An Expert-Led Tour of Select CMS Guidance for Conditions Including Dementia in a Long-term Care Setting

For optimal viewing quality, please expand video to full screen. Hi. I’m Dr. Dan Cannone. I’m chief medical consultant to United Church Homes, Incorporated, a nonprofit national nursing home chain headquartered in Marion, Ohio. I’m also consultant staff physician in geriatric medicine in the Department of Family Medicine at Western Reserve Hospital in Cuyahoga Falls, Ohio. In this program, I am going to walk you through guidance from the Centers for Medicare & Medicaid Services, or CMS, that is relevant to older adults with hallucinations and delusions associated with dementia-related psychosis and put them in the context of my experience in long-term care. Please note that this disease-awareness, non-CME program is intended only for healthcare professionals involved in the management of people with dementia-related hallucinations and delusions. It’s sponsored by Acadia Pharmaceuticals, and I’m presenting on behalf of Acadia as a paid consultant. This presentation is not meant to discuss specific treatment options for dementia-related psychosis. I’m going to highlight 4 F-tags from the State Operations Manual, beginning with F-tag 744. This guidance speaks to overall care for adults with dementia. What’s most important to highlight here is that dignity and quality of life are the primary goals for decision-making. I think all of us in long-term care would agree that this guidance is critically important in the treatment of residents with dementia. The guidance also notes that behavioral and psychological issues in residents with dementia may be caused or exacerbated by environmental triggers and may represent the person’s attempt to communicate with those around them. Behavioral disturbances are common in older people with dementia, and it’s important to examine the underlying potential causes of that behavior. In my experience in long-term care, I often see older people with dementia who have behavioral disturbances that are caused by hallucinations and delusions. However, it is also important to rule out other causes of the behavior. For example, I’ve seen residents with urinary tract infections act out because of their need to be toileted. The second F-tag I’d like to discuss, F-tag 605, concerns respect and dignity for the resident. This F-tag has been put into place to eliminate physical and chemical restraints that are imposed for purposes of discipline or convenience rather than for treating the resident’s medical symptoms. “Convenience” is here defined as an action that is intended to reduce the amount of effort or care the resident requires and not in the resident’s best interest. The guidance also notes that any medication that restricts the resident’s movement or changes their cognition may be considered a chemical restraint, so it’s important that the medication is deemed medically necessary and that medical symptoms are documented. As an example, I’ll make every effort to identify the underlying cause of a resident’s distress. I consider: How long has this resident had problems with possible hallucinations or delusions? I’ve found that it’s important also to include the family and long-term care facility staff in the discussion. When it’s decided that a medication is necessary, in addition to ensuring that it’s prescribed for the appropriate indication, I personally try to choose a medication with a low fall risk and with the least morbidity and mortality. I also provide detailed education to staff and family about monitoring for side effects and response closely. Consent for medication should always be obtained prior to initiating antipsychotic medication. An informed consent form, such as the one shown here, may be used to review the reasoning for selecting the medication, how and when the medication will be administered, and the potential benefits and risks of the medication, including any boxed warnings. The informed consent form must include a daily dose range and must be updated yearly or when dosing outside of the documented dose range. The third F-tag, F758, governs the use of psychotropic medications for people with conditions including dementia. As we see here in blue, this guidance covers several aspects of medication prescribing. I’d like to emphasize the first point: It’s extremely important to document the diagnosed condition for which you’re going to prescribe. Psychotropic medications may be used in specific circumstances of acute emergency—for example, if a resident is a threat to themselves or others around them. In these situations, if the medication is prescribed for distress, you need to identify and address any medical or physical problem or psychological cause that might have triggered the distress. The guidance also emphasizes that any prescribed antipsychotic must be administered at the lowest possible dose for the shortest period of time and is subject to gradual dose reduction, or GDR. According to the guidance, attempts at GDR may be clinically contraindicated if the resident has a documented disorder, if continued use is in accordance with relevant current standards of practice, and/or if attempts at a GDR resulted in a recurrence of or worsened the resident’s symptoms. If an attempt