Effects of Circadian Phase Tailored Light Therapy on Sleep, Mood, and Cognition in Alzheimer’s Disease: Preliminary Findings in a Pivotal Study

It is shown that the circadian system is affected in patients with Alzheimer’s disease (AD) even at an early stage of the disease and that such dysfunction may be detrimental to sleep, mood, and cognitive functioning. Light is a strong central modulator of the circadian rhythms and is potentially beneficial to mood and cognitive functioning via a direct effect or indirectly via its modulating effects on circadian rhythms. This study focuses on tracking the effect of light therapy on sleep quality, mood, and cognition in AD of mild/moderate severity. We performed a single-blind randomized controlled trial to investigate the effects of a light therapy treatment tailored to the individual circadian phase as measured by dim light melatonin onset (DLMO). Such a treatment induced an objective circadian phase shift consistent with the melatonin phase response curve to light exposure, led to a shortening of the phase angle DLMO-falling asleep time, and was associated with an improvement in subjective sleep quality and cognitive performance.

The Effects of Bipolar Disorder Risk on a Mobile Phone Keystroke Dynamics Based Biomarker of Brain Age

Background: Research by our group and others have demonstrated the feasibility of using mobile phone derived metadata to model mood and cognition. Given the effects of age and mood on cognitive performance, it was hypothesized that using such data a model could be built to predict chronological age and that differences between predicted age and actual age could be a marker of pathology.Methods: These data were collected via the ongoing BiAffect study. Participants complete the Mood Disorders Questionnaire (MDQ), a screening questionnaire for bipolar disorder, and self-reported their birth year. Data were split into training and validation sets. Features derived from the smartphone kinematics were used to train random forest regression models to predict age. Prediction errors were compared between participants screening positive and negative on the MDQ.Results: Three hundred forty-four participants had analyzable data of which 227 had positive screens for bipolar disorder and 117 had negative screens. The absolute prediction error tended to be lower for participants with positive screens (median 4.50 years) than those with negative screens (median 7.92 years) (W = 508, p = 0.0049). The raw prediction error tended to be lower for participants with negative screens (median = −5.95 years) than those with positive screens (median = 0.55 years) (W = 1,037, p= 0.037).Conclusions: The tendency to underestimate the chronological age of participants screening negative for bipolar disorder compared to those screening positive is consistent with the finding that bipolar disorder may be associated with brain changes that could reflect pathological aging. This interesting result could also reflect that those who screen negative for bipolar disorder and who engaged in the study were more likely to have higher premorbid functioning. This work demonstrates that age-related changes may be detected via a passive smartphone kinematics based digital biomarker.

Debunking the myth of ‘Blue Mondays’: No evidence of affect drop after taking clinical MDMA

Background: Incorporating 3,4-methylenedioxymethamphetamine (MDMA) as an adjunct to psychotherapy has shown promise in recent years for treating various mental health conditions, particularly those involving trauma. However, concerns about declines in mood and cognition during the days following dosing, also known as ‘Blue Mondays’, have been raised as limitations to its clinical use. Although these changes have been well-documented among recreational users, there are critical confounds to these reports that limit generalizability to clinically administered MDMA. Aims: Here, we aimed to evaluate the evidence basis for the negative side effects associated with MDMA as well as inform our understanding of the drug’s post-acute effects in a clinical context with an open-label study. Methods: The current open-label study examined MDMA therapy for alcohol use disorder (AUD; N = 14) and measured mood, sleep quality, illicit MDMA consumption and anecdotal reports after the acute drug effects had worn off. Results: Participants maintained a positive mood during the week following drug administration in a clinical context. Relative to baseline, self-reported sleep quality improved at the 3- and 6-month follow-ups. Finally, no participants reported using or desiring to use illicit MDMA, and the anecdotal reports indicated that they perceived the treatment favourably. Conclusion: The results support the overall safety and tolerability of clinically administered MDMA and, importantly, suggest that the ‘come downs’ previously associated with the substance may be explained by confounds in research relating to the illicit sourcing of the drug and specific environmental setting for recreational consumption.

The Role of Testosterone in Menopause Management: A Review of Literature

Background: Despite the lack of approved testosterone formulations for women in most countries, testosterone therapy is still being offered to women worldwide. Aging and loss of ovarian or adrenal function, among others, can lower testosterone levels in women. However, international guidelines currently do not routinely recommend androgen replacement therapy due to lack of long-term safety data. Evidence on its benefits and risks still remains uncertain. Objectives: The aim of this literature review is to present current studies and guidelines that examined the effects of testosterone therapy for postmenopausal women, including its role on cognition and mood; breast and endometrial cancer risks; musculoskeletal, cardiovascular, and genitourinary health; and sexual function. Methodology: A review of literature was done using PubMed, EMBASE, Science Direct, OVID, and Google scholar, with the following key words: androgen, testosterone, menopause, and hypoactive sexual desire dysfunction. We identified reviews, clinical trials, and guidelines. The population was limited to postmenopausal women. Results: There is no evidence from current published literature to support the use of testosterone therapy for female well-being, mood and cognition, bone and cardiovascular health. Intravaginal testosterone appears to be a promising alternative for the treatment of genitourinary symptoms of menopause (GSM) but efficacy and safety are yet to be confirmed. Well-designed, randomized, and placebo-controlled trials are needed to establish long-term safety, efficacy, and appropriate dosing and route of testosterone therapy in postmenopausal women. The only evidence-based indication for testosterone therapy in women is for the treatment of postmenopausal hypoactive sexual desire disorder (HSDD). Should a trial of testosterone therapy be given for HSDD, the transdermal route is the preferred method of delivery. Baseline total testosterone concentration should be determined before starting treatment, and repeated after 3–6 months. Serum testosterone levels should be monitored at regular intervals to avoid supraphysiologic dosing. Conclusion: Currently, there is no robust evidence to support the use of exogenous testosterone to improve female well-being, musculoskeletal health, mood and cognition, as well as bone and cardiovascular health among postmenopausal women. The only evidence-based indication for testosterone therapy in women is the treatment of postmenopausal hypoactive sexual desire disorder, but only after all other causes of sexual dysfunction have been ruled out. To date, testosterone therapy has no US Food and Drug Administration (US FDA) approval due to the lack of long-term efficacy and safety data.