Plasma levels of HDL and carotenoids are lower in dementia patients with vascular comorbidities

Elevated serum cholesterol concentrations in mid-life increase risk for Alzheimer's disease (AD) in later life. However, lower concentrations of cholesterol-carrying high density lipoprotein (HDL) and its principal apolipoprotein A1 (ApoA1) correlate with increased risk for AD. As HDL transports oxocarotenoids, which are scavengers of peroxynitrite, we have investigated the hypothesis that lower HDL and oxocarotenoid concentrations during AD may render HDL susceptible to nitration and oxidation and in turn reduce the efficiency of reverse cholesterol transport (RCT) from lipid-laden cells. Fasting blood samples were obtained from subjects with 1) AD without cardiovascular comorbidities and risk factors (AD); 2) AD with cardiovascular comorbidities and risk factors (AD Plus); 3) normal cognitive function; for carotenoid determination by HPLC, analysis of HDL nitration and oxidation by ELISA, and 3H-cholesterol export to isolated HDL. HDL concentration in the plasma from AD Plus patients was significantly lower compared to AD or control subject HDL levels. Similarly, lutein, lycopene, and zeaxanthin concentrations were significantly lower in AD Plus patients compared to those in control subjects or AD patients, and oxocarotenoid concentrations correlated with Mini-Mental State Examination scores. At equivalent concentrations of ApoA1, HDL isolated from all subjects irrespective of diagnosis was equally effective at mediating RCT. HDL concentration is lower in AD Plus patients' plasma and thus capacity for RCT is compromised. In contrast, HDL from patients with AD-only was not different in concentration, modifications, or function from HDL of healthy age-matched donors. The relative importance of elevating HDL alone compared with elevating carotenoids alone or elevating both to reduce risk for dementia should be investigated in patients with early signs of dementia

Real-world evidence on siponimod treatment in patients with secondary progressive multiple sclerosis

BACKGROUND: Therapeutic options targeting inflammation in multiple sclerosis (MS) have evolved rapidly for relapsing–remitting MS, whereas few therapies are available for progressive forms of MS, in particular secondary progressive MS (SPMS). The approval of siponimod for SPMS has allowed for optimism in the otherwise discouraging therapeutic landscape. METHODS: We conducted a retrospective, multicenter, non-interventional study analyzing the efficacy and safety of siponimod under real-world conditions in 227 SPMS patients. According to the retrospective study framework, data was acquired at prespecified time points. Clinical readouts were assessed every three months. Disease progression was determined as increase in expanded disability status scale (EDSS), radiological progression, or the occurrence of new relapses under treatment. For safety analyses, adverse events (AE) and reasons for discontinuation were documented. The collected data points were analyzed at baseline and after 6, 12 and 18 months. However, data were predominately collected at the 6- and 12-month time points as many patients were lost to follow-up. In a group consisting of 41 patients, a more detailed investigation regarding disease progression was conducted, including data from measurement of cognitive and motoric functions. RESULTS: Under siponimod therapy, 64.8% of patients experienced sustained clinical disease stability at 12 months. Out of the stable patients 21.4% of patients improved. Of the remaining patients, 31.5% experienced EDSS progression, 3.7% worsened without meeting the threshold for progression. Relapses occurred in 7.4%. Radiological disease activity was detected in 24.1% of patients after six months of treatment and in 29.6% of patients at 12 months follow-up. The in-depth cohort consisting of 41 patients demonstrated no substantial changes in cognitive abilities measured by Paced Auditory Serial Addition Test and Symbol Digit Modalities Test or motoric functions measured with Timed 25-Foot Walk, 100-m timed test, and 9-Hole Peg Test throughout the 12-month study period. Radiological assessment showed a stable volume of white and grey matter, as well as a stable lesion count at 12 months follow-up. AE were observed in nearly half of the included patients, with lymphopenia being the most common. Due to disease progression or AE, 31.2% of patients discontinued therapy. CONCLUSION: Treatment with siponimod had an overall stabilizing effect regarding clinical and radiological outcome measures. However, there is a need for more intensive treatment management and monitoring to identify disease progression and AE. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s42466-022-00219-3

Prevention of Dementia: Focus on Lifestyle

The objective of this paper is to summarize current knowledge on the possible advantages of lifestyle interventions, with particular attention to physical fitness, cognitive activity, leisure and social activity as well as nutrition. There is a large amount of published papers providing partial evidence and asserting the need for immediate, appropriate preventive lifestyle measures against dementia and AD development. Nevertheless, there are currently great difficulties in drafting effective guidelines in this field. This depends mainly upon lack of randomized controlled trials assessing benefits versus risks of particular lifestyle interventions strategies. However, due to the rapid increase of dementia burden, lifestyle factors and their amelioration should be already made part of decision making in light of their health-maintaining effects while awaiting for results of well-designed large prospective cohort studies in dementia

