Marc E. Agronin, MD - Amazon S32018/...Marc E. Agronin, MD. Vice President, Behavioral Health and Clinical Research. Miami Jewish Health. Affiliate Associate Professor of Psychiatry

Solving Clinical Challenges inGeriatric Psychiatry

Marc E. Agronin, MDVice President, Behavioral Health and Clinical ResearchMiami Jewish HealthAffiliate Associate Professor of Psychiatry and NeurologyUniversity of Miami Miller School of MedicineMiami, Florida

Disclosure• The faculty have been informed of their responsibility to disclose to the

audience if they will be discussing off-label or investigational use(s) of drugs, products, and/or devices (any use not approved by the US Food and Drug Administration).

• Applicable CME staff have no relationships to disclose relating to the subject matter of this activity.

• This activity has been independently reviewed for balance.

Solving Clinical Challenges

All questions/cases in this presentation were submitted by clinicians within the Psych Congress database which includes conference

attendees, newsletters subscribers, and more.

Part I:Diagnostic Nosology, Accuracy, and Screening

How do you screen someone for cognitive impairment?

Which screening tools are best?How do we distinguish different forms of dementia?

How do we tell dementia and depression apart?

The Problem with Delayed Screening and Assessment• On average, individuals with cognitive impairment do not see a physician for

up to 2 years, do not receive a diagnosis for up to 1 year thereafter, 2 and up to 20% of individuals in the United States with Alzheimer’s disease never receive a diagnosis!

This is a MAJOR problem because:• Reversible causes of cognitive impairment become less reversible with time

(ie, the damage is done)• Delays in diagnosis = Delays in treatment, research, assistance, safeguards• Uncertain diagnosis = Misdirected, inappropriate, unsafe treatments• NO DIAGNOSIS of dementia is a possible outcome, and this can bring great

relief and an appropriate search for other issues and comorbidities

Balasa M, et al. Neurology. 2011;76(20):1720-1725. Boise L, et al. Gerontologist. 1999;39(4):457-464. Mok W, et al. Am J Alzheimers Dis Other Demen. 2004;19(3):161-165.

A Change in Terminology…

“Dementia” has been replaced by “major neurocognitive disorder” in DSM-5. It is defined by:

• Evidence of significant cognitive decline from a previous level of performance

• Interferes with independence in everyday activities, based on individual, informant, and/or test data

• It is not accounted for by delirium or another mental disorder in ≥ 1 of 6 cognitive domains

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington, VA: American Psychiatric Association; 2013.

6 Cognitive Domains in Neurocognitive Disorders

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington, VA: American Psychiatric Association; 2013.

Domain SymptomsComplex Attention Ability to attend to and process multiple stimuliExecutive Function Ability to plan, organize, and complete tasks/projects

Learning and Memory Acquiring, manipulating, and remembering items, facts, words and their meanings, events, people, procedures, skills, etc.

Perceptual-Motor Identification and manipulation of figures, maps, and items; motor tasks; recognition of faces and colors

Language Expressive and receptive language skillsSocial Cognition Socially appropriate behaviors and decision-making; empathy

2 Levels of Neurocognitive DisordersMILD neurocognitive disorder (eg, MCI/prodromal AD)

– Mild cognitive decline (preferably by neurocognitive or other clinical testing)

– Does not interfere with independence– Not due to delirium or another major mental disorder

MAJOR neurocognitive disorder (dementia due to AD or other cause)

– Major cognitive decline (preferably by neurocognitive or other clinical testing)

– Interferes with independence– Not due to delirium or another major mental disorder

MCI = mild cognitive impairment; AD = Alzheimer’s disease.American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington, VA: American Psychiatric Association; 2013.

The Variety of Neurocognitive Disorders• Alzheimer’s disease• Vascular dementia

– Cortical– Subcortical

• Frontotemporal– Behavioral variant – Semantic dementia– Progressive aphasia– Progressive supranuclear

palsy– Corticobasal degeneration

• Dementia with Lewy bodies

• Medical– Neoplasm– Trauma– Anoxia– Normal pressure

hydrocephalus– Toxins– Infections– Neurologic illness– Organ failure

Agronin ME. Alzheimer Disease and Other Dementias. Third Edition. New York, NY: Taylor; 2011.

