Nathan Cross

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.

Sleep quality in healthy older people: relationship with ¹H magnetic resonance spectroscopy markers of glial and neuronal integrity.

The hippocampus and thalamus assume a significant role in the overnight consolidation of memories, a process that is negatively impacted by sleep disruption. Emerging evidence suggests that disturbances of sleep in older people may co-occur with underlying neurobiological changes. This study sought to assess glial and neuronal integrity in these regions in relation to subjective sleep disturbance in a healthy older sample. Forty-three healthy older people (mean age = 70, SD = 5.0) were assessed clinically and medically and screened for cognitive and depressive symptoms, as well as sleep disturbance. Single voxel hippocampal and thalamus metabolite ratios of N-acetyl aspartate (NAA) and myo-inositol (mI) with total creatine (Cr + PCr) were measured using magnetic resonance spectroscopy at 3-Tesla. Higher hippocampal mI/Cr + PCr ratios were significantly correlated with poorer self-reported sleep quality (r = .42, p < .01) and less sleep efficiency (r = -0.42, p < .01) as recorded by the Pittsburgh Sleep Quality Index (Buysse, Reynolds, Monk, Berman, & Kupfer, 1989). No other significant correlations were observed within the hippocampus or within the thalamus. These results indicate that in healthy older people, subjective sleep disturbance may be associated with glial alterations in the hippocampus. Future research is now needed to examine these associations with respect to objective sleep measures and overnight memory consolidation.

Quantitative sleep EEG and polysomnographic predictors of driving simulator performance in obstructive sleep apnea

OBJECTIVES To improve identification of obstructive sleep apnea (OSA) patients at risk of driving impairment, this study explored predictors of driving performance impairment in untreated OSA patients using clinical PSG metrics, sleepiness questionnaires and quantitative EEG markers from routine sleep studies. METHODS Seventy-six OSA patients completed sleepiness questionnaires and driving simulator tests in the evening of their diagnostic sleep study. All sleep EEGs were subjected to quantitative power spectral analysis. Correlation and multivariate linear regression were used to identify the strongest predictors of driving simulator performance. RESULTS Absolute EEG spectral power across all frequencies (0.5-32 Hz) throughout the entire sleep period and separately in REM and NREM sleep, (r range 0.239-0.473, all p<0.05), as well as sleep onset latency (r=0.273, p<0.017) positively correlated with driving simulator steering deviation. Regression models revealed that amongst clinical and qEEG variables, the significant predictors of worse steering deviation were greater total EEG power during NREM and REM sleep, greater beta EEG power in NREM and greater delta EEG power in REM (range of variance explained 5-17%, t range 2.29-4.0, all p<0.05) and sleep onset latency (range of variance explained 4-9%, t range 2.15-2.5, all p<0.05). CONCLUSIONS In OSA patients, increased EEG power, especially in the faster frequency (beta) range during NREM sleep and slower frequency (delta) range in REM sleep were associated with worse driving performance, while no relationships were observed with clinical metrics e.g. apnea, arousal or oxygen indices. SIGNIFICANCE Quantitative EEG analysis in OSA may provide useful markers of driving impairment risk. Future studies are necessary to confirm these findings and assess the clinical significance of quantitative EEG as predictors of driving impairment in OSA.

Quantitative electroencephalogram measures in adult obstructive sleep apnea – Potential biomarkers of neurobehavioural functioning

Obstructive sleep apnea (OSA) results in significantly impaired cognitive functioning and increased daytime sleepiness in some patients leading to increased risk of motor vehicle and workplace accidents and reduced productivity. Clinicians often face difficulty in identifying which patients are at risk of neurobehavioural dysfunction due to wide inter-individual variability, and disparity between symptoms and conventional metrics of disease severity such as the apnea hypopnea index. Quantitative electroencephalogram (EEG) measures are determinants of awake neurobehavioural function in healthy subjects. However, the potential value of quantitative EEG (qEEG) measurements as biomarkers of neurobehavioural function in patients with OSA has not been examined. This review summarises the existing literature examining qEEG in OSA patients including changes in brain activity during wake and sleep states, in relation to daytime sleepiness, cognitive impairment and OSA treatment. It will speculate on the mechanisms which may underlie changes in EEG activity and discuss the potential utility of qEEG as a clinically useful predictor of neurobehavioural function in OSA.