of a GDR fails, this should be documented and revisited 12 months later. One failed GDR does not exempt the resident from future GDR evaluations. The physician must clearly document the clinical rationale if a GDR is contraindicated. Of particular note, some residents with specific, enduring, progressive, or terminal conditions, such as Parkinson’s disease psychosis, may need specific types of psychotropic medications or other medications that affect brain activity indefinitely. Finally, it’s important to highlight that a diagnosis alone may not necessarily warrant the use of antipsychotic medication. This medication may be indicated if the documentation clearly shows that the resident is a danger to themselves or others or is in significant distress or if nonpharmacological approaches have been tried without success. Once an antipsychotic is prescribed for an older resident with dementia or other conditions, it’s especially important to document efficacy and side effects. The residents must be monitored for treatment-related adverse consequences. If adverse events occur, the facility and the prescriber—in consultation with the resident and/or family—must decide and document if the medication should be continued. Finally, F756 governs drug regimen review. In long-term care, our residents may be on a drug regimen that consists of multiple medications. Pharmacist input is paramount to a team approach to medical management. Review should be conducted monthly and must be accompanied by a review of the chart, and irregularities must be reported to the appropriate members of the care team. In my own practice I’ve seen that any time there’s a transition in care, medications are rarely taken out of the regimen, and in many cases, more may be added. It’s important to keep in mind that many of these residents have multiple comorbidities. In my experience I’ve seen residents sent for 1 service, but by the time you get them back they’ve seen 2 or 3 different medical services, and more medications have been added. All adverse events are looked at against the backdrop of the resident’s chart. Because of that, if a resident is stabilized and suddenly has a new adverse event going on, you have to look at any newly added drugs for potential new drug-drug interactions or drug adverse events. As I noted previously, it’s important to document resident behavior and other outcomes—for example, in response to a decrease in antipsychotic medication or other changes to care. A standardized grid or form, such as the example form shown here, may be used to track aggressive behaviors, anxiety, or lack of interest in self-care activities such as eating, toileting, showering, and so on. Tracking the resident’s behaviors in this way can help alert the treatment team to the need for intervention following medication changes or other changes to the treatment regimen. To sum up, the CMS guidance provides important standards for the care of older adults with conditions including dementia-related psychosis. This guidance seeks to ensure resident autonomy, dignity, respect, and quality of life. It makes clear that physical and chemical restraints, including antipsychotic medications, must be used for medical purposes and not for discipline or staff convenience. When using psychotropic medications, it is important to obtain consent from the resident or healthcare proxy, review the resident’s other medications, and regularly monitor outcomes. It’s also essential to document the indication for medication use, response to treatment, behavior changes, and side effects. During this program, we have seen how dementia and hallucinations and delusions associated with dementia-related psychosis may impact long-term care and transitions of care. We have also reviewed the common challenges associated with care transitions for these individuals and, most importantly, identified areas where improved communication might enhance resident outcomes. Thank you for joining me for this program. For additional resources on hallucinations and delusions associated with dementia-related psychosis, please explore MoreThanCognition.com. Reference Centers for Medicare & Medicaid Services. State Operations Manual: Appendix PP – Guidance to Surveyors for Long Term Care Facilities. Updated November 22, 2017. Accessed November 11, 2020. https://www.cms.gov/Regulations-and-Guidance/Guidance/Manuals/downloads/som107ap_pp_guidelines_ltcf.pdf.

Unmet Need for the Treatment of Dementia-Related Psychosis

For optimal viewing quality, please expand video to full screen. Dr. Stahl: Hello, my name is Dr. Stephen M. Stahl and I am an adjunct professor of psychiatry at the University of California, San Diego, an honorary visiting senior fellow at the University of Cambridge, and director of psychopharmacology for the California Department of State Hospitals. Dr. Brunton: And I’m Dr. Stephen Brunton, executive vice president for the Primary Care Education Consortium and associate adjunct clinical professor in the department of family medicine at Touro University in Vallejo, California. In this video, we will discuss proposed diagnostic criteria for dementia-related psychosis and certain considerations that may inform the management of dementia-related psychosis.  