Advanced Cognitive Impairment Research Articles

CSF progranulin increases in the course of Alzheimer's disease and is associated with sTREM2, neurodegeneration and cognitive decline

Progranulin (PGRN) is predominantly expressed by microglia in the brain, and genetic and experimental evidence suggests a critical role in Alzheimer's disease (AD). We asked whether PGRN expression is changed in a disease severity‐specific manner in AD. We measured PGRN in cerebrospinal fluid (CSF) in two of the best‐characterized AD patient cohorts, namely the Dominant Inherited Alzheimer's Disease Network (DIAN) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). In carriers of AD causing dominant mutations, cross‐sectionally assessed CSF PGRN increased over the course of the disease and significantly differed from non‐carriers 10 years before the expected symptom onset. In late‐onset AD, higher CSF PGRN was associated with more advanced disease stages and cognitive impairment. Higher CSF PGRN was associated with higher CSF soluble TREM2 (triggering receptor expressed on myeloid cells 2) only when there was underlying pathology, but not in controls. In conclusion, we demonstrate that, although CSF PGRN is not a diagnostic biomarker for AD, it may together with sTREM2 reflect microglial activation during the disease.

Sleep on the ward in intensive care unit survivors: a case series of polysomnography.

Few studies have investigated sleep in patients after intensive care despite the possibility that inadequate sleep might further complicate an acute illness impeding recovery. To assess the quality and quantity of a patient's sleep on the ward by polysomnography (PSG) within a week of intensive care unit (ICU) discharge and to explore the prevalence of key in-ICU risk factors for persistent sleep fragmentation. We enrolled 20 patients after they have been mechanically ventilated for at least 3 days and survived to ICU discharge. We included all patients over the age of 16 years and excluded patients with advanced cognitive impairment or who were unable to follow simple commands before their acute illness, primary admission diagnosis of neurological injury, uncontrolled psychiatric illness or not fluent in English. Twenty patients underwent an overnight PSG recording on day 7 after ICU discharge (SD, 1 day). ICU survivors provided 292.8 h of PSG recording time with median recording times of 16.8 h (Interquartile range (IQR), 15.0-17.2 h). The median total sleep time per patient was 5.3 h (IQR, 2.6-6.3 h). In a multivariable regression model, postoperative admission diagnosis (P = 0.04) and patient report of poor ICU sleep (P = 0.001) were associated with less slow-wave (restorative) sleep on the wards after ICU discharge. Patients reported poor sleep while in the ICU, and a postoperative admission diagnosis may identify a high-risk subgroup of patients who may derive greater benefit from interventions to improve sleep hygiene.

Evaluación cognitiva global en personas vascoparlantes con demencia en estadios avanzados. Validación al euskera de la escala Severe Mini Mental State Examination (SMMSE-eus)

IntroductionAdaptation and validation to the Basque language of tests to assess advanced cognitive impairment is a not covered need for Basque-speaking people. The present work shows the validation of the Basque version of the Severe Mini Mental State Examination (SMMSE). Material and methodsA total of 109 people with advanced dementia (MEC<15) took part in the validation study, and were classified as GDS 5-7 on the Geriatric Depression Scale (GDS). All participants were Spanish-Basque bilingual. ResultsIt was shown that SMMSE-eus has a high internal consistency (alpha=0.92), a good test-retest reliability (r=0.88; P<.01), and a high inter-rater reliability (CCI=0.99; P<.00) for the overall score, as well as for each item. ConclusionsBoth the high internal consistency and inter-rater reliability, and to a lesser extent, test-retest reliability, made the SMMSE-eus a valid test for the brief assessment of cognitive status in people with advanced dementia in Basque-speaking people. For this reason, the SMMSE-eus is a usable and reliable alternative for assessing Basque-speaking people in their mother-tongue, or preferred language.

