TOPICS IN GERIATRICS
From Johns Hopkins University School of Medicine’s Current Topics in Geriatrics
| CARING FOR A PATIENT WITH ALZHEIMER’S DISEASE — Thomas E. Finucane, MD, Professor of Medicine,
Johns Hopkins University School of Medicine, Baltimore, MD
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| Definition of dementia: acquired severe cognitive impairment; patients sometimes not delirious in mild-to-moderate
stages
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 | Global: amnesia plus ≥1 of following
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| Aphasia: language disturbance
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| Apraxia: inability to execute learned task
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| Agnosia: inability to recognize familiar object; not due to sensory impairment
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| Disorder of executive function: inability to recognize and solve problems effectively
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| Alzheimer’s-type dementia: distinguished by insidious onset and gradual progression
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| Physician’s role: to identify interventions helpful to patient and family; drug therapy seems obvious choice to physicians
as well as patients and family
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| Cholinesterase inhibitors: 2 conflicting findings from peer-reviewed literature of randomized controlled trials (RCTs);
first, drugs provide significant benefits to patients; second, patients and caregivers cannot distinguish drug from
placebo; what trials show—when group taking drug compared to group taking placebo, psychometric test scores
little better numerically but significantly higher statistically; however, based on direct or indirect measurements
of life of caregivers and patients, impossible to distinguish drug from placebo
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| Misleading terminology used to promote drugs
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| “Significant” benefits: implying drug produces greater benefits for patients than indicated by statistical use of term
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| “Stabilization” of disease: claim of significant delay in nursing home placement not supported by evidence in
trial; largest RCT found “no significant benefits in institutionalization or progression of disability, in behavioral
and psychological symptoms, carer psychopathology, formal care costs, unpaid caregiver time, adverse
events, or between 5 and 10 mg of donepezil”
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| “Catastrophic” reaction: physicians warned that stopping drugs in stable Alzheimer’s patient risks provoking catastrophic
reaction; however, ≥5 RCTs had washout periods in which donepezil stopped with no adverse events
reported
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| “Standard of care”: drug treatment said to be standard of care based on practice recommendation of American
Academy of Neurology; standard only that treatment “should be considered” (noted that benefit small)
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| Consequence: deceptive advertising plays role in channeling $1.6 billion annually from families and caregivers
of Alzheimer’s patients to drug companies, despite absence of significant benefit in institutionalization or progression
of disability
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| Nonindustry-sponsored systematic review of all RCTs of cholinesterase inhibitors found: recommendations for
use of cholinesterase inhibitors not evidence-based; benefits on rating scales minimal; methodologic quality of
available trials poor
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| Managing behavioral difficulties: eg, agitation and combativeness every evening at 5 to 6 pm (sundowning syndrome);
counsel caregivers—be understanding about difficulty of problem; pathophysiology of sundowning poorly understood;
available drug therapies unsatisfactory and endanger patient
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| Antipsychotic medications: caregiver may request atypical antipsychotics (risperidone [Risperdal] or olanzapine
[Zyprexa]); use would be off-label; drugs indicated for young people with schizophrenia and brains normal in
appearance; brain of elderly Alzheimer’s patient grossly abnormal in appearance, with different basis for behavioral
disturbance (low biologic plausibility that drug effective in these patients)
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| Evidence in medical literature: effectiveness—review found drugs “not particularly effective for management of
neuropsychiatric symptoms of dementia”; RCT found drugs no better than placebo; risk of parkinsonism—not
diminished by using high-dose atypical antipsychotics (Risperdal, 2 mg; Zyprexa, 10 mg) compared to typical
antipsychotics (haloperidol [Haldol]; thioridazine [Mellaril]); risk of death—Food and Drug Administration
(FDA) placed “black box” warning on atypical antipsychotics in April 2005; RCTs found increased rate of death
