Kirstie N. Anderson

Disrupted sleep and circadian patterns in frontotemporal dementia

Background:  A study of the pattern of Sleep/Wake disturbance in frontotemporal dementia (FTD).

Sleep disturbance in mental health problems and neurodegenerative disease

Sleep has been described as being of the brain, by the brain, and for the brain. This fundamental neurobiological behavior is controlled by homeostatic and circadian (24-hour) processes and is vital for normal brain function. This review will outline the normal sleep–wake cycle, the changes that occur during aging, and the specific patterns of sleep disturbance that occur in association with both mental health disorders and neurodegenerative disorders. The role of primary sleep disorders such as insomnia, obstructive sleep apnea, and REM sleep behavior disorder as potential causes or risk factors for particular mental health or neurodegenerative problems will also be discussed.

A Novel, Open Access Method to Assess Sleep Duration Using a Wrist-Worn Accelerometer

Wrist-worn accelerometers are increasingly being used for the assessment of physical activity in population studies, but little is known about their value for sleep assessment. We developed a novel method of assessing sleep duration using data from 4,094 Whitehall II Study (United Kingdom, 2012–2013) participants aged 60–83 who wore the accelerometer for 9 consecutive days, filled in a sleep log and reported sleep duration via questionnaire. Our sleep detection algorithm defined (nocturnal) sleep as a period of sustained inactivity, itself detected as the absence of change in arm angle greater than 5 degrees for 5 minutes or more, during a period recorded as sleep by the participant in their sleep log. The resulting estimate of sleep duration had a moderate (but similar to previous findings) agreement with questionnaire based measures for time in bed, defined as the difference between sleep onset and waking time (kappa = 0.32, 95%CI:0.29,0.34) and total sleep duration (kappa = 0.39, 0.36,0.42). This estimate was lower for time in bed for women, depressed participants, those reporting more insomnia symptoms, and on weekend days. No such group differences were found for total sleep duration. Our algorithm was validated against data from a polysomnography study on 28 persons which found a longer time window and lower angle threshold to have better sensitivity to wakefulness, while the reverse was true for sensitivity to sleep. The novelty of our method is the use of a generic algorithm that will allow comparison between studies rather than a “count” based, device specific method.

Pathogenic Mitochondrial tRNA Point Mutations: Nine Novel Mutations Affirm Their Importance as a Cause of Mitochondrial Disease

Mutations in the mitochondrial genome, and in particular the mt‐tRNAs, are an important cause of human disease. Accurate classification of the pathogenicity of novel variants is vital to allow accurate genetic counseling for patients and their families. The use of weighted criteria based on functional studies—outlined in a validated pathogenicity scoring system—is therefore invaluable in determining whether novel or rare mt‐tRNA variants are pathogenic. Here, we describe the identification of nine novel mt‐tRNA variants in nine families, in which the probands presented with a diverse range of clinical phenotypes including mitochondrial encephalomyopathy, lactic acidosis, and stroke‐like episodes, isolated progressive external ophthalmoplegia, epilepsy, deafness and diabetes. Each of the variants identified (m.4289T>C, MT‐TI; m.5541C>T, MT‐TW; m.5690A>G, MT‐TN; m.7451A>T, MT‐TS1; m.7554G>A, MT‐TD; m.8304G>A, MT‐TK; m.12206C>T, MT‐TH; m.12317T>C, MT‐TL2; m.16023G>A, MT‐TP) was present in a different tRNA, with evidence in support of pathogenicity, and where possible, details of mutation transmission documented. Through the application of the pathogenicity scoring system, we have classified six of these variants as “definitely pathogenic” mutations (m.5541C>T, m.5690A>G, m.7451A>T, m.12206C>T, m.12317T>C, and m.16023G>A), whereas the remaining three currently lack sufficient evidence and are therefore classed as ‘possibly pathogenic’ (m.4289T>C, m.7554G>A, and m.8304G>A).