Triglycerides: A Potential Hematological Marker in Animal Models of Cognitive Impairment

Mild Cognitive Impairment (MCI) is a clinical disorder characterized as an intermediate stage of cognitive impairment between normal cognitive aging and more advanced cognitive impairment associated with dementia. MCI causes measurable decline in cognitive abilities including memory and reasoning. Occurrence of MCI has been linked to altered physiological functions, co‐morbid conditions, and adverse events related to therapeutic drugs or toxins. MCI is commonly diagnosed by a physician's clinical judgement based on the following parameters: complete medical history, assessment of independent function and daily activities, input from family members, assessment of mental status (i.e. Mini Mental Status Exam), neurological examinations, and laboratory tests including blood tests and imaging of the brain's structure. The testing required is extensive and often subjective in nature. Currently, there are few biochemical markers thought to correlate with the onset of early‐stage MCI and those that do exist require expensive or invasive techniques to measure accurately. Therefore, using valid animal models representative of cognitive impairment, this study aims to determine the validity of using hematological markers as predictors of early‐stage MCI development.In this study, we measured the hematological markers in animal models of cognitive impairment compared to their respective control group. Cognitive impairment was observed in a chemotherapeutic (CT) rodent group dosed with doxorubicin (2 mg/kg, IP) and cyclophosphamide (50 mg/kg, IP) once weekly for 4 weeks. Cognitive impairment was also observed in a hyperglycemia rodent group dosed with Streptozotocin (STZ) 55 mg/kg, once, IP. Blood samples were withdrawn, and hematological markers analyzed. There was a significant increase in creatine kinase and lactate dehydrogenase (LDH) in the CT model versus control. Glucose levels were significantly increased in the STZ model versus control. With regard to BUN, there was a significant increase in the STZ model compared to their control group, however there was a decrease in the CT model compared to their control group. Interestingly, triglycerides were significantly elevated in both the STZ and CT treated animal models. Previous studies with human subjects have shown a potential link between the increase in triglyceride levels influencing cognitive impairment. Likewise, our data indicates a possible correlation with an increase in triglycerides to cognitive impairment in animal models. This suggests elevated levels of triglycerides may prove to be a potential, minimally invasive, hematological marker for the increased risk of cognitive deficit in these animal models. However, further studies are necessary to determine the causal relationship between elevated triglyceride levels and early‐stage MCI.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Reliability of three questions for the screening of advanced cognitive impairment in polypathological patients.

To determine whether answering three questions erroneously ("what is the date today?," "when were you born?" and "how old are you?") allows for the detection of advanced cognitive impairment in polypathological patients. A cross-sectional study of patients admitted to the internal medicine and geriatrics departments was carried out. Advanced cognitive impairment was diagnosed when patients made 7-10 errors in the Short Portable Mental Status Questionnaire. We included 441 polypathological patients, 330 of them from the internal medicine departments and 111 from the geriatrics department. Their mean age was 80.8 years (8.9 years). Of them, 141 (32.0%) answered one question incorrectly, 58 (13.1%) answered two and 89 (20.2%) answered all three questions incorrectly. The prevalence of advanced cognitive impairment was 27.7%. The sensitivity, specificity, and positive and negative predictive values of the test were 0.705, 0.991, 0.966 and 0.898, respectively. The accuracy of the test was 0.912. The area under the receiver operating characteristic curve was 0.947, 95% CI 0.923-0.970. The three questions test has very good specificity and positive predictive value, and it can be used for the screening of advanced cognitive impairment in polypathological patients. Geriatr Gerontol Int 2018; 18: 441-447.

Using the ecological framework to identify barriers and enablers to implementing Namaste Care in Canada's long-term care system.

Higher acuity of care at the time of admission to long-term care (LTC) is resulting in a shorter period to time of death, yet most LTC homes in Canada do not have formalized approaches to palliative care. Namaste Care is a palliative care approach specifically tailored to persons with advanced cognitive impairment who are living in LTC. The purpose of this study was to employ the ecological framework to identify barriers and enablers to an implementation of Namaste Care. Six group interviews were conducted with families, unlicensed staff, and licensed staff at two Canadian LTC homes that were planning to implement Namaste Care. None of the interviewees had prior experience implementing Namaste Care. The resulting qualitative data were analyzed using a template organizing approach. We found that the strongest implementation enablers were positive perceptions of need for the program, benefits of the program, and fit within a resident-centred or palliative approach to care. Barriers included a generally low resource base for LTC, the need to adjust highly developed routines to accommodate the program, and reliance on a casual work force. We conclude that within the Canadian LTC system, positive perceptions of Namaste Care are tempered by concerns about organizational capacity to support new programming.

