Neurocognitive Disorders Florida Conference on Aging August 25, 2020

Heather Cappello MD CMD Medical Director and Clinton Jules MD

HUMANA CONFIDENTIAL – INTERNAL USE ONLY Learning Objectives:

• Explain the differences between the most commonly encountered Neurocognitive Disorders. • Describe Delirium and other Neurocognitive Disorders in their forms and manifestations. • List the assessment and diagnostic measures to identify the correct Neurocognitive Disorder. • Explain treatment measures that are most effective for the various Neurocognitive Disorders • Apply the principles discussed to clinical examples of members with Neurocognitive Disorders

2 HUMANA CONFIDENTIAL – INTERNAL USE ONLY DSM V Neurocognitive Disorders

• Neurocognitive disorder replaces the term “dementia”:

• Dementia arose from the Latin for “mad” or “insane”

• Experts felt that the name change would reduce the stigma associated with dementia

3 HUMANA CONFIDENTIAL – INTERNAL USE ONLY DSM V© Criteria for Neurocognitive Disorders

1) Evidence of significant cognitive decline from a previous level of performance in one or more cognitive domains:

cognitionLearning and memory, language, executive function, complex attention, perceptual-motor and social

2) The cognitive deficits interfere with independence in everyday activities. At a minimum, assistance should be required with complex instrumental activities of daily living, such as paying bills or managing medications. 3) The cognitive deficits do not occur exclusively in the context of a delirium 4) The cognitive deficits are not better explained by another mental disorder ( major depressive disorder, schizophrenia)

4

HUMANA CONFIDENTIAL – INTERNAL USE ONLY DSM V© Neurocognitive Disorders In DSM V © “Neurocognitive Disorder” replaces the term “Dementia”

Clinicians still use the term “dementia,” and the DSM‐ 5 © work group considered dementia to be useful in settings where medical personnel are familiar with the term.

Neurocognitive disorders can be classified as Delirium, and Major or Mild Neurocognitive disorders with or without behavioral disturbances.

5 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Delirium

1590s; from Latin delirium "madness“, from deliriare "be crazy, rave," literally "go off the furrow," a plowing metaphor, from phrase de lire, from de "off, away" (see de‐) + lira "furrow, earth thrown up between two furrows," from PIE *leis‐ (1) "track, furrow.

6 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Delirium: A Medical Emergency

• Delirium is an acute, fluctuating syndrome of altered attention, awareness, and cognition • In practice and in the literature, it has commonly been referred to by other names: • Altered Mental Status • Acute Confusional State • Sundowning • Encephalopathy • Acute Organic Brain Syndrome

7 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Incidence And Prevalence Of Delirium

Incidence during hospital admission : • After hip fracture 28 to 61% • After surgery 15 to 53% • During hospitalization (medical inpatients) 3 to 29% Prevalence: • Intensive care unit with mechanical

8 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Excerpt from DSM V

9 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Delirium Causes ‐ 1 of 2

Drugs: anticholinergics, sedatives, hypnotics, benzodiazepines, barbiturates, opioids and polypharmacy Electrolyte imbalance: Dehydration, Sodium or Potassium Imbalance Lack of Drugs: Stopping certain medicines such as Benzodiazepines, Opioids or ETOH abruptly Infection: Urinary, Respiratory, Wounds and Sepsis t

10 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Delirium Causes ‐ 1 of 2

Reduced Sensory Input: Poor or uncorrected vision or hearing

Intracranial: Stroke, Head Trauma, ICH or SDH Urinary or Fecal Problems: Fecal impaction or urinary retention

Myocardial: Heart attack, cardiovascular condition causing lack of oxygen

11 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Hyperactive Delirium

Characterized by: Agitation restlessness pulling at catheters or intravenous tubing hitting, biting emotional lability

Treatment: Low dose Haloperidol ( 0.5 to 1.0 mg) remains standard of therapy for severe agitation Shortens duration and decreases severity

12 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Hypoactive Delirium

Characterized by:

Withdrawal, flat affect, apathy, This can go unrecognized often as can be confused with depression or dementia lethargy perhaps unresponsiveness More common than hyperactive but less recognized delirium Outcome is worse than hyperactive delirium

13 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Hypoactive Delirium

Treatment: Treat correctable cause:

Limited role for Haloperidol and some evidence supports use of methylphenidate (Methylphenidate hydrochloride improves cognitive function in patients with advanced cancer and hypoactive delirium: a prospective clinical study. Gagnon B, Low G, Schreier G , J Psychiatry Neurosci. 2005 Mar;30(2):100‐7. )

