steven tam, md tatyana gurvich, pharm.d., bcgp friday, october … · 2018. 11. 28. ·...

Steven Tam, MD

Tatyana Gurvich, Pharm.D., BCGP

Friday, October 27, 2017

This project is supported by the Health Resources and

Services Administration (HRSA) of the U.S. Department of

Health and Human Services (HHS) under 1 U1QHP28724-

01-00, Cultivating a Culture of Caring for Older Adults, for

$2.5 million. This information or content and conclusions

are those of the author and should not be construed as the

official position or policy of, nor should any endorsements

be inferred by HRSA, HHS or the U.S. Government.

2

Steven Tam, MD

Tatyana Gurvich, Pharm.D., BCGP

Friday October 27, 2017

3

Diagnosis and Management of Dementia

(Major Neurocognitive Disorder)

Faculty Disclosure Information

In the past 12 months, I have no relevant financial

relationships with the manufacturer(s) of any commercial

product(s) and/or provider(s) of commercial services

discussed in this CME activity.

I do not intend to discuss an unapproved/investigative use

of a commercial product/device in my presentation.

4

Objectives:

• Review spectrum of memory change

• Discuss presentations of common dementias

• Review evaluation and workup for dementia

• Discuss non-pharmacological treatment

measures

• Review available pharmacological treatments

6

Memory Complaints

Workup – Labs:

Metabolic panel, blood

count, thyroid, vitamin.

HIV/syphilis, others such

as LP if pertinent

Normal Memory

Changes w/ Aging

Mild Cognitive

Impairment

Dementia / Major

Cognitive Disorder

Workup – H&P:

History to include

symptoms, function,

course, Meds, Fam Hx,

Soc Hx & Exam/Mem Test

Workup – Imaging:

CT/MRI to eval for stroke,

structural changes,

atrophy. PET if deciding

between AD and FTD

Follow up and

Treatment:

Reassurance

Encourage Staying Active

Monitor and follow up

Follow up and

Treatment:

Treat Co-existing condition


Consider Medications:

Cholinesterase inhibitors

& NMDA Receptor Antag


Follow up and

Treatment:




Non Pharmacologic

Treatment of Symptoms:

Reduce agitating factors

Personal Care

Recreational/Relaxation Tx

Support Group

Environmental Change

Safety

Pharmacologic


Mood/Antipsychotic Use

Other Issues:

Caregiver Stress

Optimal Living

Environment

Advanced Care Planning

Driving and Safety

Workup and Treatment of Memory Loss

Consider Neurology Referral for

Unusual/Atypical Findings e.g., Early onset, Other

Neurological Concerns/Atypical neurologic exam

Possible Reversible Causes Metabolic disturbance

Endocrine Infectious

Alcohol/Drug/Pharm Other Medical

Sleep Depression/Anxiety

Other psychiatric

Common Dementias Alzheimer’s

Lewy Body/Parkinson’s Vascular

Fronto temporal

0

10

20

30

40 Alzheimer (Bachmann et al., 1992)

Age (years)

Pre

vale

nce

(%

)

85-93 80-84 75-79 70-74 65-69 61-64

Dementia (Jorm et al., 1987)

0.9 0.4 3.6

10.5

23.8

1.8

18

5 9

3

36

Prevalence of Dementia

Epidemiology

• 4th leading cause of disability

• 4-6 million in the US currently have dementia

and estimated 14 million by year 2050

• Annual incidence increases with age 65-69: 0.06%, 70-74: 1%, 75-79: 2%, 80-84: 8.4%

Geometric increase in prevalence of

dementia

After 60 years, doubles every 5 years

Cost of Dementia

• Major cause of disability due to

institutionalization

• Estimated cost over $200 billion annually

for care and lost productivity

• More than 60% of dementia caregivers

rate emotional stress as high or very high

Common Patient Questions

• Is it just normal

memory loss?

• What’s the difference

between Alzheimer’s

and dementia?

• How do we make a

diagnosis?

• Can’t you do some kind

of brain scan?

• What stage is it?

• What kind of treatment

can we do to stop the

memory loss?

• What can we do to help

with ____ symptoms?

• What help is available?

10

CASE

• 74 year old w/ memory loss symptoms, 2-5 years

• Repeats questions, conversation, misplacing items

• Lived on own until past year due to hospitalization for ulcer disease. Able to do ADLs/IADLs.

• Med Hx: depression, overactive bladder, sleep difficulty, HTN, hypothyroid

• Soc Hx: no alcohol, retired RN

• Fam Hx: Depression

• Meds: Ditropan, Tylenol PM, lisinopril, synthroid

• Exam: Vitals stable, gen exam without focal findings, neuro exam without focal deficits

• Labs

• Imaging

• Cognitive Screen/Testing

• Key points?

• Diagnosis?

