Associations of sleep disorders with all-cause MCI/dementia and different types of dementia - clinical evidence, potential pathomechanisms and treatment options: A narrative review.

Due to worldwide demographic change, the number of older persons in the population is increasing. Aging is accompanied by changes of sleep structure, deposition of beta-amyloid (Aß) and tau proteins and vascular changes and can turn into mild cognitive impairment (MCI) as well as dementia. Sleep disorders are discussed both as a risk factor for and as a consequence of MCI/dementia. Cross-sectional and longitudinal population-based as well as case-control studies revealed sleep disorders, especially sleep-disorderded breathing (SDB) and excessive or insufficient sleep durations, as risk factors for all-cause MCI/dementia. Regarding different dementia types, SDB was especially associated with vascular dementia while insomnia/insufficient sleep was related to an increased risk of Alzheimer's disease (AD). Scarce and still inconsistent evidence suggests that therapy of sleep disorders, especially continuous positive airway pressure (CPAP) in SDB, can improve cognition in patients with sleep disorders with and without comorbid dementia and delay onset of MCI/dementia in patients with sleep disorders without previous cognitive impairment. Regarding potential pathomechanisms via which sleep disorders lead to MCI/dementia, disturbed sleep, chronic sleep deficit and SDB can impair glymphatic clearance of beta-amyloid (Aß) and tau which lead to amyloid deposition and tau aggregation resulting in changes of brain structures responsible for cognition. Orexins are discussed to modulate sleep and Aß pathology. Their diurnal fluctuation is suppressed by sleep fragmentation and the expression suppressed at the point of hippocampal atrophy, contributing to the progression of dementia. Additionally, sleep disorders can lead to an increased vascular risk profile and vascular changes such as inflammation, endothelial dysfunction and atherosclerosis which can foster neurodegenerative pathology. There is ample evidence indicating that changes of sleep structure in aging persons can lead to dementia and also evidence that therapy of sleep disorder can improve cognition. Therefore, sleep disorders should be identified and treated early.

[Frailty phenotype and risk factor for disturbed sleep]. / Frailty-Phänotyp und Risikofaktor gestörter Schlaf.

Regardless of the nature of its operationalization, frailty has significant negative consequences for the person concerned and the community. Even if a generally accepted definition of frailty is still missing, there is no doubt about the existence of this phenomenon. Pathophysiologically, a dysfunctional interaction between multiple complex systems is discussed. Therapeutic interventions show that frailty is a dynamic state that can be improved. The pathophysiological characteristics of frailty and sleep disturbances show numerous similarities. In addition, the risk of frailty is increased in individuals with sleep disturbances. As the majority of sleep disorders can usually be well treated, screening for sleep disorders should be integrated into a comprehensive concept of management of frailty.

Observed daytime sleepiness in in-hospital geriatric patients and risk of falls.

BACKGROUND: Daytime sleepiness and falls are frequent in geriatric in-hospital patients; however, the relationship between both events is not clear. To test the hypothesis that observed daytime sleepiness is associated with falls in geriatric in-hospital patients data collected from medical records of patients who were admitted to an acute geriatric department were retrospectively analyzed. METHODS: The data from the medical records of patients who were admitted to the geriatric department of the Alfried-Krupp-Hospital in Essen, Germany in the period from January 2018 to March 2020 were retrospectively analyzed. Personal data, data concerning the geriatric assessment, observed daytime sleepiness, and falls were recorded. RESULTS: From a total of 1485 patients who were consecutively admitted to hospital, the data of 1317 (87%) patients could be included for further analysis. During the hospital stay 146 (11%) patients fell at least once, 35 (3%) patients had more than 1 fall and 64 falls (44%) occurred while patients were standing (bipedal fall). Daytime sleepiness was observed in 73% of the patients with bipedal falls and in 65% patients with nonbipedal falls (p < 0.01). Falls correlated significantly with the history of a recent fall, the length of hospital stay, the Barthel index (BI) on admission, the mini mental state examination (MMSE), dementia and observed daytime sleepiness. No correlation was found between falls and age, multimorbidity, and the number of drugs used. Drugs related to falls were medications to treat Parkinson's disease, antidepressants and neuroleptics. In a multiple logistic regression analysis in-hospital falls were significantly and independently associated with a history of falls, length of in-hospital stay, dementia, and observed daytime sleepiness. CONCLUSION: Observed daytime sleepiness is associated with in-hospital falls in geriatric patients. Prospective interventional studies are needed to confirm this relationship, and to quantify the impact of sleepiness on the risk of falling. Additionally, the impact of treatment for observed daytime sleepiness on the risk of falling should be assessed. The assessment of sleepiness should become a routine task in geriatrics.

