To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
This paper used data from the Apathy in Dementia Methylphenidate Trial 2 (NCT02346201) to conduct a planned cost consequence analysis to investigate whether treatment of apathy with methylphenidate is economically attractive.
A total of 167 patients with clinically significant apathy randomized to either methylphenidate or placebo were included. The Resource Utilization in Dementia Lite instrument assessed resource utilization for the past 30 days and the EuroQol five dimension five level questionnaire assessed health utility at baseline, 3 months, and 6 months. Resources were converted to costs using standard sources and reported in 2021 USD. A repeated measures analysis of variance compared change in costs and utility over time between the treatment and placebo groups. A binary logistic regression was used to assess cost predictors.
Costs were not significantly different between groups whether the cost of methylphenidate was excluded (F(2,330) = 0.626, ηp2 = 0.004, p = 0.535) or included (F(2,330) = 0.629, ηp2 = 0.004, p = 0.534). Utility improved with methylphenidate treatment as there was a group by time interaction (F(2,330) = 7.525, ηp2 = 0.044, p < 0.001).
Results from this study indicated that there was no evidence for a difference in resource utilization costs between methylphenidate and placebo treatment. However, utility improved significantly over the 6-month follow-up period. These results can aid in decision-making to improve quality of life in patients with Alzheimer’s disease while considering the burden on the healthcare system.
The International Psychogeriatric Association (IPA) published a provisional consensus definition of agitation in cognitive disorders in 2015. As proposed by the original work group, we summarize the use and validation of criteria in order to remove “provisional” from the definition.
This report summarizes information from the academic literature, research resources, clinical guidelines, expert surveys, and patient and family advocates on the experience of use of the IPA definition. The information was reviewed by a working group of topic experts to create a finalized definition.
We present a final definition which closely resembles the provisional definition with modifications to address special circumstances. We also summarize the development of tools for diagnosis and assessment of agitation and propose strategies for dissemination and integration into precision diagnosis and agitation interventions.
The IPA definition of agitation captures a common and important entity that is recognized by many stakeholders. Dissemination of the definition will permit broader detection and can advance research and best practices for care of patients with agitation.
To develop an agitation reduction and prevention algorithm is intended to guide implementation of the definition of agitation developed by the International Psychogeriatric Association (IPA)
Review of literature on treatment guidelines and recommended algorithms; algorithm development through reiterative integration of research information and expert opinion
IPA Agitation Workgroup
IPA panel of international experts on agitation
Integration of available information into a comprehensive algorithm
The IPA Agitation Work Group recommends the Investigate, Plan, and Act (IPA) approach to agitation reduction and prevention. A thorough investigation of the behavior is followed by planning and acting with an emphasis on shared decision-making; the success of the plan is evaluated and adjusted as needed. The process is repeated until agitation is reduced to an acceptable level and prevention of recurrence is optimized. Psychosocial interventions are part of every plan and are continued throughout the process. Pharmacologic interventions are organized into panels of choices for nocturnal/circadian agitation; mild-moderate agitation or agitation with prominent mood features; moderate-severe agitation; and severe agitation with threatened harm to the patient or others. Therapeutic alternatives are presented for each panel. The occurrence of agitation in a variety of venues—home, nursing home, emergency department, hospice—and adjustments to the therapeutic approach are presented.
The IPA definition of agitation is operationalized into an agitation management algorithm that emphasizes the integration of psychosocial and pharmacologic interventions, reiterative assessment of response to treatment, adjustment of therapeutic approaches to reflect the clinical situation, and shared decision-making.
Agitation is common across neuropsychiatric disorders and contributes to disability, institutionalization, and diminished quality of life for patients and their caregivers. In 2015 IPA convened a transparent process to build a consensus definition of agitation and agreement on what elements should be included in the syndrome that resulted in publication of provisional guidelines. (Cummings et al, 2015) In the 2020-2021 year, the two co-chairs of this symposium have led a new workgroup to make the provisional consensus definition of agitation in patients with cognitive disorders that can be applied in epidemiologic, non-interventional clinical, pharmacologic, non-pharmacologic interventional, and neurobiological studies and guide treatment final.
Co-Chairs will discuss methods used in updating and findings and compare changes made to the provisional guidelines. Dr. Sano will present new findings on the biological basis of agitation in dementia and Dr. Mintzer will present on application of guidelines in the special circumstances of persons in palliative and hospice care. Dr. Rosenberg will discuss the special circumstance of agitation care in hospital emergency departments. Mr. Splaine will present findings about the utilization of the 2015 guidelines in the peer reviewed literature, professional and government dementia care guidance, and clinical trials.
