Search

Cognitive impairment affiliated with neurological disorders has a severe impact on daily life functioning and the quality of life of patients. This is associated with a significant and long-lasting health, social and financial burden, not only for the patients, but also for families and the wider society. However, treatment for cognitive impairment is only available for the indication Alzheimer's disease (AD) and its prodromal stage Mild Cognitive Impairment (MCI), although with major adverse effects, i.e. gastrointestinal effects (drugs) or hemorrhages (antibodies). Roflumilast (selective phosphodiesterase type 4 (PDE4) inhibitor) has been approved as an anti-inflammatory drug for the treatment of chronic obstructive pulmonary disease (COPD), although still 5 % of the patients experience nausea or even vomiting at the approved dose of 500 μg. Nonclinical studies demonstrated that roflumilast appears a promising drug the treat cognitive impairment in healthy rodents and a wide variety of animal models of CNS disorders. These effects are attributed to pro-neuroplasticity and anti-inflammatory effects, which appeared dose dependent. Roflumilast has also been tested in clinical studies and showed cognition enhancement at low dosing (100-250 µg) in healthy adults, healthy elderly, MCI and schizophrenia. Currently, clinical trials are underway for testing the pro-cognitive effects in early AD, post stroke cognitive impairment and Fragile X. Overall, the data showed that roflumilast has beneficial effects on cognitive performance. These cognition-enhancing effects are found at doses that were well-tolerated. Based on this favorable therapeutic window, the repurposing of roflumilast for treating cognitive impairments in CNS diseases may offer an affordable treatment option for patients., Competing Interests: Declaration of Competing Interest Jos Prickaerts, Arjan Blokland and Anke Sambeth have a proprietary interested in roflumilast for the treatment of cognitive impairment., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.) more...

Background: Increasing life expectancy in high-income countries has been linked to a rise in fall mortality. In the Netherlands, mortality rates from falls have increased gradually from the 1950s, with some indication of stabilisation in the 1990s. For population health and clinical practice, it is important to foresee the future fall mortality trajectories., Methods: A graphical approach was used to explore trends in mortality by age, calendar period and cohorts born in the periods of 1915-1945. Population data and the numbers of people with accidental fall fatality as underlying cause of death from 1990 to 2021 were derived from Statistics Netherlands. Age-standardised mortality rates of unintentional falls per 100 000 population were calculated by year and sex. A log-linear model was used to examine the separate effects of age, period and cohort on the trend in mortality and to produce estimates of future numbers of fall deaths until 2045., Results: While the total population increased by 17% between 1990 and 2021, absolute numbers of fall-related deaths rose by 230% (from 1584 to 5234), which was 251% (an increase of 576 deaths in 1990 to 2021 deaths in 2020) for men and 219% (from 1008 to 3213) for women. Age-standardised figures were higher for women than men and increased more over time. In 2020, 79% of those with death due to falls were over the age of 80, and 35% were 90 years or older. From 2020 to 2045, the observed and projected numbers of fall deaths were 2021 and 7073 for men (250% increase) and 3213 and 12 575 for women (291% increase)., Conclusion: Mortality due to falls has increased in the past decades and will continue to rise sharply, mainly caused by growing numbers of older adults, especially those in their 80s and 90s. Contributing risk factors are well known, implementation of preventive measures is a much needed next step. An effective approach to managing elderly people after falls is warranted to reduce crowding in the emergency care and reduce unnecessary long hospital stays., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.) more...