Medication optimization according to the Fit fOR The Aged (FORTA) rules improves functional status in patients hospitalized for geriatric rehabilitation.

INTRODUCTION: Functional status is one of the most important issues of geriatric care. Polypharmacy seems to be a modifiable factor associated with functional decline in older adults. However, the impact of pharmacotherapy optimization on the activities of daily living in patients undergoing geriatric rehabilitation has not been investigated prospectively so far. METHODS: This post hoc analysis of a subsample of the VALFORTA study included individuals only undergoing geriatric rehabilitation with a length of in-hospital stay of at least 14 days. Medication was modified according to the FORTA rules in the intervention group while in the control group standard drug treatment was applied. Both groups received comprehensive geriatric treatment. RESULTS: The intervention and control groups consisted of 96 and 93 individuals respectively. They did not differ according to basic data except for age and Charlson Comorbidity Index (CCI) on admission. On discharge, activities of daily living (Barthel index, BI) were improved in both groups. An increase of at least 20 points of the BI was observed in 40% of patients in the intervention group and in 12% of patients in the control group (p< 0.001). Logistic regression analysis with an increase of at least 20 BI-points was significantly and independently associated with patient group (2.358, p< 0.02), BI on admission (0.957, p< 0.001), and the CCI (0.793, p< 0.041). CONCLUSION: This post hoc analysis of a subsample of older individuals hospitalized for geriatric rehabilitation demonstrates a significant additional improvement in activities of daily living by modification of medication according to FORTA. REGISTRATION: DRKS-ID: DRKS00000531.

[Lung function test in advanced age]. / Lungenfunktionsprüfung im höheren Lebensalter.

Advanced age is not an obstacle to carring out a lung function test. In most cases a lung function test is necessary due to the fact that about 20% of older persons are affected by an obstructive respiratory disorder. Standard values for the lung function test are available up to advanced ages. The experience of the examiner and a calm environment for the lung function test have an impact on the quality of the measurement results. Severe cognitive impairments and severe immobility make the performance of a lung function test impossible. Simple geriatric assessments can help to reliably identify these patients. Alternative lung function test procedures have to be validated in order to adequately diagnose this vulnerable subgroup of patients at risk.

Developing a novel tool to assess the ability to self-administer medication in non-demented in-hospital patients: ABLYMED study protocol.

BACKGROUND: Older people often suffer from multimorbidity resulting in polypharmacy. The correct administration of medication is a crucial factor influencing treatment efficacy. However, tools for evaluating the ability to self-administer different dosage forms of medications are lacking. The objectives of the ABLYMED study are to 1) assess the ability to self-administer different dosage forms of medication in older non-demented in-hospital patients who report autonomous management of medication, 2) identify factors influencing the ability to self-administer medication, and 3) develop a standardized tool to validly assess the ability to self-administer different dosage forms of medications based on the final study results. METHODS: One hundred in-patients from the department of orthopedics and trauma surgery of the University Hospital Düsseldorf  ≥ 70 years of age and regularly taking ≥ 5 different drugs autonomously will be prospectively recruited into the observational cross-sectional single-center ABLYMED study. Patients undergo an interview addressing demographic and clinical information, medication history (which medications are taken since when, in which dose and dosage form, and subjective proficiency of taking these medications), medication adherence, and factors possibly influencing adherence including personality traits and perceived quality of the medication regimen. Quality of the medication regimen is also rated by clinicians according to validated lists. Further, patients receive a comprehensive geriatric assessment including measures of cognition, mobility, and functional status. The ability to self-administer medication is assessed by having patients perform different tasks related to medication self-administration, which are video recorded and rated by different experts. The patients' self-reported ability will be correlated with the observed performance in the self-administration tasks. Further, factors correlating with the reported and observed ability to self-administer medication will be evaluated using correlation and regression models. Based on the final study results, a novel tool to assess the ability of older patients to self-administer medication will be developed. DISCUSSION: In addition to guideline-based pharmacotherapy, correct intake of prescribed medication is crucial for optimal therapy of multimorbidity in older people. Tools to validly assess the ability of older patients to self-administer different dosage forms of medications are lacking, but should be included in comprehensive geriatric assessments to secure functional health. TRIAL REGISTRATION: Development of an assessment instrument to evaluate the ability to manage various dosage forms, DRKS-ID: DRKS00025788 , (date of registration: 07/09/2021).