Cummings, J., Mintzer, J., Brodaty, H., Sano, M., Banerjee, S., Devanand, D., … Zhong, K. (2015). Agitation in cognitive disorders: International Psychogeriatric Association provisional consensus clinical and research definition. International Psychogeriatrics, 27(1), 7-17. doi:10.1017/S1041610214001963
The relationship between Alzheimer’s Disease (AD) and alcohol addiction is poorly characterized. Arrests for driving under the influence (DUI) can serve as a proxy for alcohol addiction. Therefore, the potential association between DUI and AD could be helpful in understanding the relationship between alcohol abuse and AD.
Materials and methods:
A retrospective, population-based cohort study using state health and law enforcement data was performed. The study cross-referenced 141,281 South Carolina Alzheimer’s Disease Registry cases with state law enforcement data.
Of the 2,882 registry cases (1.4%) found to have a history of at least one DUI arrest, cases were predominantly White (58.7%) and male (77.4%). Results showed a correlation coefficient of 0.7 (p < 0.0001) between the age of first DUI arrest and the age of AD diagnosis. A dose-response relationship between the number of DUIs and age of AD onset was found to exist, where those with a history of DUI arrest were diagnosed an average of 9.1 years earlier, with a further 1.8 years earlier age at diagnosis in those with two or more arrests for DUI. A history of DUI arrest was also found to be negatively associated with survival after diagnosis, with a 10% decreased life expectancy in those with a DUI arrest history.
Driving under the influence, a potential indicator of alcohol addiction, is associated with an earlier onset of AD registry diagnosis and shortened survival after diagnosis. This study contributes to the growing body of evidence suggesting that some cases of AD are alcohol related and, possibly, postponable or preventable.
This paper attempts to bring to the attention of the readers a concept that broadens ethical considerations for Alzheimer's disease research. We propose we move away from the ethical paradigm that focuses on avoidance of coercion for participation in studies as well as privacy and safety to a more inclusive paradigm that will not only include the principles outlined above but will also guarantee access to new treatments for individuals that participate in research and other members of society. Specifically, if the research being performed results in a new treatment for Alzheimer's disease, would the individuals participating in the research and other members of their community have access to and benefit from these treatments, given the availability of financial and other resources in the society that will allow for the implementation of these treatments. This paper will propose a model that will facilitate the achievement of these broader ethical considerations.
Placebo responses raise significant challenges for the design of clinical trials. We report changes in agitation outcomes in the placebo arm of a recent trial of citalopram for agitation in Alzheimer's disease (CitAD).
In the CitAD study, all participants and caregivers received a psychosocial intervention and 92 were assigned to placebo for nine weeks. Outcomes included Neurobehavioral Rating Scale agitation subscale (NBRS-A), modified AD Cooperative Study-Clinical Global Impression of Change (CGIC), Cohen-Mansfield Agitation Inventory (CMAI), the Neuropsychiatric Inventory (NPI) Agitation/Aggression domain (NPI A/A) and Total (NPI-Total) and ADLs. Continuous outcomes were analyzed with mixed-effects modeling and dichotomous outcomes with logistic regression.
Agitation outcomes improved over nine weeks: NBRS-A mean (SD) decreased from 7.8 (3.0) at baseline to 5.4 (3.2), CMAI from 28.7 (6.7) to 26.7 (7.4), NPI A/A from 8.0 (2.4) to 4.9 (3.8), and NPI-Total from 37.3 (17.7) to 28.4 (22.1). The proportion of CGI-C agitation responders ranged from 21 to 29% and was significantly different from zero. MMSE improved from 14.4 (6.9) to 15.7 (7.2) and ADLs similarly improved. Most of the improvement was observed by three weeks and was sustained through nine weeks. The major predictor of improvement in each agitation measure was a higher baseline score in that measure.
We observed significant placebo response which may be due to regression to the mean, response to a psychosocial intervention, natural course of symptoms, or nonspecific benefits of participation in a trial.
Alzheimer's disease (AD) is a debilitating condition affecting millions of elderly citizens. The quality of life for AD patients significantly deteriorates in the face of worsening cognitive deficits and disabling functional declines, both contributing to manifestations of difficult behaviors. Of the estimated 4 million individuals with AD, only 60% of probable AD cases are diagnosed, with little more than half of those receiving treatment. One of the possible reasons for this problem is the large role primary care physicians (PCPs) have in diagnosing and treating AD. The barriers that PCPs confront to adequately manage these patients will be discussed. Finally, the specific challenges that geriatric psychiatrists will face in addressing these issues in an environment where there is only a limited number of trained geriatric psychiatrists will be discussed, as well as the possible role that new technology could have in finding the solution to this difficult problem.