11

Eliminate Pharmacologic Cause for

Cognitive Decline

• Long Acting BZD

– Valium/Klonopin

• Short Acting BZD

– Ativan/Xanax

• Z-drugs

• Narcotics

• Alpha Agonists

• Beta Blockers

• Inhalers/Eye Drops

• Review OTC and Herbal

medications for “hidden

ingredients”

• CNS Side effects are

dose related; Cumulative

Effect

• Use of Alcohol/Marijuana

12

Drugs with Strong Anti-cholinergic

Properties

• 1st Generation antihistamines

• Artane/Cogentin

• Skeletal muscle relaxants

• TCA’s/Paroxetine*

• Old antipsychotics

• Zyprexa

• Compazine

• Promethazine

• Lomotil

• Urinary and GI antispasmodics

• Meclizine

• Scopolamine

• Dramamine

The concept of “anti-cholinergic load”

ARE THERE “NORMAL”

MEMORY CHANGES?

“Age-Related Decline”

• Mild Brain Atrophy

• Increased white matter abnormality – Significance unknown

• Decreased hemodynamic response on functional MRI

• Reduced synaptic density on examination of brain tissue

• Leads to declines in: – Information processing speed, Executive function,

Learning efficiency, Effortful retrieval

Hedden & Gabrieli 2004, Nat Rev.

Normal Aging

• Difficulty immediately retrieving well-

known information (names of people,

things)

• Increase in length of time before retrieving

missing word

NORMAL AGING ABNORMAL

Forgetting a name Not recognizing family member

Finding a right word Substituting wrong words

Forgetting the date or day Getting lost in own neighborhood

Trouble balancing checkbook Not recognizing numbers

Losing keys, glasses Putting iron in freezer

Normal versus Abnormal

Memory improves

Dementia

Memory Stable

Mild

Cognitive

Impairment

(MCI)

Normal Aging

What is Mild Cognitive Impairment (MCI)?

• Subjective memory complaint

• Objective memory impairment for age and education

• Largely intact general cognitive function • (alternatively there is also non-amnestic MCI)

• Preserved “Activities of Daily Living” (ADLs)

Petersen et al., 1999

Mayo Clinic

What causes MCI? Depression

- Memory function may improve with treatment of depression

Medical Illness (e.g. Hypothyroidism)* - Memory function may improve if corrected

Traumatic injury (e.g. Head injury)* - Memory function often stabilizes after a period of recovery

Vascular disease (e.g. Stroke)* - Memory function may stabilize or progress

Degenerative processes (e.g. Alzheimer’s disease)* - Memory function declines over time

* More likely to lead to Dementia

Memory improves

Dementia

Memory Stable

Mild

Cognitive

Impairment

(MCI)

Normal Aging

What is Dementia?

(Major Neurocognitive Disorder)

• Impairment greater than expected for age

in at least one cognitive domain

• Difficulty managing Activities of Daily

Living as a result

Causes

• Alzheimer’s • Lewy Body

• Parkinson’s • Vascular

• Huntington’s Disease • FrontoTemporal

• Other Neurodegenerative Diseases

• Prion Diseases

• Infectious (HIV, Syphilis)

• Psychiatric

• Medical Diseases/medications

• Normal Pressure Hydrocephalus

• Nutritional

• Alcohol

• REVERSIBLE CAUSES OF DEMENTIA 2-20%

ALZHEIMER’S DISEASE

Alzheimer’s Disease

• The most common cause of dementia

- 75% of dementia cases

• A degenerative disorder of the brain, with

memory loss as its hallmark.

• Affects > 4.5 million people in the USA

• Declarative memory usually lost early

• Increases with age:

- 1% at 65

- 4% at 75

- 24% at 85

1901, Mrs. Auguste Deitch

Healthy Brain AD Brain

http://socrates.berkeley.edu/~brandley/courses/ib131l/histo/nervous/pictures/pyramidalcells.html

Alzheimer's Disease

• Hallmark is short term memory loss – Memory for recent events, items

• Can be tested by asking patients to learn and then recall a series of words immediately and then at a later delay (5-10 minutes).

• Also can be tested on orientation and recent current events.

– Executive dysfunction and visuospatial impairment often present relatively early

• Less organized, or less motivated; Multitasking often particularly compromised

• Poor insight; Reduced ability for abstract reasoning

– Language and behavior symptoms often manifest later in the disease.

• Can begin as apathy, social disengagement and irritability

• Agitation, aggression, wandering, psychosis can emerge.

Alzheimer’s – other signs and symptoms

• Apraxia, usually later in the disease.

– Show me how you would use …

– Difficulties with complex/multi – step tasks:

dressing, using utensils, other self-care activities

– Olfactory dysfunction

– Sleep disturbances

– Seizures

– Motor signs – usually later stage findings.

