Sleep-Disordered Breathing in Neurodegenerative Diseases

Sleep disorders are common in neurodegenerative diseases such as Parkinson’s disease (PD), multiple system atrophy (MSA), amyotrophic lateral sclerosis (ALS), hereditary ataxias, and Alzheimer’s disease (AD). Type, frequency, and severity of sleep disturbances vary depending on each of these diseases. Cell loss of the brainstem nuclei that modulates respiration, and dysfunction of bulbar and diaphragmatic muscles increase the risk for sleep-disordered breathing (SDB) in MSA and ALS. The most relevant SDB in MSA is stridor, whereas in ALS nocturnal hypoventilation due to diaphragmatic weakness is the most common sleep breathing abnormality. Stridor and nocturnal hypoventilation are associated with reduced survival in MSA and ALS. In contrast, sleep apnea seems not to be more prevalent in PD than in the general population. In some PD patients, however, coincidental obstructive sleep apnea (OSA) can be the cause of excessive daytime sleepiness (EDS). SDB can also occur in some hereditary ataxias, such as stridor in spinocerebellar ataxia type 3 (Machado-Joseph disease). The presence of concomitant OSA in patients with AD can have deleterious effects on nocturnal sleep, may result in EDS, and might aggravate the cognitive deficits inherent to the disease. However, whether OSA is more frequent in patients with AD than in the general population is uncertain. Recognition of SDB in neurodegenerative disease is important because they are associated with significant morbidity and potential effective treatments are available.     

Sleep-Disordered Breathing and Stroke: Therapeutic Approaches

The majority of stroke patients have clinically significant obstructive sleep apnea (OSA). Also, recent evidence demonstrates that OSA serves as an independent risk factor for stroke. Treatment of OSA following stroke is associated with neurologic and functional improvements, as well as long-term reduced risk of cardiovascular events. Identification of stroke patients at risk of OSA and subsequent diagnosis and treatment is essential in stroke recovery and reducing recurrent stroke risk. Continuous positive airway pressure (CPAP), the standard modality of treating OSA, is highly effective, but is often inadequately tolerated by stroke patients. Education and medical provider support are essential in establishing CPAP use in this population. However, in cases where CPAP therapy is not feasible, it is important for clinicians to be familiar with alternative modalities in treating OSA.     

Positive Airway Pressure Therapy in Sleep-Disordered Breathing

Obstructive sleep apnea (OSA) is a highly prevalent condition with major neurocognitive and cardiovascular health effects. Positive airway pressure (PAP) therapy prevents the collapse of the pharyngeal airway to improve hypoxemia, hypercapnia, and sleep fragmentation caused by OSA. While adherence to PAP therapy has been thought to be a barrier to use, consistent usage is likely much higher than commonly thought. In addition, many strategies have been developed to assist providers in improving their patients’ PAP adherence.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-020-00971-x.Key Words: Sleep-disordered breathing, obstructive sleep apnea, positive airway pressure therapy.     

A Multimodal Intervention to Improve Cognition in Community-dwelling Older Adults

ObjectiveTo examine the effects of a multimodal intervention composed of cognitive training, physical exercise, and group counseling on cognitive function in community-dwelling older adults.DesignA four-armed, quasi-experimental intervention study.Setting and ParticipantsCommunity-dwelling adults aged 60 years and older (n = 153).InterventionParticipants were allocated into multimodal intervention, cognitive training plus Taichi exercise, cognitive training, or control group. The multimodal intervention included 18 sessions of cognitive training, 18 sessions of Taichi, and 6 sessions of group reminiscence over six weeks.MeasurementsCognitive function, depressive symptoms, and psychological well-being were assessed at the baseline, postintervention, and three-month follow-up. The primary outcome was the change in overall cognition measured by the Montreal Cognitive Assessment (MoCA) and a composite cognitive score derived from a battery of neuropsychological tests.ResultsFor MoCA, there was no significant difference between any of the three intervention groups and controls. For composite cognition, all three intervention groups showed improvements at the three-month follow-up, with a large effect size in the cognitive training plus Taichi group (change difference 0.37, 95% CI 0.18–0.56, Hedge's g = 0.92), and medium effect sizes in the multimodal intervention group (change difference 0.23, 95% CI 0.0 –0.42, g = 0.58) and cognitive training group (change difference 0.22, 95% CI 0.03–0.42, g = 0.55).ConclusionsMultimodal intervention, cognitive training plus Taichi, and cognitive training could foster cognitive function in community-dwelling older adults. The combination of cognitive training and Taichi showed greater efficacy than the other two interventions.     