Differentiating Between Apathy and Depression in Patients With Parkinson Disease Dementia.

In Parkinson disease (PD), apathy and depression often overlap, making it difficult to differentiate between them. This study sought to analyze apathy and depression in patients with PD dementia (PDD). Forty patients were diagnosed with PDD using the Movement Disorder Society criteria. A statistically significant correlation was identified between worsening dementia and an improvement in depression ( r = .3695; r2 = .1365, 95% confidence interval [CI]: 0.0985 to 05.894, P = .0044) and between worsening dementia and worsening apathy ( r = -.2578, r2 = .0664, 95% CI: -0.5025 to .0251, P = .036). Depression had a greater correlation with advanced motor symptoms ( r = .4988, r2 = .2438, 95% CI: 0.2218-0.7013, P = .0005]. In conclusion, depression was associated with less advanced PDD and more intense motor features, while apathy was associated with more advanced cognitive impairment.

Association of Physician Specialty with Hospice Referral for Hospitalized Nursing Home Patients with Advanced Dementia.

Hospitalists hospice referral patterns have been unstudied. This study aims to examine hospice referral rates by attending type for hospitalized nursing home (NH) residents with advanced cognitive impairment (ACI) at the time of discharge between 2000 and 2010. Retrospective cohort study. Hospitalized NH residents age ≥66 drawn from the 20% sample of Medicare beneficiaries with ACI, 4 or more activities of daily living (ADL) impairments on last minimum data set (MDS) assessment completed within 120days of admission (n=128,989). Hospice referral was defined as referral to hospice within 1day after hospital discharge. Attending physician type was determined by Part B physician billing for 100% of the billings during that admission. Continuity of care was defined as the hospital physician also billing for an outpatient visit within 120days of that hospital admission. Number of ADL impairments, cognitive measures, pre-admission illnesses and illness severity were derived from the MDS. Of the 105,329 hospitalized patients with ACI that survived to discharge (72.3% white, 30.6% male), the hospice referral rate at the time of hospital discharge increased from 2.8% in 2000 to 11.2% in 2010. Using a multivariate, hospital fixed effects model examining changes in the distribution of inpatient attending physicians, hospitalists compared to generalist physicians were more likely to refer these patients to hospice at discharge (AOR 1.17, 95% CI 1.09-1.26). Continuity of physician care from the outpatient setting to the hospital was associated with lower hospice referral (AOR 0.78, 95% CI 0.73-0.85). Hospice referrals for NH-dwelling persons with ACI admitted to the hospital increased between 2000 and 2011 and disproportionately so when the attending physician was a hospitalist.

Abstract 179: Determinants of Cerebral Microbleeds in Acute Ischemic Stroke Patients With Non-valvular Atrial Fibrillation: SAMURAI-NVAF Study

Background and Purpose: Cerebral microbleeds (CMBs) are now considered to be one of the neuroimaging markers of cerebral small vessel disease. It has been reported that CMBs are associated with age, hypertension, cognitive impairment, and use of antithrombotic drugs. We aimed at identifying factors associated with the presence of CMBs among acute ischemic stroke patients with non-valvular atrial fibrillation (NVAF) who participated in the multicenter Stroke Acute Management with Urgent Risk-factor Assessment and Improvement (SAMURAI)-NVAF study. Methods: Acute ischemic stroke/transient ischemic attack (within 7 days of onset) patients with NVAF who underwent T2*-weighted images on magnetic resonance imagings at baseline were included in the analysis. Factors associated with the presence of CMBs were assessed in univariable and multivariable logistic regression models. Results: Of 1,099 (77.6±10.0 years, 620 male) participants, 256 (23.2%) had CMBs: single CMB in 96 (8.7%), 2-4 of CMBs in 109 (9.9%), and ≥5 CMBs in 51 (4.6%). The presence of CMBs was associated with age [per 10 years, odds ratio (OR) 1.21; 95% confidence interval (CI) 1.02-1.44], past history of stroke (OR 1.52; 95% CI 1.09-2.11), and advanced cognitive impairment (OR 1.64; 95% CI 1.02-2.61) in multivariable analysis adjusted for sex, hypertension, arterial disease, ever smoking, premorbid antithrombotic medications, and estimated glomerular filtration rate. Among 514 patients (46.8% of the participants) with the data of urinary albumin, clinical albuminuria (urinary albumin ≥300 mg/gCr) and past history of stroke were identified as independent factors associated with CMBs (OR 1.91; 95% CI 1.06-3.42 and 1.67; 1.04-2.66, respectively). Conclusions: Approximately one fourth of acute ischemic stroke patients with NVAF had CMBs. Past history of stroke and clinical albuminuria were identified as independent determinants of CMBs on top of established ones. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01581502.

