![]() These measures were similar between trazodone users and non-users, indicating successful propensity matching ( Table 1). ![]() Trazodone users were propensity matched to 25 participants who did not use trazodone, according to age, sex, education, diagnostic group, type, and severity of sleep deficit, and baseline MMSE ( Fig. 1). The median prescribed dosage was 50 mg per day before bedtime (25th percentile 50 mg 75th percentile 100-125 mg), consistent with insomnia, rather than antidepressant, dosing. Detailed longitudinal dosage and indication for trazodone use was available for 16 out of 25 trazodone users, all of which listed insomnia as the reason for trazodone use. From the eligible pool of volunteers, we identified 25 participants who reported regular trazodone use for at least two consecutive annual visits. Molecular AD biomarkers were available for 14 participants (amyloid PET performed in eleven and CSF amyloid- β/tau levels obtained in five two participants underwent both tests). The diagnoses of AD, amnestic MCI, and non-amnestic MCI were made using NINCDS-ADRDA criteria for probable AD, and the MCI criteria developed by Petersen et al. Since only two participants had severe sleep symptoms, sleep variables were binarized as present or absent at each visit for further analysis. ![]() Presence of insomnia, hypersomnia, or parasomnia was documented by a physician in an ordinal manner as absent, mild (i.e., present and not interfering significantly with daily function), or severe (i.e., interfering significantly with daily function) ( Table 1). All participants provided informed consent according to the Declaration of Helsinki. We identified participants from the UCSF Memory and Aging Center cohort who satisfied the following criteria: 1) presence of sleep disturbances (insomnia, hypersomnia, or parasomnia) as documented on the National Alzheimer’s Coordinating Center assessment form, 2) longitudinal clinical, medication, and neuropsychological data, 3) and diagnostically grouped as AD, mild cognitive impairment (MCI), or cognitively non-impaired (CN) on their first visit ( Fig. 1). To test whether such an association exists, we retrospectively analyzed longitudinal cognitive decline trajectories dependent on prolonged use of trazodone in volunteers from our research cohort. We thus hypothesized that trazodone, a SWS enhancer, may correlate with delayed cognitive decline over prolonged use. To date, no studies have assessed long-term effects of trazodone on cognitive performance. ![]() Although these studies did not reveal a change in cognitive performance, improvement or worsening, they were too short in duration to observe possible SWS-mediated effects on course of neurodegeneration, and did not specifically test overnight sleep-mediated memory consolidation that may have been a more sensitive test for sleep-mediated synaptic potentiation. Furthermore, there were no cognitive side effects or daytime somnolence after a 2-week intervention period, thus diminishing concerns for possible cholinergic, α-adrenergic, or histaminergic antagonistic effects in sleep-promoting doses. While melatonin, ramelteon, or mirtazapine use did not produce significant improvement on sleep measures, trazodone, previously shown to enhance SWS by 50–56% on polysomnography in younger and older adults, increased total sleep time by 42.5 minutes on actigraphy in patients with AD. Several double-blind randomized placebo-controlled trials for sleep consolidation in AD have tested the effectiveness of commonly used hypnotic agents: melatonin, ramelteon, mirtazapine, and trazodone. Furthermore, patients with AD have less SWS, and cognitively non-impaired adults with decreased SWS exhibit increased amyloid- β burden and worse sleep-mediated episodic memory consolidation. Recent studies in transgenic mouse models of Alzheimer’s disease (AD) reveal that SWS restriction accelerates activity-dependent amyloid- β aggregation, whereas SWS enhancement delays aggregation. SWS in humans, as part of non-rapid eye movement (NREM) sleep, mediates episodic memory consolidation. Sleep changes with aging include decreased total sleep time and efficiency, increased waking after sleep onset, and decreased slow wave sleep (SWS). Sleep disorders increase in frequency with aging, and their manifestation, even in cognitively non-impaired individuals, can be a harbinger of subsequent cognitive decline.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |