**1. Introduction**

Dementia is a prominent symptom of various diseases and not just a disease in and of itself. It is part of brain disease transition such as following virus-infected inflammation through increased neurodegeneration and brain network dysfunctioning.

It renders difficulty in recognition and response to daily environmental information which are needed in short-term learning and recall and decision-making [1, 2]. In general, one of the most disturbing characteristics of neuroinflammatory diseases is loss of conscious-state transition [3]. This is a type of disability or impairment that results in the presence of persistently high levels of antisomnogenic cytokines [4, 5], and common to Alzheimer's Disease patients [6]. It is alsoo associated with disruption of circadian synchronization between neuronal networks of the brain [7, 8].

A dementia patient's care-giving team is presumed to include certified doctors and nurses qualified in early diagnosis and strategies for dementia-symptom management. The targets of such caregiving include optimizing physical health, cognition, activity and well-being identifying and treating accompanying physical illness detecting and treating challenging behavioral and psychological symptoms providing information and long-term support to carers (WHO).

arrest [16] simply because of the nature of the disease's impact on the brain (see

*The Need for XR-Measurement of Decision-Making Decline and Conscious-State Transition…*

brain and sensory management throughout the entire system [20–23]. The

brainwave activities related to conscious-state transition and measured by Bispectral Index (BIS) monitors [24] or Guedel's classification system [25] are logistically absent, thereby theoretically preventing patient awakening and patient

GABAergic thalamic neurons would also therefore inhibit retinally-driven activity, and likewise disable input to the geniculo-hypothalamic pathway which is activated by crossed retinal inputs leading to the suprachiasmatic nucleus (SCN). In this way,

However, the research shows that brain death and cardiac death are not simultaneously correlated [26–29]). In research review by Robijn (2020) as part of an academic thesis submission, Robijn reports correlation between BIS and the Richmond Agitation-Sedation Scale (RASS) (p < 0.0004) including reporting patients 'awake' during euthanization despite observational physician [30] decisions that the patients were dead [31, 32]. Also, memory formation also continues under anaesthesia [12, 33, 34]. On closer inspection of the events, one finds that the high dosage anesthetics such as 9 mg/L pentobarbital intravenous injection used in euthanization in the Netherlands has explicit pharmacological warnings that the neurotoxic compound cannot reach the brain in one minute intravenous application and that that the accelerated injection causes gangrene, body-wide joint pain and tissue irritation for any intravenous-administered dosages above 0.5 mg/l. Furthermore, it reduces IL-1beta cytokine release by only 30–40%, while endogenous tumor necrosis factor (TNF-α) transport becomes elevated in a process that remains

*A list of features in the progression of amnesiac-related brain inflammation from disease or neurological*

*disorders leading to risks that may compromise euthanization patient safety.*

The euthanization method which is intended as a pain-free killing is error-prone with patient re-awakening rather than instant dying [17, 18] on record. Anesthetic drugs targeted to ion channels affect neuronal activity in the Central Nervous System (including the brain), the peripheral nervous system (PNS) and all connected organs, and the cardiovascular system [19]. Barbiturates such as pentobarbital suppress the central nervous system (CNS) by binding to gammaaminobutyric acid (GABA) A subtype receptors, alters inhibitory postsynaptic CL- currents while simultaneously inhibiting excitatory presynaptic nerve terminal signal event transmission. This is supposed to sustain the opening of chloride channels and results in the suppressed neuronal activation of oscillations throughout the

**Figure 1** below).

*DOI: http://dx.doi.org/10.5772/intechopen.97384*

awareness or memory.

**Figure 1.**

**267**

Section 4.1 of the Dutch euthanization law [9] declares that euthanasia may be given to a patient who is no longer mentally competent as a result of advanced dementia, and that the doctor does not need to agree with the patient regarding the time or manner of euthanatic execution based on a physician declaration of patient inability to comprehend the subject.

Euthanization is delivered via anesthetics without acknowledging the surge of neurophysiological coherence and connectivity in the forced-dying brain [10] or on the basis of any measured disability of a patient to change from one conscious-state to any other. The degree that sensory information processing and conscious memory, awareness, learning and recall are supposed to be fully disabled [11] by the simple observation of delirium seems to possibly have led to an unchecked medical assumption that an overdosage of anesthetic-euthanatic neurotoxins is sufficient to overcome the disability and trigger instant brain death. However, the research shows that this is invalid and that memory formation- and indeed, brain survival mechanisms - are evolved to be much smarter, enabling survival-related learning related neuronal synaptic plasticity changes to occur even under deep anesthesia [12, 13].

