Zoe Terpening

Disturbances in melatonin secretion and circadian sleep–wake regulation in Parkinson disease

OBJECTIVE Using salivary dim light melatonin onset (DLMO) and actigraphy, our study sought to determine if Parkinson disease (PD) patients demonstrate circadian disturbance compared to healthy controls. Additionally, our study investigated if circadian disturbances represent a disease-related process or may be attributed to dopaminergic therapy. METHODS Twenty-nine patients with PD were divided into unmedicated and medicated groups and were compared to 27 healthy controls. All participants underwent neurologic assessment and 14 days of actigraphy to establish habitual sleep-onset time (HSO). DLMO time and area under the melatonin curve (AUC) were calculated from salivary melatonin sampling. The phase angle of entrainment was calculated by subtracting DLMO from HSO. Overnight polysomnography (PSG) was performed to determine sleep architecture. RESULTS DLMO and HSO were not different across the groups. However, the phase angle of entrainment was more than twice as long in the medicated PD group compared to the unmedicated PD group (U = 35.5; P = .002) and was more than 50% longer than controls (U = 130.0; P = .021). The medicated PD group showed more than double the melatonin AUC compared to the unmedicated group (U = 31; P = 0.001) and controls (U = 87; P = .001). There was no difference in these measures comparing unmedicated PD and controls. CONCLUSIONS In PD dopaminergic treatment profoundly increases the secretion of melatonin. Our study reported no difference in circadian phase and HSO between groups. However, PD patients treated with dopaminergic therapy unexpectedly showed a delayed sleep onset relative to DLMO, suggesting dopaminergic therapy in PD results in an uncoupling of circadian and sleep regulation.

Sleep disturbance relates to neuropsychological functioning in late-life depression

BACKGROUND Sleep-wake disturbance in older people is a risk factor for depression onset and recurrence. The aim of this study was to determine if objective sleep-wake disturbance in late-life depression relates to neuropsychological functioning. METHODS Forty-four older patients with a lifetime history of major depression and 22 control participants underwent psychiatric, medical and neuropsychological assessments. Participants completed self-report sleep measures, sleep diaries and wore wrist actigraphy for two weeks. Outcome measures included sleep latency, the number and duration of nocturnal awakenings and the overall sleep efficiency. RESULTS Patients with depression had a greater duration of nocturnal awakenings and poorer sleep efficiency, in comparison to control participants. Sleep disturbance in patients was associated with greater depression severity and later ages of depression onset. It also related to poorer psychomotor speed, poorer verbal and visual learning, poorer semantic fluency as well as poorer performance on tests of executive functioning. These relationships largely remained significant after controlling for depression and estimated apnoea severity. LIMITATIONS This sample had only mild levels of depression severity and results require replication in patients with moderate to severe depression. The inclusion of polysomnography and circadian markers would be useful to delineate the specific features of sleep-wake disturbance that are critical to cognitive performance. CONCLUSIONS Sleep-wake disturbance in older patients with depression is related to neuropsychological functioning and to later ages of illness onset. This study suggests that common neurobiological changes may underpin these disease features, which may, in turn, warrant early identification and management.

Sleep-wake cycle in young and older persons with a lifetime history of mood disorders.

Considering the marked changes in sleep and circadian rhythms across the lifespan, age may contribute to the heterogeneity in sleep-wake profiles linked to mood disorders. This study aimed to investigate the contributions of age and depression severity to sleep-wake disturbances. The Hamilton Depression Rating Scale (HDRS) was administered to assess current symptoms severity in 238 persons with a history of a mood disorder between 12 and 90 years of age (y.o.). Actigraphy was recorded over five to 22 days. Regression analyses and analyses of variance [age (12–19 y.o., 20–39 y.o., 40–59 y.o., and ≥60 y.o.) by depression severity (HDRS< and ≥8)] were conducted. The 12–19 y.o. and 20–39 y.o. groups had a delayed sleep schedule and acrophase compared to all other groups. The ≥60 y.o. group had a lower rhythmicity and amplitude (p≤.006) than the 12–19 y.o. group (p≤.046). Participants with a HDRS≥8 spent longer time in bed, had later sleep offset times and had lower circadian rhythmicity than those with a HDRS<8 (p≤.036). Younger age and higher HDRS score correlated with later sleep onset and offset times, longer time in bed, higher WASO, lower sleep efficiency and later acrophase (p≤.023). Age was a significant predictor of delayed sleep and activity schedules (p≤.001). The profile of sleep-wake cycle disturbances associated with mood disorders changes with age, with prominent sleep phase delay during youth and reduced circadian strength in older persons. Conversely, disruptions in sleep consolidation seem more stable across age.

