These data indicate that Alzheimer's disease causes disturbances of circadian rhythms and that sundowning is related to a phase delay of body temperature caused by Alzheimer's disease.

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Background: Caregiver exhaustion is a frequent consequence of sleep disturbance and rest-activity rhythm disruption that occurs in dementia. This exhaustion is the causal factor most frequently cited by caregivers in making the decision to institutionalize patients with dementia. Recent studies have implicated dysfunction of the circadian pacemaker in the etiology of these disturbances in dementia.

Background Patients treated with anti-CD20 therapy are particularly at risk of developing severe COVID-19, however little is known regarding COVID-19 vaccine effectiveness in this population. Methods This prospective observational cohort study assesses humoral and T-cell responses after vaccination with 2 doses of mRNA-based COVID-19 vaccines in patients treated with rituximab for rheumatic diseases or ocrelizumab for multiple sclerosis (n=37), compared to immunocompetent individuals (n=22). Results SARS-CoV-2-specific antibodies were detectable in only 69.4% of patients and at levels that were significantly lower compared to controls who all seroconverted. In contrast to antibodies, Spike (S)-specific CD4+ T cells were equally detected in immunocompetent and anti-CD20 treated patients (85-90%) and mostly of a Th1 phenotype. Response rates of S-specific CD8 + T cells were higher in ocrelizumab (96.2%) and rituximab-treated patients (81.8%) as compared to controls (66.7%). S-specific CD4 + and CD8 + T cells were polyfunctional but expressed more activation markers in patients than in controls. During follow-up, three MS patients without SARS-CoV-2-specific antibody response had a mild breakthrough infection. One of them had no detectable S-specific T cells after vaccination. Conclusions Our study suggests that patients on anti-CD20 treatment are able to mount potent T-cell responses to mRNA COVID-19 vaccines, despite impaired humoral responses. This could play an important role in the reduction of complications of severe COVID-19.

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