In 2019, 146 dementia patients were euthanized in the Netherlands, 14% less frequently than the previous year [14].

The English version Regional Euthanization Review Committees- The Netherlands, report (2018) [9] states that.

#### Dementia

*Two notifications in 2018 involved patients in an advanced or very advanced stage of dementia who were no longer able to communicate regarding their request and in whose cases the advance directive was decisive in establishing whether the request was voluntary and well considered.* See case 2018-41, described in Chapter II, and case 2018-21, published on www.euthanasiecommissie.nl.

*In 144 cases the patient's suffering was caused by early-stage dementia. These patients still had insight into their condition and its symptoms, such as loss of bearings and personality changes. They were deemed decisionally competent with regard to their request because they could still grasp its implications. Case 2018-123, described in Chapter II, is an example.*

But, the section titled Advanced Directive Points to Consider (Section 4.1, f, (see Annual Reports, Dutch Euthanasia Committee [15]) requires physicians to answer: *Are there any contraindications that are inconsistent with the advance directive and preclude the performance of euthanasia?*

If so, this statement represents one opportunity to provide an argument that all dementia patients deserve medically-meaningful conscious-state transition monitoring and decision-competence evidence before non-voluntary euthanization can be legally authorized.

Such monitoring technology would enable demonstration of key factors of noneligibility when a patient is unable to transition into unconsciousness or brain death instantaneously or for up to 36 hours - even following severe anesthesia and cardiac *The Need for XR-Measurement of Decision-Making Decline and Conscious-State Transition… DOI: http://dx.doi.org/10.5772/intechopen.97384*

arrest [16] simply because of the nature of the disease's impact on the brain (see **Figure 1** below).

The euthanization method which is intended as a pain-free killing is error-prone with patient re-awakening rather than instant dying [17, 18] on record. Anesthetic drugs targeted to ion channels affect neuronal activity in the Central Nervous System (including the brain), the peripheral nervous system (PNS) and all connected organs, and the cardiovascular system [19]. Barbiturates such as pentobarbital suppress the central nervous system (CNS) by binding to gammaaminobutyric acid (GABA) A subtype receptors, alters inhibitory postsynaptic CL- currents while simultaneously inhibiting excitatory presynaptic nerve terminal signal event transmission. This is supposed to sustain the opening of chloride channels and results in the suppressed neuronal activation of oscillations throughout the brain and sensory management throughout the entire system [20–23]. The GABAergic thalamic neurons would also therefore inhibit retinally-driven activity, and likewise disable input to the geniculo-hypothalamic pathway which is activated by crossed retinal inputs leading to the suprachiasmatic nucleus (SCN). In this way, brainwave activities related to conscious-state transition and measured by Bispectral Index (BIS) monitors [24] or Guedel's classification system [25] are logistically absent, thereby theoretically preventing patient awakening and patient awareness or memory.

However, the research shows that brain death and cardiac death are not simultaneously correlated [26–29]). In research review by Robijn (2020) as part of an academic thesis submission, Robijn reports correlation between BIS and the Richmond Agitation-Sedation Scale (RASS) (p < 0.0004) including reporting patients 'awake' during euthanization despite observational physician [30] decisions that the patients were dead [31, 32]. Also, memory formation also continues under anaesthesia [12, 33, 34]. On closer inspection of the events, one finds that the high dosage anesthetics such as 9 mg/L pentobarbital intravenous injection used in euthanization in the Netherlands has explicit pharmacological warnings that the neurotoxic compound cannot reach the brain in one minute intravenous application and that that the accelerated injection causes gangrene, body-wide joint pain and tissue irritation for any intravenous-administered dosages above 0.5 mg/l. Furthermore, it reduces IL-1beta cytokine release by only 30–40%, while endogenous tumor necrosis factor (TNF-α) transport becomes elevated in a process that remains

#### **Figure 1.**

*A list of features in the progression of amnesiac-related brain inflammation from disease or neurological disorders leading to risks that may compromise euthanization patient safety.*

A dementia patient's care-giving team is presumed to include certified doctors and nurses qualified in early diagnosis and strategies for dementia-symptom management. The targets of such caregiving include optimizing physical health, cognition, activity and well-being identifying and treating accompanying physical illness detecting and treating challenging behavioral and psychological symptoms provid-

