EXECUTIVE DYSFUNCTION/SLEEP IN THE ELDERLY
| EXECUTIVE DYSFUNCTION— Adam Rosenblatt, MD, Associate Professor, Department of Psychiatry, Johns
Hopkins University School of Medicine, and Senior Faculty, The Copper Ridge Institute, Baltimore, MD
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| Definition: brief—paradoxic combination of apathy and disinhibition; description—“frontal” pseudoanatomic
term; also in subcortical dementias (eg, Huntington’s disease, Parkinson’s disease, strokes) and diffuse brain injuries
and diseases (eg, Alzheimer’s disease [AD]); reflects dysfunction in circuits that connect subcortical areas with
frontal lobes; profound loss of insight; out of proportion to cognitive impairment
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| Frontal Behavioral Inventory: deficit—apathy, aspontaneity, indifference, inflexibility, concreteness, personal
neglect, disorganization, inattention, loss of insight, logopenia, verbal apraxia, and alien hand (action performed by
someone else’s hand); disinhibition—perseveration, irritability, jocularity, irresponsibility, inappropriateness, impulsivity,
restlessness, aggression, hyperorality, hypersexuality, utilization behavior, and incontinence; utilization
behavior—use objects in front of them in inappropriate manner (eg, use pencil sharpener to sharpen pencils without
permission); jocularity—patient finds everything funny, difficult to interview; not unusual for demented patients
to feel that someone else in house (eg, cannot find things, clothes don’t belong to them)
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| Pharmacotherapy: 3 ways; nonspecific—neuroleptic or anticonvulsant for agitation; neuroleptics detrimental in
non-AD dementias; symptom-oriented—selective serotonin reuptake inhibitor (SSRI) for obsessionality, neuroleptic
for psychotic symptoms; rational—amantadine or amphetamine for hypofrontality; neuroleptics risky (increased
mortality risk) in elderly patients with dementia-related psychoses; still used, but symptom-targeted for severe irritability
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| Acetylcholinesterase inhibitors: well tolerated; speaker gives to all AD patients, unless contraindicated; some efficacy
in other dementias, but not all; tacrine (Cognex) not used anymore; donepezil (Aricept), rivastigmine (Exelon),
and galantamine (Razadyne) shown to improve cognitive function, caregiver burden, and behavior; unclear
whether behavior direct or indirect result of improvement in confusion; long-term effects controversial, allows patient
to remain at home or at assisted living level of care longer; donepezil (Aricept)—improved Neuropsychiatric
Inventory (NPI) total score, agitation/aggression, anxiety, delusions, disinhibition, and irritability; rivastigmine
(Exelon)—similar results seen; improved aberrant motor behavior, irritability, nighttime behavior, hallucinations,
and apathy; galantamine—improved aberrant motor behavior, anxiety, disinhibitions, and hallucinations
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| Selective serotonin reuptake inhibitors: advantages of safety and tolerability; sertraline and citalopram safest
and easiest; used to target specific symptoms (eg, dysphoria, perseveration, apathy); benefit in nondepression-related
agitation
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| SSRI case: 82-yr-old married woman; mild dementia with insidious onset, gradual progression (diagnosis of AD);
convinced husband having affair; unable to recognize own clothes, claims they belong to “sloozy” (neologism); interprets
wrong numbers as calls from girlfriend; never seen girlfriend, claims he sneaks her in and out; husband 90
yr of age, blind; patient writes hostile messages to her on mirrors; marital relationship deteriorating; goes only few
minutes without bringing up subject; tried 3 different neuroleptics, with no benefit; taking donepezil; Mini-Mental
Status Exam (MMSE) increased 2 points, but obsessive jealousy persists; started on sertraline 25 mg, increased to
50 mg after 1 wk; stops writing messages on mirror and marked improvement in marital relationship; patient feels
husband unfaithful but does not argue about it; feels comfortable in marriage and rarely thinks about affair
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| Amphetamines: can increase concentration and focus attention (eg, attention-deficit/hyperactivity disorder); target
specific symptoms (eg, apathy, distractibility); could make irritability worse, but tend to focus attention; potential
for tolerance, withdrawal symptoms, and abuse; recommend starting with small test dose and gradual titration
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| Amphetamine case: 79-yr-old woman with moderately severe dementia; dressed in conservative suit, wears large
crucifix, attends church every day, sits silently, and says rosary repeatedly; refuses most food; observed emptying
food and drink into plants; lost weight; sudden bursts of odd behavior; mostly silent during interview; crosses
room, hugs and kisses interviewer, lies down on floor, and refuses to rise when interview concluded; diagnosed
with non-AD dementia; did not respond to neuroleptics (food paranoia) or antidepressants; treated with dextroamphetamine
5 mg/day, increased to 5 mg bid; started eating and communicating better; gained weight; no odd behaviors
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| Amantadine: regarded as last medication to use for agitation; precise mechanism unknown (believed related to
dopamine augmentation); success with frontal patients as executive syndrome described; retrospective Johns Hopkins
data revealed behavior much improved in 57% of patients, 76% discharged on amantadine; may need to taper
off amantadine and restart to gain results
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| Amantadine case: 63-yr-old man admitted to hospital with rapidly progressive dementia of recent origin; for long
periods, will sit quietly and interact congenially; believes he is at sea; at other times, becomes anxious, intrudes in
other patients’ rooms, tries to leave unit, has striking visual hallucinations, and engages in bizarre behavior;
dumped several gallons of water on floor, shouting that ship on fire; diagnosed with frontotemporal dementia; no
response to typical and atypical neuroleptics, SSRI, and divalproex; neuroleptic exacerbated symptoms; started on
amantadine 50 mg bid, advanced to 100 mg bid; behavior symptoms resolved within few days; participated in occupational
therapy; admitted, then escaped from nursing home; readmitted to hospital; amantadine increased to 100
mg tid; returned to nursing home and made satisfactory accommodation; 6 mo later, symptoms recurred; readmitted
to hospital and started on amantadine 200 mg bid with good results
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| Nonpharmacologic interventions: music therapy; walking, light exercise, massage, comprehensive psychosocial
programs, pet therapy, appropriate direction, bright light, reduced noise; cognitive remediation; care environment alterations
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| Nonintervention case: 45-yr-old man with early Huntington’s disease brought to clinic by brother for depression;
patient sits in front of television all day; eats and sleeps normally; attends to hygiene with reminders; brother took
him fishing, which he used to enjoy; initially objected, but enjoyed once outdoors; resumed seat in front of television
on return without acknowledgement of fishing trip; neat and not malodorous on exam; intermittent chorea in
all extremities; mild dysarthric speech; good mood, no change in self-attitude or vital sense, pessimism, or suicidality;
enjoys television and puzzled by family’s attempts to get him out of house; no delusions or hallucinations;
scores 24 of 30 on MMSE; apathy and constriction of activities common symptom of Huntington’s disease; patient
not depressed or suffering; brother told that patient will have more trouble initiating than sustaining behaviors;
brother adjusts expectations; on patient’s birthday, brother and patient watch football game on television
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| Reminders: behavioral problems in dementia most treatable aspect of disease; to choose the right tool, you have to
know what the job is; not every psychiatric disorder in Diagnostic and Statistical Manual of Mental Disorders
(DSM); not all unusual behaviors in dementia require pharmacologic (or any) treatment
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| SLEEP IN THE ELDERLY —Daniel F. Kripke, MD, Research Professor, Department of Psychiatry, University of
California, San Diego, School of Medicine
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| Key points: 5 to 7 hr sleep enough; risks of hypnotics outweigh benefits for elderly patients; cognitive-behavioral
therapy best for chronic insomnia; sleep apnea most common cause of excessive sleepiness; lowest mortality with
7 hr sleep, higher mortality with 8 hr sleep than with 5 to 7 hr sleep; do not need 8 hr sleep to survive; may need 8
hr sleep to avoid sleepiness
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| Two types of people >60 yr of age: those who awaken frequently during night and do not worry about it and
those who awaken frequently and worry about it; all people >60 yr of age awaken frequently at night
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| Multiple causes of sleep complaints: usually combined and complex cause; sleep apnea—24% of people 65 yr
of age have 5 apneic episodes per hour of sleep, 50% have 15 hypopneic episodes per hour of sleep; 45% have 5 periodic
limb jerks per hour of sleep; other causes—nocturia, aches and pains, habit disturbances, napping, depression,
sedative drugs, and early AD damage to suprachiasmatic nucleus (body clock; controls sleep)
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| Hypnotics: not recommended for chronic insomnia; produce daytime impairment (digit symbol substitution, reaction
time, and memory worse); impairment greater with hypnotics with half-life >4 hr (benzodiazapine agonist inhibits firing