Is Obstructive Sleep Apnoea Related to Neuropsychological Function in Healthy Older Adults? A Systematic Review and Meta-Analysis

Previous systematic reviews and meta-analyses have identified cognitive deficits in adults with obstructive sleep apnoea (OSA). However, quantitative analysis of the association between OSA and neuropsychological performance has not been conducted specifically in older adults, for whom there is a greater risk of cognitive decline. We searched Medline, Embase and PsycINFO through August 2016 for studies describing associations between OSA and neuropsychological outcomes in people aged>50 years. Meta-analyses were performed on these studies for overall cognition and within cognitive domains. Subgroup analyses were performed taking into account risk of bias and moderating differences in study design. 13 studies met eligibility criteria for analysis. A small negative association was found between OSA and all neuropsychological outcomes combined, g=0.18(95% CI 0.04–0.32), and in memory and processing speed domains. Small case-control studies from sleep clinic populations observed the greatest associations, while larger cohort studies from community samples illustrated no association. Analysis accounting for publication bias resulted in a null overall association, g=0.02 (95%CI -0.12 to 0.16). Associations between OSA and cognition in later life are highly variable and the findings differ based on the type and setting of study. It appears some older adults may be at risk of cognitive impairments attributable to OSA; however, the risk of bias renders the evidence inconclusive. High quality research is warranted in clinically diagnosed OSA patients as well as those already experiencing neuropsychological impairment and who may be regarded at higher risk of further cognitive decline.

Functional Connectivity in the Default Mode Network is Reduced in Association with Nocturnal Awakening in Mild Cognitive Impairment

BACKGROUND Sleep disturbance is prevalent in MCI, and is a risk factor for cognitive deterioration. OBJECTIVE To identify functional connectivity deficits in the default mode network (DMN) in patients with mild cognitive impairment (MCI) and sleep disturbance, relative to MCIs with intact sleep. METHODS Participants comprised 47 adults aged 55 years and over, recruited from the Healthy Brain Ageing Clinic at the Brain and Mind Centre, Sydney, Australia. This sample contained 15 controls and 32 participants meeting criteria for MCI. Participants underwent resting-state fMRI and actigraphy, along with comprehensive neuropsychological, medical and psychiatric assessment. MCIs were split into two groups according to average wake after sleep onset (WASO) per night. WASO equal to or greater than 1 standard deviation (SD) above the control mean was deemed to reflect disturbed sleep. There were 11 patients in the MCI sleep-disturbed group, and 21 in the MCI sleep-intact group. RESULTS Relative to controls, MCIs demonstrated significant connectivity reductions between parietal and temporoparietal regions, and between temporal regions. Relative to MCIs with intact sleep, MCIs with sleep disturbance demonstrated reductions in functional connectivity between temporal and parietal regions, and between temporal and temporoparietal regions. CONCLUSIONS MCIs with nocturnal awakenings demonstrate reductions in DMN connectivity. These reductions comprise brain regions that are crucially involved in sleep and memory processes. These results strengthen our previous findings, which found reduced connectivity in MCIs with self-reported sleep disturbances. Future studies may build on these findings through incorporating complementary neuroimaging techniques and experimental manipulations of sleep.

Association of Anterior Cingulate Glutathione with Sleep Apnea in Older Adults At-Risk for Dementia.

STUDY OBJECTIVES Sleep disordered breathing (SDB) is common in older adults and is strongly associated with cognitive decline, with increasing evidence suggesting that it may represent a risk factor for dementia. Given that SDB is characterized by intermittent episodes of hypoxemia during sleep, it is possible that cognitive impairment may relate to cerebral oxidative stress. This study aimed to examine the relationship between nocturnal markers of hypoxemia and proton magnetic resonance spectroscopy ((1)H-MRS) markers of oxidative stress within the anterior cingulate cortex (ACC) of the brain. METHODS Twenty-four older adults (mean age = 67.9 y) at-risk for dementia were recruited from our Healthy Brain Ageing Research Clinic. At-risk was defined as participants seeking help for assessment and/or intervention for cognitive decline, including those with subjective and/or objective cognitive complaints. This could occur in the context of prior depression or risk factors (e.g., vascular) for dementia. All participants underwent psychiatric, medical and neuropsychological assessment followed by overnight polysomnography. In addition, participants underwent (1)H-MRS to derive levels of ACC metabolite glutathione (GSH) reported as a ratio to creatine (GSH/Cr). RESULTS Increased levels of GSH/Cr were associated with lower oxygen desaturation (r = -0.54, P = 0.007) and more severe apnea-hypopnea index scores during rapid eye movement sleep (r = 0.42, P = 0.050). In addition, ACC GSH/Cr correlated with poorer executive functioning (i.e., response inhibition: r = -0.49, P = 0.015; set shifting: r = -0.43, P = 0.037). CONCLUSIONS Markers of nocturnal hypoxemia and SDB are associated with cerebral oxidative stress in older people at-risk for dementia, suggesting a potential mechanism by which SDB may contribute to brain degeneration, cognitive decline, and dementia. Further work focused on utilizing this biomarker for the early identification and treatment of this possible modifiable risk factor in older persons is now warranted.

