the production of immunomodulant cytokines (IFN-gamma, IL-4, and IL-2). The experimental addition of Cr(VI) to the in vitro lymphocyte culture determined a significant inhibition of phagocytosis percentage, index, and killing percentage. These effects were neutralized by exogenous IFN-gamma. Cr(VI) could represent an environmental immunological stressor whose effects can be evaluated through laboratory surveys. The lymphocyte mitogen-induced proliferation, GR receptor on PBMC, and IL-6 plasma levels may represent a discriminating element between Cr(VI)-induced stress and other kinds of stress

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

Brain volume changes in Alzheimer’s disease patients treated with a cholinesterase inhibitor plus the cholinergic precursor choline alphoscerate

Cholinergic precursors have represented the first approach recognized from a regulatory point of view to counter cognitive impairment occurring in adult-onset dementia disorders. ASCOMALVA [Effect of association between a cholinesterase inhibitor (ChE-I) and choline alphoscerate on cognitive deficits in AD associated with cerebrovascular injury] is a double-blind, controlled, randomized clinical trial investigating if the ChE-I donepezil and the cholinergic precursor choline alphoscerate in combination are more effective that donepezil alone. In this study, MRI from ACOMALVA patients were analyzed for the evaluation of brain atrophy. Participants to the ASCOMALVA trial underwent yearly MRI for diagnostic purposes. In 56 patients who achieved two years of therapy, MRI scans were analyzed by voxel morphometry techniques to assess if addition of choline alphoscerate to treatment with donepezil had an effect on brain volume changes known to occur in AD. Reference group patients (treated with donepezil alone) developed a greater atrophy of the gray and white matter compared with the group treated with donepezil plus choline alphoscerate. In the reference group a concomitant increase of the space of the cerebrospinal fluid and of the volume of the ventriculi was noticeable. One of the most affected areas was the hippocampus. Neuropsycological tests over the 24-month observation period showed in patients of the reference group a moderate time-dependent worsening in all the parameters investigated. Treatment with donepezil plus choline alphoscerate resulted in better scores of the cognitive and functional items and in an improvement in behavioural parameters, superior to that induced by donepezil alone. The above results have shown that treatment with choline alphoscerate plus donepezil versus donepezil alone counters to some extent hippocampal volume loss occurring in the brain of AD patients. The observation of a parallel improvement of cognitive and functional tests in patients treated with the cholinergic precursor loading strategy using choline alphoscerate indicates that morphological changes observed by MRI may have functional relevance