Section 4.1 of the Dutch euthanization law [9] declares that euthanasia may be given to a patient who is no longer mentally competent as a result of advanced dementia, and that the doctor does not need to agree with the patient regarding the time or manner of euthanatic execution based on a physician declaration of patient

Euthanization is delivered via anesthetics without acknowledging the surge of neurophysiological coherence and connectivity in the forced-dying brain [10] or on the basis of any measured disability of a patient to change from one conscious-state to any other. The degree that sensory information processing and conscious memory, awareness, learning and recall are supposed to be fully disabled [11] by the simple observation of delirium seems to possibly have led to an unchecked medical assumption that an overdosage of anesthetic-euthanatic neurotoxins is sufficient to overcome the disability and trigger instant brain death. However, the research shows that this is invalid and that memory formation- and indeed, brain survival mechanisms - are evolved to be much smarter, enabling survival-related learning related neuronal synaptic plasticity changes to occur even under deep anesthesia

In 2019, 146 dementia patients were euthanized in the Netherlands, 14% less

*Two notifications in 2018 involved patients in an advanced or very advanced stage of dementia who were no longer able to communicate regarding their request and in whose cases the advance directive was decisive in establishing whether the request was voluntary and well considered.* See case 2018-41, described in Chapter II, and case

*In 144 cases the patient's suffering was caused by early-stage dementia. These patients still had insight into their condition and its symptoms, such as loss of bearings and personality changes. They were deemed decisionally competent with regard to their request because they could still grasp its implications. Case 2018-123,*

But, the section titled Advanced Directive Points to Consider (Section 4.1, f, (see Annual Reports, Dutch Euthanasia Committee [15]) requires physicians to answer: *Are there any contraindications that are inconsistent with the advance directive and*

If so, this statement represents one opportunity to provide an argument that all dementia patients deserve medically-meaningful conscious-state transition monitoring and decision-competence evidence before non-voluntary euthanization can

Such monitoring technology would enable demonstration of key factors of noneligibility when a patient is unable to transition into unconsciousness or brain death instantaneously or for up to 36 hours - even following severe anesthesia and cardiac

The English version Regional Euthanization Review Committees- The

ing information and long-term support to carers (WHO).

*Suggestions for Addressing Clinical and Non-Clinical Issues in Palliative Care*

inability to comprehend the subject.

frequently than the previous year [14].

Netherlands, report (2018) [9] states that.

*described in Chapter II, is an example.*

*preclude the performance of euthanasia?*

be legally authorized.

**266**

2018-21, published on www.euthanasiecommissie.nl.

[12, 13].

Dementia

persistent on behalf of neurotoxin breakdown and elimination that can last for as many hours as the 36-hour half life of the anesthetic itself [30]. This process is part of inherent mechanisms of survival, regardless the neurotoxic, and it is automatically geared to protect the brain with interleukin-1β (IL-1β), and interleukin-6 (IL-6) pleiotropic mechanisms [6, 35–37].

In this chapter, a description is given of both. It includes:

accommodate euthanatic administration.

*DOI: http://dx.doi.org/10.5772/intechopen.97384*

and,

**dementia**

I.Measurement of decisionmaking decline in brain-disease related dementia;

II.Measurement of conscious-state transition impairment, and capacity to

*The Need for XR-Measurement of Decision-Making Decline and Conscious-State Transition…*

**2. Measurement of decision-making decline in brain-disease related**

are described abundantly throughout the literature as the basis of cognitive

ease progression, long before stages of delirium have arrived.

meaningful in investigations of decision-making decline and more. For example, these include psychiatric considerations for:

the night to inflammatory protection during the day;

on the patient bioreceptive retinal cells;

disorientation and injury;

**269**

Decision-making decline in dementia patients [45] can be measured by using tests for autonomic non-conscious learning and recall expression [46]. The rates of learning and recall are measured from responses to an unconditioned stimulus (US) that is associated with a subsequent aversive conditioned stimulus (CS) [47]. Tests

*decisionmaking* [48–50] *evaluation.* The results are matched with the arrival of shortterm neurosynaptic plasticity changes in corresponding neocortical amygdaloidhippocampal-prefrontal cortical networks [51], as demonstrated by fMRI images offered in the Human Connectome Project (HCP) database [52, 53], relative to the disease etiology. XR-investigations are appropriate before stages of profound delirium in advanced dementia [54]. Delirium is defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) to include acute disturbance in attention, awareness, and cognition. The European Delirium Association and American Delirium Society (2014) describe its increased mortality rate [55]. Delirious patients suffer from severe disturbances of the circadian system [56]. And so, XR sessions as described in this chapter offer a diurnal monitoring method to predict the arrival of impaired day-night rhythm in patient dementia-related dis-