within 10 wk of starting therapy; subsequent report in New England Journal of Medicine found risk of death at
least as high with conventional antipsychotics (should not be substituted for atypical agents in response to FDA
warning)
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| Concluding comments on drug therapy: while quick and satisfying to watchers of direct-to-consumer advertising, remains
dangerous, expensive, and ineffective
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| Empathic strategies: require creativity; not panacea, but less toxic and less expensive than drugs; worth spending
time trying to identify trigger of behavior; eg, for difficult-to-manage patient disturbed by sight of nurse’s aide
(imagined to be sleeping with her husband), turning her wheel chair so no longer facing aide proved effective;
“never confront a patient” (eg, if patient says, “I have to go home now,” rather than saying, “you are at home,” say,
“maybe we’ll go home later, but let’s have dinner now”)
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| Managing caregivers: sexuality—eg, nursing home patient touching staff members; while manifestation of disease,
behavior inappropriate and must be limited to protect rights of staff (valuable resource); cleanliness—elderly patients
resist being made naked before people they do not recognize; daily bathing not essential; maintain cleanliness
at level acceptable cosmetically while protecting health; bigotry—patient mistreatment of staff members from
minority groups; managing problem involves education more than medication
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| Driving: elderly drivers may pose less risk than some others allowed to drive legally, eg, 16-yr-old boys; physicians
may be left balancing patient confidentiality with public safety; laws on physician reporting vary among states
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| Final remarks: estimated that by 2050, 1 in 4 Americans will have Alzheimer’s or be caregiver; burden placed on family;
government programs currently offer few benefits to patients with Alzheimer’s (considered social, not medical,
problem); cholinesterase inhibitors—speaker suggests Alzheimer’s represents final common pathway of many diseases
with different etiologies and treatments; may explain why small subset of patients respond to cholinesterase inhibitors;
studies to identify subset not initiated by drug companies; some patients may benefit from treatment with
antidepressants
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| VENOUS THROMBOEMBOLIC DISEASE —David B. Pearse, MD, Associate Professor of Medicine, Johns Hopkins
University School of Medicine, Baltimore, MD
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| Deep venous thrombosis (DVT): underlying disease; starts in calf; often self-limited; extends through thigh; only
≈33% of DVT symptomatic; extensive proximal DVT often asymptomatic; untreated proximal DVT leads to
≈20% short-term mortality from pulmonary embolism (PE); silent PE present in ≈50% of symptomatic DVT;
DVT present in ≤90% of symptomatic PE; pathogenic mechanisms—venous stasis; vessel wall damage; increased
coagulability
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| Risk factors: increasing age (DVT or PE diagnosed in 11% of men by 80 yr of age); recent surgery; major trauma;
previous DVT; pregnancy; oral contraception; risk factors in patients >65 yr of age include limited mobility, immobilization
in chair or bed, heart failure, chronic leg edema, and limb paresis or paralysis
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| Preventing DVT: PE causes estimated 10% of hospital deaths and 30% of deaths within 30 days of surgery; 80% of
deaths unexpected; prophylaxis reduces risk 60% to 80%; study in teaching hospital found 68% of deaths preventable
with appropriate prophylaxis; aging itself produces hypercoagulability; only ≈30% of elderly inpatients receive
correct prophylaxis; fatal DVT and PE occur even in patients receiving correct prophylaxis, eg, after
orthopedic surgery; ≈50% of DVT and PE in elderly occurred in hospital or within 3 mo of discharge
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| DVT prophylaxis: low-dose unfractionated heparin (LDUH); low molecular weight heparin (LMWH); mechanical devices
(benefits limited; to be used only when anticoagulants contraindicated); fondaparinux (new agent; synthetic
heparin analogue; no heparin-induced thrombocytopenia; safe and effective in elderly); medical illness—
accounts for majority of venous thromboembolic events (VTE) and 70% to 80% of fatal PE
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| Acute ischemic stroke: problem with highest risk in medical patients; 40% to 60% of patients have DVT by 2 wk,
20% to 30% proximal; usually in paralyzed leg (bilateral in 25%); 5% to 15% of deaths from PE; 90% of patients
did not receive adequate prophylaxis (aspirin and compression stockings do not work; heparin required); risk
factors—age ≥70 yr; stroke severity; leg involvement; cancer; atrial fibrillation; history of DVT