Alzheimer's disease (AD) is a debilitating condition currently affecting 4.5 million elderly citizens in the United States alone. It is the most common form of dementia and is associated with significant disability. For many years the prognosis of the disease has remained largely unchanged. Those patients who develop AD face progressive cognitive and functional decline that ultimately shortens their life expectancy and destroys their quality of life. At the same time, the disease has a significant adverse impact on the lives of those family members who serve as caregivers. With the aging of the baby-boomer generation and the expected associated increase in the number of patients with AD, clinicians who treat the elderly will clearly be in need of some new answers. Recent advances in assessment, diagnosis, and treatment offer some hope for relief from this bleak prognosis.
Advances in AD include the establishment of clear diagnostic criteria, the validation of disease-specific assessment instruments, and pharmacologic and behavioral therapies for management of symptoms. A handful of medications that enhance cognition have obtained the approval of the Food and Drug Administration, and more are currently in development. Trials of existing medications have demonstrated benefit in the management of the psychiatric symptoms (eg, psychosis and agitation) typically associated with the disease. But much still remains to be done.
In the first article in this supplement, Michael A. Rogawski, MD, PhD, explains what is known about the pathogenesis and the behavioral and psychological symptoms of AD. He discusses the scientific basis for empirical therapies currently being used to relieve the symptoms of this disease, focusing on drug therapies approved by the FDA, including the newest AD medication to market memantine.
With the increase in aging all over the world, and the elderly population nearly tripling from 524 million (8% of the world's population) in 2010 to 1.5 billion (16% of the world's population) in 2050, we will face new challenges and opportunities in providing healthcare. In 2050, it is estimated that Europe will see an increase of 70% in elderly population aged over 65 years, and 170% in those aged over 80 years (World Health Organization (WHO), 2011). It is vital to respond to the needs of this emerging population and the consequent rise in chronic diseases, especially dementia and mental health disorders, which will overload the healthcare system, as well as raise health and social costs, and demand new policies from national governments (World Health Organization, 2012). We urgently need to know how to organize healthcare for elderly people in the years to come.
Agitation is common across neuropsychiatric disorders and contributes to disability, institutionalization, and diminished quality of life for patients and their caregivers. There is no consensus definition of agitation and no widespread agreement on what elements should be included in the syndrome. The International Psychogeriatric Association formed an Agitation Definition Work Group (ADWG) to develop a provisional consensus definition of agitation in patients with cognitive disorders that can be applied in epidemiologic, non-interventional clinical, pharmacologic, non-pharmacologic interventional, and neurobiological studies. A consensus definition will facilitate communication and cross-study comparison and may have regulatory applications in drug development programs.
The ADWG developed a transparent process using a combination of electronic, face-to-face, and survey-based strategies to develop a consensus based on agreement of a majority of participants. Nine-hundred twenty-eight respondents participated in the different phases of the process.
Agitation was defined broadly as: (1) occurring in patients with a cognitive impairment or dementia syndrome; (2) exhibiting behavior consistent with emotional distress; (3) manifesting excessive motor activity, verbal aggression, or physical aggression; and (4) evidencing behaviors that cause excess disability and are not solely attributable to another disorder (psychiatric, medical, or substance-related). A majority of the respondents rated all surveyed elements of the definition as “strongly agree” or “somewhat agree” (68–88% across elements). A majority of the respondents agreed that the definition is appropriate for clinical and research applications.
A provisional consensus definition of agitation has been developed. This definition can be used to advance interventional and non-interventional research of agitation in patients with cognitive impairment.
Nerve growth factor (NGF), a trophic factor involved in the development, maintenance, and survival of the peripheral nervous system and the cholinergic neurons of the central nervous system, is significantly reduced in Alzheimer's Disease (AD) patients (Aloe et al., 2012). Particularly basal forebrain complex (BFC) neurons are highly affected in AD patients. NGF protects BFC neurons in experimental trauma models and in age-associated cholinergic decline. Therefore, administration of NGF is investigated as a therapeutic option for AD patients (Aloe et al., 2012). NGF therapy is limited by hyperalgesia, limited bioavailability, and use of invasive methods including intracranial injection of adeno-associated virus-based gene delivery vector, which constitutively expresses human NGF. In this context, non-pharmacological modes of treatment such as meditation and Yoga have been considered as alternative approaches to treat neurological disorders. Yogic breathing (YB, also called Pranayama) is a collection of techniques to regulate breathing voluntarily. YB induces a strong relaxation response via vagal and parasympathetic stimulation (Jerath et al., 2006). Such responses are causally linked to rapid changes in gene expression, particularly to those genes controlling stress, inflammation, and metabolism. Saliva is a known source of NGF, and incidentally, Yoga and relaxation stimulate salivation. Saliva (0.75–1.5 L/day in humans) contains numerous biologically active molecules to be potentially useful as diagnostic markers and as therapeutic clues. Salivary secretion regulates the digestive, nervous, immune, and respiratory systems. We conducted a pilot study to investigate whether YB could potentially stimulate salivary expression of NGF in cognitively normal healthy volunteers. This could serve as a model for future studies in AD patients.
