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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
This study describes the performance of the Multilingual Naming Test (MINT) by Chinese American older adults who are monolingual Chinese speakers. An attempt was also made to identify items that could introduce bias and warrant attention in future investigation.
The MINT was administered to 67 monolingual Chinese older adults as part of the standard dementia evaluation at the Alzheimer’s Disease Research Center (ADRC) at the Icahn School of Medicine at Mount Sinai (ISMMS), New York, USA. A diagnosis of normal cognition (n = 38), mild cognitive impairment (n = 12), and dementia (n = 17) was assigned to all participants at clinical consensus conferences using criterion sheets developed at the ADRC at ISMMS.
MINT scores were negatively correlated with age and positively correlated with education, showing sensitivity to demographic factors. One item, butterfly, showed no variations in responses across diagnostic groups. Inclusion of responses from different regions of China changed the answers from “incorrect” to “correct” on 20 items. The last five items, porthole, anvil, mortar, pestle, and axle, yielded a high nonresponse rate, with more than 70% of participants responding with “I don’t know.” Four items, funnel, witch, seesaw, and wig, were not ordered with respect to item difficulty in the Chinese language. Two items, gauge and witch, were identified as culturally biased for the monolingual group.
Our study highlights the cultural and linguistic differences that might influence the test performance. Future studies are needed to revise the MINT using more universally recognized items of similar word frequency across different cultural and linguistic groups.
Caregivers of persons with Alzheimer’s Disease and Other Dementias are a population in need of support as they are vulnerable to emotional, physical, and mental exhaustion associated with caregiver burnout. While CDC guidelines state that social distancing is the greatest protective factor, it can already exacerbate feelings of isolation and stress. Technology offers the opportunity to maximize socialization and access to healthcare; however, research shows that digital platforms are most underutilized by older and lower socioeconomic patients.
This report describes the transition of a weekly caregiver support group from telephone to video conferencing to improve connectedness during a period of social isolation.
In 2020, the caregiver support group met weekly over the phone. At each session, there were increased discussions of moving the telephone support group to a video platform. A focused discussion about technology platforms was held to gain an understanding of caregiver attitudes and thoughts regarding technology in which caregivers worried that a video platform would be intrusive and invasive. In June 2020, unreliable phone service resulted in the group transitioning to video.
The caregiver group consisted of 5 active members, 2 African American, 2 Asian, and 1 Caucasian. Initial problems included connectivity issues, needing to switch to multiple devices, and assistance with troubleshooting and utilizing the platform. However, caregivers reported feeling that the transition to video was the most natural next step and assisted with reducing feelings of isolation, anxiety, and fear they reported as a result of social distancing due to COVID-19. Caregivers reported feeling connected and because they knew each other so intimately, no longer felt video was intrusive.
For older populations who are not familiar with technology, it is important to take steps before beginning a new platform service. This allows for a natural progression to unfamiliar technology. The video platform provided an opportunity for caregivers to be together while apart, which is important for mental health and decreasing caregiver burden.
Older adults, especially those above age 80, are the fastest growing segment of the population in the United States and at risk for age-related cognitive decline and dementia. There is growing evidence that cognitive activity and training may allow adults to maintain or improve cognitive functioning, but little is known about the potential benefit in the oldest old. In this randomized trial, the effectiveness of a computerized cognitive training program (CCT program) was compared to an active control games program to improve cognition in cognitively normal individuals aged 80 and older.
Sixty-nine older adults were randomized to a 24-session CCT program (n = 39) or an active control program (n = 30). Participants completed a pre- and post- training neuropsychological assessment. The primary outcome measure was a global cognitive composite, and the secondary outcomes were the scores on specific cognitive domains (of memory, executive function/attention, and language).
Using linear mixed models, there were no significant differences between the CCT and the active control program on the primary (p = 0.662) or any of the secondary outcomes (language functioning, p = .628; attention/executive functioning, p = .428; memory, p = .749).
This study suggests that short-term CCT had no specific benefit for cognitive functioning in non-demented individuals aged 80 and older.
Depression and cognitive impairment are highly prevalent in type 2 diabetes (T2D), yet little is known about how their relationship varies by sex. We examined this question in a large T2D sample (N = 897) of non-demented elderly (≥ 65) participating in the Israel Diabetes and Cognitive Decline (IDCD) Study. Cognition was evaluated by a comprehensive neuropsychological battery and depressive symptoms were assessed by the Geriatric Depression Scale (GDS). The results showed that in all but the executive function domain, the association of depressive symptoms with poorer cognitive function was stronger in women than men, with a significant interaction for language/semantic categorization and missed significance for episodic memory. When defining clinical depression as GDS of ≥6, women with depression had significantly poorer language/semantic categorization, episodic memory, and overall cognitive function. Inclusion of antidepressants in the model did not alter substantively the associations. Our results suggest that depressed T2D women may have poorer cognitive performance, highlighting the significance of sex-specific personalized management of depression in elderly diabetics.
