Drugs Affecting Glutamatergic Neurotransmission
Metabotropic Glutamate 2 Receptor Agonist: LY2812223
In the early 1990s, it was first proposed that dysfunction in glutamatergic neurotransmission could be implicated in mental disorders . Therefore, it was postulated that modulation of glutamatergic activity may constitute a novel nondopaminergic strategy for the treatment of psychosis . Additionally, previous studies highlighted the activation of glutamate receptors exerts neuroprotective and memory-enhancing effects in animal models, which might be particularly beneficial to patients with dementia . Eli Lilly and Company discovered LY2812223 , a mGluR2 agonist . LY2812223 was found active in an animal model of psychosis, sensitive to mGluR2 . Unfortunately, in the pharmacokinetic studies, LY2812223 showed a poor oral bioavailability . However, this did not limit the further development of the mGluR2 agonist for the treatment of mental disorders. Low bioavailability of LY2812223 was overcome by designing its alanine prodrug MP-101 . MP-101 is administered orally and absorbed in the gastrointestinal tract through active transport and then, it is rapidly hydrolyzed to .
Chemical structure and metabolic activation of MP-101, a prodrug of . cAMP cyclic adenosine monophosphate, hmGluR2 human metabotropic glutamate receptor type 2
Inhibitors of D-Amino Acid Oxidase
Determining The Cause Of The Behavior
Taking the time to listen and assess the situation can help pinpoint the source of anxiety and intent of the behavior. Is there a pattern to the behavior? Has anything changed in the patient’s health, environment, treatment plan, or daily routine?
Ask these kinds of questions when determining the cause of violent behavior and remember: Don’t take it personally. It may seem like the dementia patient is attacking you, but really they are anxious and you happen to be around.
When behavioral disturbances occur, give the person space you may need to leave the room until you’re both calm, according to the Alzheimer’s Society. Showing your anxiety may make the dementia patient more agitated, so make sure you can approach them calmly. Tell the person you can see they’re upset.
Take Care Of Yourself Too
Itâs not easy to care for a person with Alzheimerâs disease, especially when they lash out at you. Itâs completely normal to feel overwhelmed, isolated, or sad.
If you are a caregiver, do yourself and the person you care for a favor. Let someone know if you start to feel depressed, anxious, exhausted, or irritable. If you take good care of yourself, you can take better care of others.
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What Causes These Behaviours
There are many reasons why behaviours change. Every person with dementia is an individual who will react to circumstances in their own way. Sometimes the behaviour may be related to changes taking place in the brain. In other instances, there may be events or factors in the environment triggering the behaviour. In some instances a task may be too complex. Or the person may not be feeling well.
Causes Of Agitation And Aggression
Most of the time, agitation and aggression happen for a reason. When they happen, try to find the cause. If you deal with the causes, the behavior may stop. For example, the person may have:
Look for early signs of agitation or aggression. If you see the signs, you can deal with the cause before problem behaviors start. Try not to ignore the problem. Doing nothing can make things worse.
A doctor may be able to help. He or she can give the person a medical exam to find any problems that may cause agitation and aggression. Also, ask the doctor if medicine is needed to prevent or reduce agitation or aggression.
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Care Options For Aggression In Dementia
Caregiving to dementia patients requires a lot of effort, time, and patience. Depending on the stage of dementia, these patients exhibit different symptoms which are managed accordingly. In the mid-to-late course of the disease when the patient starts showing aggression, caregiving becomes challenging. At this point, both the patient and family can suffer a lot. At Hometouch, we believe in empathy and compassion. The different care options for aggression in dementia are:
Live in Care for Dementia Aggression:
In this, a professional caregiver resides with a dementia patient in their own home. This option is more feasible for the aggression experienced by dementia sufferers. One of the causes of aggravation of dementia symptoms is unfamiliar surroundings and people. The inability to recognise the location and unfamiliar faces increases confusion in patients and ultimately worsens symptoms. When a live in carer resides with the dementia patient, matters can often settled down.
At Hometouch, our professional caregivers for dementia are experts in providing round the clock care. They help the patient with their daily tasks, provide companionship, takes them to social gatherings and doctor’s appointments. They are also trained to manage anger, agitation, and aggression in dementia.
Care homes for aggressive dementia patients:
Assessment Scales For Agitation
Several assessment scales are currently available to investigate the presence and severity of agitation . The Agitated Behavior Scale assesses an agitated state’s occurrence and duration after brain injury. The scale’s primary purpose is to monitor behavioral changes after admission to a hospital ward . The Behavioral Activity Rating Scale is often used in clinical trials. According to this scale, patients are classified into seven different levels of agitation . The Overt Agitation Severity Scale offers a helpful approach to detect and rate agitation when spanning from anxiety to aggression . The Modified Overt Aggression Scale , a scale divided into four sections, examines the frequency and severity of aggressive episodes . Another easy-to-use tool is the Pittsburgh Agitation Scale , which measures the dementia-related agitation severity . The Agitated Behavior Mapping Instrument is a diagnostic scale that evaluates 14 different physical and verbal agitated behavior features. Finally, the Cohen-Mansfield Agitation Inventory is a frequency rating scale completed by caregivers .