Look at the Symptomatic Timeline

Time Point 1 Time Point 2 Time Point 3 Time Point 4

Cognition

TimePoint 1

TimePoint 2

TimePoint 3

TimePoint 4

TimePoint 5

TimePoint 6

TimePoint 7

TimePoint 8

Cognition

Progressive Decline over Time Rapid / Fluctuating Changes over Time


• The basic question in history-taking is: “What changed when?”• Examine the accrual of symptoms and changes in cognition over time

Look for Key Clues in the History• Medical and psychiatric issues may cause or exacerbate cognitive

changes– Examples: Brain trauma, diabetes, stroke, substance use, stress,

mood changes

• Medications can harm cognition– Common culprits: Opiates, steroids, sedative-hypnotics

• Social factors influence the presentation– Poor care and presentation due to lack of resources, neglect, or

abuse– Better care and presentation with highly involved and

knowledgeable caregivers


Be Cautious and Precise during the Exam• Get detailed descriptions from both patient and reliable informants• Don’t base a diagnosis on a single episode

Otherwise it is hard to know:• Is it a delusion or confusion?• Is it an illusion, confusion, or hallucination?• Is it depression, apathy, dementia, or more than one?


3 Key Caveats

• Do not assume that age = memory problems• Do not assume that memory problems = dementia• Do not assume that dementia = AD


Comprehensive Evaluation• Thorough mental status examination, with a brief cognitive screen• Physical and neurological examination

– See how the person walks and observe for abnormal movements• Basic labs

– Most important: Thyroid function, CBC, electrolytes, liver function, B12, folate

– More extensive labs only when suspected (eg, Lyme titer, CSF analysis)• Always get a brain scan

– To rule out major anatomical causes rather than rule in most dementias– CT if needed quickly after trauma or MRI not possible– MRI is better; will identify smaller infarcts and white matter changes– PET scan can assess function (FDG-PET) as well as the presence of beta-

amyloid plaques and now tau protein• Neuropsychological Testing

CBC =complete blood count; CSF = cerebrospinal fluid; CT = computed tomography; MRI = magnetic resonance imaging; FDG-PET = fluorodeoxyglucose-positron emission tomography. Agronin ME. Alzheimer Disease and Other Dementias. Third Edition. New York, NY: Taylor; 2011.

The Cognitive ScreenCognitive Screen CommentsMini-Mental State Examination (MMSE)

Has norms for age, ethnicity, educationLimited executive function assessmentTakes 5–8 minutes

Montreal Cognitive Assessment (MoCA)

Most accessible/multiple languagesMore difficult than MMSEGood for executive function assessmentTakes 8–10 minutes

St. Louis University Mental Status Examination (SLUMS)

Similar to MOCA Takes 8–10 minutes

Mini-Cog Excellent specificity (93%) / sensitivity (99%)Good executive function assessmentNot affected by language or education levelTakes 3–5 minutes

Folstein MF, et al. J Psychiatr Res. 1975;12(3):189-198. Nasreddine ZS, et al. J Am Geriatr Soc. 2005;53(4):695-699. Tariq SH, et al. Am J Geriatr Psychiatry. 2006;14(11):900-910. Borson S, et al. Int J Geriatr Psychiatry. 2000;15(11):1021-1027.

How to Distinguish among Different DementiasDementia Key FactorsAD Slow but steady decline. Look for key biomarkersVascular Dementia Brain scan must show either major strokes or bleeds or an evolving pattern of

smaller (eg, lacunar) infarcts or white matter changes that are temporallyrelated to cognitive impairment, slowing, and neurological signs

Dementia with Lewy Bodies

Cardinal symptoms: Fluctuating symptoms (often with delirium-like episodes), recurrent vivid hallucinations, later onset of parkinsonism, medication sensitivity (especially antipsychotics), REM sleep behavior disorder

Parkinson’s Disease Dementia

Parkinsonism predates cognitive changes by at least 12 months

Frontotemporal Dementia

Earlier onset. Behavioral variant with inappropriate / bizarre behaviors; language variants with progressive aphasia or loss of semantic meaning

Medical-Induced Appears linked to accident, illness, or exposure; onset at earlier age than expected; movement disorders other than parkinsonism

REM = rapid eye movement.

Biomarkers for Alzheimer’s Disease

Sperling RA, et al. Neuron. 2009;63(2):178-188. Morris JC, et al. Arch Neurol. 2009;66(12):1469-1475. Fagan AM, et al. Arch Neurol. 2007;64(3):343-349. de Leon MJ, et al. AJNR Am J Neuroradiol. 1983;4(3):568-571. Atiya M, et al. Alzheimer Dis Assoc Disord. 2003;17(3):177-195.