Oxidative Stress Mediates the Association Between Dietary Fat Intake and Cognition in US Older Adults

OBJECTIVEDietary fat intake was considered as a modifiable factor influencing cognitive performance. The objective was to 1) examine the associations between different types of dietary fat intakes and cognitive outcomes among elder adults (≥60 years old); 2) assess whether peripheral oxidative stress and antioxidant biomarkers are potential mediators of dietary fat intake and cognitive impairment relationship.METHODSUsing data from National Health and Nutrition Examination Survey 2011-2014, total fat, saturated fatty acid (SFAT), monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), cholesterol, ω-3 and ω-6 fatty acids were used to evaluate dietary fat intakes. Cognitive outcomes were assessed by word learning and recall modules from the consortium to establish a registry for Alzheimer's Disease (CERAD), animal fluency test, and digit symbol substitution test (DSST). Antioxidant biomarkers were assessed by gamma glutamyl transpeptidase (GGT), bilirubin, uric acid, and vitamin D levels. Linear regression models and causal mediation analysis were applied to quantify the associations.RESULTSA total of 2,253 elder adults were included in the data analyses. Dietary intake of PUFA and ω-6 fatty acid were positively associated with DSST [β (95% CI): 0.06 (0.01,0.10), t statistic = 2.39, df= 2238, p = 0.02; β (95% CI): 0.06 (0.01,0.11), t statistic = 2.54, df= 2238, p = 0.01, respectively]. GGT was negatively associated with DSST [β (95% CI): -0.04 (-0.07, -0.01), t statistic = -2.73, df= 2239, p = 0.01], whereas uric acid was positively associated with CERAD total score [β (95% CI): 0.04 (0.00,0.08), t statistic = 2.03, df= 2233, p = 0.04]. The association between dietary intake of PUFA/ω -3/ω -6 and DSST performance was partially mediated by GGT level.CONCLUSIONOur findings support that PUFAs in dietary sources were associated with lower risks for cognitive impairment partially via lowering oxidative stress. Dietary PUFA supplementation may potentially reduce risk of cognitive impairment via antioxidative mechanism.     

Sleep Duration and Cognition in a Nationally Representative Sample of U.S. Older Adults

ObjectiveExcessive and insufficient sleep have been associated with cognitive dysfunction in older adults in U.S. and non-U.S. studies. However, the U.S. studies were not in nationally representative samples. The authors investigated the association between sleep duration and cognitive performance in a nationally representative sample of U.S. older adults.ParticipantsThe authors studied 1,496 survey participants aged 60 years or older from the National Health and Nutrition Examination Survey 2013–2014 dataset.MeasurementsOur primary predictor was weekday (or workday) nighttime sleep duration, categorized as 2–4, 5, 6, 7 (reference), 8, 9, and 10 hours or more. The authors studied five cognitive outcomes: Consortium to Establish a Registry for Alzheimer's Disease Word Learning (CERAD-WL) immediate recall, CERAD-WL delayed recall, Animal Fluency Test (AFT), Digital Symbol Substitution Test (DSST), and subjective cognitive problems (SCP).ResultsAfter adjusting for age, sex, race, education, depressive symptoms, and sedative-hypnotic use, sleep duration of 10 hours or more was significantly associated with lower scores on CERAD-WL immediate recall, CERAD-WL delayed recall, AFT, and DSST, and greater odds of SCP; sleep duration of 8 hours or more was associated with lower CERAD-WL delayed recall scores: 8, 9, and 10 hours or more. After adjustment, there were no significant associations of shorter sleep duration with cognition.ConclusionIn U.S. adults aged 60 years or older, long nighttime weekday or workday sleep duration is associated with poorer verbal memory, semantic fluency, working memory, and processing speed in addition to greater odds of self-reported cognitive problems. Long sleep duration may be a marker of fragmented sleep or neurodegeneration in U.S. older adults.     

Reading the Mind in the Eyes: A Population-Based Study of Social Cognition in Older Adults

BackgroundSocial cognition indicates the cognitive processes involved in perceiving, interpreting, and processing social information. Although it is one of the six core DSM-5 cognitive domains for diagnosing neurocognitive disorders, it is not routinely assessed in older adults. The Reading the Mind in the Eyes Test assesses Theory of Mind, the social cognition mechanism which forms the root of empathy.ObjectivesTo describe the distribution of, and factors associated with, scores on a 10-item version of Reading the Mind in the Eyes Test (RMET-10) in older adults.DesignPopulation-based cross-sectional study.SettingSmall-town communities in Pennsylvania.ParticipantsAdults aged 66–105 years (N = 902, mean age = 76.6).MeasurementsThe assessment included RMET-10, demographics, cognitive screening, literacy, depression symptoms, anxiety symptoms, cognitive composites derived from a neuropsychological test battery, Social Norms Questionnaire, and Clinical Dementia Rating (CDR).ResultsRMET-10 score was normally distributed in our overall study sample. Normative RMET-10 scores among those rated as CDR = 0 were calculated by age, sex, and education. RMET-10 score was significantly higher with younger age, higher education, white race, higher cognitive screening scores, literacy, social norms scores, higher scores in all five domains in cognitive composites, and lower CDR. RMET-10 score was also significantly higher with fewer depression and anxiety symptoms after adjusting for demographics.ConclusionsThe RMET is a potentially useful measure of social cognition for use in the research assessment of older adults. With appropriate calibration it should also have utility in the clinical setting.     

Mild Cognitive Impairment in Older Adults

Mild cognitive impairment (MCI) is the intermediate stage between the cognitive changes of normal aging and dementia. MCI is important because it constitutes a high risk group for dementia. Ideally, prevention strategies should target individuals who are not even symptomatic. Indeed, the field is now moving towards identification of asymptomatic individuals who have underlying Alzheimer's disease (AD) pathology that can be detected using biomarkers and neuroimaging technologies. To this effect, the Alzheimer's Association and the National Institute on Aging have developed a new classification scheme that has categorized AD into a preclinical phase (research category), MCI due to AD, and dementia of Alzheimer's type. However, there are also ongoing research studies to understand high-risk groups for non-Alzheimer's dementia.