Neuropsychological functioning in Parkinson's disease: differential relationships with self-reported sleep-wake disturbances.

Sleep disturbance may represent a risk factor for the development of dementia in Parkinsons disease. However, prior studies exploring the association between specific sleep–wake disturbances and neuropsychological functions have been limited.

Utility and Limitations of Addenbrooke's Cognitive Examination-Revised for Detecting Mild Cognitive Impairment in Parkinson's Disease

Background/Aims: To evaluate the utility of the Addenbrooke’s Cognitive Examination-Revised (ACE-R) as a screening tool for mild cognitive impairment in Parkinson’s disease (PD-MCI). Methods: PD patients underwent comprehensive neuropsychological and neurological evaluations and ACE-R assessment. Results: The ACE-R was superior to the Mini-Mental State Exam (MMSE) in detecting PD-MCI, with a cutoff score of ≤93 offering a sensitivity of 61% and a specificity of 64%. The utility of the ACE-R in detecting PD-MCI is largely influenced by the fluency sub-domain score, and has optimal discriminability when utilized in patients with lower levels of education (≤12 years of formal schooling). Conclusion: The ACE-R must be used cautiously as a screening tool for PD-MCI, with results being most influenced by its fluency sub-domain score and patient education levels.

Investigating rapid eye movement sleep without atonia in Parkinson's disease using the rapid eye movement sleep behavior disorder screening questionnaire.

Rapid eye movement (REM) sleep behavior disorder (RBD) is frequently observed in patients with Parkinsons disease (PD). Accurate diagnosis is essential for managing this condition. Furthermore, the emergence of idiopathic RBD in later life can represent a premotor feature, heralding the development of PD. Reliable, accurate methods for identifying RBD may offer a window for early intervention. This study sought to identify whether the RBD screening questionnaire (RBDSQ) and three questionnaires focused on dream enactment were able to correctly identify patients with REM without atonia (RWA), the neurophysiological hallmark of RBD. Forty‐six patients with PD underwent neurological and sleep assessment in addition to completing the RBDSQ, the RBD single question (RBD1Q), and the Mayo Sleep Questionnaire (MSQ). The REM atonia index was derived for all participants as an objective measure of RWA. Patients identified to be RBD positive on the RBDSQ did not show increased RWA on polysomnography (80% sensitivity and 55% specificity). However, patients positive for RBD on questionnaires specific to dream enactment correctly identified higher degrees of RWA and improved the diagnostic accuracy of these questionnaires. This study suggests that the RBDSQ does not accurately identify RWA, essential for diagnosing RBD in PD. Furthermore, the results suggest that self‐report measures of RBD need to focus questions on dream enactment behavior to better identify RWA and RBD. Further studies are needed to develop accurate determination and quantification of RWA in RBD to improve management of patients with PD in the future.

Napping in older people ‘at risk’ of dementia: relationships with depression, cognition, medical burden and sleep quality

Sleep disturbance is prevalent in older adults, particularly so in those at a greater risk of dementia. However, so far the clinical, medical and neuropsychological correlates of daytime sleep have not been examined. The aims of this study were to investigate the characteristics and effects of napping using actigraphy in older people, particularly in those ‘at risk’ of dementia. The study used actigraphy and sleep diaries to measure napping habits in 133 older adults ‘at risk’ of dementia (mean age = 65.5 years, SD = 8.4 years), who also underwent comprehensive medical, psychiatric and neuropsychological assessment. When defined by actigraphy, napping was present in 83.5% (111/133) of participants; however, duration and timing varied significantly among subjects. Nappers had significantly greater medical burden and body mass index, and higher rates of mild cognitive impairment. Longer and more frequent naps were associated with poorer cognitive functioning, as well as higher levels of depressive symptoms, while the timing of naps was associated with poorer nocturnal sleep quality (i.e. sleep latency and wake after sleep onset). This study highlights that in older adults ‘at risk’ of dementia, napping is associated with underlying neurobiological changes such as depression and cognition. Napping characteristics should be more routinely monitored in older individuals to elucidate their relationship with psychological and cognitive outcomes.