Psychosis in Parkinson’s Disease: Epidemiology, Pathophysiology, and Management

Psychotic symptoms are common in Parkinson's disease (PD) and are associated with poorer quality of life and increased caregiver burden. PD psychosis is correlated with several factors, such as more advanced disease, cognitive impairment, depression, and sleep disorders. The underlying causes of psychosis in PD thus involve a complex interplay between exogenous (e.g., drugs, intercurrent illnesses) and endogenous (e.g., PD disease pathology) factors. Current theories of the pathophysiology of PD psychosis have come from several neuropathological and neuroimaging studies that implicate pathways involving visual processing and executive function, including temporo-limbic structures and neocortical gray matter with altered neurotransmitter functioning (e.g., dopamine, serotonin, and acetylcholine). Treatment of PD psychosis requires a step-wise process, including initial careful investigation of treatable triggering conditions and a comprehensive evaluation with adjustment of PD medications and/or initiation of specific antipsychotic therapies. Clozapine remains the only recommended drug for the treatment of PD psychosis; however, because of regular blood monitoring, quetiapine is usually first-line therapy, although less efficacious. Emerging studies have focused on agents involving other neurotransmitters, including the serotonin 5-HT2A receptor inverse agonist pimavanserin, cholinesterase inhibitors, and antidepressants and anxiolytics.

Management of persistent pain in older people

AbstractPersistent pain is a commonly experienced symptom. It affects 25% of community‐dwelling older adults and up to 80% of nursing home residents, and can have a major impact on quality of life and functional capacity. Unfortunately pain in older patients is often undertreated and misunderstood. Assessment of pain type and severity is important. Most older people, even with moderately impaired cognition, are able to self‐report pain. Validated assessment tools using non‐verbal pain cues are available for people with more advanced cognitive impairment. Management of pain in older people can be challenging. Physiological changes may impact on pain perception and the pharmacodynamics and pharmacokinetics of medications. Older people are often more sensitive to the adverse effects of analgesic medications and are at risk of drug–drug interactions due to the presence of co‐morbidities and polypharmacy. In general, analgesic medications should be commenced at low doses, titrated based on effect and tolerability, and regularly reviewed. Contemporary pain management often utilises multiple analgesics in lower doses to optimise efficacy and avoid dose‐related toxicity. A bio‐psycho‐social approach to the management of persistent pain, utilising a multidisciplinary team and including non‐drug strategies, may produce the best results. The goal of pain management is not always to eliminate pain, since this may not be attainable, but rather to enhance function and improve quality of life. This article discusses persistent non‐cancer pain in older people, its assessment and management, and the risks and benefits of pharmacological treatment in this population.

Person-centered Feeding Care: A Protocol to Re-introduce Oral Feeding for Nursing Home Patients with Tube Feeding.