The Sex-Specific Impact of the FORTA (Fit-fOR-The-Aged) List on Medication Quality and Clinical Endpoints in Older Hospitalized Patients: Secondary Analysis of a Randomized Controlled Trial.

BACKGROUND: Little is known about the sex-specific impact of drug optimization tools such as the Fit fOR The Aged (FORTA) list on drug use and relevant clinical endpoints in older people. OBJECTIVE: We aimed to detect gender differences of interventional effects on medication quality and related clinical effects in the VALFORTA trial. PATIENTS AND METHODS: A sex-specific analysis of data from 409 patients (147 men and 262 women, mean age 79.4 and 82.7 years, respectively) in acute geriatric care comparing the control and FORTA intervention groups was performed. Changes of the FORTA score (sum of over- and undertreatment errors per patient), the incidence of adverse drug events (ADEs) during hospitalization, and several clinically relevant endpoints [e.g., the Barthel index (BI)] were tested for equivalence at a 20% margin. "Success" or "failure" for the development of these clinical endpoints was defined and their frequencies compared by a risk reduction analysis. RESULTS: Sex differences were insignificant for the reduction of the FORTA score, the improvement of BI, or over- and undertreatment errors (p > 0.05). In women only, the FORTA intervention significantly increased the number of patients without an ADE (p = 0.010). Statistical sex equivalence was found for the improvement of the FORTA scores, BI, and the number of prevented events (e.g., falls, confusion, or renal failure) (p < 0.05), but not for the improvement of specific mistreatments or over- and undertreatment scores under altered inclusion criteria (p > 0.05). CONCLUSIONS: Both sexes benefit equally from the FORTA intervention regarding the amelioration of the quality of drug treatment as well as several clinically relevant outcomes. In addition, the positive impact of the FORTA intervention on the number of adverse drug events appears to be greater in women. TRIAL REGISTRATION NUMBER: DRKS00000531.

[Sleep and sleep disorders in old age]. / Schlaf und Schlafstörungen im hohen Lebensalter.

The increasing interruptions of night sleep with normal ageing must be distinguished from sleep disorders. Somatic and psychiatric morbidity as well as medication have a huge impact on sleep. Furthermore, the relationship between sleep and morbidity is mutual. Disturbed sleep modifies the clinical appearance of diseases and morbidity affects the ability to sleep. Especially in geriatric medicine, geriatric syndromes such as falls, depression or dementia are modified by sleep disorders. Therefore, treatment for sleep disorders offers the chance to improve geriatric syndromes.When treating, it is important to identify the individual sleep disorders. Coincidences of different sleep disorders are common in the elderly. The history of a patient in connection with a sleeping diary is the basic diagnostic procedure. Sleep medicine provides further technical methods for further examination. Older people should also be examined in a sleep laboratory if the results have consequences that will be accepted by the patient. However, this should be clarified in advance.

[Sleep and Sleep Disturbance in Subjetcs with Dementia]. / Schlaf und Schlafstörungen bei Demenzerkrankungen.