14 HUMANA CONFIDENTIAL – INTERNAL USE ONLY 15 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Risk Factors for Delirium

Alcoholism Dementia

Chronic Pain Depression

History of lung, liver, kidney, heart or brain disease Falls

Terminal illness History of Delirium Age older than 65 Polypharmacy Male Sex Sensory impairment

16 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Prevention of Delirium Assess those at risk within 24 hours of Mobilize after surgery hospital admission Assess for pain Address cognition Nutritional support Provide appropriate lighting, calendar, 24 hour clock that is visible Dentures if needed

Regular visits from friends and family Glasses in place and hearing aids

Keep patient hydrated and bowels moving Encourage calm sleep environment

17 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Major and Mild Neurocognitive Disorders

The severity of the cognitive decline is the distinguishing factor between major and minor neurocognitive disorders

The decline in function and ones ability to carry out activities of daily living are affected in both major and minor, most noted in major (Activities of Daily Living):

Bathing/Grooming Dressing/Undressing Meal prep/Feeding Functional Transfers Safe restroom use and continence Ambulation and Memory care

18 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Major and Mild Neurocognitive Disorders

There will be a decline in one or more domains in both major and mild including:

complex attention

executive function

learning and memory

Language

social cognition

19 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Major and Mild Neurocognitive Disorders

Should not occur in the context of delirium

Should not occur in the context of another mental disorder/psychosis

Frequently observed: mood disturbances agitation apathy Other behavioral symptoms

20 HUMANA CONFIDENTIAL – INTERNAL USE ONLY 21 HUMANA CONFIDENTIAL – INTERNAL USE ONLY World wide Demographics

22 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Alzheimer’s Disease

Irreversible and progressive brain disorder that destroys memory and thinking skills

Symptoms typically first appear in the mid 60s

Sixth leading cause of death in the United States with an estimated 5 million Americans affected

Most common cause of Dementia amongst older adults

1906 Dr. Alois Alzheimer examined the brain tissue of a woman with unexplained mental illness highlighted by memory loss, language problems and unpredictable behavior

23 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Progression of the brain with Alzheimer’s

24 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Diagnosis of Alzheimer’s Disease

Definitive diagnosis is histopathologic examination

Should be suspected in any older adult with subtle gradual onset , progressive memory decline and a cognitive domain that leads to impaired function

Detailed Neurological and Physical Exam

Montreal Cognitive Assessment preferred brief tool due to higher sensitivity (the MMSE had a sensitivity of 78%, whereas the MoCA detected 100%)

25 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Montreal Cognitive Assessment

26 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Routine evaluation of Dementia

CBC, Vitamin B12, TSH,

Electrolyte panel, glucose

Syphilis screening only if high suspicion

Non contrast head CT or MRI is routine

Brain biopsy has limited role in diagnosis of dementia

PET scan has more of a use for Frontotemporal dementia

27 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Neuroimaging for Dementia Evaluation

28 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Treatment for Alzheimer's Dementia

29 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Alzheimer's Disease Treatment

There is no cure

Pharmacologic therapy with Donepezil (Aricept), Rivastigmine (Exelon) and Galantamine (Razadyne)

These drugs have shown modest beneficial impact on neuropsychiatric and functional outcomes for patients with Alzheimer's Dementia (Efficacy of cholinesterase inhibitors in the treatment of neuropsychiatric symptoms and functional impairment in Alzheimer disease: a meta‐analysis, Trinh NH, Hoblyn J, Mohanty S, Yaffe K JAMA. 2003;289(2):210. )

30 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Vascular Dementia

This is the second most common form of dementia after Alzheimer’s

Caused by problems in the supply of blood due to damage to the vascular system

Damage typically caused by strokes, hypertension, hyperlipidemia and diabetes

Symptoms often present as confusion, agitation, memory loss, decrease ability to organize and poor attention and concentration

31 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Progression of Vascular Dementia

32 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Treatment of Vascular Dementia

Acetylcholinesterase inhibitors have been studied and approved for use in Vascular dementia (Donepezil, Galantamine and Rivastigimine).

Improved cognition and functional outcomes can be seen with these medications

Memantine is approved for treatment of moderate to severe AD. Two studies have compared memantine 20 mg/day with placebo in patients with mild to moderate VaD. These were of short duration, 28 weeks. Benefit was seen on cognitive scales but not on clinical global impression or activities of daily living [61,66]. Memantine was safe and well tolerated.