Lewy Body Dementia

Lewy Body Dementia

• 2nd most common type of degenerative dementia after Alzheimer disease.

• Distinctive features include: – Visual hallucinations

– Parkinsonism

– Cognitive fluctuations

– Dysautonomia

– Sleep disorders

– Neuroleptic sensitivity

Vascular Dementia

Vascular Dementia

• No pathologic criteria for diagnosis of Vascular Dementia – Memory impairment appears somewhat later

– Concept of vascular cognitive impairment • use of VCI as cognitive impairment that is caused by or

associated with vascular factors.

• Criteria as to what deficits qualify as cognitive impairment are ill-defined

• Heterogeneous rather than a distinct

• High incidence of cognitive impairment and dementia after stroke

• 6-32% in patients 3 months to 20 years after a stroke.

Vascular Dementia

• Mixed dementia (AD w/ cerebrovascular disease)

– About 1/3 or patients diagnosed with vascular dementia will have AD pathology at autopsy

– Using relatively loose definitions of pathologic criteria for AD and VaD, patients with clinical dementia are in fact more likely to have combined pathology rather than either AD or VaD in isolation

Frontotemporal Dementia

Presentation – Frontotemporal

• Prominent changes in social behavior and personality; aphasia

• Relative preservation of episodic memory and other cognitive domains

• Language dysfunction during conversations and assessments

• ADLs maintained except those relating to language (using telephone)

• Other cognitive functions may be affected later in the course

• Motor syndromes include parkinsonism or motor neuron disease

• More common causes of early-onset dementia (6th decade)

Causes • Alzheimer’s • Lewy Body • Parkinson’s • Vascular` • Huntington’s Disease • FrontoTemporal • Other

Neurodegenerative Diseases

• Prion Diseases

• Infectious (HIV, Syphilis)

• Psychiatric

• Medical Diseases/medications

• Normal Pressure Hydrocephalus

• Nutritional

• Alcohol

• REVERSIBLE CAUSES OF DEMENTIA 2-20%


• Is it just normal memory

loss?

• What’s the difference

between Alzheimer’s

and dementia?

• How do we make a

diagnosis?

• Can’t you do some

kind of brain scan?


• What kind of treatment

can we do to stop the

memory loss?

• What can we do to help

with ____ symptoms?


37

Diagnosis?

commons.wikimedia.org

Making the Diagnosis

• History & Exam, Neurological & Psychiatric Assessments

• Cognitive evaluation

• Brain Imaging (CT, MRI, PET, Amyloid)

• Laboratory Testing (Blood Tests including B12 and thyroid, CSF)

• Look Carefully for primary Medical & Psychiatric causes (Potentially Reversible Causes)

History May need informant

Ask about NWCALMS:

NATURE: forget appointment, lost while driving, misplacing

things, word finding difficulties, missed payments, affect

language, behavior change (hallucination, agitation, depressed)

WHEN: days/months/years/decades

COURSE: abrupt, stepwise, progressive

ADL/IADL'S: functional impairment

LIVING SITUATION: bereavement, home situation, move

MOOD: depression (anorexia/insomnia/anhedonia)

STATUS OF HEALTH: such as thyroid, delirium, electrolytes

History

Past medical history (including DM, HTN, CVA,

brain injury, surgery)

Family history of dementia

Medications

Social history (illicit drugs/ETOH)

ROS: gait imbalance, falls, tremors, incontinence, weight loss, headache/blurry vision, asymmetric

weakness, mood, insomnia, rash

Physical Exam Observation

– Involuntary

movements

(tremor, dystonia,

chorea,

myoclonus)

– Speech

– Facial expression

– Disinhibition

Gait (shuffle, fall risk)

Neuro Findings

– Asymmetrical

deficits

– Primitive reflexes

– Visual field

abnormality

– Apraxia evaluation

– Pronator drift

– Cogwheel rigidity

Work Up Labs

– CBC

– CMP (renal function, uremia, calcium)

– TSH, B12, RPR (If indicated)

– Urinalysis

Neuro-imaging

– Structural evaluation (CT, MRI)

– Functional evaluation (SPECT, PET – If looking

for AD vs FTD)

Diagnosis Cognitive Evaluation

• Some available office evaluations – MMSE

– Montreal Cognitive Assessment (MoCA) • Typical cutoff for normal is 26

• www.mocatest.org

– Mini-cog

• Formal Neuropsychological testing • Establish baseline, helps with differentiation

• 1-3 hours

• To assess competencies and guide recommendations

http://www.mocatest.org/

Screening Exams Mini-mental status exam (MMSE)

– Early dementia: score < 24

– Mild dementia: score 20-24

– Moderate dementia: score 13-20

– Severe dementia: score < 12

Montreal Cognitive Assessment (MoCA) (20 minutes)

– MCI: score 19-25

– Alzheimer's dementia: 11-21

Mini-Cog (3 minutes)

– 0: dementia

– 1-2: need to look at drawing

– 3: not dementia

MoCA

Attention and concentration

Executive function

Memory

Language

Visuospatial skills

Conceptual thinking

Calculations

Orientation

Mini-Cog Exam

Screen for dementia

– 3 item re-call

– Clock drawing test: visual-spatial evaluation but

also used as an informative distractor

Benefits

– 3 minute instrument validated to screen for

cognitive impairment in primary care setting

– Less affected by subject ethnicity, language,

education compared to MMSE

Mini-Cog Instructions

“Remember the following words: apple, table,

penny.”