To develop an educational video to reach elderly Latinos in order to improve understanding and encourage evaluation of cognitive changes by 1) using focus groups to identify dementia knowledge gaps, health communication preferences and trusted advisors for health concerns; 2) collaborating with elderly Latino community members to create a video; and 3) collecting survey data regarding community response to the video.
Grounded theory qualitative approach using focus groups; collaborative community based model to create the video and anonymous survey at community screenings.
Community senior centers in East Harlem, New York.
A team of low-income mono and bilingual elderly Latino community residents, researchers, clinicians, and a film professional.
Thematic analysis of focus group transcripts; three item survey.
A collaboratively produced video and initial assessment in 49 Latino elders that indicated the video had a positive effect on interest in obtaining a brief memory screening at outreach events (71%).
The project demonstrates the feasibility of this interdisciplinary partnership to create a culturally and linguistically sensitive video to promote service use concerning memory loss and cognitive evaluations among elderly Latinos. Initial survey results suggested a positive response and an increase in interest in memory screening.
This study aimed to determine the diagnostic utility of a Chinese test battery for evaluating cognitive loss in elderly Chinese Americans.
Data from a pilot study at the Mount Sinai Alzheimer’s Disease Research Center was examined. All participants were > 65 years old, primarily Chinese speaking, with adequate sensorimotor capacity to complete cognitive tests. A research diagnosis of normal mild cognitive impairment (MCI) or Alzheimer’s disease (AD) was assigned to each participant in consensus conference. Composite scores were created to summarize test performance on overall cognition, memory, attention executive function, and language. Multivariable logistic regression models were used to assess the sensitivity of each cognitive domain for discriminating three diagnostic categories. Adjustment was made for demographic variables (i. e., age, gender, education, primary language, and years living in the USA).
The sample included 67 normal, 37 MCI, and 12 AD participants. Performance in overall cognition, memory, and attention executive function was significantly worse in AD than in MCI, and performance in MCI was worse than in normal controls. Language performance followed a similar pattern, but differences did not achieve statistical significance among the three diagnostic groups.
This study highlights the need for cognitive assessment in elderly Chinese immigrants.
A major challenge in the management of Alzheimer's disease (AD) is accurate diagnosis of the condition. Aging itself is associated with cognitive change, and physicians must first distinguish between age-associated complaints and true memory impairment as in AD before optimal management can begin. This article reviews tools used to assess and diagnose AD patients in both the primary care and clinical trial setting. AD assessment instruments commonly used in research may be too cumbersome for use in primary care. Tools specifically designed to meet the needs of busy practitioners that can accurately assess function, cognition, and global change will be reviewed. The issues of cognitive screening in old age and age-associated memory impairment will be discussed. Similarly, the pitfalls and advantages of routine cognitive screening in daily practice will be addressed.
Alzheimer's disease represents a significant challenge to the aging population. Since most estimates suggest that AD has a multifactorial etiology, the challenge to find preventative approaches is particularly great. With the aging of the population and the very high incidence from the eighth decade on, the challenge is further enhanced by the need to think of relatively safe interventions given the relative frailty of this elderly population. The need to find safe treatments, or ones with well-understood safety profiles, has led to the examination of known agents for potential dementia-preventing properties. Data supporting these interventions comes from observational studies, laboratory analyses, and clinical trials. Potential mechanisms for prevention of AD include anti-inflammatory and antioxidant approaches. Modulation of risk factors associated with cardiac disease may also reduce the risk of AD. Known agents have been examined for their potential to modify amyloid pathology. Trial designs to address prevention of AD include both primary and secondary prevention studies as well designs to assess slowing disease progression. Information can also be gathered when dementia evaluation is added to ongoing studies. As results from these studies becoming available, we will be able to refine our approach to managing this disease.
The introduction of the amyloid hypothesis, which identifies amyloid as the primary target for treating Alzheimer’s disease (AD), was a watershed in the field of AD research. Treatment approaches have since focused on how amyloid might be manipulated. In fact, there are challenges to amyloid manipulation. First, removal of amyloid has shown minimal clinical effects. Second, some data indicate that secretase modulation shows hints of stimulating feedback systems, which cause concern over how to effectively manipulate amyloid. Third, side-effect profiles of the direct manipulation of amyloid are not currently optimal. Finally, evidence suggests that cell and synapse loss may be better markers of dementia and its severity. Alternative approaches to direct manipulation of amyloid include antioxidant mechanisms for prevention, anti-inflammatory mechanisms for neuroprotection, manipulation of metabolic risks, modification of tau accumulation, and neuroregeneration.
These alternative mechanisms of action provide support for a wide range of potential agents for clinical trials. The exact connection between mechanism of action and clinical outcomes is not well defined, but typically trial designs using these mechanisms attempt to measure affects on disease progression, often with longer studies that include established clinical outcomes accompanied by putative biomarkers of disease. One trend that has provided much information has been to examine the effects of these drugs in subjects at risk for AD, thereby expanding the intervention to prevention of disease. These studies include both secondary prevention studies, for example deferring onset in those with prodromal disease such as mild cognitive impairment (MCI), and primary prevention directed at those with no specific signs or symptoms.