Rhythmic movement disorder (Head Banging) in an adult during rapid eye movement sleep

Sleep‐related rhythmic movements (head banging or body rocking) are extremely common in normal infants and young children, but less than 5% of children over the age of 5 years old exhibit these stereotyped motor behaviors. They characteristically occur during drowsiness or sleep onset rather than in deep sleep or rapid eye movement (REM) sleep. We present a 27‐year‐old man with typical rhythmic movement disorder that had persisted into adult life and was restricted to REM sleep. This man is the oldest subject with this presentation reported to date and highlights the importance of recognizing this nocturnal movement disorder when it does occur in adults.

REM sleep behaviour disorder treated with melatonin in a patient with Alzheimer's disease.

We report a case of a 68-year-old man with probable Alzheimers disease who developed rapid eye movement (REM) sleep behaviour disorder. This was confirmed with polysomnography but the patient also had some sleep apnea, which prevented the use of clonazepam for treatment. Melatonin was successfully used as an alternative treatment.

Novel assessment of microvascular changes in idiopathic restless legs syndrome (Willis–Ekbom disease)

Many patients with restless legs syndrome (Willis–Ekbom disease) complain of burning sensations in their feet associated with the desire to move, such that they seek cooler environments. This pilot study aimed to characterise the microvascular skin changes in 12 patients with restless legs syndrome compared with 12 age‐ and sex‐matched controls. Patients with moderate or severe restless legs syndrome and controls underwent detailed thermovascular assessment in a controlled temperature room at three different stages (normothermic phase 23 °C, hot phase 30 °C, cold phase 18 °C). Microvascular activity was recorded during all phases by bilateral great toe laser‐Doppler flowmetry and also by whole‐body thermography. Patient and control measurements were compared. The study protocol was well tolerated. Parameters extracted from the laser‐Doppler flowmetry measurements were used to model a logistic function using binary logistic regression. This demonstrated a statistically significant difference between patients with restless legs syndrome and healthy controls (P < 0.001). Visual inspection of the body thermography image sequences showed increased lower limb movement in patients with restless legs syndrome patients compared with controls. Thermography analysis also showed significant differences between foot temperatures in patients with restless legs syndrome compared with controls during the hot phase (P = 0.011). Notably, patients with restless legs syndrome had more uniform foot temperatures, whereas controls had a wider variability in surface temperature across the feet. This novel study demonstrates impaired microvascular circulation in patients with restless legs syndrome in comparison to matched controls and a potential mechanism for the sensation of burning feet. The protocol also provides an experimental paradigm to test therapeutic interventions for the future.

Primary sleep disorder prevalence in patients with newly diagnosed Parkinson’s disease

Sleep disturbance occurs in up to 96% of patients with established Parkinsons disease (PD). We aimed to assess the prevalence of sleep disturbance in newly diagnosed PD.

Cortisol awakening response and spatial working memory in man: a U-shaped relationship.

The association between hypothalamic–pituitary–adrenal (HPA)‐axis function and cognition has long been investigated. An inverted U‐shaped relationship has been described between various measures of HPA‐axis function and neuropsychological performance in animals and man. Work with glucocorticoid receptor manipulation has corroborated these findings, with particular effects observed in relation to spatial working memory (SWM). As HPA‐axis dysfunction is frequently found in patients with psychiatric illness, research in this area has potential implications for the treatment of the commonly observed cognitive impairment in such disorders. Here, we present the results of a pilot study examining the relationship between cortisol awakening response (CAR) and cognitive functions known to be susceptible to HPA‐axis manipulation.

Restless leg syndrome is a treatable cause of sleep disturbance and fatigue in primary biliary cirrhosis

Primary biliary cirrhosis (PBC) patients frequently describe sleep problems. The cause remains unclear and treatment is challenging. Restless leg syndrome (RLS) is a common sleep disorder. In this study, we systematically screened PBC patients for the presence of RLS.