Dr. Stahl: We will also explore the unmet need for FDA-approved treatments for dementia-related psychosis, and the evidence for efficacy and adverse events associated with the use of atypical antipsychotic medications in patients with dementia. Dr. Stahl: There is a need for specific diagnostic criteria for psychosis in dementia. The following criteria, published by Jeste and Finkel, were intended to distinguish symptoms of delusions and hallucinations in Alzheimer’s disease from those seen in schizophrenia and related psychotic disorders after excluding other causes of psychotic symptoms.1 Dr. Stahl: A. Characteristic symptoms. To meet this criterion, a patient must exhibit visual or auditory hallucinations, delusions, or both.1  Dr. Stahl: B. Primary diagnosis. All criteria for dementia of the Alzheimer’s type must be met. For other dementias, Criterion B will need to be modified appropriately.1 Dr. Stahl: C. Chronology of symptom onset. Evidence from patient history should indicate that the symptoms defined in Criterion A have not been present continuously since prior to the onset of dementia symptoms.1 Dr. Stahl: D. Duration and severity. To fulfill this criterion, the symptoms present in criterion A must be present, at least intermittently, for 1 month or longer. Additionally, the symptoms must be severe enough to cause disruption in the patient’s and/or others’ functioning.1 Dr. Brunton: Criterion E specifies that schizophrenia and related disorders should be excluded in order to reach a diagnosis of dementia-related psychosis. Criteria for schizophrenia, schizoaffective disorder, delusional disorder, or mood disorder with psychotic features should never have been met.1  Dr. Brunton: F. Relationship to delirium. The disturbance must not occur exclusively during the course of a delirium, although the two can coexist for a time.1 Dr. Brunton: G. Other causes of psychotic symptoms must be excluded. The disturbance should not be better accounted for by another general medical condition or direct physiological effect of a substance, for example, a drug of abuse or a medication.1 Dr. Brunton: The Jeste and Finkel criteria also suggest that certain associated features should be considered. Specifically, it should be noted when there is evidence, from history or examination, of prominent agitation with or without physical or verbal aggression in association with a patient’s psychosis. Additionally, it should be specified whether prominent negative symptoms, such as apathy, affective flattening, avolition, or motor retardation, are present. Lastly, it should be noted if there is evidence of depressive symptoms, such as depressed mood, insomnia or hypersomnia, feelings of worthlessness or excessive or inappropriate guilt, or recurrent thoughts of death.1 Dr. Stahl: Decision-making regarding the use of antipsychotic therapy in patients with dementia may involve several key considerations. The Alzheimer’s Association recommends nonpharmacologic interventions as first-line therapy for individuals experiencing behavioral and psychological symptoms of dementia, or BPSD, and provides several considerations relevant to decision-making regarding the use of antipsychotics for BPSD.2 Dr. Brunton: The Alzheimer’s Association recommends that triggers of behavioral disturbances be identified and removed, and that nonpharmacologic alternatives should be considered as first-line therapy. Additionally, the severity and consequences of BPSD should be evaluated with respect to the overall risk to the self or others. The risks and benefits with and without antipsychotic therapy should be considered. Lastly, it is important to accept that interventions for the treatment of BPSD are short-term and must be regularly re-evaluated.2 Dr. Stahl: Currently, no antipsychotic medications are approved to treat dementia-related psychosis and all antipsychotic medications carry a boxed warning indicating that elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.3 Dr. Brunton: The FDA analyzed 17 placebo-controlled trials that demonstrated an approximately 1.6- to 1.7-fold increase in mortality with the use of atypical antipsychotics in older patients with dementia-related psychosis compared to placebo-treated patients.3 Most of the deaths appeared to be either cardiovascular, for example heart failure or sudden death, or infectious, for example pneumonia, in nature.3 Dr. Stahl: Following the FDA analysis, an independent, individual study-based meta-analysis of 15 placebo-controlled atypical antipsychotics clinical trials was conducted by Schneider and colleagues to assess the evidence for efficacy and adverse events associated with the use of atypical antipsychotic medications in patients with dementia.4 The included trials were parallel group, double-blind, placebo-controlled, and randomized.4 All of the included patients had Alzheimer’s disease, vascular dementia, mixed dementia, or a primary dementia.4 Overall, 3,353 patients were randomized to drug and 1,757 to placebo.4 Dr. Brunton: This analysis revealed inconsistent evidence of efficacy for the treatment of BPSD in patients with dementia, and that the use of atypical antipsychotics in patients with dementia may be associated with adverse events, as shown here.4 Schneider and colleagues also analyzed the odds ratio of death associated with the