To CAREGIVERS — Live Webinar: Betwixt and Intermixed—Dementia With Lewy Bodies

Friends,

I wanted to pass along an exciting announcement about an upcoming webinar on dementia with Lewy bodies, by the Alzheimer’s Research Forum.  This is free to the public, so please pass the word!

Live Webinar: Betwixt and Intermixed—Dementia With Lewy Bodies

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By some estimates, some one to two million people in the U.S. alone are suffering from dementia with Lewy bodies (DLB), a disease that combines features of AD and of PD with additional symptoms that arise from their combined protein pathologies. All this adds up to a double whammy of a neurodegenerative disease, and researchers from both AD and PD proper are developing an active interest to understand it, diagnose it better and earlier, and find molecular or imaging biomarkers. Join DLB experts Ian McKeith, Brit Mollenhauer, James Galvin, James Leverenz, and Walter Schulz-Schaeffer for a discussion of the large and often overlooked overlap between Alzheimer and Parkinson diseases. Join us on Monday, 15 June 2009, noon to 1 p.m. EST for this Webinar on dementia with Lewy bodies.

Thanks,

Angela Taylor

LBDA

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Chickens Lay Eggs in Bright Light

There are 12+ inches of snow in the front yard with 2-4 more coming! Erie’s Mayor declared an emergency for the city. Can you tell I have very fond memories of deep snow and powerful snow storms from childhood?

Last night I continued to feel sleep deprived which didn’t help the brain synapses. My step-father’s sister lived on a farm. I thought my Aunt Lu told me that the chickens would lay eggs better with more light since it’s so dark in the winter, so I turned on all the lights in the house. Pam had stepped out for a few minutes. Pam returned shortly and reminded me that Aunt Lu had died when I was in high school. I had some trouble finding where the kitchen was too. Today is better after some good sleep! Thank the Lord………one day at a time.

Amy and Gerald Throop were gracious enough to send me a complementary copy of their book, “Living with Lewy’s.” I’ll be posting a review of it on the blog. I still need to post the reviews for two other books. Just need to get around to it.

Living With Lewy’s

Empowering Today’s Dementia Caregiver

A Revolutionary New Survival Guide For All Caregivers
Especially for Caregivers of Patients with Dementia With Lewy Bodies, Alzheimer’s and Other Dementias

Foreword by

Dr. Carol F. Lippa, M.D., Professor of Neurology,

Drexel University College of Medicine,

Chair, Medical advisory Committee of the

Lewy Body Dementia Association

Written By Family Caregivers, For Family Caregivers
by

Amy J. Throop and Gerald S. Throop

If You’re One Of America’s 52 Million Caregivers, This Book Is For You!
Living With Lewy’s Answers A Thousand Questions For Caregivers. This book is easy to understand and organized so you can find answers quickly, day or night. It’s the companion book that you will refer to time and time again. This Is A Must Have Book For All Caregivers!

This book contains vital information about Dementia With Lewy Bodies, Alzheimer’s and other dementias.

ALL Caregivers Will Benefit From Information About:

*Support systems *Your personal health *Simple-safe care methods *Sleep improvement for caregiver and patient *Stress relieving techniques *Safe bath time *Continence management *Reducing falls *Diet, exercise and more

America’s 9 million dementia caregivers will discover:

•Life saving information about medications. •Up to date information from leading dementia specialists. •How to better understand each specific type of dementia. •How to seek professional help or a second diagnosis. •Care methods to cope with specific disabilities. •How to manage dangerous behaviors and much more.

Complete Financial Information About:

*Low or no cost respite *Tax breaks for caregivers
*Medicare Parts A, B and D – Prescription Drug Coverage
*Social Security Disability Insurance *Sick leave *Asset protection *Early retirement and much, much more.

Here is Hope’s response to the great folks who commented to her.

Warmly……….David Thomas


Lewy Body Dementia — * Overview * Differential Diagnoses & Workup * Treatment & Medication * Follow-up

Since some web pages come and go, I would like to save this article in its entirety. It can be used for education and as a reference for Lewy Body Dementia in the future. I take no credit in writing any of the content in the article. I am posting it verbatim from eMedicine from WebMD.

Dementia With Lewy Bodies

Howard A Crystal, MD, Professor, Departments of Neurology and Pathology, State University of New York Downstate; Consulting Staff, Department of Neurology, University Hospital and Kings County Hospital Center      Updated: Dec 10, 2000       

Introduction

Background

Frederick Lewy first described Lewy bodies (LBs), cytoplasmic inclusions found in cells of the substantia nigra in patients with idiopathic Parkinson’s disease, in 1914. In the 1960s, several pathologists described patients with dementia who had LBs of the neocortex. However, such cases were presumed to be rare until the mid 1980s, when sensitive immunocytochemical methods to identify LBs were developed. Dementia with LBs (DLB) was then recognized as being far more common than previously thought. The relationship of DLB and Parkinson’s disease is an area of considerable controversy, particularly because dementia frequently occurs in Parkinson’s disease. Many investigators believe that a spectrum of LB disorders exists. The third report of the DLB Consortium headed by Ian McKeith discusses an arbitrary 1-year rule to distinguish DLB from Parkinson’s disease with dementia.1 If parkinsonism has been present for 12 months or longer before cognitive impairment is detected, the disorder is called Parkinson’s disease with dementia; otherwise, it is called DLB. The report recognizes that this rule may be difficult to apply in clinical practice. When dementia precedes motor signs, particularly with visual hallucinations and episodes of reduced responsiveness, the diagnosis of DLB should be considered. Clinical criteria for DLB were first proposed in 19962 and modified in the subsequent DLB Consortium reports3. Several clinicopathological studies have assessed the sensitivity and specificity of these clinical criteria.4, 5 These clinical features are discussed below. Postmortem examinations in both Parkinson’s disease and DLB patients demonstrate LBs in the substantia nigra and possibly in the locus ceruleus, dorsal raphe, substantia innominata, and dorsal motor nucleus of the vagus. LBs are found in the neocortex of many patients with idiopathic Parkinson’s disease and in all patients with DLB. DLB overlaps parkinsonian dementias.