The contribution of nocturnal sleep to the consolidation of motor skill learning in healthy ageing and Parkinson's disease.

The benefits of sleep for the consolidation of procedural motor skills are less robust in older adults, although the precise reasons for this remain unclear. To date, even less is known about these processes in older adults with neurodegenerative diseases, particularly those which impact on motor functioning. While sleep disturbance and motor symptoms are frequent disabling features of Parkinsons disease, no known studies have directly probed sleep‐dependent memory consolidation for motor skill learning in Parkinsons disease. Forty patients with idiopathic Parkinsons disease (age = 63.7 years ± 7.7; disease duration 4.1 years ± 4.4) completed a motor skill learning task pre‐ and post‐sleep and were compared to 20 age‐ and sex‐matched controls recruited from the community. Polysomnography was undertaken during the post‐training night and measures of sleep architecture were derived. Parkinsons disease patients did not demonstrate any apparent deficits in within‐session learning and overnight stabilization compared to controls, with both groups failing to demonstrate offline improvements in performance (i.e. memory consolidation). In controls, longer duration in slow wave sleep was associated with improved next‐day session learning (P = 0.007). However, in Parkinsons disease, no relationships between sleep parameters and learning measures were found. Slow wave sleep microarchitecture and the use of dopaminergic medications may contribute to impaired sleep‐dependent multi‐session acquisition of motor skill learning in Parkinsons disease.

Prevalence and predictors of poor sleep quality in mild cognitive impairment.

Aims: To investigate the prevalence of and contributors to poor sleep quality in patients with mild cognitive impairment (MCI). Methods: Data were collected for 158 patients meeting the criteria for MCI. Measures included the Pittsburgh Sleep Quality Index, Geriatric Depression Scale, and Mini-Mental State Examination. Demographic, lifestyle, medication, and substance use data were also collected. Results: A total of 63% of patients with MCI demonstrated sleep disturbance, a significantly higher rate than that of the controls (44%; chi-square = 8.77; P = .003). Depressive symptoms, cognition, antidepressant usage, alcohol consumption, age, and education were identified as significant predictors of self-reported sleep quality in patients with MCI (R 2 = .327, F 6,145 = 11.729, P < .0001). Conclusions: Sleep disturbance occurs in around two-thirds of patients with MCI. Interventions addressing depression, cognition, and substance and medication use may improve sleep quality in MCI.

Objective Measurement of Daytime Napping, Cognitive Dysfunction and Subjective Sleepiness in Parkinson’s Disease

Introduction Sleep-wake disturbances and concomitant cognitive dysfunction in Parkinson’s disease (PD) contribute significantly to morbidity in patients and their carers. Subjectively reported daytime sleep disturbance is observed in over half of all patients with PD and has been linked to executive cognitive dysfunction. The current study used daytime actigraphy, a novel objective measure of napping and related this to neuropsychological performance in a sample of PD patients and healthy, age and gender-matched controls. Furthermore this study aimed to identify patients with PD who may benefit from pharmacologic and behavioural intervention to improve these symptoms. Methods Eighty-five PD patients and 21 healthy, age-matched controls completed 14 days of wrist actigraphy within two weeks of neuropsychological testing. Objective napping measures were derived from actigraphy using a standardised protocol and subjective daytime sleepiness was recorded by the previously validated Epworth Sleepiness Scale. Results Patients with PD had a 225% increase in the mean nap time per day (minutes) as recorded by actigraphy compared to age matched controls (39.2 ± 35.2 vs. 11.5 ± 11.0 minutes respectively, p < 0.001). Significantly, differences in napping duration between patients, as recorded by actigraphy were not distinguished by their ratings on the subjective measurement of excessive daytime sleepiness. Finally, those patients with excessive daytime napping showed greater cognitive deficits in the domains of attention, semantic verbal fluency and processing speed. Conclusion This study confirms increased levels of napping in PD, a finding that is concordant with subjective reports. However, subjective self-report measures of excessive daytime sleepiness do not robustly identify excessive napping in PD. Fronto-subcortical cognitive dysfunction was observed in those patients who napped excessively. Furthermore, this study suggests that daytime actigraphy, a non-invasive and inexpensive objective measure of daytime sleep, can identify patients with PD who may benefit from pharmacologic and behavioural interventions to improve these symptoms.