scholarly journals Burden of Insomnia and Sleep Disturbances and the Impact of Sleep Treatments in Patients with Probable or Possible Alzheimer’s Disease: A Structured Literature Review

2022 ◽  
pp. 1-27
Author(s):  
Ruth Benca ◽  
W. Joseph Herring ◽  
Rezaul Khandker ◽  
Zaina Qureshi

Background: Sleep disturbances are frequent in Alzheimer’s disease (AD). This review summarizes the impact of sleep disturbances on AD patients and their caregivers and the effects of currently available sleep therapies. Methods: Published studies (January 1985–March 2020) assessing the burden associated with insomnia/sleep disturbances in the AD population and insomnia treatment effects were identified by searching PubMed, Embase and Cochrane Library and screened against inclusion criteria. Findings: This review included 58 studies which assessed patient and caregiver burden, institutionalization, and insomnia treatments in AD patients with sleep disturbances. Sleep disturbances were associated with worse cognition, functional ability, and behavioral and neuropsychological functioning, including increased depression and anxiety. Health status and quality of life of both patients and caregivers were reduced in the presence of sleep disturbances, with caregiver burden driven largely by disruptive nocturnal behaviors including nighttime awakenings and wanderings. Sleep disturbances were also associated with institutionalization. Although significant associations between sleep problems and clinical outcomes were apparent, there was generally no control for other influencing factors (e.g. cognitive status). With respect to insomnia treatments, bright light, and behavioral therapies as well as drugs such as trazodone, risperidone and suvorexant showed some promise in AD patients, but studies were primarily small and limited data were available, particularly in regard to insomnia treatment effects on associated clinical burden. Interpretation: Sleep disturbances are a significant problem for AD patients and caregivers. They are associated with behavioral and psychological problems and cognitive decline and impose a burden on caregivers, but remain poorly characterized and under-researched. As the global population is aging and AD is on the rise, data from larger, prospective trials are required to fully understand the clinical correlates of sleep disturbances and the impact of insomnia treatments on AD patients and their caregivers.

2002 ◽  
Vol 18 (3) ◽  
pp. 497-507 ◽  
Author(s):  
Andrew Clegg ◽  
Jackie Bryant ◽  
Tricia Nicholson ◽  
Linda McIntyre ◽  
Sofie De Broe ◽  
...  

Objectives: Systematic review of the clinical and cost-effectiveness of donepezil, rivastigmine, and galantamine for people suffering from Alzheimer's disease.Methods: Sixteen electronic databases (including MEDLINE, the Cochrane Library, and Embase) and bibliographies of related papers were searched for published/unpublished English language studies, and experts and pharmaceutical companies were consulted for additional information. Randomized controlled trials (RCTs) and economic studies were selected. Clinical effectiveness was assessed on measurement scales assessing progression of Alzheimer's disease on the person's global health, cognition, functional ability, behavior and mood, and quality of life. Cost-effectiveness was presented as incremental cost per year spent in a nonsevere state (by Mini Mental Health State Examination) or quality-adjusted life-year.Results: Twelve of 15 RCTs included were judged to be of good quality. Although donepezil had beneficial effects in Alzheimer's patients on global health and cognition, rivastigmine on global health, and galantamine on global health, cognition, and functional scales, these improvements were small and may not be clinically significant. Measures of quality of life and behavior and mood were rarely assessed. Adverse effects were usually mild and transient. Cost-effectiveness base case estimates ranged from £2,415 savings to £49,476 additional cost (1997 prices) per unit of effect for donepezil and a small savings for rivastigmine. Estimates were not considered robust or generalizable.Conclusions: Donepezil, rivastigmine, and galantamine appear to have some clinical effect for people with Alzheimer's disease, although the extent to which these translate into real differences in everyday life remains unclear. Due to the nature of current economic studies, cost-effectiveness remains uncertain and the impact on different care sectors has been inadequately investigated. Further research is needed to establish the actual benefits of acetylcholinesterase inhibitors (AChEls) for people with Alzheimer's disease and their caregivers, the relationship of these changes to clinical management, and careful prospective evaluation of resource and budgetary consequences.