use of atypical antipsychotics in patients with dementia. This analysis reported an odds ratio of 1.54, with a 95% confidence interval of 1.06 to 2.23, which was consistent with the FDA analysis.3,5 It may be important to consider these findings when evaluating the risks and potential benefits of antipsychotic therapy in patients with dementia. Dr. Stahl: The use of antipsychotic medications may be associated with clinical cognitive decline.4 Schneider and colleagues analyzed MMSE scores from 7 clinical trials to determine the overall effect of atypical antipsychotics on cognitive function in patients with dementia. The results of this analysis indicated that atypical antipsychotics are associated with greater worsening of cognitive function compared to placebo.4 Moreover, a nested case-control study of 1812 patients and 3400 matched controls conducted by Coupland and colleagues found an increased risk of dementia associated with the use of antipsychotic medications with anticholinergic activity.6 Dr. Brunton: Additionally, the use of antipsychotics for dementia-related psychosis may be associated with an increased risk of metabolic events in older adults.7 In a retrospective chart review of 81 patients, Trinkley and colleagues determined that 30% of adults with dementia treated with atypical antipsychotics for BPSD experienced metabolic events, including hypo- or hyperglycemia, elevated lipids or increased weight.7 It is important to note that due to the small sample size utilized in the Trinkley study, additional studies are warranted to further evaluate these findings. Lastly, antipsychotics functioning as D2 antagonists can induce movement disorders in adults with Parkinson’s disease.8 As you can see, there are several factors to consider when evaluating the risks and benefits of antipsychotic therapy in patients with dementia, including the type of dementia that a patient may have.  Dr. Stahl: Jeste and Finkel published diagnostic criteria for psychosis in dementia. These criteria were intended by the authors to distinguish delusions and hallucinations in Alzheimer's disease from those seen in other disorders.1 Dr. Brunton: Currently, no antipsychotic medications are approved to treat dementia-related psychosis. The use of atypical antipsychotics in older patients with dementia-related psychosis is associated with increased mortality.3 Moreover, the use of atypical antipsychotics in patients with dementia is associated with inconsistent evidence of efficacy and an increased risk of certain adverse events, such as clinical cognitive decline.4,6 We hope that the information presented in this video may be relevant as you navigate the management of dementia-related psychosis. Please view the other videos in this series, and thank you for watching! References Jeste DV, Finkel SI. Psychosis of Alzheimer's disease and related dementias. Am J Geriatr Psychiatry. 2000;8(1):29-34. Alzheimer’s Association. Position on Challenging Behaviors. https://www.alz.org/national/documents/statements_antipsychotics.pdf. Accessed October 2019. US Food and Drug Administration. FDA Public Health Advisory: Deaths with Antipsychotics in Elderly Patients with Behavioral Disturbances. Silver Spring, MD: US Food and Drug Administration; April 11, 2005. Schneider LS, Dagerman K, Insel PS. Efficacy and adverse effects of atypical antipsychotics for dementia: meta-analysis of randomized, placebo-controlled trials. Am J Geriatr Psychiatry. 2006;14(3):191-210. Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA. 2005;294(15):1934-1943. Coupland CAC, Hill T, Dening T, et al. Anticholinergic drug exposure and the risk of dementia: a nested case-control study. JAMA Intern Med. 2019. Trinkley KE, Sturm AM, Porter K, Nahata MC. Efficacy and safety of atypical antipsychotics for behavioral and psychological symptoms of dementia among community dwelling adults. J Pharm Pract. 2020;33(1):7-14. Goldman JG, Vaughan CL, Goetz CG. An update expert opinion on management and research strategies in Parkinson's disease psychosis. Expert Opin Pharmacother. 2011;12(13):2009-2024.

A Proposed Neural Pathway Associated With Delusions and Hallucinations in Dementia-Related Psychosis

For optimal viewing quality, please expand video to full screen. Dr. Stahl: Hello, my name is Dr. Stephen M. Stahl and I am an adjunct professor of psychiatry at the University of California, San Diego, an honorary visiting senior fellow at the University of Cambridge, and director of psychopharmacology for the California Department of State Hospitals.  Dr. Brunton: And I’m Dr. Stephen Brunton, executive vice president for the Primary Care Education Consortium and associate adjunct clinical professor in the department of family medicine at Touro University in Vallejo, California. In this video, we will discuss a proposed neurobiological mechanism by which cortical damage and/or dysfunction leads to hyperactivation of a neural pathway associated with delusions and hallucinations in dementia-related psychosis. Dr. Stahl: Let’s begin by discussing the relationship between the cortical damage that is thought to occur in dementia, and the neurotransmitter systems that regulate neural circuits associated with delusions and hallucinations in patients with dementia.  