Structural brain correlates of obstructive sleep apnoea in older adults at risk for dementia

This study aimed to investigate associations between obstructive sleep apnoea (OSA) and cortical thickness in older adults with subjective and objective cognitive difficulties, who are considered “at-risk” for dementia. 83 middle-aged to older adults (51–88 years) underwent neuropsychological testing, polysomnography assessment of OSA and a structural magnetic resonance imaging brain scan. A principal components analysis was performed on OSA measures. Cortical thickness and subcortical volumes were compared to extracted components of “oxygen desaturation” and “sleep disturbance”. Oxygen desaturation was significantly related to reduced cortical thickness in the bilateral temporal lobes (left: r=−0.44, p<0.001; right: r=−0.39, p=0.003). Conversely, sleep disturbance was associated with increased thickness in the right postcentral gyrus (r=0.48, p<0.001), pericalcarine (r=0.50, p=0.005) and pars opercularis (r=0.46, p=0.009) and increased volume of the hippocampus and amygdala. Decreased thickness in the bilateral temporal regions was associated with reduced verbal encoding (r=0.28, p=0.010). Given the clinical significance of this sample in terms of dementia prevention, these changes in grey matter reveal how OSA might contribute to neurodegenerative processes in older adults. This study demonstrates how obstructive sleep apnoea might contribute to neurodegenerative processes in older adults http://ow.ly/frH030jWFJn

REDUCED SPINDLE FREQUENCY ACTIVITY DURING SLEEP IN MILD COGNITIVE IMPAIRMENT: DISTINCT RELATIONSHIPS WITH THALAMUS AND HIPPOCAMPUS

Figure 1. CSF values by biomarker group. Results are boxplots (displaying first quartile, median and third quartile) and scatterplots for all CSF measures by each biomarker subgroup: (A) Neurofilament-light, (B) Neurogranin, (C) YKL-40, (D) amyloid-b1-38, (E) amyloid-b1-40, (F) amyloid-b142, (G) amyloid-b142/1-40, (H) total tau, (I) phosphorylated tau. The MCI A-T+ group is presented in blue and the CN A-T-, MCI A-T-, MCI A+T-, MCI A+T+, and AD dementia A+T+ groups are presented in grey. CSF biomarker values were logtransformed. *indicates statistically significant differences compared to the MCI A-T+ group after Bonferroni correction for multiple comparisons. A1⁄4amyloid-pi-42, T1⁄4total or phosphorylated tau, CN1⁄4cognitively normal, MCI1⁄4mild cognitive impairment.

Association between Sleep Disordered Breathing and Nighttime Driving Performance in Mild Cognitive Impairment

OBJECTIVES The effect of sleep disordered breathing (SDB) on driving performance in older adults has not been extensively investigated, especially in those with mild cognitive impairment (MCI). The aim of this study was to examine the relationship between severity measures of SDB and a simulated driving task in older adults with and without MCI. METHODS Nineteen older adults (age ≥50) meeting criteria for MCI and 23 age-matched cognitively intact controls underwent neuropsychological assessment and a driving simulator task in the evening before a diagnostic sleep study. RESULTS There were no differences in driving simulator performance or SDB severity between the two groups. In patients with MCI, a higher oxygen desaturation index (ODI) was associated with an increased number of crashes on the simulator task, as well as other driving parameters such as steering and speed deviation. Poorer driving performance was also associated with poorer executive functioning (set-shifting) but the relationship between ODI and crashes was independent of executive ability. CONCLUSIONS While driving ability did not differ between older adults with and without MCI, oxygen saturation dips in MCI were related to worse driving performance. These results suggest that decreased brain integrity may render those with SDB particularly vulnerable to driving accidents. In older adults, both cognition and SDB need to be considered concurrently in relation to driving ability. (JINS, 2017, 23, 502-510).