“Inside the circle, draw in the hours of the clock

and set the hands to ten past eleven.”

“Repeat the 3 words I asked you to remember.”

Diagnosis – Probable Alzheimer’s

• Cognitive impairment involving a minimum of

two of the following domains:

– Acquire and remember new information

– Reasoning and handling of complex tasks,

poor judgment

– Visuospatial abilities

– Language functions

– Changes in personality, behavior

Diagnosis – Probable Alzheimer’s

• Other core clinical criteria

– Insidious onset, clear history of decline,

not caused by other etiology

– Initial and most prominent cognitive

deficits

• Amnestic presentation

• Nonamnestic presentations

Diagnosis – Possible Alzheimer’s

• Possible AD

– Atypical course – core clinic criteria are met,

but with sudden onset, or insufficient history

– Mixed presentation – evidence of other

possible neurodegenerative, neuro or non

neuro medical comorbidity or medication.

Structural Imaging:

MRI The Hippocampus Stores and Retrieves

our memories

http://www.stress.org/wp-

content/uploads/2014/01/Picture3.png

Diagnosis - Lewy Body Dementia

• Probable Dementia with Lewy Bodies: – Must have dementia. Must have at least two of three

“core clinical features” • Cognitive fluctuations

• Visual hallucinations

• Parkinsonism

– OR presence of one suggestive feature in combination with one core clinical feature

• Possible DLB: • Presence of only one core clinical feature OR

• presence of one or more suggestive features in the absence of a core clinical feature suggests possible DLB


• Suggestive features

– REM sleep disorder

– Severe neuroleptic sensitivity

– Low dopamine transporter uptake in basal

ganglia on SPECT or PET


• Supportive features – Repeated falls

– Syncope

– Severe autonomic dysfunction

– Hallucinations in other modalities

– Systematized delusions

– Depression

– Relative preservation of medial temporal lobe

– Generalized low uptake on SPECT or PET perfusion imaging with reduced occipital activity

– Abnormal (low uptake) MIBG myocardial scintigraphy

– Prominent slow wave activity and temporal lobe transient sharp waves on EEG


• Conflicting features (DLB less likely) • Cerebrovascular disease evidenced by focal neurologic

signs or neuroimaging

• Other physical illness or brain disorder which is consistent with some or all of clinical features

• First appearance of parkinsonism at late stage (severe dementia)

• Temporal sequence: dementia should occur before or concurrently with onset of parkinsonism.

Diagnosis – Vascular Dementia

• Cognitive decline in one or more cognitive

domains

• Interferes with every day activities

• Not better explained by delirium, another mental

disorder, or system disorder

• Consistent with vascular etiology

Diagnosis – Vascular Dementia.

Hachinski Ischemic Score Feature Value Abrupt onset 2

Stepwise deterioration 1

Fluctuating course 2

Nocturnal confusion 1

Preservation of personality 1

Depression 1

Somatic complaints 1

Emotional incontinence 1

Hypertension 1

History of stroke 2

Associate atherosclerosis 1

Focal neurologic symptoms 2

Focal neurologic signs 2

Diagnosis – Vascular Dementia

• Imaging to evaluate for infarcts.

• White matter lesions (WML) non specific

– Can be associated with nonvascular etiologies

– In patient with vascular risk factors and/or vascular dementia

• Neurospych testing can provide baseline measurement:

– May have less impairment on tests of recognition memory

Diagnosis – Frontotemporal Dementia

• Behavior changes – Has patient said or done anything in public that has

embarrassed others?

– Does the patient appear to have a lack of disgust?

– Does the patient seem indifferent or oblivious to others’ feelings and less affectionate

– Have food preferences changed?

– Does the patient seem more concerned with timekeeping or tend to watch the clock?

– Has there been a change in the patient's sense of humor?

– Has the patient developed new hobbies or interests pursued obsessively, especially with a religious or spiritual bent?


• Generally lack exam findings initially

• Frontal release signs may be seen, but

not specific

• Parkinsonism may arise at more advanced

stages

• 15-20% with motor neuron disease.

– May also have features of CBGD or PSP


• Generally score well on tests early on.

• As disease progresses, focal frontal or

temporal atrophy manifests in 50-65% of

patients.