Biomarker Measurement Biomarker Changes Consistent with AD

Aβ42 accumulation Aβ42 levels decrease in CSFAβ42 can be seen in amyloid-based PET scan

TAUHP accumulation TAUHP levels increase in CSF

Synaptic dysfunction Hypometabolism seen on FDG-PET

Loss of brain volume Atrophy is seen on MRI and can be measured with MRI volumetrics

Other Conditions That Look Like Dementia But are NotCondition How to Tell the DifferenceDepression Neurovegetative factors may overlap (apathy, social withdrawal, poor

concentration) but depression has more precipitous onset and moreprominent changes in sleep, appetite, energy as well as sadness, poor self-image, and suicidality

Bipolar Disorder Look for a history of erratic behaviors predating any cognitive changesPseudodementia Look for changes in mood and motivation that predated cognitive changes,

along with prominent depression symptoms, as notedAdult ADHD Look for longstanding inattention, clumsiness, frequent accidentsDelirium Look for rapid onset in the setting of medical problems, and fluctuating

symptomsMedication Effects

Look for sudden onset of fluctuating symptoms along with selective changes in alertness and attention. Look for other side effects as well (eg, sedation, tremor, or other movement disorders; GI effects, etc.)

ADHD = attention-deficit/hyperactivity disorder; GI = gastrointestinal.

Pseudodementia (“fake” or “reversible” dementia)

• Pseudodementia involves cognitive deficits associated with depression that improve with treatment

• The depression tends to be severe and often involves motor retardation, hopelessness, helplessness, and psychosis

• The cognitive impairment is usually mild and involves problems with attention, recall, motor speed, and syntactic complexity. Symptoms may fluctuate with motivation, which can affect neuropsychiatric testing. Aphasia, apraxia, and long-term memory deficits are not seen

• In one study of 57 individuals hospitalized for depression, 43% with pseudodementia later developed an actual dementia after several years, vs 12% without

Alexopoulos GS, et al. Am J Psychiatry. 1993;150(11):1693-1699.

Manifestations of Depression in Dementia

MDD = major depressive disorder.Agronin ME. Alzheimer Disease and Other Dementias. Third Edition. New York, NY: Taylor; 2011.

MDD Symptom in Adults Expression in Dementia

Depressed or sad mood Irritability; agitation; anxiety; excessive somaticcomplaints

Loss of interest and energy Apathy; resistance to care; slow or absent progress in rehabilitation

Poor appetite Failure to thrive; refusing to eat

Psychomotor agitation or slowing Physical agitation or aggression; lying in bed all day

Suicidal ideation; worthlessness; hopelessness

Indirect life-threatening behaviors (eg, refusing food, medications, and necessary procedures)

Detection of Depression in Dementia:The Cornell Scale for Depression in Dementia (CSDD) CSDD was developed to detect depressive symptoms within the setting of dementia, using semi-structured interviews with both patient and informant:

– Mood-related signs: Anxiety, sadness, lack or reactivity to pleasant events, irritability

– Behavioral disturbance: Agitation, retardation, multiple physical complaints

– Physical signs: Appetite loss, weight loss, lack of energy– Cyclic functions: Diurnal variation of mood, difficulty falling asleep,

multiple awakenings, early morning awakenings– Ideational disturbance: Suicide, self-depreciation, pessimism, mood-

congruent delusions

Scoring: Rated from 0–2 (0 = absent, 1 = mild or intermittent, 2 = severe) based on the last week, with > 10 probable MDD and > 18 definite MDD

Alexopoulos GS, et al. Biol Psychiatry. 1988;23(3):271-284..

Apathy is Common in Dementia and Resembles Depression

• Apathy is a fundamental problem of motivation, manifested in behavior, cognition, and emotional expression

• It is not a mood disorder and does not imply an underlying depression

• Apathy is the most common behavioral problem in dementia

• Apathy is seen in 60% to 90% of patients with AD

• Apathy interferes with patient adherence and the degree of participation in treatment

Vilalta-Franch J, et al. J Alzheimers Dis. 2013;33(2):535-543.

I DON’T GIVE A DAMN ABOUT APATHY!

Groucho Marx

What is the incidence of bipolar disorder in late life?

