Consideration of sleep and circadian rhythm in most cited drug research articles related to Alzheimer's disease and dementia

The most typical symptoms of dementia include impairment of cognitive brain functions, such as memory and thinking. Most common forms of dementia include Alzheimer's disease, vascular dementia, Lewy body dementia, and frontotemporal dementia, which is caused by degeneration of the frontotemporal lobe. Alzheimer's disease is the most common form of dementia, covering about 75% of all the cases. The pathophysiology of Alzheimer's disease includes beta-amyloid plaques and tau proteins, which accumulate in the brain, and which have been linked to damage to nerve pathways and the appearance of the typical symptoms of the disease. The disorder is progressive, but the exact cause remains unknown. However, old age (>65 years), the APOE-4 gene, lifestyle, and some comorbidities, such as cardiovascular diseases, are considered risk factors. Even though extensive research has been conducted, there is currently no curative treatment for Alzheimer's disease. Sleep disorders can be both a symptom of Alzheimer's disease and a risk factor for the onset of the disorder. Therefore, the mechanisms of sleep and circadian rhythm are connected to the pathophysiology of Alzheimer's disease, for example through the glymphatic system that cleans the brain mainly during deep sleep. Many drugs for Alzheimer's disease have a recommended time of administration. The dosing time can be very important issue in terms of the effectiveness of the drug. According to a recent study, sleep and circadian rhythm have not been considered in most studies on new rapid-acting antidepressants. Therefore, we carried out an analogous systematic literature review for Alzheimer's disease and dementia. The aim of this study was to find out whether sleep and circadian rhythm have been considered in the most cited preclinical and clinical drug research articles for Alzheimer's disease and dementia during the last decade (2010–2020). In addition, it was examined which drug groups the studied compounds belonged to, and what was the sex distribution of the test subjects in the studies. The number of subjects was also determined from clinical studies, and the animal species from preclinical studies. The research articles analysed in the study were collected with a systematic literature review of Scopus database. The study found that most studies did not include any consideration of sleep or circadian rhythm. Most of the investigated compounds were small molecules, followed by supplements and herbs, and rest classified as biological drugs. Most of the clinical trials were relatively small studies with less than a hundred subjects or hundreds of subjects. Among the 100 most cited clinical research articles, there were 14 reanalyses and observational studies that were not included in this analysis of subject numbers. In clinical studies, most of the test subjects were usually female, while preclinical studies used commonly male animals. To conduct more open and reliable science in the future, drug research should pay more attention to the subjects’ sleep patterns, the time of drug administration, and reporting on these issues in the articles, which is usually part of the requirements of scientific journals. This could potentially narrow the translational gap between preclinical and clinical research.