– Functional neuroimaging can demonstrate

frontal or frontotemporal hypoperfusion or

hypometabolism


• bvFTD – diagnosis made by clinical assessment; imaging and neuropsych may provide supportive findings.

• Diagnostic criteria – 6 features – Disinhibition

– Apathy/inertia

– Loss of sympathy/empathy

– Perseverative/compulsive behaviors

– Hyperorality

– Dysexecutive neuropsychological profile

Diagnosis - Frontotemporal Dementia

• Diagnostic criteria

– 3 out of 6 is possible FTD

– Probable based on same criteria + functional decline & positive imaging findings.

• Exclusion of other disorders that better account for the deficits and behavior disturbances.

• Nonfluent Primary progressive aphasia

• Semantic progressive aphasia

66

Examples

https://www.youtube.com/watch?v=f_fnzxK6sGUhttps://www.youtube.com/watch?v=f_fnzxK6sGUhttps://www.youtube.com/watch?v=f_fnzxK6sGUhttps://www.youtube.com/watch?v=fkKrsbwQvrE

Summary

Dementia Onset Cognitive Symptoms Other symptoms

Alzheimer's Gradual

Memory, visuospatial

initially Apraxia late

Lewy Body Gradual

Hallucinations, Fluctuating

Course, visuospatial Parkinsonism

Vascular Stepwise

Location specific, cortical

versus subcortical Location specific

Frontotemporal

Gradual,

younger

patient

Disinhibition, behavior

changes, semantic and

language/aphasia difficulties

Can have Parkinsonian findings,

ALS association

RATING/STAGING SCALES

68

• For the clinical side, often get questions regarding stage of the dementia

• Helps patients/families with planning

– Legal

– Financial

– Living arrangements

• Difficulties include history taking, overlap of stages, interpretation, lengthy administration

69

Staging

• Mild – might still function independently • Memory difficulties are noticeable; some difficulties

performing tasks; trouble with planning/organizing

• May still be able to drive, handle work/house/driving tasks

• Moderate • More troubles with everyday tasks, orientation; needs

assistance

• Severe • Unable to do everyday tasks; needs around the clock

assistance.

• More physical symptoms may arise

70

Staging


• Is it just normal memory loss?

• What’s the difference between Alzheimer’s and dementia?

• How do we make a diagnosis?

• Can’t you do some kind of brain scan?


• What kind of treatment can we do to stop the memory loss?

• What can we do to help with ‘BLANK’ symptoms?


71

Challenges in Dementia Management

• Challenges: • Establishing the diagnosis

• Presenting/Communicating the diagnosis

• Non-pharmacologic and pharmacologic

management of symptoms

• Post-diagnosis support/challenges for patient and

family

Challenges for Dementia Management

• Presenting the diagnosis • Helpful to build time into the patient’s appt to be

able to adequately assess, give diagnosis, answer

questions.

• Separate appointments if needed to ensure

adequate time to gather info and present

• Setting proper expectations

Management

• Current Medical Treatment

– Identify reversible causes

– Optimize Health: Blood Pressure, Blood Sugars, etc

– Nonpharmacological methods

– Treat any concurrent disorder that may be affecting cognition (sleep, depression)

– Acetylcholinesterase inhibitors (Donepezil, Galantamine, Rivastigmine) & Memantine

– Supportive care and planning

• New Treatments: gamma secretases, antibodies/immunologic agents, tau directed therapy

Management

• Cognitive Rehab

• Identifying events preceding agitation

• Environment

• Personal care

• Recreational therapy, including aromatherapy, music, pet, exercise training

• Support group early on

• Safety

Management

• Nutrition

• Exercise programs

• Physical therapy, occupational therapy programs

• Alcohol / Drug

• Surgery and hospital admission

• Changes in Environment

• Driving

• Optimal living situation

• Ensure accurate review of prior medication lists

• Caution with introducing new medications

• Behavior therapy • Environmental restructuring

• Management of polypharmacy

• Sleep hygiene education

• Stabilization and maintenance of consistent sleep-

wake schedules

• Stimulus control

Management of Behavioral Symptoms -

Sleep disturbances

Medications which Contribute to

Insomnia

• Diuretics

• Dopamine agonists

• Antidepressants

• Thyroid replacement

• HRT

• Stimulant Herbal

Supplements

• Some anti-psychotics

• Dementia Medications

• Steroids

• Decongestants

• Beta agonists

• Appetite suppressants

• ADHD medications

• http://sites.uci.edu/gwep/

79

http://sites.uci.edu/gwep/

Management of Dementia

• Become familiar with community resources

– Adult Day Care/Senior Centers

– Family support services, Support Groups (Church, Community, Alzheimer’s Association)

– Meals on Wheels, food services

– Transportation

– Financial and Legal

Management

• What to do for Follow up MD appointments, scheduled visits 3-6 months

– Ongoing education • Review safety issues

– Review Medication use and effectiveness

– Support for caregivers • Advanced care directives, financial management

• Discuss living situations, long term care discussions

Case

• 81 y/o M, came in w/ Dtr. Widowed, prev living on own, dtr w/ infrequent contact. Noted to no longer be cooking, unpaid bills past year, meds in disarray.