Bipolar Disorder in Late Life• MANIA or hypomania is not common in late life, but when it occurs it is

more often due to dementia and medical conditions than to bipolar disorder

• Various epidemiological studies have found rates of bipolar disorder in late life (ranges: 0.1%–0.5%) to be less than half of that seen in corresponding young and middle-age adults (0.4%–1.17%)

• Older adults more commonly present as depressed or with mixed features

• Given the long lag between depressive and manic symptoms, major depression misdiagnosis is common

• Bipolar disorder in late life respond to the same treatments as with younger adults

Desai A, et al. Psychiatric Consultation in Long-Term Care: A Guide for Healthcare Professionals. Second Edition. Cambridge University Press; 2017. Beyer JL. In: Steffens DC, et al (Eds). The American Psychiatric Association Textbook of Geriatric Psychiatry. Fifth Edition. American Psychiatric Association Publishing; 2015.

Secondary Mania• Later onset• Less family history compared to bipolar disorder• Medical causes

– Frontal lobe lesions– Right hemisphere lesions– Fronto-temporal dementia– Neurological disorders (multiple sclerosis, Huntington’s disease)– Neurosyphilis– Medications (steroids, stimulants, antidepressants, dopamine

agonists)

Desai A, et al. Psychiatric Consultation in Long-Term Care: A Guide for Healthcare Professionals. Second Edition. Cambridge University Press; 2017.

Part II: Pharmacologic Treatments

What are the key pharmacologic guidelines in long-term care?

PIP, OBRA, Beers Criteria, and Antipsychotic Usage

Potentially Inappropriate Prescription (PIP)PIPs can occur when medications are given under the following circumstances:• No clear evidence-based indication• Higher dose or longer time than necessary• Combined with medication from same class• Combined with a drug with known drug-drug interactions• Given with high risk for drug-disease interaction• Given after incorrect diagnosis• Not adjusted for hepatic, renal, cardiac, or other changes• Withheld or given due to ageism or prejudice, or for punitive reasons• Continued despite lack of efficacy or ongoing side effects• Given without non-drug strategies

Desai A, et al. Psychiatric Consultation in Long-Term Care: A Guide for Healthcare Professionals. Second Edition. Cambridge University Press; 2017.

OBRA / CMS Guidelines / F329OBRA contained a series of Nursing Home Reform Amendments to improve care in nursing homes, including ways to reduce unnecessary use of psychotropic medications:

• Requirement to involve mental health providers to provide adequate assessment and documentation

• There is a focus on surveillance of antipsychotics and benzodiazepines• LTC institutions must work with pharmacies to ensure proper management • Surveyors will review this documentation and facilities can be cited for

noncompliance• F-tag 329 looks specifically at unnecessary drug use

OBRA = Omnibus Budget Reconciliation Act of 1987; CMS = US Centers for Medicare & Medicaid Services; LTC = long-term care.Scheinthal S. OBRA Guidelines. In: Agronin ME, et al (Eds). Principles and Practice of Geriatric Psychiatry. Second Edition. Philadelphia, PA: Lippincott, Williams & Wilkins; 2011:829-837.

How to Manage Psychotropics in Long-Term Care• Have a psychiatrist or psychiatric ARNP conduct assessment and

follow-up• Implement and document nonpharmacologic strategies • For each psychotropic medication prescribed, document the relevant

diagnosis and the rationale for using the medication• PRN antipsychotics not recommended except for brief tapers• When possible, attempt gradual dose reductions or document why it is

not recommended or possible (eg, chronic symptoms in schizophrenia and risk of relapse; previous relapse when taper attempted)

• Ideally, document conversations with patients and families with respect to consent and risks vs benefits

Unnecessary Drug Use According to F329Drug therapy (especially antipsychotic use) is considered “unnecessary” after determining that the facility’s use of the drug involves one of the following:

• Excessive dose • Excessive duration• Inadequate monitoring• Lack of indication• Adverse consequences

www.health.state.mn.us/divs/fpc/profinfo/guidsurv.pdf. Accessed July 30, 2018.

OBRA / CMS Guidelines

Name Max Rec. Daily DoseDiazepam 5 mgClonazepam 1.5 mgLorazepam 2 mg (1 mg / sleep)Alprazolam 0.75 mg (0.25 / sleep)Temazepam 7.5 mg (sleep)Zolpidem 5 mg (sleep)

Benzodiazepines Antipsychotics

Scheinthal S. OBRA Guidelines. In: Agronin ME, et al (Eds). Principles and Practice of Geriatric Psychiatry. Second Edition. Philadelphia, PA: Lippincott, Williams & Wilkins; 2011:829-837.