Dr. Stahl: The pathology of dementia is associated with the loss of cortical neurons.1-5 Dr. Stahl: Such neuronal loss can profoundly affect the surviving neurons and the neurotransmitter systems that regulate them.6 Dysfunction in these neurotransmitter systems may play a key role in the pathophysiology of dementia-related delusions and hallucinations.7  Dr. Stahl: Dysfunction in neurotransmitter systems can affect the activity of neurons and the neural pathways they comprise. In theory, cortical neurotransmitter dysfunction can lead to neuronal dysregulation in the cortex and activation of the mesolimbic pathway, which projects from the ventral tegmental area to the ventral striatum, as seen here. This network of cortical and mesolimbic neurons comprises a neural pathway that may be associated with delusions and hallucinations.7 Dr. Stahl: It is thought that hyperactivity in this neural pathway may underlie the development of delusions and hallucinations.7 Theoretically, modulation of such pathways may be able to address delusions and hallucinations.7,8 Dr. Brunton: To understand this theory, we must first familiarize ourselves with the role neurotransmitters play in regulating neural activity. Neurotransmitters such as serotonin can modulate neural pathways by binding to their corresponding receptors at neuronal synapses.7-9 Dr. Brunton: When serotonin is released into synapses, it can bind 5-HT2A  serotonin receptors and activate them. 5-HT2A receptors are one member of the serotonin receptor family.7-9 Dr. Brunton: 5-HT2A receptors are thought to modulate the activity of cortical neurons that participate in neural pathways associated with delusions and hallucinations.7,8 Dysregulation of cortical neurons and/or excessive 5-HT2A activity can lead to hyperactivation of such neural pathways, which can theoretically promote the development of delusions and hallucinations.7,8 Thus, blockade of 5-HT2A activity is thought to modulate certain neural pathways associated with delusions and hallucinations.7,8 Dr. Stahl: In summary, the pathology of dementia is associated with the loss of cortical neurons.1-5 Such neuronal loss can profoundly affect the surviving neurons and the neurotransmitter systems that regulate them.6 Dr. Brunton: Dysfunction in neurotransmitter systems can lead to hyperactivation of neural pathways associated with delusions and hallucinations in patients with dementia.7 Blockade of serotonin 5-HT2A receptors is thought to modulate certain neural pathways associated with delusions and hallucinations.7,8 We hope this video has been informative. Please view the other videos in this series, and thank you for watching! References Colom-Cadena M, Pegueroles J, Herrmann AG, et al. Synaptic phosphorylated alpha-synuclein in dementia with Lewy bodies. 2017;140(12):3204-3214. Hamilton RL. Lewy bodies in Alzheimer's disease: a neuropathological review of 145 cases using alpha-synuclein immunohistochemistry. Brain Pathol. 2000;10(3):378-384. Hyman BT, Phelps CH, Beach TG, et al. National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease. Alzheimers Dement, 2012;8(1):1-13. Rosso SM, Donker Kaat L, Baks T, et al. Frontotemporal dementia in The Netherlands: patient characteristics and prevalence estimates from a population-based study. 2003;126(9):2016-2022. Jellinger KA, Stadelmann C. Problems of cell death in neurodegeneration and Alzheimer’s disease. J Alzheimers Dis. 2001;3(1):31-40. Stahl SM. Stahl’s Illustrated Alzheimer’s Disease and Other Dementias. New York, NY: Cambridge University Press; 2019. Stahl SM. New hope for Alzheimer’s dementia as prospects for disease modification fade: symptomatic treatments for agitation and psychosis. CNS Spectr. 2018;23(5):291-297. Stahl SM. Parkinson’s disease psychosis as a serotonin-dopamine imbalance syndrome CNS Spectr. 2016;21(5):355-359. Ballanger B, Strafella AP, van Eimeren T, et al. Serotonin 2A receptors and visual hallucinations in Parkinson’s disease. Arch Neurol. 2010;67(4):416-421.

The Prevalence, Impact, and Proposed Neurobiology of Delusions and Hallucinations Associated With Dementia-Related Psychosis

For optimal viewing quality, please expand video to full screen. Dr. Stahl: Hello, my name is Dr. Stephen M. Stahl and I am an adjunct professor of psychiatry at the University of California, San Diego, an honorary visiting senior fellow at the University of Cambridge, and director of psychopharmacology for the California Department of State Hospitals. Dr. Brunton: And I’m Dr. Stephen Brunton, executive vice president for the Primary Care Education Consortium and associate adjunct clinical professor in the department of family medicine at Touro University in Vallejo, California. In this video, we will discuss the prevalence, impact, and proposed neurobiology of delusions and hallucinations associated with dementia-related psychosis. Dr. Stahl: Delusions and hallucinations are prevalent across the dementias, as shown here.1-15 Although the rates of delusions and hallucinations vary, they occur in each of the 5 most common dementia types.1-15 Delusions and hallucinations are most common in patients with dementia with Lewy bodies, or DLB, and least common in patients with frontotemporal dementia.1-15 Overall, approximately 2.4 million people in the US have dementia-related psychosis, meaning that