• Moved to ALF with med mgmt. Meds regular; pt still with STML symptoms

• No depression, sleep changes. Did okay w/ basic ADLs.

• Med Hx: HTN, Diabetes, MI in his 60s.

• Meds: amlodipine, metformin, aspirin, tylenol

• FamHx, SocHx, ROS NC

• Exam: no localizing symptoms

• Labs A1c 6.9

• Imaging: generalized atrophy

• MOCHA 20/30 -4 on memory, -1 visuosp, -1 clock, -1 serial subtractions, -3 orientation

• BEST Diagnosis?

• How do we manage?

BEST DIAGNOSIS?

Dementia Onset Cognitive Findings Other symptoms

Alzheimer's Gradual



Lewy Body Gradual



Vascular Stepwise



Frontotemporal

Gradual,

younger

patient





ALS association

85

Memory Complaints

Workup – Labs:




as LP if pertinent

Consider Neurology

Referral for

Unusual/Atypical Findings

e.g., Early onset, Other

Neurological

Concerns/Atypical

neurologic exam

Possible Reversible

Causes

Metabolic disturbance

Endocrine

Infectious

Alcohol/Drug/Pharm

Other Medical

Sleep

Depression/Anxiety

Other psychiatric

Normal Memory

Changes w/ Aging

Mild Cognitive

Impairment

Dementia / Major

Cognitive Disorder

Workup – H&P:

History to include

symptoms, function,



Workup – Imaging:


structural changes,


between AD and FTD

Follow up and

Treatment:

Reassurance



Follow up and

Treatment:







Follow up and

Treatment:




Non Pharmacologic



Personal Care


Support Group


Safety

Pharmacologic



Other Issues:

Caregiver Stress

Optimal Living

Environment


Driving and Safety

Workup and Treatment of Memory Loss 81 year old w/ memory

changes, decrease in

IADLs

No alcohol, labs/imaging

nonrevealing

MOCA 20/30 Dementia, Prob Alzheimer’s

Has HTN, DM, CAD but

stable

Participate in activities

Consider support group

Continue with supportive

care – ALF

Discuss driving

Trial with cholinesterase

inhibitor


• Alzheimer disease, reduced cerebral production of choline acetyl transferase

• For use in mild to moderate disease, severe disease – small improvement in cognition and ADLs

• Side effects: Cholinergic side effects • GI symptoms (nausea 5-19%, diarrhea 8-

15%,vomiting3-8% anorexia 3-7%, weight loss 3% 3%), usually transient

• Bradycardia, Dizziness 8%, Syncope 2%

• Sleep disturbances

• Frequency in urination, incontinence

Comparison of Cholinesterase Inhibitors

Medication Dosing Considerations

Donepezil

Start 5mg daily x 4

weeks, then increase to

10mg

23mg formulation

available

Easy to administer. Better side effect

profile.

High dose questionable increased efficacy

with more adverse events

Rivastigmine Start 1.5mg twice daily,

increase every 2 weeks

to max of 6mg twice

daily

Patch formulation available

PO formulation poorly tolerated

Galantamine Start 4mg twice daily,

increase every 4 weeks

to max of 12mg twice

daily

Less convenient no more effective

Memantine

• NMDA receptor antagonist “neuroprotective”

• Study involving moderate to severe Alzheimer’s disease (based on Standardized MMSE), had 1.2 points higher.

• May be beneficial if used in combination in advanced AD.

• Fewer side effect than the cholinergic agents – Dosing: Start with 5mg qday; increase weekly to 10bid; XL

formulations available: 7,14,28mg

Case

• 68 year old, without education. Memory changes, disorganization for past year. Also with hallucinations (seeing women in the home) and confusion (thinks only 1 child rather than 3)

• Other history for longstanding history of depression, not on meds

• Med Hx: hypothyroidism on synthroid

• SOC Hx, Fam Hx non contrib

• Meds: PCP had on seroquel, aricept.

• Exam: no parkinsonian features

• Labs

• Imaging

• Neuropsych testing – MOCA 21/30, -4 visuospatial, -1 on serial, -2 orientation, -2 memory

• BEST Diagnosis?

• How do we manage?

BEST DIAGNOSIS?