33 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Prevention of Vascular Dementia

Hypertension treatment

Hyperlipidemia treatment

Antiplatelets

Physical Activity

Modify diet and lifestyle choices

34 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Frontotemporal Dementia

35 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Frontotemporal Dementia

Arnold Pick M.D. in 1892 first described a patient with symptoms affecting language which is why at times the term “Picks disease” is used

There are two types of FTD: Behavior variant FTD and Primary Progressive Aphasia (PPA)

Behavior variant typically presents in people in their 50s and 60s Change is most prominent in personality and behavior

36 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Behavior Variant FTD

1) Disinhibition: touching or kissing strangers, public urination, and invading others space

2) Apathy: loss of interest in activities or social relationships ( can be mistaken for depression)

3) Hyperorality: Bingeing on sweet foods, carb cravings, increased alcohol consumption and consumption of inedible objects

4) Compulsive Behaviors: repetitive movements, inflexibility to routine changes and hoarding

37 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Primary Progressive Aphasia

Language is the earliest and most severely affected aspect of cognitive functioning

Decreased speech output

Language dysfunction is apparent during routine conversation

Activities of daily living are preserved except those relating to language (difficulty using the phone)

38 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Pharmacologic Treatment for FTD

Evidence is strongest for SSRIs (Sertraline, Paroxetine and Fluvoxamine)

SSRIs decrease anxiety, disinhibition, impulsivity and repetitive behaviors (Frontotemporal dementia: treatment response to serotonin selective reuptake inhibitors: Swartz JR, Miller BL, Lesser IM, Darby AL ; J Clin Psychiatry. 1997;58(5):212. )

Atypical antipsychotics (Olanzapine, quetiapine and aripiprazole) can help with agitation and behaviors

Be aware of extrapyramidal side effects with antipsychotics

39 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Pharmacologic Treatment for FTD

Limited evidence for cholinesterase inhibitors (Donepezil)

No pharmacy management includes exercise, physical therapy, occupational therapy and speech therapy (Rehabilitation applications in caring for patients with Pick's disease and frontotemporal dementias. Robinson KM ; Neurology. 2001;56(11 Suppl 4):S56. )

Caregiver support and home modification

40 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Lewy Body Disease

41 HUMANA CONFIDENTIAL – INTERNAL USE ONLY The Face of Lewy Body Disease

42 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Lewy Body Disease

Among the most common forms of degenerative dementia in older adults

Characterized by deficits in attention, visualspatial function, fluctuating cognition, recurrent visual hallucinations; and spontaneous motor features of parkinsonism

Repeated falls, syncope, autonomic dysfunction, delusions, hallucinations and neuroleptic sensitivity

43 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Lewy Body Disease

Parkinsonian symptoms are seen in approximately 70 to 90 per cent of patients with Lewy Body disease

Approximately 30 to 50 per cent of individuals have severe sensitivity to antipsychotic drugs

Acute reactions include severe, sometimes irreversible parkinsonism and impaired consciousness, sometimes with other features suggestive of neuroleptic malignant syndrome. This can occur in individuals without baseline parkinsonism.

Adverse reactions are more common with first‐generation antipsychotics (eg, haloperidol), but reactions to second‐generation antipsychotics have also been described

44 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Treatment of Lewy Body Disease

A treatment trial with a cholinesterase inhibitor to ameliorate cognitive and behavioral symptoms in patients with Lewy Body disease is recommended to start (Cholinesterase inhibitors for dementia with Lewy bodies, Parkinson's disease dementia and cognitive impairment in Parkinson's disease, Rolinski M, Fox C, Maidment I, McShane R )

Levodopa for patients with Parkinsonism that is disabling

Disabling psychotic symptoms can be treated cautiously with very low dose atypical neuroleptic agents (Quetiapine 12.5mg daily)

45 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Case Vignette #1

Mrs. P is an 84 year old female

She presents with her son with increasing forgetfulness and decreased ambition

She smoked for 30 years, has atrial fibrillation, high cholesterol and is an insulin dependent diabetic

High school education and worked In a factory

She lives in an ALF and has a very involved son for her caregiver

46 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Case Vignette # 1

Mrs. P is having difficulty remembering her medications and is forgetting to eat a snack at bedtime resulting in low blood sugars as low as 40 in the morning.

She has a short fuse and is yelling more frequently at her son. She has less of a desire to go to meals in the Alf and has stopped doing puzzles which she loved to do.