2019 ◽  
Vol 77 (11) ◽  
pp. 815-824 ◽  
Author(s):  
Conrado Regis Borges ◽  
Dalva Poyares ◽  
Ronaldo Piovezan ◽  
Ricardo Nitrini ◽  
Sonia Brucki

ABSTRACT The association between Alzheimer's disease (AD) and sleep disturbances has received increasing scientific attention in the last decades. However, little is known about the impact of sleep and its disturbances on the development of preclinical AD stages, such as mild cognitive impairment. This review describes the evolution of knowledge about the potential bidirectional relationships between AD and sleep disturbances exploring recent large prospective studies and meta-analyses and studies of the possible mechanisms through which sleep and the neurodegenerative process could be associated. The review also makes a comprehensive exploration of the sleep characteristics of older people, ranging from cognitively normal individuals, through patients with mild cognitive impairment, up to the those with dementia with AD.


2012 ◽  
Vol 27 (8) ◽  
pp. 579-583 ◽  
Author(s):  
Charles Van Liew ◽  
Terry A. Cronan

Objective: Alzheimer’s disease (AD) is associated with considerable caregiver and social burden. It is important to examine ways to minimize the negative effects of AD. Health care advocates (HCAs) may be one means of limiting the aversive effects of AD. Method: Participants completed a short survey that assessed their perceptions of the impact of comorbid AD on health status and their likelihood of hiring an HCA to assist in managing it. A mediational model was proposed: cognitive status (AD vs cognitively healthy) was the independent variable, perception of severity was the mediator, and the probability of hiring an HCA was the dependent variable. Results: The results indicated that the relationship between cognitive status and probability of hiring an HCA was fully mediated by perceptions of severity. Conclusion: This study demonstrated that participants appreciated the impact of AD on health status, and this translated into a greater probability of hiring an HCA.


2019 ◽  
Vol 31 (10) ◽  
pp. 1509-1516 ◽  
Author(s):  
Adelaide de Mauleon ◽  
Maria Soto ◽  
Pierre Jean Ousset ◽  
Fati Nourhashemi ◽  
Benoit Lepage ◽  
...  

ABSTRACTObjectives:To study potentially modifiable factors associated with the severity of agitation or aggression (A/A) symptoms among Alzheimer’s disease (AD) patients.Design:Data from the Impact of Cholinergic Treatment Use (ICTUS) study, European longitudinal prospective observational study.Setting:Community dwelling outpatients included in 29 European memory clinics.Participants:1375 participants with probable AD (Mini-Mental State Examination score of 10–26) with an informal caregiver.Measurements:At baseline and twice yearly over the two-year follow-up, patients underwent comprehensive clinical and neuropsychological assessments: sociodemographic data, cognitive status, functional impairment, and assessment of neuropsychiatric symptoms based on Neuro-Psychiatric Inventory (NPI). The ZARIT scale assessed the caregiver’s burden. The variable of interest was the severity of the item of A/A of the NPI. To study factors associated to the severity of A/A symptoms six months later, a multivariate mixed regression model was used.Results:Frequency of A/A symptom varied from 30% to 34% at each visit. Two factors were found to be independently associated with the severity of A/A: (1) the presence of affective disorder (anxiety, depression, and/or irritability) that increased the severity of the A/A by 0.89 point (coefficient:0.89; 95% Confidence Interval (CI) = [0.48,1.30], p < 0.001), and (2) a severe caregiver burden that increased the severity of the A/A by 1.08 point (coefficient:1.08; 95% CI = [0.69,1.47], p < 0.001).Conclusion:Research should evaluate whether the identification and treatment of an affective disorder along with the evaluation and optimal management of the caregiver would have a positive impact on the course of A/A in mild to moderate AD patients.