Alzheimer's Gradual



Lewy Body Gradual



Vascular Stepwise



Frontotemporal

Gradual,

younger

patient





ALS association

92

Memory Complaints

Workup – Labs:




as LP if pertinent

Consider Neurology

Referral for



Neurological

Concerns/Atypical

neurologic exam

Possible Reversible

Causes


Endocrine

Infectious

Alcohol/Drug/Pharm

Other Medical

Sleep

Depression/Anxiety

Other psychiatric

Normal Memory

Changes w/ Aging

Mild Cognitive

Impairment

Dementia / Major

Cognitive Disorder

Workup – H&P:

History to include

symptoms, function,



Workup – Imaging:


structural changes,


between AD and FTD

Follow up and

Treatment:

Reassurance



Follow up and

Treatment:







Follow up and

Treatment:




Non Pharmacologic



Personal Care


Support Group


Safety

Pharmacologic



Other Issues:

Caregiver Stress

Optimal Living

Environment


Driving and Safety


changes, disorganization

hallucinations, confusion

Labs nl, CT report pending.

Poss Lewy Body.

Long H/o Depression

MOCA 21/30

Behavioral Symptoms

• Sundowning

– Can affect up to 2/3rds of dementia patients

– Risk factors include poor light exposure and disturbed

sleep

– Causes functional impairment, can lead to placement

• Hallucinations – May be fleeting or unobtrusive

– Pharmacotherapy is NOT always necessary

Behavioral Symptoms - Mood

– Can produce symptoms and signs of cognitive impairment

– Patients with dementia may develop apathy, sleep

impairment and social withdrawal (can be due to the

cognitive deficits

– May be depressed in reaction to slipping mental capacity

or as a consequence of the dementia

– Lack of reliable tools to measure the relative contributions

of depression and dementia in individual patients

– Therapeutic trial with antidepressant medication may be

the only reasonable diagnostic strategy in difficult cases

Behavioral Symptoms - Sleep

disturbances

• Types of sleep disturbances • Difficulties falling or staying asleep

– Insomnia disorder

– Irregular sleep-wake rhythm disorder

• Abnormal movements/behaviors during sleep

– Restless legs syndrome

– Periodic limb movement disorder

– Rapid eye movement sleep behavior disorder

• Abnormal breathing patterns during sleep

– Obstructive Sleep Apnea

• Excessive daytime sleepiness

• Not all behaviors need to treated

• Try non-drug approach first

• Identify specific behavior which endanger

the pt or caregivers

Management of Behavioral Symptoms

Class Dose (mg) Side effects Considerations Used for anxiety?

SSRI’s

Sertraline

Paroxetine

Citalopram

Escitalopram

Fluoxetine

25-200

10-40

10-20

5-10

10-60

Bruising/Bleeding;

GI, Weight changes;

Anxiety/insomnia/sedation;

Low Na;

Falls/hypotension

Sexual dysfunction

Prozac: long half life

Activating

QT prolongation

Paxil: Some

anticholinergic activity

Yes for all except

fluoxetine

SNRI’s

Venlafaxine

Duloxetine

Desvenlafaxine

37.5-225

20-120

25-50

Same as SSRi’s

Hypertension

At higher doses NE

effect with Effexor

Liver disease

Renal insufficiency

YES

NDRI

Bupropion

150-450

Anxiety, insomnia, weight

loss, nausea, diarrhea,

agitation

Seizures;

Helpful in smoking

cessation and ADHD

NO

NE Blocker/5HT

Mirtazapine

7.5-45

Sedation, weight gain,

dizziness

More sedating at

lower dose

Not FDA approved,

but may be helpful

Selected Drugs Which can be Safely

Used in Geriatrics for Anxiety and

Depression

Drugs Dose (mg) PK Side effects Geriatric Considerations

Clonazepam Start with 0.25mg

and titrate up slowly

T1/2 up to 40 hrs

Peak Onset 1-4 h

Sedation, dizziness,

mental status changes

LONG acting BZD

Risk of falling, confusion

Lorazepam Start with 0.25mg


T1/2 10-20 hr

Peak Onset 1-1.5hr

Not effected by age

Sedation dizziness,

Mental status changes

Risk of falling, confusion

Alprazolam Start with 0.25mg


T1/2 6-20 hrs

Peak Onset 30 min-

1.5hr

Sedation, dizziness

mental status changes

Risk of falling confusion

Buspirone 5-60 Dosed bid or tid GI, Dizziness, Weight

changes, sexual

dysfunction, bleeding

Must be dosed on a schedule.

Similar to SSRI’s.

Takes 4-6 weeks for full effect

Medications Used for Anxiety

Management of Behavioral

Symptoms - Agitation/Anxiety • Pharmacologic Management

• Anti-seizure medications – Valproate: earlier reports suggested improved aggressive

behaviors; later studies showed not effective:

– Gabapentin, lamotrigine: unproven efficacy, mild side effect

• Methylphenidate: can help w/ apathy, but may precipitate agitation

• Dextromethorphan – Quinidine: used for pseudobulbar affect

– Limited evidence showing benefit for severe agitation.