of neurons); risks include increased automobile accidents, falls, memory loss, and confusion; meta-analysis of
drug company data show that for patients ≥60 yr of age, risk greater than benefit; 10 studies show increased mortality
with use; 25% increase in mortality associated with nightly use; zolpidem (Ambien)—rapidly absorbed; short half-
life; no accumulation in elderly; 5-mg dose recommended; no dosage adjustment necessary for renal disease, but reduced
dose for liver disease; binds selectively to some benzodiazepine receptors; less respiratory depression; less of
antianxiety or anticonvulsant drug; at higher dose, will bind to more benzodiazepine receptors; rapid onset (<30 min);
taken just before bedtime; prolongs sleep 20 to 40 min; causes early awakening; no daytime sedation in younger patients;
causes rebound insomnia and does not suppress slow-wave sleep; causes hallucination (4% of patients), somnambulistic
night eating, and confusion (one of these occurs in 1% of patients); zolpidem extended-release (Ambien
CR) will produce more of hangover that zolpidem (Ambien) and impairs daytime performance; pharmacokinetics of
zolpidem, triazolam, and zaleplon—level rises early in night and mostly gone in morning; possible early morning
awakening; little daytime sedation; pharmcokinetics of temazepam, lorazepam, and oxazepam—12-hr half-life; still
present in morning, thinking and performance impaired; gone by next bedtime; lorazepam and oxazepam—absorbed
slowly; taken before bedtime; pharmacokinetics of diazepam, flurazepam, and quazepam—half-life of several days
and accumulates with next dose; in elderly, will accumulate over several weeks, causing dementia and other impairments
(most common cause of dementia); zoleplon—no benefit for total sleep time, just helps patient to fall asleep;
eszopiclone (Lunesta)—twice half-life of zolpidem in young people, 3 times in elderly; little receptor specificity and
broader spectrum of action; causes significant hangover; impairs morning digit symbol substitution performance; approved
for long-term use with subjective data; severe adverse effects more common than with placebo; same active
ingredient as zopiclone (in Europe, associated with excessive auto accidents); increased incidence of viral infections,
hallucinations, and unpleasant taste; ramelteon (Rozerem)—approved for long-term use; melatonin agonist, circadian-clock
drug; complex metabolism with active metabolite (present more in blood than parent compound); sleep induced
7 to 16 min faster; in 3 of 4 trials, patients did not feel that they slept better than with placebo; some daytime
side effects; no objective daytime impairment; nonaddictive; does not help patient sleep; reproductive endocrinology
effects (eg, prolactin)
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| Other medications: trazodone—most commonly prescribed drug for sleep; unlabeled (off-label) use; increases
sleep slightly, not more than other drugs; no dependency; more adverse effects than benzodiazepine agonist; ≈50% of
patients with sleep disturbance depressed; use low doses; has rapid onset; little disturbance to sleep stages; causes hypotension
and dizziness; rarely causes priapism; melatonin—night hormone; in animals, makes gonads atrophy and
fur turn white; weak effect, if any; meta-analysis shows no effect; causes gonadal suppression in young men and
women; suspected risk for seizure, myocardial infarction, and stroke; purity and potency variable; animal data suggest
protection against cancer; weak effect in jet lag; weak effect in shift work; antipsychotics—“killer” drugs in elderly;
significant mortality in drug group vs placebo; use for sleep not justified
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| Cognitive-behavioral treatment: better evidence for efficacy than long-term use of sleeping pills; no adverse effects;
only 200 therapists trained in technique for sleep
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| Other sleep disturbances: sleep apnea—most common cause of sleepiness; obesity and snoring key symptoms; periodic
limb movement disorder insomnia (PLMDI)—limb movements can occur 100 times/night; bed partner complains;
patient reports hypersomnia or insomnia; associated with restless legs syndrome (RLS); RLS—squirmy feeling
in legs before sleep; all day movement with akathisia; onset in evening before bedtime; lifelong, and increases with age;
treatment of PLMDI and RLS—benzodiazepines or narcotics palliative; carbidopa and other dopamine agonists; ropinirole
latest; low iron may cause; iron supplementation for serum ferritin <50 ng/mL; shift work—always impairs
sleep; associated with depression, shortened life, and accidents; bright light effective; no long-term studies of treatment
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Educational Objectives
| The goal of this activity is to discuss executive dysfunction and sleep in the elderly. After hearing and assimilating
this program, the clinician will be better able to:
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 | 1. Identify the clinical features of executive dysfunction syndrome.