2020 ◽  
Vol 32 (S1) ◽  
pp. 117-117

PRESENTING AUTHOR:Mary Michael, Vice President, Patient Advocacy and Stakeholder Management, Otsuka America Pharmaceutical, Inc.OBJECTIVE:To evaluate the extent to which the cost of both treated and untreated agitation in Alzheimer’s disease has been studied in order to inform future research and development of predictive models of the cost of untreated agitation in Alzheimer’s disease.BACKGROUND:There is inadequate understanding of the costs of agitation in Alzheimer’s disease in the scientific and academic literature. Agitation in Alzheimer’s disease contributes to negative social and financial outcomes for people with the condition, their care partners, and health systems. When left untreated, the impact of these outcomes is exacerbated, yet the scale of this impact is unknown. This gap in the literature both reflects and perpetuates the broader under-recognition of agitation as a serious unmet need in the Alzheimer’s community. Conversely, a better understanding of the costs can help elevate agitation within the global Alzheimer’s dialogue.METHODS:We used MEDLINE, PubMed, PsychINFO the Cochrane Library and Google Scholar databases to identify relevant articles published between 2000 until May 2020. We also reviewed reliable literature published outside of these databases. Keywords utilized in the search include agitation in Alzheimer’s, neuropsychiatric symptoms of Alzheimer’s, cost of informal and formal care, Medicare and Medicaid costs, economic costs associated to delirium, among others. Only articles in English were included. Inclusion and exclusion criteria were determined by study design, data source and population studied, number of cases included in analysis, source of health service use or cost data, statistical methods and agitation in Alzheimer’s attributable and/or incremental costs.RESULTS:Results will describe the breadth and depth to which costs of treated and untreated agitation in Alzheimer’s have been examined, indicating data and statistical methodology used.CONCLUSIONS:This literature review serves as the basis for understanding global costs of agitation in Alzheimer’s disease. From our analysis, we recommend that further cost modeling activities be conducted. We also urge the greater community to use these findings to elevate agitation to the top of the Alzheimer’s agenda.


2016 ◽  
Vol 26 (9-10) ◽  
pp. 1291-1300 ◽  
Author(s):  
Shuai Liu ◽  
Chonghui Li ◽  
Zhihong Shi ◽  
Xiaodan Wang ◽  
Yuying Zhou ◽  
...  

2003 ◽  
Vol 15 (4) ◽  
pp. 385-398 ◽  
Author(s):  
Deborah Marin ◽  
Karine Amaya ◽  
Roman Casciano ◽  
Katherine L. Puder ◽  
Julian Casciano ◽  
...  

Background: Alzheimer's disease (AD) places a significant burden on health care systems worldwide. As new treatments are developed, their cost-effectiveness is often assessed to help health care professionals make informed decisions. In addition to the more common practice of assessing direct medical costs, indirect costs, including time spent in caregiving, should be evaluated. Methods: This study examined the potential effects of the dual cholinesterase inhibitor rivastigmine (Exelon) on caregivers of patients with AD. Results from two 26-week, placebo-controlled trials have demonstrated the clinically relevant and statistically significant efficacy of rivastigmine (6–12 mg/day) compared to placebo, on cognition, activities of daily living, and global functioning. By delaying progression of AD, significant savings in caregiver burden are anticipated, as measured by time spent caregiving and its related costs. Data collected in a prospective, observational study of AD patients and their caregivers were used to establish the relationship between disease severity (based on Mini-Mental State Examination [MMSE] score) and time spent caregiving (according to the 5-item Caregivers Activity Survery score). A significant correlation was observed between the two scores (N = 43, r = −.56, p < .0001), demonstrating that more time for supervision from caregivers is required as the disease progresses. This finding was used to estimate the reduced caregiver burden resulting from the delay in disease progression that was demonstrated with use of rivastigmine. Results: Over a 2-year period, the reduction in time spent in caregiving reached 691 hours for caregivers of patients with mild AD (MMSE score 21–30), resulting in a total savings of approximately $11,253. Treatment of patients with moderately severe AD was also evaluated. The trend was similar but the impact was less, suggesting an economic benefit to early therapy. Conclusion: Early diagnosis and a pharmacologic intervention that allows the patients to remain at home longer by delaying disease progression would have a beneficial impact on patients, caregivers, and payers, and should therefore be encouraged through initiatives designed to identify and treat patients early in the course of disease.