Symptoms - Agitation/Anxiety

• Pharmacologic Management • Antipsychotics: Not approved for treatment of

behavioral disorders in patients with dementia.

• Benefits often outweigh risks in patients with

dementia when hallucinations and delusions

interfere with safety and well being

– Regular intervals of attempting to discontinue


Agitation/Anxiety • Antipsychotics – Side effects & Mortality

• Older low potency typical – sedation, anticholinergic (Mellaril/Thorazine)

• Older high potency – higher incidence of EPS (Haldol)

• Older/Typical Antipsychotics cause TD and EPS symptoms

• Precautions for QT prolongation

• Confusion

• Somnolence

• Falls/Orthostatic Hypotension

• Agranulocytosis (clozapine)

• Increased risk of stroke, myocardial infarction, death, unknown mechanism

» Highest for olanzapine and risperidone

» Lowest for quetiapine

» Must inform families of risk


Symptoms - Agitation/Anxiety Antipsychotic Considerations

Olanzapine

2.5mg-5mg

daily

Low incidence of EPS symptoms,

High sedation

High Orthostatic Hypotension. On the Beers list

Metabolic SE most likely

Risperidone

0.25-2mg daily

Low EPS, but higher with increasing dose

Low sedation

Low Orthostatic Hypotension

Quetiapine

12.5-100mg

daily

Low EPS

Moderate sedation

Some Orthostatic Hypotension

EPS: Dystonic rxn /pseudo PD / Akathisia


Sleep disturbancess

• Pharmacotherapy • No controlled trials; increased susceptibility to adverse

effects; Very little objective evidence for efficacy

• Often at request of a caregiver, when

nonpharmacological measures not fully explored

• Melatonin: 1-10mg

• Trazodone 25-150mg

• Use antidepressants/anticonvulsants/antipsychotics for

sedative properties if needed for other indications

CASE

• 85 year old w/ memory loss for 9 years. Lives with daughter, who has been helping more with ADLs/IADLs.

• 4-5 months, increasing paranoia, delusions, poor safety insight. Thinks man in the house.

• Med Hx: constipation

• Soc Hx: no alcohol, retired Police, in Asian country

• Fam Hx: non contributory

• Meds: Miralax

• Exam: Vitals stable, exam – notable for unsteady gait, apraxic with walker

• MMSE 12/30 -

• Labs –mild renal insufficiency

• Imaging – lacunar infarcts

• BEST Diagnosis?

• How do we manage this patient

104

BEST DIAGNOSIS?


Alzheimer's Gradual



Lewy Body Gradual



Vascular Stepwise



Frontotemporal

Gradual,

younger

patient





ALS association

106

Memory Complaints

Workup – Labs:




as LP if pertinent

Consider Neurology

Referral for



Neurological

Concerns/Atypical

neurologic exam

Possible Reversible

Causes


Endocrine

Infectious

Alcohol/Drug/Pharm

Other Medical

Sleep

Depression/Anxiety

Other psychiatric

Normal Memory

Changes w/ Aging

Mild Cognitive

Impairment

Dementia / Major

Cognitive Disorder

Workup – H&P:

History to include

symptoms, function,



Workup – Imaging:


structural changes,


between AD and FTD

Follow up and

Treatment:

Reassurance



Follow up and

Treatment:







Follow up and

Treatment:




Non Pharmacologic



Personal Care


Support Group


Safety

Pharmacologic



Other Issues:

Caregiver Stress

Optimal Living

Environment


Driving and Safety


loss, paranoia, delusions

Labs mild renal insuff, CT

w/ old lacunar infarcts

Likely Mixed

Renal Insufficiency

MMSE 12/30

• Review medication list at each visit

• Be aware of prior medication use and response

• Introduce one new drug at a time

• Start LOW go SLOW but DO GO

• Monitor for new delirium, confusion

• Make families aware of worsening and potential side effects

107

Useful tips: Managing Medications

For the clinician: 1st time visit(s) for

Dementia

• History and physical

• Screen/eval for

contributory factors

(med review, drugs,

sleep, mood disorder,

comorbidities)

• Workup (cognitive

tests, labs, imaging)

• Discuss diagnosis

• Consideration for

medications

• Provide resources,

address

social/environmental/

safety (e.g., driving)

issues

109

For the clinician: follow up visits for

Dementia • 3-6 months, sooner in

as needed – Such as if starting

medication

• History taking: review for cognitive, behavioral, physical, functional changes

• Changes in medications, medical conditions

• Follow up cognitive tests, 3-6 months

• Review status of pharmacotherapy

• Review for safety issues

• Provide resources if needed

110

Questions

111

steven tam, md tatyana gurvich, pharm.d., bcgp friday, october … · 2018. 11. 28. ·...

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