Background: Caffeine is a central nervous system stimulant that influences both the sleep-wake cycle and the circadian clock and is known to influence neuronal activity in the lateral hypothalamus,... Show moreBackground: Caffeine is a central nervous system stimulant that influences both the sleep-wake cycle and the circadian clock and is known to influence neuronal activity in the lateral hypothalamus, an important area involved in sleep-wake regulation. Light is a strong zeitgeber and it is known to interact with the effect of caffeine on the sleep-wake cycle. We therefore wanted to investigate the long-term effects of a single dose of caffeine under constant dark conditions. Methods: We performed long-term (2 days) electroencephalogram (EEG)/electromyogram recordings combined with multi-unit neuronal activity recordings in the peduncular part of the lateral hypothalamus (PLH) under constant darkness in Brown Norway rats, and investigated the effect of a single caffeine treatment (15 mg/kg) or saline control given 1 h after the onset of the endogenous rest phase. Results: After a reduction in sleep and an increase in waking and activity in the first hours after administration, also on the second recording day after caffeine administration, rapid eye movement (REM) sleep was still reduced. Analysis of the EEG showed that power density in the theta range during waking and REM sleep was increased for at least two days. Neuronal activity in PLH was also increased for two days after the treatment, particularly during non-rapid eye movement sleep. Conclusion: Surprisingly, the data reveal long-term effects of a single dose of caffeine on vigilance states, EEG, and neuronal activity in the PLH. The absence of a light-dark cycle may have enabled the expression of these long-term changes. It therefore may be that caffeine, or its metabolites, have a stronger and longer lasting influence, particularly on the expression of REM sleep, than acknowledged until now. Show less
Background: Whether certain activities can trigger spontaneous intracerebral hemorrhage (ICH) remains unknown. Insights into factors that trigger vessel rupture resulting in ICH improves knowledge... Show moreBackground: Whether certain activities can trigger spontaneous intracerebral hemorrhage (ICH) remains unknown. Insights into factors that trigger vessel rupture resulting in ICH improves knowledge on the pathophysiology of ICH. We assessed potential trigger factors and their risk for ICH onset. Methods: We included consecutive patients diagnosed with ICH between July 1, 2013, and December 31, 2019. We interviewed patients on their exposure to 12 potential trigger factors (eg, Valsalva maneuvers) in the (hazard) period soon before onset of ICH and their normal exposure to these trigger factors in the year before the ICH. We used the case-crossover design to calculate relative risks (RR) for potential trigger factors. Results: We interviewed 149 patients (mean age 64, 66% male) with ICH. Sixty-seven (45%) had a lobar hemorrhage, 60 (40%) had a deep hemorrhage, 19 (13%) had a cerebellar hemorrhage, and 3 (2%) had an intraventricular hemorrhage. For ICH in general, there was an increased risk within an hour after caffeine consumption (RR=2.5 [95% CI=1.8-3.6]), within an hour after coffee consumption alone (RR=4.8 [95% CI=3.3-6.9]), within an hour after lifting >25 kg (RR=6.6 [95% CI=2.2-19.9]), within an hour after minor head trauma (RR=10.1 [95% CI=1.7-60.2]), within an hour after sexual activity (RR=30.4 [95% CI=16.8-55.0]), within an hour after straining for defecation (RR=37.6 [95% CI=22.4-63.4]), and within an hour after vigorous exercise (RR=21.8 [95% CI=12.6-37.8]). Within 24 hours after flu-like disease or fever, the risk for ICH was also increased (RR=50.7 [95% CI=27.1-95.1]). Within an hour after Valsalva maneuvers, the RR for deep ICH was 3.5 (95% CI=1.7-6.9) and for lobar ICH the RR was 2.0 (95% CI=0.9-4.2). Conclusions: We identified one infection and several blood pressure related trigger factors for ICH onset, providing new insights into the pathophysiology of vessel rupture resulting in ICH. Show less
Objective Although behavioral changes are common in nursing home residents with dementia and caffeine is known to influence behavior in healthy adults, the effects of caffeine on the behavior of... Show moreObjective Although behavioral changes are common in nursing home residents with dementia and caffeine is known to influence behavior in healthy adults, the effects of caffeine on the behavior of persons with dementia has received little attention. In this study we assessed the relationship of caffeine and behavioral symptoms in older persons with dementia. Design A multicenter sub-cohort study embedded in the Elderly Care Physicians (ECP) training program. Setting Dutch nursing homes associated with the ECP training program. Participants A total of 206 individuals with both diabetes and dementia resident in Dutch nursing homes. Measurements Trainee ECPs collected data on caffeine consumption, cognition and behavioral symptoms using the NPI-NH, MDS-DRS and AES-C. Data on factors known to influence behavior in persons with dementia (e.g. marital status, kidney function, urinary tract infection and medication) were also collected. Results Of the 206 participants, 70% showed behavioral symptoms. An increase in caffeine consumption was associated with a decrease in the presence of behavioral symptoms in the NPI-NH cluster affect and NPI-NH item agitation. Caffeine consumption groups also differed on the presence of disinhibition and depression. In addition, the severity of dementia influenced agitation, anxiety and the clusters affect and psychomotor. Conclusion In a large group of older persons with dementia resident in nursing homes, a low daily consumption of caffeine was associated with greater behavioral symptoms. Show less