A screening tool for delirium is the 4AT, in which a score higher than four indicates a high risk for delirium . However, the Confusion Assessment Method for the ICU is a more sensitive and specific assessment to diagnose a delirium state .
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Repeating The Same Question Or Activity
Repeating the same question or activity may be a result of memory loss where the person cannot remember what they’ve said or done.
It can be frustrating for the carer, but it’s important to remember that the person is not being deliberately difficult.
Try to:
- be tactful and patient
- help the person find the answer themselves, for example, if they keep asking the time, buy an easy-to-read clock and keep it in a visible place
- look for any underlying theme, such as the person believing they’re lost, and offer reassurance
- offer general reassurance, for example, that they do not need to worry about that appointment as all the arrangements are in hand
- encourage someone to talk about something they like talking about, for example, a period of time or an event they enjoyed
Poor Communication & Mental Triggers
Confusion or misunderstanding can also lead to anger and aggression. According to Visiting Angels, Confusion is one of the leading causes of anger and aggression in Alzheimers and dementia sufferers. Confusion can be triggered by lost trains of thought, mixed up memories, or a sudden change in the environment, such as a change from one caregiver to another.
This is especially important to note for communication as well. As a caregiver, you are in direct communication and contact with the patient, therefore, it is crucial that you articulate your instructions in a simple, concise manner.
Additionally, its important that you as the caregiver try to communicate with as little irritability and stress as possible. We understand that caregiving is a strenuous job, but for the benefit of you and your loved one, it is crucial to make sure you properly communicate with someone who has dementia.
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How Dementia Changes Our Thinking Skills
Everyone agrees that people experiencing dementia are often unreasonable. But whether Im teaching families or professional caregivers, I rarely find anyone in the audience who understands that because dementia takes away our rational thinking skills, expecting people to use them and be reasonable or rational is no different than expecting someone who is blind to see or deaf to hear. Please think about this for a moment: if Ive lost my ability to use reasoning, why would it be helpful to explain to me why I should do something?
It is also rare that I find someone who understands that we all have two separate and complete thinkingsystemsand that only the secondary one is lost to dementia.
Yes, the rational thinking skills we lose to dementia comprise our secondary thinking system, not our primary thinking system. Our primary thinking system is our intuitive thinking skills. Its misleading to think of this complex and essential set of skills as intuition. These thinking skills provide us with the broad and unfiltered data that our rational thinking skills sort to help us make sense of the world around us. Without our intuitive thinking skills, our rational thinking skills would have nothing to work with and we could not function.
Agitation In Acute Medical Conditions: Differential Diagnosis With Dementia
In elderly patients, acute agitation can be the expression of a wide range of conditions, including medical, psychiatric, and substance-induced alterations .
Table 1. Differential diagnoses in case of dementia-related agitation and other conditions.
In addition to hyperkinetic delirium, which can also arise during the hospitalization of cognitively unimpaired older people , other acute neurological conditions, such as stroke , intracranial neoplastic masses or hemorrhages, meningitides, encephalitides, and head injuries, may generate agitation that can be the first or unique symptom of the underlying condition.
The ascertainment of a history of psychiatric illnesses is critical, as these conditions may often determine the onset of acute mental alterations, including agitated behavior .
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When Does Aggression Start In Dementia
Aggression usually starts in the mid-stage of dementia. This is the time when other behaviours, such as hoarding wandering, and compulsive behaviour are also prone to develop. In most types of dementia, the aggressive symptoms occur when the patient becomes more dependent with daily activities. This can create a sense of helplessness the inability to communicate and call for help can trigger anger and agitation.
Alzheimers Care Challenges: Handling Dementia & Anger
Handling anger is one of the biggest challenges when caring for a person whos suffering from Alzheimers or another form of dementia. While almost everybody shows some form of aggression every now and again, Alzheimers and dementia can make anger issues much worse or develop anger issues in people who previously had none. Studies show that anger issues generally worsen the more severe an Alzheimers or dementia sufferers condition becomes.
Managing anger in dementia sufferers can be difficult. It may often mean reacting against your first instincts, but proper anger and dementia strategies can make care much easier for loved ones and caregivers alike.
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Can Dementia Cause Aggressive Behaviour
As a persons dementia progresses, they may sometimes behave in ways that are physically or verbally aggressive.
This can be very distressing for the person and for those around them. Looking at what causes this behaviour and being aware of the persons needs can help to reduce this behaviour or make it easier to manage.
- verbal for example, swearing, screaming, shouting or making threats
- physical for example, hitting, pinching, scratching, hair-pulling, biting or throwing things.
Some people assume that aggressive behaviour is a symptom of dementia itself. This can be true, but its more likely that there is another cause. Its important to see beyond the behaviour and think about what may be causing it. Reasons for the persons behaviour could include:
- difficulties to do with dementia for example, memory loss, language or orientation problems
- their mental and physical health for example, they may have pain or discomfort that they are unable to communicate
- the amount and type of contact they have with another person or other people
- their physical surroundings for example, if the room is too dark the person may become confused and distressed because they cant work out where they are
- a sense of being out of control, frustration with the way others are behaving, or a feeling that theyre not being listened to or understood
- frustration and confusion at not being able to do things, or at not being able to make sense of what is happening around them.