Modulation of cholesterol in midlife affords cognitive advantage during ageing - a role for altered redox balance

General practitioners, geriatricians, neurologists and health care professionals all over the world will be facing by 2040 the diagnostic, therapeutic and socioeconomic challenges of over 80 million people with dementia. Dementia is one of the most common diseases in the elderly which drastically affects daily life and everyday personal activities, is often associated with behavioural symptoms, personality change and numerous clinical complications and increases the risk for urinary incontinence, hip fracture, and – most markedly – the dependence on nursing care. The costs of care for patients with dementia are therefore immense. Serum cholesterol levels above 6.5 mmol/L are known to be associated with an increased RR of 1.5 and 2.1 to develop Alzheimer’s disease, the most common form of dementia, and a reduction of serum cholesterol in midlife is associated with a lowered dementia risk. The aim of this work is to critically discuss some of the main results reported recently in the literature in this respect and to provide the pathophysiological rationale for the control of dyslipidemia in the prevention of dementia onset and progression

Palliativmedizinische Versorgung neurologischer Patienten

Although patients with incurable neurological diseases suffer from a variety of distressing symptoms and may die from their neurological condition and associated complications, palliative and hospice care for these patients to date remains rare. First estimates envisage that on average 10% of all patients suffering from a neurological disease need palliative and hospice care. However, within German neurology departments, only few physicians (on average 1.3/department) and nurses (on average 2.2./department) are specialized in palliative and hospice care and only about 3% of patients cared for in palliative or hospice care structures suffer from neurological diseases (in contrast to patients suffering from oncological diseases, approximately 80%). Responsible for this rather low number is a just gradual increase in the awareness of palliative and hospice care needs for neurological patients and a currently predominant supply of oncological patients in palliative and hospice care structures which are primarily aimed at these patients. In line with this is that the special aspects of neurological patients are currently not adequately addressed in the palliative training curricula of health care professionals. Rather, patients with advanced neurological conditions are medically cared for by general practitioners and by the existing inpatient and outpatient neurological structures, which may also offer sub-specialty services. Consequently, adequate care for severely affected neurological patients becomes difficult as soon as these patients are hardly able to visit these structures since home-based specialist treatment is currently only limitedly carried out and financed. Novel yet to date rare approaches, mostly of international origin, suggest that these patients may benefit from specialized home based services, combining neurological and palliative care expertise. At present, data that characterize the situation of neuro-palliative care in Germany remain scarce. In addition to the already known supply gaps (e.g. low rate of neurologists trained in palliative medicine as well as of nurses working in neurology trained in palliative care, lacking consideration of the specific (care) needs of neurological patients in general and specialized palliative and hospice care structures, hardly available home-based outpatient specialists) research is a prerequisite to identify current gaps in palliative care of neurological patients in more detail and how these might be overcome in the future

A Stepped Health Services Intervention to Improve Care for Mental and Neurological Diseases: Protocol for a Prospective Cohort Trial

BackgroundMental and neurological disorders cause a large proportion of morbidity burden and require adequate health care structures. However, deficits in the German health care system like long waiting times for access to specialized care and a lack of coordination between health care providers lead to suboptimal quality of care and elevated health care costs. ObjectiveTo overcome these deficits, we implement and evaluate a unique stepped and coordinated model of care (the Neurologisch-psychiatrische und psychotherapeutische Versorgung [NPPV] program) for patients with mental and neurological diseases. MethodsPatients included in the program receive an appropriate treatment according to medical needs in a multiprofessional network of ambulatory health care providers. The therapy is coordinated by a managing physician and complemented by additional therapy modules, such as group therapy, internet-based cognitive behavioral therapy, and a case management. Statutory health insurance (SHI) routine data and data from a longitudinal patient survey will be used to compare the program with regular care and evaluate SHI expenditures and patient-related outcomes. A health care provider survey will evaluate the quality of structure and processes and provider satisfaction. Finally, an analysis of ambulatory claims data and drug prescription data will be used to evaluate if health care providers follow a needs-led approach in therapy. Ethics approval for this trial was obtained from the ethics committee of the chamber of physicians in North Rhine (September 13, 2017, reference No. 2017287). ResultsPatient enrollment of NPPV ended in September 2021. Data analysis has been completed in 2022. The results of this study will be disseminated through scientific publications, academic conferences, and a publicly available report to the German Federal Joint Committee, which is expected to be available in the first half of 2023. ConclusionsThe NPPV program is the first intervention to implement a stepped model of care for both mental and neurological diseases in Germany. The analysis of several data sources and a large sample size (more than 14,000 patients) enable a comprehensive evaluation of the NPPV program. Trial RegistrationGerman Clinical Trials Register DRKS00022754; https://tinyurl.com/3mx9pz5z. International Registered Report Identifier (IRRID)DERR1-10.2196/3756