Although the literature on nursing home (NH) patients with tube feeding (TF) has focused primarily on the continuation vs. discontinuation of TF, the reassessment of these patients for oral feeding has been understudied. Re-assessing patients for oral feeding may be better received by families and NH staff than approaches focused on stopping TF, and may provide an opportunity to address TF in less cognitively impaired patients as well as those with end-stage conditions. However, the literature contains little guidance on a systematic interdisciplinary team approach to the oral feeding reassessment of patients with TF, who are admitted to NHs. This project had two parts that were conducted in one 170-bed intermediate/skilled, Medicare-certified NH in Honolulu, Hawai'i. Part 1 consisted of a retrospective observational study of characteristics of TF patients versus non-tube fed patients at NH admission (2003-2006) and longitudinal follow-up (through death or 6/30/2011) with usual care of the TF patients for outcomes of: feeding and swallowing reassessment, goals of care reassessment, feeding status (TF and/or per oral (PO) feedings), and hospice status. Part 2 involved the development of an interdisciplinary TF reassessment protocol through working group discussions and a pilot test of the protocol on a new set of patients admitted with TF from 2011-2014. Part 1: Of 238 admitted patients, 13.4% (32/238) had TF. Prior stroke and lack of DNR status was associated with increased likelihood of TF. Of the 32 patients with TF at NH admission, 15 could communicate and interact (mild, moderate or no cognitive impairment with prior stroke or pneumonia); while 17 were nonverbal and/or bedbound patients (advanced cognitive impairment or terminal disease). In the more cognitively intact group, 9/15 (60%) were never reassessed for tolerance of oral diets and 10/15 (66.7%) remained with TF without any oral feeding until death. Of the end-stage group, 13/17 (76.5%) did not have goals of care reassessed and remained with TF without oral feeding until death. Part 2: The protocol pilot project included all TF patients admitted to the facility in 2011-2014 (N=33). Of those who were more cognitively intact (n=22), 21/22 (95.5%) had swallowing reassessed, 11/22 (50%) resumed oral feedings but 11 (50%) failed reassessment and continued exclusive TF. Of those with end-stage disease (n=11), 100% had goals of care reassessed and 9 (81.8%) families elected individualized oral feeding (with or without TF). Using findings from our retrospective study of usual care, our NH's interdisciplinary team developed and pilot-tested a protocol that successfully reintroduced oral feedings to tube-fed NH patients who previously would not have resumed oral feeding.

A Review of Hospice Characteristics and Patient Outcomes Associated with Exceeding the Medicare Hospice Annual Aggregate Reimbursement Cap (SA517C)

physician and degree of fragmentation with referral to hospice. This model adjusted for resident characteristics, cognition, functional status and diagnosis prior to admission. Results. We captured 130,833 hospitalizations of Medicare beneficiaries with advanced cognitive impairment who were residing in NHs between 2000 and 2010 (mean patient age of 83.6, 68.0% female, 74.3% white, 70.2% one-year mortality). Of the hospitalizations that involved only one type of provider acting as the attending physician, the primary provider for that admission was a non-hospitalist general practitioner, a hospitalist, or a specialist in 67.4%, 25.6% and 7.1% of admissions respectively. Hospitalists had 1.44 increased odds of hospice referral compared to non-hospitalist generalists (95% CI 1.31-1.58). Specialists were not statistically significantly different from non-hospitalist generalist. Conclusion. Hospice referrals for NH residents with ACI are more likely when the attending physician is a hospitalist. Implications for Research, Policy, and Practice. Hospitalists, a growing class of physicians, are more likely to appropriately refer NH residents with a high 1-year mortality to hospice at hospital discharge.

Cardiac Rupture: New Features of the Old Disease

Objectives: Myocardial rupture is a rare but a fatal complication of acute myocardial infarction. During recent years, treatment strategies of acute myocardial infarction have changed. Primary percutaneous coronary interventions have replaced fibrinolytic therapy, thus reducing one of the major risk factors for myocardial rupture. In this work, we describe a group of patients who suffered myocardial rupture, none of whom were treated with thrombolytic therapy. Methods: The digital database of our hospital was searched for all patients who experienced myocardial rupture between 2008 and 2015. The demographic, clinical, angiographic and echocardiographic data of these patients were analyzed. Results: Out of 2,380 patients admitted with acute myocardial infarction, 12 (0.5%) developed myocardial rupture. The mean age was 78 years, and there were 7 males and 5 females. Ten patients already had pericardial effusion on admission. Seven patients underwent coronary angiography, whilst primary percutaneous intervention was performed in 4 patients. Six patients entered the operating room and all survived the procedure. All patients who were treated conservatively died due to rupture. Factors related to the treatment strategy were advanced age (≥90 years) and cognitive impairment. Conclusions: The risk of myocardial rupture may be diminished by primary coronary intervention during myocardial infarction, but mortality remains high. An early, comprehensive echocardiographic examination and rapid surgery may contribute to improved survival.