Name Max Rec. Daily DoseHaloperidol 4 mgRisperidone 2 mgOlanzapine 10 mgQuetiapine 200 mgClozapine 50 mgPerphenazine 8 mg

Acceptable Indications for Antipsychotics• Schizophrenia • Schizoaffective Disorder • Mood Disorder (eg, bipolar disorder, severe depression with psychosis) • Delusional Disorder • Psychosis in the absence of Dementia • Schizophreniform Disorder • Medical illness with psychotic symptoms (eg, delirium) • Mania (due to medical causes) • Tourette’s Disorder or Huntington’s Disease • Hiccups • Nausea and vomiting due to chemotherapy

Beers Criteria• The Beers Criteria for Potentially Inappropriate Medication Use in Older

Adults, also called the Beers List, were first developed in 1991 by geriatrician Mark Beers, MD to improve the care of older individuals by providing a list of potentially dangerous medications

• Since 2011, the American Geriatric Society have been revising and updating the list based on both consensus and evidence-based approaches

• Examples of problematic medications include:– Anticholinergics – Antihistamines (first generation: diphenhydramine)– Tricyclic antidepressants (eg, nortriptyline)– Antipsychotics– Benzodiazepines

American Geriatrics Society 2015 Beers Criteria Update Expert Panel. J Am Geriatr Soc. 2015;63(11):2227-2246. www.sigot.org/allegato_docs/1057_Beers-Criteria.pdf. Accessed August 21, 2018.

Reasons to Use Antipsychotics

= FDA Indication = NO FDA Indication

• Schizophrenia and other chronic psychotic disorders

• Bipolar disorder• Augmentation for Major Depression

• Delirium• Dementia with psychosis• Dementia with agitation

Atypical Antipsychotics: Mortality WarningFDA Black Box Warning Concerning the Potential Increased Mortality in Elderly Patients with Dementia-Related Psychosis Treated with Antipsychotic Agents:

• Affects elderly patients with dementia-related psychosis • Analyses of 17 placebo controlled trials revealed risk of death in drug-

treated patients between 1.6 and 1.7 × that seen in placebo-treated patients (4.5% vs 2.6%)

• Most deaths cardiovascular (eg, heart failure, sudden death) or infectious (pneumonia)

• Differences between individual antipsychotics not reported• No study showed a statistically significant difference in mortality, but

trend of increased mortality appeared in 15 / 17 studies

Pharmacologic Treatment Dilemmas• There is no universally recognized or FDA-designated indication for

agitation and psychosis in dementia (or Behavioral and Psychological Symptoms of Dementia [BPSD])

• All psychotropic medication use is thus off-label• Most studies are of short duration, use small samples, multiple

instruments, variable definitions, limited samples, are not always controlled, and have high placebo responses

• Clinical trials have not always consistently established significant efficacy of psychotropic medications for dementia-related behavioral disruption

Kindermann SS, et al. Drugs Aging. 2002;19(4):257-276. Ballard C, et al. Cochrane Database Syst Rev. 2006;(1):CD003476.

Prescribing Cognitive Enhancers in Dementia

What are the Main Goals of Treatment?

Treatmentimplemented

Time

Func

tion

Disease arrest

Slowed progression

Symptomatic benefit

No effect

2 Different Approaches to Treatment of Alzheimer’s Disease

• All therapies aimed at slowing down the build-up of beta-amyloid plaques and/or tau tangles in the brain. Examples in current clinical trials include:– Immunotherapy– Secretase inhibitors– Anti-aggregation– Neuroprotection

• Acetylcholinesterase inhibitors• NMDA (glutamate) - receptor

antagonist• There is NO significant evidence

that any other agents provide any benefit for AD or other forms of dementia

Disease Modification Symptomatic Improvement

NMDA = N-methyl-D-aspartate.

Dosing for AChEIs and Memantine

AChEI = acetylcholinesterase inhibitor.