Treating sleep disorders is a challenge in individuals with dementia. A precondition for treatment success is thorough diagnostics of sleep disorders. Sleep diaries and observational questionnairs represent important diagnostic tools. In addition to general treatment strategies including optimal treatment of comorbidities, behavioral therapy is a main intervention. Drugs for the treatment of a sleep disorder should only be prescribed with a clear indication and prolongation of prescription should regularly be checked. The active search for and the treatment of sleep disorders should always be performed in individuals with dementia.

[Pneumonia in old age]. / Pneumonie im hohen Lebensalter.

Pneumonia is a common and severe disease in older people. In this group of patients pneumonia is among the four most frequent diseases leading to death. The diagnosis can often be difficult due to an atypical clinical presentation. Therefore, pneumonia should always be considered as the cause of any deterioration in an older person. Geriatric problems, such as frailty, physical and psychological limitations should be recorded as well as the social situation, as all these factors are of prognostic importance. Pneumonia acquired in a nursing home or by people in need of long-term care has a less favorable prognosis. Although this type of pneumonia is considered to be community acquired, special attenion is required. The treatment of pneumonia does not fundamentally differ from the treatment of younger patients but should take special situations into account, such as the patient's wishes documented in a living will when planning therapy. Older people in particular often show atypical clinical pictures with a coronavirus disease 2019 (COVID-19) infection. Therefore, in any acute change in the health condition of an older person COVID-19 should be considered.

[Aging of the lungs and immune system as hellmark in the pathogenesis of idiopathic pulmonary fibrosis and COVID-19]. / Alterung von Lunge und Immunsystem als Meilensteine in der Pathogenese von idiopathischer Lungenfibrose und COVID-19.

Idiopathic pulmonary fibrosis (IPF) does not occur in younger persons. Therefore, it is not surprising that the nine hallmarks of biological aging can all be found in the pathomechanism of IPF. In this respect the homeostasis of cellular protein synthesis, degradation and recycling becomes unbalanced, which causes a dysregulation of repair mechanisms in the case of lung damage. Severve acute respiratory syndrome coronarvius type 2 (SARS-CoV-2) infections may also predominantyl seen in aged persons. In this situation cellular aging of the lungs also plays a role but additionally, the aging of the immune system is also of great importance. Immunosenescence is associated with a loss of naïve T­cells. Moreover, there are gender-specific differences with a loss of B­cells only in men but not in women, which partly explains the more severe course of COVID-19 pneumonia in older men.

Developing an Alternative Version of the Epworth Sleepiness Scale to Assess Daytime Sleepiness in Adults with Physical or Mental Disabilities.

INTRODUCTION: Excessive daytime sleepiness (EDS) is a frequent symptom with many possible causes, and many of these can be treated. EDS and its underlying causes have been associated with various negative health consequences. Recognition of EDS is thus an important public health concern. The concept of EDS is, however, not yet well defined, and different measures are used to diagnose EDS. The Epworth Sleepiness Scale (ESS) is the most widely used tool to assess daytime sleepiness in a broad range of populations. Its applicability in patients exhibiting physical or mental disabilities, like older multimorbid patients, is limited, since the ESS was not developed and validated in this patient group. METHODS: Within an expert study with 35 sleep medicine experts and a pilot study with 52 geriatric in-patients, who frequently exhibit physical or mental disabilities, and patients' close relatives, we adapted the original ESS to develop an alternative version to assess daytime sleepiness in adults with physical or mental disabilities (ESS-ALT). RESULTS: In this adapted version, items 3 (sitting inactively in a public place) and 8 (sleepy in traffic) were replaced by 2 new items (sitting in a waiting room, sitting and eating a meal) and an interview format was used. This ESS-ALT achieved fewer missing responses (23 vs. 73%) and a higher level of internal consistency (Cronbach's α = 0.64 vs. 0.23) than the original ESS while keeping its somnificity structure. CONCLUSION: The ESS-ALT achieves better psychometric properties than the original ESS for individuals with physical or mental disabilities.