Decision-making capacity for research participation among addicted people: a cross-sectional study.

BackgroundInformed consent is a key element of ethical clinical research. Addicted population may be at risk for impaired consent capacity. However, very little research has focused on their comprehension of consent forms. The aim of this study is to assess the capacity of addicted individuals to provide consent to research.Methods53 subjects with DSM-5 diagnoses of a Substance Use Disorder (SUD) and 50 non psychiatric comparison subjects (NPCs) participated in the survey from December 2014 to March 2015. This cross-sectional study was carried out at a community-based Outpatient Treatment Center and at an urban-located Health Centre in Spain. A binary judgment of capacity/incapacity was made guided by the MacArthur Competence Assessment Tool for Clinical Research (MacCAT–CR) and a clinical interview. Demographics and clinical characteristics were assessed by cases notes and the Mini-Mental State Examination, the Global Assessment Functional Scale and the Clinical Global Impression Scale.ResultsNPCs performed the best on the MacCAT–CR, and patients with SUD had the worst performance, particularly on the Understanding and Appreciation subscales. 32.7 % SUD people lacked research-related decisional capacity. There were no statistically significant differences between the groups in terms of capacity to consent to research.ConclusionsThe findings of our study provide evidence that a large proportion of individuals with SUD had decisional capacity for consent to research. It is therefore inappropriate to draw conclusions about capacity to make research decisions on the basis of a SUD diagnosis. In the absence of advanced cognitive impairment, acute withdrawal or intoxication, we should assume that addicted persons possess decision-making capacity. Thus, the view that people with SUD would ipso facto lose decision-making power for research consent is flawed and stigmatizing.

Delirium after open cardiac surgery:systematic review of prevalence, risk factors and consequences

Delirium is a sudden and usually transient disturbance in consciousness, attention, cognition, perception and emotions. The pathophysiology is unknown but possible causes include neurotransmitter disturbances and inflammation reaction. Delirium is common in patients after open cardiac surgeries and can lead to serious consequences. Research shows that delirium is an underdiagnosed and undertreated problem. The purpose of this systematic review is to illuminate the prevalence, risk factors and outcome of postoperative delirium following open cardiac surgery. A systematic literature review from 2005-2013 was performed aiming to determine the prevalence, predisposing and precipitating factors and outcome after postoperative delirium following cardiac surgery. Web of Science, PubMed and Cinahl were searched. Findings of the systematic review shows that about one third of patients become delirious after cardiac surgery. Primary predisposing factors are advanced age, cognitive impairment, atrial fibrillation, depression and prior history of stroke. Among precipitating factors are pulmonary bypass, duration of mechanical ventilation, low cardiac output, respiratory failure, pneumonia, infections, blood cell transfusion and post-operative arrhythmias. Delirium causes prolonged hospital stay, reduced activity and higher mortality. Delirium prevention includes reducing risk factors. Delirium is a common and serious complication of open cardiac surgery. Knowledge of risk factors of delirium and regular screening for symptoms of delirium are important to reduce prevalence and to facilitate diagnosis and treatment.

Development of the Adolescent Cancer Suffering Scale.