they experience delusions and hallucinations.1-15 Before we explore the impact delusions and hallucinations can impose on patients, let’s take a moment to understand what delusions and hallucinations are and how they manifest in patients with dementia. Dr. Stahl: Delusions can be defined as false, fixed beliefs that are not amenable to change in light of conflicting evidence.16 There are several common types of delusions in patients with dementia, including delusions of reference, which is an individual’s belief that a neutral event has a special meaning for them, delusions relating to theft or possessions being hidden, and delusions relating to the presence of strangers in the house.9 Dr. Stahl: Delusions are distinct from hallucinations, which are perception-like experiences that occur without an external stimulus and are sensory, meaning that they involve 1 or more of the 5 senses. Patients may see, hear, taste, smell, or feel something that is not there.16 Some patients may realize they are hallucinating, but others may not be able to distinguish their hallucinations from reality.17 Now that we’ve become familiar with the prevalence of delusions and hallucinations in patients with dementia-related psychosis, and the key defining features of delusions and hallucinations, let’s explore the impact of delusions and hallucinations in patients with dementia. Dr. Stahl: To determine whether the presence of delusions and hallucinations affected clinical outcomes for people with Alzheimer’s disease, Scarmeas and colleagues conducted a study that followed 456 individuals with early Alzheimer’s disease for up to 14 years. Cognitive and functional outcomes were assessed in addition to rates of institutionalization and death. Cognition was assessed with the Columbia Mini-Mental State Examination, or MMSE, and function was assessed with the Blessed Dementia Rating Scale, or BDRS. Delusions were noted for 34% of subjects at baseline and for 70% of subjects at any subsequent evaluation. Hallucinations were present in 7% of subjects at the initial visit and in 33% of subjects at any subsequent visit. In this study, the term “any delusions” or “any hallucinations” includes both transient and persistent delusions or hallucinations. Statistical modeling of the study data, adjusted for the factors indicated in the footnote below this graph, showed that the presence of delusions and hallucinations was associated with a significantly increased risk of cognitive and functional decline, indicated in the graph as a risk ratio greater than 1. In this study, the presence of hallucinations, but not delusions, was associated with a significantly increased risk of institutionalization and death. These data suggest the presence of delusions and hallucinations may increase the risk of worse outcomes in patients with Alzheimer’s disease.18 Dr. Brunton: Now that we’ve become familiar with delusions and hallucinations in patients with dementia, let’s take a moment to discuss the basic pathological features of dementia, and how damage to certain regions of the brain can be implicated in delusions and hallucinations in the 5 most common dementias. In most dementia types, pathological findings indicate neuronal loss and/or dysfunction in association with the accumulation of protein deposits in the brain. These protein deposits can be referred to as plaques, fibrils, tangles, or Lewy bodies depending on their composition.19-23 Dr. Brunton: The pathology of vascular dementia is distinct from that of other dementia types. In vascular dementia, neuronal loss and/or dysfunction is thought to be caused by impaired cerebral blood flow.24 Dr. Brunton: Structural and functional neuroimaging implicates certain regions of the cortex in delusions and hallucinations across the dementias.25-28 The cortex is the outer layer of the cerebrum and integrates neural functions including cognition and sensory processing.29 Dr. Brunton: The cortex can be divided into 4 distinct lobes, each of which governs different functional domains.29 The frontal lobe is involved in motor function and higher-level cognition while the temporal lobe regulates memory as well as olfactory and auditory processing. The parietal lobe governs the processing of tactile sensory information, and the occipital lobe plays a role in interpreting visual stimuli.29 Dr. Brunton: Damage to the frontal and temporal regions of the cortex has been implicated in delusions and hallucinations across dementia types.25-28 Dr. Brunton: In Parkinson’s disease dementia and dementia with Lewy bodies, damage and/or dysregulation in the occipital region has also been associated with delusions and hallucinations.30,31 Dr. Stahl: In summary, approximately 2.4 million people in the US have dementia-related psychosis.32 The data collected by Scarmeas and colleagues suggest that the presence of hallucinations, but not delusions, may be associated with a significantly increased risk of institutionalization and death.18 Dr. Brunton: These data also suggest that the presence of delusions and hallucinations may be associated with a significantly increased risk of cognitive and functional decline.18 The pathology of dementia involves neuronal loss and/or dysfunction.19-23 Certain regions of the cortex are implicated in delusions and hallucinations across dementia types.25-31 We hope that the information presented in this video has been educational. Please watch the other videos in this series, and thank you for watching! References Ballard C, Neill D, O’Brien J, McKeith IG, Ince P, Perry R. Anxiety, depression and psychosis in vascular dementia: prevalence and associations. J Affect Disord. 