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| Moderate-risk conditions: congestive heart failure; respiratory failure; immobility with previous VTE, cancer, sepsis,
central nervous system (CNS) disease, or inflammatory bowel disease; prophylaxis—LDUH (5000 units
bid) or LMWH (enoxaparin, 20 mg/0.4 mL qd)
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| High risk conditions: ischemic stroke; acute myocardial infarction (MI); prophylaxis—LMWH (enoxaparin, 40
mg/0.4 mL qd) or LDUH (5000 units tid)
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| Diagnostic modalities: effects of advanced age—reduced ability to sense symptoms; increased D -dimer levels; history
of DVTs; more indeterminate ventilation perfusion (V/Q) studies; increased risk of renal failure from intravenous
(IV) contrast; less tolerance of small emboli (due to limited cardiopulmonary reserve); D -dimer test—
becomes less specific as function of age; only useful result is negative one; <5% of patients ≥80 yr of age have negative
result; high prevalence of elevated D -dimer levels render results unhelpful; B-mode compression
ultrasonography—visualizes noncompressible clot in proximal veins; accuracy not affected by patient age; useful
initial test in patient with symptoms in leg, eg, pain, swelling; sensitivity 50%; useful if abnormal, not useful if negative;
computed tomography (CT) and magnetic resonance imaging (MRI)—visualize venous system from abdomen
to calf; compression not required (useful in obesity, leg with cast); CT can be combined with spiral chest CT
study; safety advantage with MRI (avoids radiation and IV contrast of CT)
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| Recurrent DVT: after 3 mo of anticoagulation, relapse 30% within 8 yr; patients with secondary DVT (clearcut risk
factors) have smaller risk for recurrence, compared to patients with idiopathic DVT; 50% of recurrences in other
leg; recurrent VTE indication for lifelong anticoagulation; diagnosis—compression ultrasonography (US); document
site of initial clot to determine whether subsequent clot represents recurrence; in half of patients, US remains
abnormal 1 yr after original clot, making it difficult to sort out new from old in patients who present with recurrent
pain and swelling in leg; at conclusion of therapy, obtain new baseline US
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| Pulmonary embolism: geriatric presentation—less pain and more cardiovascular collapse than in young patients;
absence of symptoms less reliable in patients >65 yr of age; more patients cyanotic at presentation, indicating
greater morbidity and mortality of PE in elderly; V/Q study—traditional test of choice; 100% sensitive (ie, if
normal, no further work-up, regardless of pretest probability); no contrast dye or breath-hold; detects recurrent
PE; however, nonspecific (most abnormal results false positive); percentage of nonspecifically abnormal scans
increases as function of age
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| Spiral CT: replacing V/Q as initial study; advantages—rapid; additional diagnostic information; accuracy not age-
dependent; disadvantages—requires contrast dye and breath-hold; difficult to know whether PE new or old
(does not give total picture of perfusion pattern of lung); difficulty estimating loss of vascular surface area; promotes
overuse of thrombolytic therapy in stable patients when saddle embolus seen (base therapy on appearance
of patient, not clot); sensitivity—detects 94% of PE but only 20% of peripheral emboli; therapeutic decisions—
according to study, negative result in high-risk patient (≥1 unexplained signs and symptoms of PE) requires further
testing before withholding therapy; when diagnosis based on isolated subsegmental filling defect, 75% of results
false-positive
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| New-generation multidetector CT: ie, 4, 8, 16, or 32 detectors; previous spiral CT single-detector (1 lung section
per scanner rotation); shorter breath-hold reduces motion artifact; thinner slice enables 3-dimensional reconstruction;
may exceed sensitivity of angiography
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| Key points: DVT and PE common in geriatric patients; prophylaxis effective but underutilized; clinical presentation
changes with age; although approach to diagnosis not different in elderly, remember effects of age (reduced accuracy
of D -dimer and V/Q studies; increased complications of IV contrast; difficulty in detecting small distal emboli);
multidetector CT may solve problems with traditional CT; potential advantages of newer diagnostic methods
such as MRI (eg, avoiding risk of contrast-induced nephropathy)
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Educational Objectives
| The goal of this program is to educate the listener about caring for patients with Alzheimer’s disease and about
venous thromboembolic disease in geriatric patients. After hearing and assimilating this program, the clinician will be
better able to:
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| 1. Advise caregivers of patients with Alzheimer’s disease.