Medication Starting Dose Dosing RangeDonepezil 5 mg/day for 4–6 weeks 5–15 mg/day

After 3 months, consider 23 mg dose

Rivastigmine 1.5 mg BID, increasingby 1.5 mg every 2 weeks

6–12 mg/day

Rivastigmine patch 4.6 mg/day for 4 weeks 9.5 mg/day; if worsening, consider 13.3 mg maximum dose

Galantamine 4 mg BID (8 mg once daily for XR) for 4 weeks

8–24 mg/day

Memantine (immediate release)

5 mg/day, increasing by 5 mg every week

10–20 mg/day

Memantine XR 7 mg/day, increasing by 7 mg every week

14–28 mg/day

Memantine/Donepezil Combination of donepezil (10 mg) and memantine XR (7 mg / 14 mg / 21 mg / 28 mg). Titrate from 10 mg / 7 mg each week to 10 mg / 28 mg

A Model of Cognitive Benefit

ADAS-cog = AD Assessment Scale cognitive subscale. Adapted from Raskind MA, et al. Neurology. 2000;54(12):2261-2268.

Galantamine over 12 mos.

Historical placebo groupPlacebo → galantamine at 6 mos.

Open-extensionDouble-blind Improvement

Deterioration0 3 6 9 12

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Combination Therapy Slows Long-Term Decline in Cognition

Atri A, et al. Alzheimer Dis Assoc Disord. 2008;22(3):209-221.

Years1 2 3 40

5

10

15

20

25

30

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No medicationChEI monotherapyMemantine combination therapy

Common Side Effects of Cognitive Enhancers

Birks J. Cochrane Database Syst Rev. 2006;(1):CD005593. Emre M, et al. J Alzheimers Dis. 2008;14(2):193-9. Homma A, et al. Dement Geriatr Cogn Disord. 2008;25(5):399-407.

AChEIs Memantine

Nausea/vomiting ConfusionDiarrhea Sedation

Loss of appetite ConstipationDizzinessSyncope

Leg crampsUlcers

Cardiac arrhythmias

To mitigate GI effects of AChEIs:• Always start with ½ (or less) of

therapeutic dose for 2–4 weeks• Consider giving with food• For minor symptoms, give time• For intolerable symptoms with

oral medications, consider using a different agent or giving a transdermal patch

• Rule out pre-existing or other causes of GI distress

Tips on Cognitive Enhancers• Existing cognitive enhancers are only FDA approved for AD (except

one also for Parkinson’s Disease Dementia) but they have been studied in other forms of dementia

• Keep expectations modest: The goal is symptomatic improvement, NOT a cure

• Monitor for the most important side effects • Educate patients and caregivers about side effects and realistic

expectations• The later you start the cognitive enhancer in the disease course, the

less benefit you may see – BUT there may still be benefit even in moderate to severe disease states

Part III: Side Effect Management

Metabolic Changes with Age

• Absorption unchanged since decreases in GI membrane transport offset by increased GI transit time

• Volume of distribution is less due to decreases in lean body mass and total body water

• Clearance rate decreases due to lower GFR and hepatic metabolism

• Half-life of drugs increases

• Receptor sensitivity is altered, making drug response less predictable

• Older individuals tend to be more sensitive to drug effects, requiring lower doses

• Side effects tend to be more likely and problematic, especially ones that are anticholinergic, antihistaminic, and sedating

Pharmacokinetics Pharmacodynamics

GFR = glomerular filtration rate.Kaiser RM, et al. Physiological and clinical considerations of geriatric patient care. In: Blazer DG, et al (Eds). The American Psychiatric Association Textbook of Geriatric Psychiatry. Third Edition. Arlington, VA: American Psychiatric Publishing; 2004.

The Effects of Aging on the Brain• General loss of neurons, especially in neuronal centers that regulate mood,

behavior, memory, and neurovegetative functions (eg, sleep, appetite)• Build-up of intracellular degradation products and extracellular amyloid and

other protein plaques, causing– Decreases in neurotransmitter synthesis and release– Decreased axonal transport – Decreased overall cerebral metabolic rate

• Cholinergic deficits are associated with cognitive impairment, agitation, and aggression

• Serotonergic deficits are associated with depression, agitation, aggression, and impulse dyscontrol

• Dopaminergic deficits may render individuals more sensitive to developing spontaneous and drug-induced movement disorders

Sultzer DL, et al. J Neuropsychiatry Clin Neurosci. 1995;7(4):476-484. Tekin S, et al. Ann Neurol. 2001;49(3):355-361. McLoughlin DM, et al. Am J Psychiatry. 1994;151(11):1701-1703.