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| 2. Discuss the pharmacologic treatments and their applications for executive dysfunction syndrome.
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| 3. List the nonpharmacologic interventions for executive dysfunction syndrome.
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| 4. Understand the characteristics of sleep and causes for sleep disturbance in the elderly.
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| 5. Discuss the treatment for sleep disturbances in the elderly.
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Discussed on this Program
Amantadine HCl [Symmetrel]
Citalopram HBr [Celexa]
Dextroamphetamine sulfate [Dexedrine, Dexedrine Spansules, DextroStat]
Diazepam [Diastat, Diazepam Intensol, Valium]
Donepezil HCl [Aricept, Aricept ODT]
Flurazepam HCl [Dalmane]
Galantamine HBr [Reminyl, Razadyne]
Lorazepam [Ativan, Lorazepam Intensol]
Melatonin
Oxazepam [Serax]
Quazepam [Doral]
Ramelteon [Rozerem]
Ropinirole HCl [Requip]
Rivastigmine tartrate [Exelon]
Sertraline HCl [Zoloft]
Tacrine HCl (tetrahydroacridinamine; THA) [Cognex]
Temazepam [Restoril]
Trazodone HCl [Desyrel, Desyrel Dividose]
Triazolam [Halcion]
Zaleplon [Sonata]
Zolpidem tartrate [Ambien, Ambien CR]
Suggested Reading
Cosentino S et al: How does the brain support script comprehension? A study of executive processes and semantic
knowledge in dementia. Neuropsychology 20:307, 2006; Drayton S et al: Amantadine for executive dysfunction in
patients with dementia. Psychosomatics 45:205, 2004; Glass J et al: Sedative hypnotics in older people with insomnia:
meta-analysis of risks and benefits. BMJ 331:1169, 2005; Holmes C et al: The efficacy of donepezil in the
treatment of neuropsychiatric symptoms in Alzheimer disease. Neurology 63:214, 2004; Jenner C et al: Can cognitive
and behavioral disorders differentiate frontal variant-frontotemporal dementia from Alzheimer’s disease at early
stages?. Behav Neurol 17:89, 2006; Kripke D et al: Mortality associated with sleep duration and insomnia. Arch
Gen Psychiatry 59:131, 2002; Krystal A et al: Sustained efficacy of eszopiclone over 6 months of nightly treatment:
results of a randomized, double-blind, placebo-controlled study in adults with chronic insomnia. Sleep 26:793,
2003; Lyketos C et al: Forgotten frontal lobe syndrome or “executive dysfunction syndrome. Psychosomatics
45:247, 2004; Schnedier L et al: Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis
of randomized placebo-controlled trials. JAMA 294:1934, 2005; Sivertsen B et al: Cognitive behavioral therapy
vs zopiclone for treatment of chronic primary insomnia in older adults: a randomized controlled trial. JAMA
295:2851, 2006; Zanetti M et al: mild cognitive impairment sub-types and vascular dementia in community-dwelling
elderly people: a 3-year follow-up study. J Am Geriatr Soc 54:580, 2006.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclosure any significant
financial relationship with the manufacturer or provider of any commercial product or service discussed. Dr. Rosenblatt
receives grant/research support from Amarin Corporation and Forrest Laboratories, Inc. He is a consultant for
Nova Research Company and Pfizer, Inc. and has an honorarium from Pfizer, Inc. Dr. Kripke has no relevant financial
relationship with commercial interests to report.
Dr. Rosenblatt was recorded in Baltimore, MD, at the 12th Annual Treatment of Alzheimer’s and Related Disorders:
Defining the Standard of Care, sponsored by Johns Hopkins University School of Medicine, on March 25, 2006. Dr.
Kripke was recorded in San Diego, CA, at Advances in Psychopharmacology, sponsored by the University of California,
San Diego, School of Medicine, held April 6-8, 2006. The Audio-Digest Foundation thanks the speakers and the
sponsors for their cooperation in production of this program.
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