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| 2. Evaluate the role of cholinesterase inhibitors and antipsychotic medications in the management of patients
with Alzheimer’s disease.
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| 3. Employ empathic strategies in caring for patients with Alzheimer’s disease.
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| 4. Provide prophylaxis, diagnosis, and treatment of deep venous thrombosis in geriatric patients.
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| 5. Evaluate and manage pulmonary embolism in geriatric patients.
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Discussed on This Program
Enoxaparin sodium [Lovenox] Fondaparinux sodium [Arixtra]
Haloperidol [Haldol, Haldol Decanoate 50, Haldol Decanoate 100]
Olanzapine [Zyprexa, Zyprexa Intramuscular, Zyprexa Zydis]
Risperidone [Risperdal, Risperdal Consta, Risperdal M-TAB]
Thioridazine HCl [Mellaril]
Suggested Reading
Doody RS: Refining treatment guidelines in Alzheimer's disease.Geriatrics Suppl:14, 2005; Geerts WH et al: Prevention
of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.
Chest 126:338S, 2004; Jacobs LG: Prophylactic anticoagulation for venous thromboembolic disease in geriatric patients.
J Am Geriatr Soc 51:1472, 2003; Kaduszkiewicz H et al: Cholinesterase inhibitors for patients with Alzheimer's
disease: systematic review of randomised clinical trials. BMJ 331:321, 2005; Kearon C: Natural history of
venous thromboembolism. Circulation 107:I22, 2003; Righini M et al: Effect of age on the assessment of clinical
probability of pulmonary embolism by prediction rules. J Thromb Haemost 2:1206, 2004; Sink KM et al: Pharmacological
treatment of neuropsychiatric symptoms of dementia: a review of the evidence. JAMA 293:596, 2005; Tariot
PN et al: A randomized, double-blind, placebo-controlled study of the efficacy and safety of donepezil in patients
with Alzheimer's disease in the nursing home setting. J Am Geriatr Soc 49:1590, 2001; Timmons S et al: Pulmonary
embolism: differences in presentation between older and younger patients. Age Ageing 32:601, 2003; Wang PS et al:
Risk of death in elderly users of conventional vs. atypical antipsychotic medications. N Engl J Med 353:2335, 2005;
Weill-Engerer S et al: Risk factors for deep vein thrombosis in inpatients aged 65 and older: a case-control multicenter
study. J Am Geriatr Soc 52:1299, 2004; Wells PS et al: Diagnosis of pulmonary embolism: when is imaging
needed? Clin Chest Med 24:13, 2003; Zierler BK: Ultrasonography and diagnosis of venous thromboembolism. Circulation
109:I9, 2004.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial
relationship with the manufacturer or provider of any commercial product or service discussed. For this issue,
the faculty reported nothing to disclose.
Drs. Finucane and Pearse were recorded at Current Topics in Geriatrics, sponsored by Johns Hopkins University
School of Medicine, February 9-11, 2006, in Baltimore, MD. The Audio-Digest Foundation thanks the speakers and
the sponsor for their cooperation in the production of this program.
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