2021 ◽  
Vol 12 ◽  
Author(s):  
James R. Hall ◽  
Melissa Petersen ◽  
Leigh Johnson ◽  
Sid E. O’Bryant

Depression and related neurobehavioral symptoms are common features of Alzheimer’s disease and other dementias. The presence of these potentially modifiable neurobehavioral symptoms in cognitively intact older adults may represent an early indication of pathophysiological processes in the brain. Tau pathology is a key feature of a number of dementias. A number of studies have found an association between tau and neurobehavioral symptoms. The current study investigated the relationship of a blood-based biomarker of tau and symptoms of depression, anxiety, worry, and sleep disturbances in 538 community based, cognitively normal older adults. Logistic regression revealed no significant relationship between plasma total tau and any measures of neurobehavioral symptoms. To assess the impact of level of tau on these relationships, participants were divided into those in the highest quintile of tau and those in the lower four quintiles. Regression analyses showed a significant relationship between level of plasma total tau and measures of depression, apathy, anxiety, worry and sleep. The presence of higher levels of plasma tau and elevated neurobehavioral symptoms may be an early indicator of cognitive decline and prodromal Alzheimer’s disease. Longitudinal research is needed to evaluate the impact of these factors on the development of dementia and may suggest areas for early intervention.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 655-656
Author(s):  
Meina Zhang ◽  
Young-Eun Cho ◽  
Chooza Moon

Abstract Alzheimer's disease (AD) commonly involves neuropsychiatric symptoms (NPS), such as nighttime behaviors (or sleep disturbance), hallucination, delusion, or mood changes. However, it is unclear how NPS and sleep disturbances are correlated with AD biomarkers. The purpose of this analysis was to examine how NPS and nighttime behaviors are associated with AD CSF biomarkers by cognitive status. A total of 1,667 subjects’ (mean age = 69.4 SD=9.3, 48 % (808) were male) data from the National Alzheimer’s Disease Coordinating Center (NACC) were used, including subjects with dementia (n = 577), mild cognitive impairment (MCI, n = 363), cognitive impairment but not MCI (n = 47), cognitive impairment due to Alzheimer’s etiology (n= 608), and normal cognition (n = 680). The nighttime symptoms, number, and severity of NPS were assessed using the Neuropsychiatric Inventory Questionnaire Quick Version (NPI-Q). Cerebrospinal fluid (CSF) samples were analyzed for Aβ42,dft5 t-tau, p-tau. We used generalized linear models to explore the associations accounting for age, sex, APOE4 alleles, and BMI. We found the number of NPS were associated with Aβ42 (p = 0.042) in individuals with MCI, impaired, or dementia due to Alzheimer’s etiology. Yet, the number of NPS were not associated with t-tau or p-tau in individuals with and without dementia. The severity of NPS including nighttime symptoms were not associated with biomarkers. Our results could suggest that the number of NPS can be reflected by higher CSF Aβ42 levels in the individuals with Alzheimer’s etiology. Future longitudinal analyses are warranted to understand the causal relationships.


2006 ◽  
Vol 3 (4) ◽  
pp. 441-445 ◽  
Author(s):  
Leopoldo Luiz dos Santos-Neto ◽  
Maria Alice de Vilhena Toledo ◽  
Patrícia Medeiros-Souza ◽  
Gustavo Almeida de Souza

The treatments of choice in Alzheimer's disease (AD) are cholinesterase inhibitors and NMDA-receptor antagonists, although doubts remain about the therapeutic effectiveness of these drugs. Herbal medicine products have been used in the treatment of Behavioral and Psychological Symptoms of Dementia (BPSD) but with various responses. The objective of this article was to review evidences from controlled studies in order to determine whether herbs can be useful in the treatment of cognitive disorders in the elderly. Randomized controlled studies assessing AD in individuals older than 65 years were identified through searches of MEDLINE, LILACS, Cochrane Library, dissertation Abstract (USA), ADEAR (Alzheimer's Disease Clinical Trials Database), National Research Register, Current Controlled trials, Centerwatch Trials Database and PsychINFO Journal Articles. The search combined the terms Alzheimer disease, dementia, cognition disorders, Herbal, Phytotherapy. The crossover results were evaluated by the Jadad's measurement scale. The systematic review identified two herbs and herbal formulations with therapeutic effects for the treatment of AD:Melissa officinalis,Salvia officinalisand Yi-Gan San and BDW (Ba Wei Di Huang Wan).Ginkgo bilobawas identified in a meta-analysis study. All five herbs are useful for cognitive impairment of AD.M. officinalisand Yi-Gan San are also useful in agitation, for they have sedative effects. These herbs and formulations have demonstrated good therapeutic effectiveness but these results need to be compared with those of traditional drugs. Further large multicenter studies should be conducted in order to test the cost-effectiveness of these herbs for AD and the impact in the control of cognitive deterioration.


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