What Causes Aggressive Behaviour In People With Dementia
As human beings, we all have the same basic needs. These include physical, psychological and social needs. We do things consciously and unconsciously to meet these needs. The symptoms of dementia can make it more difficult for someone to do this.
For example, people with dementia can find it hard to understand whats going on around them. This can be confusing and frightening for them. It is likely that they are trying to stop feeling distressed and to feel calmer again. For example, if someone they do not know well or who they no longer recognise is trying to help them undress, they may feel threatened and try to push the person away. Aggressive behaviour may be:
- caused by the person feeling agitated because of a need that isnt being met
- the persons attempt to meet a need
- the persons attempt to communicate a specific need to others .
See below for examples of how different types of needs may cause a person with dementia to act aggressively.
Physical needs
Psychological needs
Consider whether they may benefit from psychological therapies with professionals, such as cognitive stimulation therapy or counselling.
Social needs
The persons aggressive behaviour may be their response to feeling theyre not able to contribute or are not valued by others. Try to encourage the person to have a daily routine and to do as much as they can for themselves. Support them to be as independent as they are able to be.
Dementia Connect support line
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Drugs Affecting Cholinergic Neurotransmission
Selective Muscarinic M4 Receptor Agonist: HTL0016878
Another promising example of compounds being developed for treating dementia-related psychosis and agitation/aggression is the selective muscarinic M4R agonist HTL0016878 . The muscarinic receptors are abundantly expressed in the cortex and hippocampus, the areas involved in cognitive and neurobehavioral functions . In animal models, nonselective M1R/M4R agonists improved psychotic behaviors and cognitive performance . These findings have been confirmed in muscarinic M4R-knockout mice, and thus, it has been suggested that M4R agonists represent an attractive molecular target for the development of novel antipsychotic agents . A first-in-class selective M4R agonist, HTL0016878, developed by Sosei Heptares for the treatment of neurobehavioral symptoms in patients with AD, has advanced to phase I clinical trials . This randomized, double-blind, placebo-controlled study evaluated the safety, pharmacokinetics, and pharmacodynamics of this compound in 106 healthy young volunteers as well as in elderly patients . The results have not been revealed yet.
Prevention Strategies For Home
Person-centered care is an operating system in healthcare, which considers the health practitioner and the patients as partners in achieving tailored care that meets patients’ needs in a unique way . In the PCC framework, the social and historical background, the personality, and the lifestyle of the patients are considered to promote a positive social environment, good compliance, and best outcomes for patients with dementia . The PCC approach is considered a successful option to prevent agitation in home-living and care home patients with dementia and reduce antipsychotic use . Nonetheless, not every PCC-based strategy is effective. For instance, the Dementia Care Mapping , which is based on patients’ systematic observations, has generated conflicting results. In contrast, the Managing Agitation and Raising Quality of Life intervention has failed to improve agitation prevention in care home settings.
Previous studies have indicated a role for boredom in the onset of physical agitation . Thus, activity-based strategies have been developed to prevent this condition. The application of combined stimuli has shown to be more effective than a single activity . However, the most effective activity was live socialization .
Data that emerged from other non-pharmacological approaches, such as acupuncture and electroconvulsive therapy, are mostly conflicting. Some ongoing trials could possibly clarify a potential role for these therapies .
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Overview Of Potential Druggable Targets For Pharmacological Treatment Matching The Etiology Of Dementia
The etiology of dementia-related psychosis and agitation/aggression is very complex and is often a cluster of biological factors as well as psychological and social aspects . Alzheimers disease is the most common type of dementia, and the pathophysiology of this particular disease is related to the loss of neurons. Depending on the degree of neurodegeneration, the cerebral region involved, and consequently the extent of deficits in neurotransmitters, various psychiatric symptoms may appear . For instance, psychosis has been associated with neurodegeneration in the frontal and mesotemporal areas of the brain , while depression has been linked to the degeneration of brainstem aminergic nuclei and a decrease in serotonergic neurotransmission . Additionally, neuropathological changes that cause hypofunction of the cholinergic and serotonergic systems and hyperfunction of dopaminergic and noradrenergic transmission have been linked to agitation manifested by patients with dementia . Alterations in multiple neurotransmitter systems cause changes in the expression of specific receptors, which have a direct impact on the regular functioning of the central nervous system .
Dont Be Afraid To Ask For Alzheimer’s Support
“Knowing how to detect, defuse, and prevent anger is one of the most important skills for Alzheimers care providers, says Larry Meigs, CEO of Visiting Angels. Its one of the skills we value most in our Alzheimers caregivers.
If you find that you need support in handling a loved ones dementia or Alzheimers care, help from an Alzheimers care provider can be invaluable. To discuss your options for professional, in-home Alzheimers care, call your local Visiting Angels office today.
If you are concerned about sudden changes in your loved ones behavior or have questions about caring for your loved one, please also contact your loved ones healthcare provider for information and support.
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