2000;59(2):97-106. Burns A, Jacoby R, Levy R. Psychiatric phenomena in Alzheimer’s disease. I: Disorders of thought content. Br J Psychiatry. 1990;157:72-76, 92-94. Burns A, Jacoby R, Levy R. Psychiatric phenomena in Alzheimer’s disease. II: Disorders of perception. Br J Psychiatry. 1990;157:76-81, 92-94. Johnson DK, Watts AS, Chapin BA, Anderson R, Burns JM. Neuropsychiatric profiles in dementia. Alzheimer Dis Assoc Discord. 2011;25(4):326-332. Lyketsos CG, Lopez O, Jones B, Fitzpatrick AL, Breitner J, DeKosky S. Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: results from the cardiovascular health study. JAMA. 2002;288(12):1475-1483. Lyketsos CG, Steinberg M, Tschanz JT, Norton MC, Steffens DC, Breitner JC. Mental and behavioral disturbances in dementia: findings from the Cache County Study on Memory in Aging. Am J Psychiatry. 2000;157(5):708-714. Leroi I, Voulgari A, Breitner JC, Lyketsos CG. The epidemiology of psychosis in dementia. Am J Geriatr Psychiatry. 2003;11(1):83-91. Lopez OL, Becker JT, Sweet RA, et al. Psychiatric symptoms vary with the severity of dementia in probable Alzheimer’s disease. J Neuropsychiatry Clin Neurosci. 2003;15(3):346-353. Ballard C, Saad K, Patel A, et al. The prevalence and phenomenology of psychotic symptoms in dementia sufferers. Int J Geriatr Psychiatry. 1995;10(6):477-485. Nagahama Y, Okina T, Suzuki N, Matsuda M, Fukao K, Murai T. Classification of psychotic symptoms in dementia with Lewy bodies. Am J Geriatr Psychiatry. 2007;15(11):961-967. Aarsland D, Ballard C, Larsen JP, McKeith I. A comparative study of psychiatric symptoms in dementia with Lewy bodies and Parkinson’s disease with and without dementia. Int J Geriatr Psychiatry. 2001;16(5):528-536. Ballard C, Ballard C, Holmes C, et al. Psychiatric morbidity in dementia with Lewy bodies: a prospective clinical and neuropathological comparative study with Alzheimer’s disease. Am J Psychiatry. 1999;156(7):1039-1045. Lee WJ, Tsai CF, Gauthier S, Wang SJ, Fuh JL. The association between cognitive impairment and neuropsychiatric symptoms in patients with Parkinson’s disease dementia. Int Psychogeriatr. 2012;24(12):1980-1987. Mendez MF, Shapira JS, Woods RJ, Licht EA, Saul RE. Psychotic symptoms in frontotemporal dementia: prevalence and review. Dement Geriatr Cogn Disord. 2008;25(3):206-211. Mourik JC, Rosso SM, Niermeijer MF, Duivenvoorden HJ, Van Swieten JC, Tibben A. Frontotemporal dementia: behavioral symptoms and caregiver distress. Dement Geriatr Cogn Disord. 2004;18(3-4):299-306. 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Alzheimers Dement. 2012;8(1):1-13. Rosso SM, Donker Kaat L, Baks T, et al. Frontotemporal dementia in The Netherlands: patient characteristics and prevalence estimates from a population-based study. Brain. 2003;126(9):2016-2022. Jellinger KA, Stadelmann C. Problems of cell death in neurodegeneration and Alzheimer’s disease. J Alzheimers Dis. 2001;3(1):31-40. Roman GC, Tatemichi TK, Erkinjuntti T, et al. Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. Neurology. 1993;43(2):250-60. Mega MS, Lee L, Dinov ID, Mishkin F, Toga AW, Cummings JL. Cerebral correlates of psychotic symptoms in Alzheimer’s disease. J Neurol Neurosurg Psychiatry. 2000;69(2):167-171 Nagahama Y, Okina T, Suzuki N, Matsuda M. Neural correlates of psychotic symptoms in dementia with Lewy bodies. Brain. 2010;133(Pt 2):557-567. Devenney EM, Landin-Romero R, Irish M, et al. 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The True Constant in Dementia Care: A Caregiver’s Story

Constance, a caregiver to her mother Bettie, shares her story with Stephen A. Brunton, MD. Bettie is currently living with Alzheimer’s disease dementia and experiences dementia-related delusions. For optimal viewing quality, please expand video to full screen. DR. BRUNTON: Hi, I’m Dr. Stephen Brunton, Adjunct Associate Clinical Professor in the Department of Family Medicine at Touro University in Vallejo, California, and I’m also board certified in both family medicine and geriatrics. Today, we’re going to explore the true impact of dementia-related psychosis from the perspective of a caregiver. In addition to my clinical background in speaking with caregivers of patients who are experiencing delusions and hallucinations in dementia, I can relate to these challenges based on my personal experience with my mother, who suffered from Alzheimer’s disease. It’s a difficult journey, and today we’ll hear directly from a caregiver regarding her perspective. I’m privileged to be joined by Constance, who is a caregiver to her mother, Bettie. Bettie is currently living with Alzheimer’s disease dementia and experiences dementia-related psychosis. We are speaking today on behalf of Acadia Pharmaceuticals Inc. as paid consultants. Thank you, Constance, for inviting me into your parents’ home and, really, into your world, so that we can better understand the far-reaching effects of dementia-related psychosis. CONSTANCE: