Disease-modifying treatment strategies for Alzheimer disease (AD) are still under extensive research. Nowadays, only symptomatic treatments exist for this disease, all trying to counterbalance the neurotransmitter disturbance: 3 cholinesterase inhibitors and memantine. To block the progression of the disease, therapeutic agents are supposed to interfere with the pathogenic steps responsible for the clinical symptoms, classically including the deposition of extracellular amyloid β plaques and intracellular neurofibrillary tangle formation. Other underlying mechanisms are targeted by neuroprotective, anti-inflammatory, growth factor promotive, metabolic efficacious agents and stem cell therapies. Recent therapies have integrated multiple new features such as novel biomarkers, new neuropsychological outcomes, enrollment of earlier populations in the course of the disease, and innovative trial designs. In the near future different specific agents for every patient might be used in a “precision medicine” context, where aberrant biomarkers accompanied with a particular pattern of neuropsychological and neuroimaging findings could determine a specific treatment regimen within a customized therapeutic framework. In this review, we discuss potential disease-modifying therapies that are currently being studied and potential individualized therapeutic frameworks that can be proved beneficial for patients with AD.

Alzheimer's dementia (AD) is increasingly being recognized as one of the most important medical and social problems in older people in industrialized and non-industrialized nations. To date, only symptomatic treatments exist for this disease, all trying to counterbalance the neurotransmitter disturbance. Three cholinesterase inhibitors (CIs) are currently available and have been approved for the treatment of mild to moderate AD. A further therapeutic option available for moderate to severe AD is memantine, an N-methyl-D-aspartate receptor noncompetitive antagonist. Treatments capable of stopping or at least effectively modifying the course of AD, referred to as 'disease-modifying' drugs, are still under extensive research. To block the progression of the disease they have to interfere with the pathogenic steps responsible for the clinical symptoms, including the deposition of extracellular amyloid β plaques and intracellular neurofibrillary tangle formation, inflammation, oxidative damage, iron deregulation and cholesterol metabolism. In this review we discuss current symptomatic treatments and new potential disease-modifying therapies for AD that are currently being studied in phase I-III trials.

Despite all scientific efforts and many protracted and expensive clinical trials, no new drug has been approved by FDA for treatment of Alzheimer disease (AD) since 2003. Indeed, more than 200 investigational programs have failed or have been abandoned in the last decade. The most probable explanations for failures of disease-modifying treatments (DMTs) for AD may include late initiation of treatments during the course of AD development, inappropriate drug dosages, erroneous selection of treatment targets, and mainly an inadequate understanding of the complex pathophysiology of AD, which may necessitate combination treatments rather than monotherapy. Clinical trials’ methodological issues have also been criticized. Drug-development research for AD is aimed to overcome these drawbacks. Preclinical and prodromal AD populations, as well as traditionally investigated populations representing all the clinical stages of AD, are included in recent trials. Systematic use of biomarkers in staging preclinical and prodromal AD and of a single primary outcome in trials of prodromal AD are regularly integrated. The application of amyloid, tau, and neurodegeneration biomarkers, including new biomarkers—such as Tau positron emission tomography, neurofilament light chain (blood and Cerebrospinal fluid (CSF) biomarker of axonal degeneration) and neurogranin (CSF biomarker of synaptic functioning)—to clinical trials allows more precise staging of AD. Additionally, use of Bayesian statistics, modifiable clinical trial designs, and clinical trial simulators enrich the trial methodology. Besides, combination therapy regimens are assessed in clinical trials. The above-mentioned diagnostic and statistical advances, which have been recently integrated in clinical trials, are relevant to the recent failures of studies of disease-modifying treatments. Their experiential rather than theoretical origins may better equip potentially successful drug-development strategies.

Background The novel coronavirus disease (COVID‐19) was first detected in Mainland China in December 2019, and soon it spread throughout the world, with multiple physical and psychological consequences across the affected populations. Aims The aim of the current study was to analyze the impact of COVID‐19 pandemic on older adults with mild cognitive impairment (MCI)/dementia and their caregivers as well. Materials and Methods Two hundred and four caregivers took part in the study, completing a self‐reported questionnaire about the person with MCI/dementia and their own, since the lockdown period which started in February and ended in May of 2020 in Greece. Results Results indicated a significant overall decline of the people with MCI/dementia. Further, the domains in which people with MCI/dementia were mostly affected were: communication, mood, movement and compliance with the new measures. Caregivers also reported a great increase in their psychological and physical burden during this period, where the available support sources were limited. Discussion The pandemic threatens to disrupt the basic routines that promote mental and physical health of both people with MCI/dementia and t heir caregivers. Conclusion Further measures to protect and provide support to people who suffer and their families are needed.

Current views suggest that prothrombotic properties of antiphospholipid antibodies (aPL) have a role in the development of acute transverse myelitis (ATM) in patients with systemic lupus erythematosus (SLE). Consequently, empiric anticoagulation may be included in these patients' treatment. We performed a systemic review of the literature to explore the clinical value of the presence of aPL in patients with lupus myelitis and the possible effectiveness of anticoagulation. We analyzed clinical and laboratory data extracted from published cases of SLE-associated ATM, fulfilling the Transverse Myelitis Consortium Working Group diagnostic criteria, that provided information on aPL. We report on a total of 70 patients. aPL, detected upon ATM onset in 54% of patients, neither predicted the involvement of the thoracic part of the spine, which has been postulated to reflect a predominantly thrombosis-induced injury, nor correlated with relapsing ATM, additional lupus CNS manifestations, or worse clinical outcome. An unfavorable outcome could be predicted by paralysis (P=0.02) and abnormal CSF findings at presentation (P=0.02). Whilst all patients received major immunosuppressive regimens, severe neurologic impairment (estimated Expanded Disability Status Scale score>7) was found primarily in aPL-negative patients (P=0.03). Anticoagulation was more frequently applied in aPL-positive patients (P=0.04), but any additional therapeutic effect was not evident. Detection of circulating aPL at ATM onset appears unreliable to suggest a thrombotic cause and perhaps not enough to dictate therapeutic anticoagulation. Registry creation of ATM in patients with SLE is needed to obtain more definite answers on the role of aPL in this condition.