While mortality due to pediatric cancer has decreased, suffering has increased due to complex and lengthy treatments. Cancer in adolescence has repercussions on personal and physical development. Although suffering can impede recovery, there is no validated scale in French or English to measure suffering in adolescents with cancer. To develop an objective scale to measure suffering in adolescents with cancer. A methodological design for instrument development was used. Following a MEDLINE search, semistructured interviews were conducted with adolescents 12 to 19 years of age who had undergone four to six weeks of cancer treatment, and with a multidisciplinary cohort of health care professionals. Adolescents with advanced terminal cancer or cognitive impairment were excluded. Enrollment proceeded from the hematology-oncology department⁄clinic in Montreal, Quebec, from December 2011 to March 2012. Content validity was assessed by five health care professionals and four adolescents with cancer. Interviews with 19 adolescents and 16 health care professionals identified six realms of suffering: physical, psychological, spiritual, social, cognitive and global. Through iterative feedback, the Adolescent Cancer Suffering Scale (ACSS) was developed, comprising 41 questions on a four-point Likert scale and one open-ended question. Content validity was 0.98, and inter-rater agreement among professionals was 88% for relevance and 86% for clarity. Adolescents considered the scale to be representative of their suffering. The ACSS is the first questionnaire to measure suffering in adolescents with cancer. In future research, the questionnaire should be validated extensively and interventions developed. Once validated, the ACSS will contribute to promote a holistic approach to health with appropriate intervention or referral.

A randomized, placebo controlled pilot trial of botulinum toxin for paratonic rigidity in people with advanced cognitive impairment.

ObjectiveEvaluate safety and efficacy of Incobotulinumtoxin A in elderly patients with dementia and paratonia.SettingUniversity-affiliated hospital, spasticity management Clinic.ParticipantsTen subjects were enrolled. Inclusion criteria: 1) severe cognitive impairment 2) diagnosis of Alzheimer’s disease, vascular dementia, or frontotemporal dementia, and 3) score >3 on the paratonic assessment instrument, with posture in an arm(s) interfering with provision of care. Exclusion criteria: 1) alternate etiologies for increased tone and 2) injection with botulinum toxin within the 6 months preceding the study.DesignSingle center, randomized, double blind, placebo-controlled, crossover trial with two treatment cycles of 16 weeks. Assessments occurred at 2, 6, 12 and16 weeks following injections. Subjects received up to 300 U of Incobotulinumtoxin A in arm(s).Primary and Secondary Outcome MeasuresPrimary outcome measure was the modified caregiver burden scale (mCBS); exploratory secondary outcome measures were also performed. Analysis of variance and mixed modeling techniques were used to evaluate treatment effects.ResultsIncobotulinumtoxin A treatment produced significant improvement in mCBS total score −1.11 (–2.04 to −0.18) (Treatment effect and 95% CI), dressing sub-score −0.36 (–0.59 to 0.12), and cleaning under the left and right armpits sub-score −0.5 (–0.96 to −0.04), −0.41 (–0.79 to −0.04) respectively. PROM in the left and right elbow increased by 27.67 degrees (13.32–42.02) and 22.07 degrees (9.76–34.39) respectively. PROM in the left and right shoulder increased by 11.92 degrees (5.46–18.38) and 8.58 degrees (3.73–13.43) respectively. No significant treatment effect was found for GAS, VAS and PAINAD scales or change in time to perform care. No adverse drug reactions occurred.ConclusionsAdministration of Incobotulinumtoxin A in elderly people with advanced dementia and paratonia may be an efficacious and safe treatment to increase range of motion and reduce functional burden. Further studies are needed to confirm results.Trial RegistrationClinicalTrials.Gov NCT02212119

Hip fracture: a trigger for palliative care in vulnerable older adults.