Portable virtual reality devices that can simulate 360-degrees of 3D- immersive

1.Duration of each session which is minimized to avoid optogenetic influence

2.Diurnal (circadian) times of day that can report challenges due to brain inflammation transition stages, i.e. from inflammatory repair periods during

3.Patient locomotor stabilization and non-navigational requirements against

environments in videogame processing have been used in cognitive decisionmaking diagnostics and therapeutics. They can be scripted with internally-animated virtual cameras and objects, known as *assets* to trigger patient sensorimotor interaction and focus. The engagement parlays into recognition behaviors which can be recorded as data with simultaneous autonomic cardiologic variation measurements as frequently as needed in devices that stream the videogame up to 60 or more frames a second. Also known as serious games or medical virtual reality behavioral tests [54, 57], these videogames require a minimum set of calibration so that the collection of data from the patient (also referred to as the *player*) is medical-

This is significant considering the fact that, in the Netherlands alone, more than 32,000 killed patients have reportedly also died in conditions of unconsciousness with profound dehydration; and where, at least one pro-euthanization physician promoted the killing of a schizophrenic mentally ill patient to a general public readership with significant reference to the patient's ethnicity and immigrant socioeconomic demeaning reference to drug-addiction [38]. In this chapter, it is particularly relevant to disclose the fact that dementia patients can be proven to be inappropriate for euthanization treatment, both on the basis of their majority highlevel of anti-somnogenic cytokine levels and on the basis of brain survival mechanisms that are successful enough to preserve the brain in the oldest dementiasymptomatic victims.

Generally speaking, anesthetics bind to gamma-aminobutyric acid (GABA) A subtype receptors of the central nervous system, the post-synaptic NMDA receptors of hippocampal pathways for memory, and the two-pore-domain K+ channels of the central nervous system, depressing signal transmission associated with conscious awareness for a surgical period. Extreme intravenous euthanatic administration does not reach the brain, according to manufacturer related research and instead produces risk of organ-wide tissue damage plius gangrene [30]. This is because the higher dosages trigger instant release of the pro-inflammatory cytokines tumor necrosis factor α (TNFα), interleukin-1β (IL-1β), and interleukin-6 (IL-6) which are powerful repair and survival brain protective cytokines [39, 40].

These cytokines modulate centers of wakefulness regulation located in the hypothalamus, the basal forebrain and the brain stem by influencing substances involved in sleep–wake-behavior such as adenosine, nitric oxide (NO), nuclear factor-κB (NF-κB), prostaglandin D2 (PGD2), the neurotransmitters γaminobutyric acid (GABA), glutamate and norepinephrine, as well as hormones such as growth hormone-releasing hormone (GHRH) and corticotropin-releasing hormone (CRH). However, several key cytokines including IL-4, IL-13 and TGF-β are anti-somnogenic (wakefulness triggering) [41]. If so, queries against forced euthanization of Alzheimer's disease should include high-risk of patient awakening susceptibility during the process, resulting in opportunity for greater error and patient suffering (see **Figure 1** below).

At the time of researching, Dutch physicians reportedly still seem to choose to administer pentobarbital at 9 g/L as the primary euthanatic, which is well above the 0.5 mg/L safe maximum (see online pharmaceutical manufacturing warnings [42, 43]. 71% of patients, dementia and non-dementia, are euthanised at home [30]. Methods of testing brain death and pain detection still include the Bispectral Index monitor (BIS), NeuroSense monitor and Analgesia Nociception Index monitor. There are evidence of pain and suffering, awakening, and discomfort during the euthanization, despite that it is promoted as a dignified pain-free method of termination from irreversible disease conditions [44].

And yet, the law refers to the patient's advance request to receive euthanization on behalf of preserving self-dignity which is separated from medical decisionmaking in itself. If so, there is an unchecked expression that could be interpreted as a mandate to destroy dementia-patients who visibly fail to prevent their symptoms from violating rules of local social dignity. If so, then this contradicts the claim of compassionate reasons for euthanization in the law-making.

*The Need for XR-Measurement of Decision-Making Decline and Conscious-State Transition… DOI: http://dx.doi.org/10.5772/intechopen.97384*

In this chapter, a description is given of both. It includes:

I.Measurement of decisionmaking decline in brain-disease related dementia; and,

II.Measurement of conscious-state transition impairment, and capacity to accommodate euthanatic administration.