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.
Background: Physicians often miss diagnosis of mild cognitive impairment (MCI) or early dementia and screening measures can be insensitive to very mild impairments. Other cognitive assessments may take too much time or be frustrating to seniors. This study examined the ability of an audio-recorded scale, developed in Australia, to detect MCI or mild Alzheimer's disease (AD) and compared cognitive domain-specific performance on the audio-recorded scale to in-person battery and common cognitive screens.
Method: Seventy-six patients from the Mount Sinai Alzheimer's Disease Research Center were recruited. Patients were aged 75 years or older, with clinical diagnosis of AD or MCI (n = 51) or normal control (n = 25). Participants underwent in-person neuropsychological testing followed by testing with the audio-recorded cognitive screen (ARCS).
Results: ARCS provided better discrimination between normal and impaired elderly individuals than either the Mini-Mental State Examination or the clock drawing test. The in-person battery and ARCS analogous variables were significantly correlated, most in the 0.4 to 0.7 range, including verbal memory, executive function/attention, naming, and verbal fluency. The area under the curve generated from the receiver operating characteristic curves indicated high and equivalent discrimination for ARCS and the in-person battery (0.972 vs. 0.988; p = 0.23).
Conclusion: The ARCS demonstrated better discrimination between normal controls and those with mild deficits than typical screening measures. Performance on cognitive domains within the ARCS was well correlated with the in-person battery. Completion of the ARCS was accomplished despite mild difficulty hearing the instructions even in very elderly participants, indicating that it may be a useful measure in primary care settings.
Alzheimer's disease (AD) is characterized by progressive decline in memory, language and other cognitive functions. Deficits in attentional processes have also been suggested. A simple reaction time (RT) task was used to assess global attention in AD. The length and consistency of a warning signal given prior to the response stimulus were manipulated to determine if patients with AD and age-matched controls benefit from predictability in RT tasks. Overall reaction time was slower in the AD group than in the and control group. Both groups demonstrated significant improvement in RT with long warning signals compared to short warning signals, but only the control group benefited from the consistency of the warning. (JINS, 1995, I, 56–61.)
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.
Atypical Parkinsonian Disorders: Clinical and Research
Aspects. Irene Litvan (Ed.). 2005. Totowa, NJ: Humana Press, 512 pp.,
This edited collection of perspectives on Atypical Parkinson's
Disease, or Parkinson's plus as it is often called, is both a
treasure and a pleasure. The editor, Irene Litvan, ably accomplishes the
daunting task of bringing order to what might be considered a grab bag of
diagnostic leftovers in Chapter 1. To the generalist, fair warning that
Parkinson's plus may be misconstrued as Parkinson's minus, since
tremor, the most commonly recognized symptom may not be a feature of at
least some of these syndromes. Litvan provides us with an organizational
structure for summarizing clinical features and surmising etiologies. An
extensive literature review is distilled to give impressions of when to
suspect these diagnoses, hints to the natural progression, and discussion
of the validity of specific diagnoses within the atypical PD spectrum.
Chapter 2, on historical perspectives, is one that is so tempting to skip
in the rush to get to the most up to date science. Please don't,
because it is one of the gems of this tome. In his readable style,
Christopher Goetz reminds us that clinical skill begins with being a good
observer and this will serve the field throughout time. His selection of
historical anecdotes, literary passages, and classic photographs
illustrates the timelessness of some of these clinical entities. The
photograph from the 1925 Lhermitte et al. report so captured the syndrome
of cortical basal degeneration, that I suddenly recalled several similar
patients and was reassured that there was something more than
idiosyncratic imposition of this diagnosis.
Over the past decade medications have been approved for the treatment of Alzheimer's disease (AD). The first of these worked via cholinergic stimulation, and targeted the symptoms of attention and memory. More recently Memantine, an NMDA receptor antagonist, has been added to the list of approved medications for AD. These treatments provide symptomatic benefits. Initiative for new therapeutics target the characteristic neuropathological features of AD or other biological mechanisms that may reflect the etiology of the disease in the hope of identifying preventative or curative agents.
Research into treatment of AD tends to focus on interventions at the earliest stage of the disease and the concept of mild cognitive impairment (MCI), a prodrome to dementia, has become the target of many interventions. This approach has the added challenge of determining diagnostic specificity of an entity, which does not yet constitute a diagnosis. At the same time, interest in treating the more impaired patient has grown with the approval of the first drug with an indication for moderate to severe AD and with new studies examining cholinesterase inhibitors in more advanced patients.
Awareness that AD may coexist with other CNS diseases or be difficult to distinguish from dementia of other etiologies may have contributed to the interest in treatments for individuals with other conditions including vascular and mixed dementia.