Little is known about the effect of methylphenidate (MPH) on attention in Alzheimer's disease (AD). MPH has shown to improve apathy in AD, and both apathy and attention have been related to dopaminergic function. The goal was to investigate MPH effects on attention in AD and assess the relationship between attention and apathy responses.
MPH (10 mg PO twice daily) or placebo was administered for six weeks in a randomized, double-blind trial in mild-to-moderate AD outpatients with apathy (Neuropsychiatric Inventory (NPI) Apathy ≥ 4). Attention was measured with the Wechsler Adult Intelligence Scale – Digit Span (DS) subtest (DS forward, selective attention) and apathy with the Apathy Evaluation Scale (AES). A mixed effects linear regression estimated the difference in change from baseline between treatment groups, defined as δ (MPH (DS week 6–DS baseline)) – (placebo (DS week 6–DS baseline)).
In 60 patients (37 females, age = 76 ± 8, Mini-Mental State Examination (MMSE) = 20 ± 5, NPI Apathy = 7 ± 2), the change in DS forward (δ = 0.87 (95% CI: 0.06–1.68), p = 0.03) and DS total (δ = 1.01 (95% CI: 0.09–1.93), p = 0.03) favored MPH over placebo. Of 57 completers, 17 patients had improved apathy (≥3.3 points on the AES from baseline to end point) and 40 did not. There were no significant associations between AES and NPI Apathy with DS change scores in the MPH, placebo, AES responder, or non-responder groups. DS scores did not predict apathy response to MPH treatment.
These results suggest MPH can improve attention and apathy in AD; however, the effects appear independent in this population.
Global population aging is pervasive, profound, and enduring, with the projected proportion of older persons reaching nearly 21% in 2050 (UNFPA and Help Age International, 2012). Accordingly, there is an increasing need for geriatric mental health services with the rapid growth of the aging population worldwide (Bragg et al., 2012).
To compare patients with posttraumatic stress disorder (PTSD) to patients without psychiatric or cognitive disorders on neuropsychological measures of attention.
The sample included 19 patients with PTSD and 22 participants with no cognitive or psychiatric diagnosis. All had been referred for clinical neuropsychological evaluation at a VA Medical Center. None were diagnosed with dementia, delirium, or current substance dependence except nicotine or caffeine, and none had a history of stroke or of traumatic brain injury with loss of consciousness. Patients were excluded if they failed to exert adequate effort on testing.
PTSD patients performed significantly more poorly than patients without psychiatric diagnoses on Digit Span.
PTSD patients were impaired relative to participants without psychiatric diagnoses on a measure of focused attention. Several factors, including the small sample size, suggest that the results should be considered preliminary.
Objective: Despite numerous clinical trials, it is unknown whether ethnicity affects treatment response to cognitive enhancers in Alzheimer's disease (AD). There is convincing evidence of ethnic and genetic variability in drug metabolism. This article reviews the available data on ethnicity in clinical trials for AD to answer two questions: (1) what are the challenges to diagnose and treat AD across different ethnic groups, and (2) are there differences in response to pharmacologic interventions for AD across these different ethnic groups?
Method: Available data from Alzheimer's Disease Cooperative Study (ADCS) randomized controlled clinical trials and from randomized controlled industry-sponsored trials for four cognitive enhancers (donepezil, galantamine, rivastigmine and sabeluzole) were pooled to assess the numbers of non-Caucasian participants.
Results: The participation of ethnic minority subjects in clinical trials for AD was dependent on the funding source, although Caucasian participants were over-represented and non-Caucasian participants were under-represented in the clinical trials. Because of the low participation rate of ethnic minorities, there were insufficient data to assess any differences in treatment outcome among different ethnic groups. Strategies to improve diversity in clinical trials are discussed.
Conclusion: Greater participation of ethnically diverse participants in clinical trials for AD would generate additional information on possible differences in metabolism, treatment response, adverse events to therapeutic agents, and could foster the investigation of genetic variability among ethnic groups.
Anxiety symptoms in dementia can be seen as an expression of stress in predisposed patients who become aware of their cognitive decline. In later stages of the disease, when awareness is lost, the presence of anxiety symptoms cannot be explained as a reaction to this type of stress. The presence of anxiety symptoms in the more impaired patients becomes similar and probably as complex in its etiology and clinical manifestations as other behavioral and psychological symptoms of dementia (BPSD). In this review, we will discuss anxiety symptoms in BPSD.
Alzheimer's disease and other dementing disorders have been reported in most ethnic groups living in the United States. Although the presence of these disorders in different U.S. ethnic groups is well documented, the characteristics of dementing disorders, such as the presence of behavioral disturbances, in these groups remains unexplored.
Email your librarian or administrator to recommend adding this to your organisation's collection.