You’re welcome, Dr. Brunton. DR. BRUNTON: Before we get into the details of your mother’s diagnosis and your role as her caregiver, could you tell me what inspired you to share your story? CONSTANCE: Sure. Really, it’s my mother who has inspired me. Throughout my life, she has instilled in me and my siblings the importance of helping others when able. We hope that sharing our experience can help someone—anyone—realize that they are not alone. DR. BRUNTON: Well, thank you. If you would, please take us back to when your mother first starting exhibiting troubling symptoms and ultimately when she was diagnosed with Alzheimer’s disease dementia. CONSTANCE: Sure. My family and I first noticed changes in my mother’s behavior around 2001. She would get lost after work and could not find her way home. Then slowly, over time, she started having trouble recognizing us. Eventually, she didn’t recognize anyone, except for my father. My mother was formally diagnosed with Alzheimer’s disease dementia in November 2005. The doctors then confirmed that the delusions that my mother was experiencing was a symptom of her dementia. I was in denial for a long time. DR. BRUNTON: That’s understandable. How did your mother react to the diagnosis? CONSTANCE: My mother is a very strong individual, and she really tried to fight her diagnosis, if that makes sense. She tried to keep us comfortable about it as long as she possibly could. Then it came to a point when she could no longer comfort us. Within the last 2 to 3 years, we really haven’t been able to directly communicate with her at all. DR. BRUNTON: What was that turning point like for you? CONSTANCE: So at that point we had to take over and accept what was going on. My father and I formed a strong team. We decided that we would do whatever we could to keep my mother comfortable and to keep her at home. We wanted her to continue her activities. So the first thing I had to do was move my family out of state to be close to my mom. That was an adjustment in and of itself. DR. BRUNTON: Yeah, I’m sure it was. I would imagine the move must have been very difficult for your entire family. Now I’d like to get back to the idea of the symptoms your mother has exhibited—specifically, the delusions that she has experienced as a result of her Alzheimer’s disease dementia. CONSTANCE: Of course. Early in my mom’s diagnosis, she believed that I was not her daughter, but rather her sister, Ann. She would call me “Ann” and would introduce me to others as her sister Ann. To keep my mother happy, I played along and allowed her to think of me as Ann. Some of her more disruptive delusions occur when any of us would try to help dress or bathe her; she claims that she was being assaulted. This causes stress for her. She would cry out and call for my dad and for myself. She would even threaten to call the police. For several years, these outbursts happened out of nowhere for no apparent reason. As soon as the sun went down, she would start with this behavior. She would yell and scream and cause a lot of distress. DR. BRUNTON: That must have been very hard for you. I want to thank you for sharing that, Constance. The delusions you described are not uncommon with Alzheimer’s disease dementia. Unfortunately, caregivers are often the target of those outbursts. Since you moved your family to be closer to your mother, you’ve been a full-time caregiver, correct? CONSTANCE: That’s right. Caring for my mother is something that I promised to do before she became sick. I told her that I’d be there for her when she needed me. I have been blessed to have a supportive husband who has stood by my side and understood that I needed to make my mother’s care a priority. In 2011, I had to stop working full-time, because caring for my mother became my full-time job. But it hasn’t been easy. DR. BRUNTON: I’m sure it hasn’t. What about you? How have the transition to a full-time caregiver and your mother’s symptoms of dementia-related psychosis impacted your health and your life? CONSTANCE: To be honest, my mother’s symptoms have taken a great toll on my life. Physically, since becoming a caregiver, I’ve developed multiple chronic diseases. And knowing that there is a family link scares me as well. It’s a conflicting situation for me. I’ve spent many nights crying and feeling overwhelmed. I’ve had to come to terms with her Alzheimer’s and how it will affect the rest of our lives. Emotionally, it has been very difficult. I’m really sad most days, because I miss my mother; but at the same time, I’m happy that she’s still here. My mother is 81 years old, so we know that she will die with this disease. I’ve come to terms with this, and I struggle with it every day. It’s been the hardest thing I’ve ever had to endure. But at the same time, I feel blessed that I have been able to fulfill this promise that I made to my mom. I told her that we would take care of her, and my family and I are fulfilling that promise. It truly takes a village to care for someone who is experiencing delusions when they have Alzheimer’s dementia. DR. BRUNTON: Well, I really want to thank you again for sharing and telling your story. CONSTANCE: It’s my pleasure to share our story. If we can help even one family going through this, I know we would have made my mother proud.