examined the survival and functional outcomes after hip fracture in 60 111 US long-term nursing home residents who were hospitalized with an acute hip fracture. Using a retrospective cohort study design and large national data sets (Medicare claims and Nursing Home Minimum Data Set), this study characterized patterns and risk factors of survival and new total dependence in locomotion after hip fracture in this uniquely vulnerable subset of patients with hip fractures. By 180 days after hip fracture, 36% of patients had died, including 46% of all male patients. Moreover, among patients who had some degree of functional independence in locomotion at baseline, 54% had either died or developed new total dependence in locomotion within 180 days of hip fracture. In these patients, risk factors most highly associated with decreased survival and new total dependence in locomotion after hip fracture were nonoperative fracture management, male sex, age over 90 years, advanced comorbidity, and severe cognitive impairment. The novel findings from the study by Neuman and colleagues 4 have tremendous implications on the clinical care of vulnerable older adults with hip fractures. The prognostication of survival and functional outcomes after hip fracture in long-term nursing home patients has historically been a challenge for practitioners because of limited evidence in the medical literature. Results from the current study strongly demonstrate that mortality and functional dependence, particularly among the very old and those with advanced comorbidity and cognitive impairment, are exceedingly common among nursing home residents after hip fracture. These extreme rates of mortality and functional disability place palliative care, front and center, in the clinical management of hip fracture in vulnerable older adults. Palliative care is a new interdisciplinary specialty that focuses on improving quality of life for patients and families by providing an added layer of support (pain and symptom management, goals of care discussions, care coordination) in the setting of serious illness. Palliative care is provided concurrently with all other disease-directed or curative treatments. Hospice, conversely, is care focused exclusively on comfort for patients with a prognosis of 6 months or less if the disease follows its usual course and who are willing to relinquish curative treatments. Orthopedic surgery and rehabilitation facilitate early mobilization and are the standard and mainstay of hip fracture treatment (Figure). More often than not, palliative and hospice care are only considered in instances when a patient with hip fracture deteriorates beyond the point of achieving meaningful recovery despite receiving this “old” model of care. Given the high rates of mortality and functional dependence after hip fracture in nursing home residents, we conceive a “new” model for hip fracture care in which palliative care is implemented at the onset of hip fracture and complements standard care in postfracture management. Furthermore, hospice care should be considered and administered early if appropriate, in the most vulnerable nursing home residents including the oldest-old and those with advanced comorbidity and cognitive impairment. Palliative care program for long-term nursing home residents who sustained hip fracture must provide patientcentered comprehensive interdisciplinary care for the residents and their families, with particular focus on effective communication, care planning and coordination, symptom management, psychosocial, spiritual and bereavement sup

Survival and functional outcomes after hip fracture among nursing home residents.

Little is known regarding outcomes after hip fracture among long-term nursing home residents. To describe patterns and predictors of mortality and functional decline in activities of daily living (ADLs) among nursing home residents after hip fracture. Retrospective cohort study of 60,111 Medicare beneficiaries residing in nursing homes who were hospitalized with hip fractures between July 1, 2005, and June 30, 2009. Data sources included Medicare claims and the Nursing Home Minimum Data Set. Main outcomes included death from any cause at 180 days after fracture and a composite outcome of death or new total dependence in locomotion at the latest available assessment within 180 days. Additional analyses described within-residents changes in function in 7 ADLs before and after fracture. Of 60,111 patients, 21,766 (36.2%) died by 180 days after fracture; among patients not totally dependent in locomotion at baseline, 53.5% died or developed new total dependence within 180 days. Within individual patients, function declined substantially after fracture across all ADL domains assessed. In adjusted analyses, the greatest decreases in survival after fracture occurred with age older than 90 years (vs ≤75 years: hazard ratio [HR], 2.17; 95% CI, 2.09-2.26 [P < .001]), nonoperative fracture management (vs internal fixation: HR for death, 2.08; 95% CI, 2.01-2.15 [P < .001]), and advanced comorbidity (Charlson score of ≥5 vs 0: HR, 1.66; 95% CI, 1.58-1.73 [P < .001]). The combined risk of death or new total dependence in locomotion within 180 days was greatest among patients with very severe cognitive impairment (vs intact cognition: relative risk [RR], 1.66; 95% CI, 1.56-1.77 [P < .001]), patients receiving nonoperative management (vs internal fixation: RR, 1.48; 95% CI, 1.45-1.51 [P < .001]), and patients older than 90 years (vs ≤75 years: RR, 1.42; 95% CI, 1.37-1.46 [P < .001]). Survival and functional outcomes are poor after hip fracture among nursing home residents, particularly for patients receiving nonoperative management, the oldest old, and patients with multiple comorbidities and advanced cognitive impairment. Care planning should incorporate appropriate prognostic information related to outcomes in this population.