Important Side Effects• Anticholinergic effects

– Dry mouth– Constipation– Urinary retention– Blurred vision– Tachycardia – Confusion / Delirium

• Antihistamine effects (sedation, confusion, unsteadiness)• Sedation• Falls (from sedation, dizziness, imbalance, weakness)• Elevated glucose or cholesterol levels• Extrapyramidal side effects (tremor, rigidity, slowed gait)

Managing Side Effects in Late Life• The old mantra: “Start Low, Go Slow … But Go” (and don’t stop abruptly)• Know baseline symptoms so you don’t confuse them with potential side

effects• Make only ONE change in medication at a time• Assess for baseline physical and mental risk factors, such as impaired gait

or balance, cognitive impairment, obesity, impaired vision, brittle diabetes• Look for potential duplicative therapy (eg, adding a sedating medication

when someone is already on a sleeping pill)• Look for underlying substance abuse, especially alcohol• Assess adherence to regimen (taking too much or inappropriate mixing

with over-the-counter or other drugs; forgetting to take)

Part IV: Nonpharmacologic Treatments

Optimizing the Brain Through Exercise and Diet

Exercise, Exercise, Exercise !

Carvalho A, et al. Clin Interv Aging. 2014;9:661-682. Colcombe SJ, et al. J Gerontol A Biol Sci Med Sci. 2003;58(2):176-180. Kramer AF, et al. J Appl Physiol. 2006;101(4):1237-1242. Colcombe SJ, et al. Proc Natl Acad Sci U S A. 2004;101(9):3316-3321.

Moderate physical exercise can: • Maintain or enhance cognition• Lower the risk of dementia• Improves blood flow to brain• Decrease loss of brain cells• Increase neural growth factors

Do what you ENJOY30–60 minutes 5 to 6 days / week

Does Brain Training Help?Study Design ResultsIMPACTImprovement in Memory with Plasticity-based Adaptive Cognitive Training

Brain Fitness Program5 days / week for 8 weeks vs educational DVDs, in 487 cognitively-intact participants≥ 65 years

USING COMPUTER

Treatment group scored significantly greater improvements in all cognitive domains and in positive perceptions of their cognition

ACTIVEThe Advanced Cognitive Training for Independent and Vital Elderly

Cognitive training in memory, reasoning, and processing speed vs no training in 2832 participants 65–94 years

NO COMPUTER

Treatment group did better in selected domains. Booster training helped. Results were less noticeable after 5 years

Smith GE, et al. J Am Geriatr Soc. 2009;57(4):594-603. Ball K, et al. JAMA. 2002;288(18):2271-2281. Willis SL, et al. JAMA. 2006;296(23):2805-2814.

Brain Fitness Recommendations• Do what you enjoy (so you keep on doing it)• Challenge your brain with something different

– Learn a new language– Learn to play a musical instrument– Study a new subject– Start a new hobby

• Stimulate and socialize at the same time (eg, walking and talking with a friend)

• Prep your brain with adequate sleep, nutrition, and hydration

Lampit A, et al. PLoS Med. 2014;11(11):e1001756.

The MIND Diet

Morris MC, et al. Alzheimers Dement. 2015;11(9):1007-1014.

•Moderate adherence to the MIND Diet (Mediterranean-DASH Intervention for Neurodegenerative Delay) has been associated with a reduced incidence of AD

•Eat from 10 brain-healthy food groups: Vegetables (especially green leafy ones), nuts, berries, beans, whole grains, fish, poultry, olive oil, and wine

•Avoid 5 brain-unhealthy groups: Red meats, butter and stick margarine, cheeses, pastries and sweets, and fried or fast food

Practical Take-Aways• Always base your understanding and management of cognitive

impairment on a comprehensive evaluation• Depression may mimic dementia, or be a key comorbid condition. Key

clues in the evaluation can help you tell the difference• Unnecessary use of antipsychotic and other psychotropics in late life can

usually be traced to inadequate work-up and inattentive or spotty follow-up. Regardless, it is critically important to avoid such use in LTC settings, based on several important guidelines

• Cognitive enhancing medications can help symptoms of AD to a modest degree, but are better than the many unproven and costly brain tonics that lack any evidence base

• Start low, go slow, but go when treating older patients with medications, and be aware of risky side effects

• Brain healthy strategies are relatively easy to follow and inexpensive

Marc E. Agronin, MD - Amazon S32018/...Marc E. Agronin, MD. Vice President, Behavioral Health and Clinical Research. Miami Jewish Health. Affiliate Associate Professor of Psychiatry

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