Medications: ASA 81mg daily, Plavix 75mg daily, Lantus Insulin, Lipitor 40mg HS, Ambien 10mg HS, Norvasc 10mg daily and Lisinopril 40mg

47 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Case Vignette # 1

General: No distress

Cardiovascular: Irregularly irregular rate and rhythm

Neurological: within normal limits

Cognitive Screen: Clock is abnormal and three word recall is 1 (3 item recall test: give 3 unrelated words, ask to repeat, divert and ask after the clock is drawn

48 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Abnormal Clock by Mrs. P

49 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Mrs. P’s MRI of the brain

50 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Name the neurocognitive disorder of Mrs. P

51 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Case Vignette #2

Mrs. Jones presented to the memory disorder clinic with recent onset short term memory problems and a fine hand tremor (not ‘pill‐rolling’ in nature).

She self reported a 6 week history of well‐formed visual hallucinations that included the grim reaper in her closet and little children stealing her cookies.

She would barricade herself in her room due to fear She had poor mobility with a slow and shuffling gait and several recent falls

52 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Case Vignette #2

There was no family history of psychiatric disorders

Mrs. Jones did not drink or smoke and she was a retired saleswoman from Macys

She has three children who are actively engaged in her life and they have noted their mothers changes and that she has slowed down significantly

A neurological exam, MRI of the brain, lab work and MMSE was done.

The neurological exam was consistent with parkinsonian features and she scored 20/30 on the MMSE

53 HUMANA CONFIDENTIAL – INTERNAL USE ONLY Case Vignette #2

Clinical diagnosis of Lewy Body disease was made

Mrs. Jones hallucinations worsened as time went on which resulted in a transition to a memory unit in an ALF

She was trialed on Quetiapine 25mg daily and improved with regards to the hallucinations.

54 HUMANA CONFIDENTIAL – INTERNAL USE ONLY References

Methylphenidate hydrochloride improves cognitive function in patients with advanced cancer and hypoactive delirium: a prospective clinical study. Gagnon B, Low G, Schreier G , J Psychiatry Neurosci. 2005 Mar;30(2):100‐7.

Efficacy of cholinesterase inhibitors in the treatment of neuropsychiatric symptoms and functional impairment in Alzheimer disease: a meta‐analysis, Trinh NH, Hoblyn J, Mohanty S, Yaffe K JAMA. 2003;289(2):210. )

55 HUMANA CONFIDENTIAL – INTERNAL USE ONLY References

Cholinesterase inhibitors for dementia with Lewy bodies, Parkinson's disease dementia and cognitive impairment in Parkinson's disease, Rolinski M, Fox C, Maidment I, McShane R

https://www.alz.org/

http://n.neurology.org/content/87/13/1308

Montreal Cognitive Assessment (MoCA) for the diagnosis of Alzheimer's disease and other dementias; 29 October 2015 ; Davis DHJ, Creavin ST, Yip JLY, Noel‐ Storr AH, Brayne C, Cullum S

56 HUMANA CONFIDENTIAL – INTERNAL USE ONLY References

Inouye SK. The dilemma of delirium: clinical and research controversies regarding diagnosis and evaluation of delirium in hospitalized elderly medical patients. Am J Med 1994; 97:278.

Clegg A, Siddiqi N, Heaven A, et al. Interventions for preventing delirium in older people in institutional long‐term care. Cochrane Database Syst Rev 2014; :CD009537.

Gagnon B, Low G, Schreier G. Methylphenidate hydrochloride improves cognitive function in patients with advanced cancer and hypoactive delirium: a prospective clinical study. J Psychiatry Neurosci 2005; 30:100.

57 HUMANA CONFIDENTIAL – INTERNAL USE ONLY References

Frequency of stages of Alzheimer‐related lesions in different age categories; Braak H, Braak E ; Neurobiol Aging. 1997;18(4):351.

Ratnavalli E, Brayne C, Dawson K, Hodges JR. The prevalence of frontotemporal dementia. Neurology 2002; 58:1615.

Warren JD, Rohrer JD, Rossor MN. Clinical review. Frontotemporal dementia. BMJ 2013; 347:f4827.

Boxer AL, Miller BL. Clinical features of frontotemporal dementia. Alzheimer Dis Assoc Disord 2005; 19 Suppl 1:S3

58 HUMANA CONFIDENTIAL – INTERNAL USE ONLY THANK YOU

59 HUMANA CONFIDENTIAL – INTERNAL USE ONLY