Pathophysiology

Symptoms and signs of DLB probably result, in part, from disruption of bidirectional information flow from the striatum to the neocortex, especially the frontal lobe. The cause is multifactorial. Altered neuromodulator and/or neurotransmitter levels (eg, acetylcholine [ACh], dopamine) influence the function of many neuronal circuits. In DLB, nonpyramidal cells in layers V and VI of the neocortex may contain LBs. Their function in neocortical information processing and in relaying data to subcortical regions probably is impaired. The etiology of the fluctuations in cognitive function, which characterize DLB, is unknown.

Frequency

United States

Findings from autopsy studies suggest that DLB accounts for 10-20% of dementias. Up to 40% of patients with Alzheimer’s disease have concomitant LBs. These mixed cases are sometimes called the LB variant of Alzheimer’s disease (LBV-AD) and represent an overlap syndrome between DLB and Alzheimer’s disease. Signs and symptoms of LBV-AD also overlap between DLB and Alzheimer’s disease. Because the sensitivity and specificity of clinical diagnosis are poor, no good epidemiologic data on incidence or prevalence of DLB are available.

International

Autopsy studies in Europe and Japan indicate that the frequency of DLB is comparable with that reported in studies from the United States.

Mortality/Morbidity

  • Dementing illnesses (including DLB) shorten life expectancy.
  • With severe disease, patients may experience swallowing problems that can lead to impaired nutrition.
  • Patients are at risk for falls because of impaired mobility and balance.
  • Because of prolonged bed rest, patients are at risk for decubitus ulcers.
  • Dysphagia and immobility also can lead to pneumonia.

Race

DLB has been described in Asian, African, and European races. Data concerning the relative frequency of DLB in different races are not available.

Sex

Most studies suggest that DLB is slightly more common in men than in women.

Age

DLB is a disease of late middle age and old age.

Clinical

History

  • DLB is a progressive degenerative dementia.
  • The following clinical features that help distinguish DLB from Alzheimer’s disease:
    • Fluctuations in cognitive function with varying levels of alertness and attention: Clues to the presence of fluctuations include excessive daytime drowsiness (if nighttime sleep is adequate) or daytime sleep longer than 2 hours, staring into space for long periods, and episodes of disorganized speech.
    • Visual hallucinations
    • Parkinsonian motor features
  • Although extrapyramidal features may occur late in the course of Alzheimer’s disease, they appear relatively early in DLB.
  • Whereas patients with Alzheimer’s disease virtually always have anterograde memory loss as a prominent symptom and sign early in the course of the illness, anterograde memory loss may be less prominent in DLB. McKeith et al have suggested that patients with DLB do relatively better on tests of confrontation naming, short and medium recall, and recognition than Alzheimer’s disease patients, whereas Alzheimer’s disease patients do better on tests of verbal fluency, visual perception, and performance tasks.6
  • Executive function deficits and visuospatial impairment may be more prominent in persons with DLB than in those with Alzheimer’s disease (eg, Stroop, digit span backwards).
  • Other symptoms that may alert clinicians to the diagnosis of DLB (versus Alzheimer’s disease) include the following:
    • Nonvisual hallucinations
    • Delusions
    • Unexplained syncope
    • Rapid eye movement sleep disorder
    • Neuroleptic sensitivity

Physical

  • Patients usually have impaired cognition consistent with dementia.
  • An important observation during mental status testing is that the patient has periods of being alert, coherent, and oriented that alternate with periods of being confused and unresponsive to questions (although awake). This fluctuation is a relatively specific feature of DLB.
  • Retrieval from memory may be relatively worse than memory storage.
  • Patients may do relatively well with confrontation naming tests and poorly on tests of visuospatial skills (eg, drawing a clock, copying figures).
  • Patients may have some parkinsonian signs but usually not enough to meet the criteria for a diagnosis of Parkinson’s disease.
  • Mild gait impairment is relatively frequent and should not be ascribed to old age or osteoarthritis.
  • Resting tremor occurs less frequently than in Parkinson’s disease.
  • Myoclonus may occur before severe dementia.

Causes

  • The etiology of DLB is not known.
  • Rare cases of familial DLB have been reported.
  • Apolipoprotein E subtype 4 (ApoE4) genotype is overrepresented only when DLB occurs with concomitant Alzheimer’s disease.

Differential Diagnoses

Alzheimer Disease Lacunar Syndromes
Cortical Basal Ganglionic Degeneration Parkinson-Plus Syndromes
Frontal and Temporal Lobe Dementia Prion-Related Diseases
Hydrocephalus Progressive Supranuclear Palsy

Other Problems to Be Considered

Dementia in Parkinson’s disease Dementia in progressive supranuclear palsy

Workup

Laboratory Studies

  • Laboratory studies should include those usually ordered in a dementia evaluation, including tests of the following:
    • Chemistry panel
    • Complete blood cell count
    • Thyroid studies
    • Vitamin B-12 levels
    • Syphilis, Lyme disease, or HIV testing, when appropriate
  • No sensitive or specific blood, cerebrospinal fluid (CSF), or urine tests are currently available for DLB.

Imaging Studies

  • Because vascular dementia can cause symptoms and signs similar to those of dementia with Lewy bodies (DLB), brain MRI is indicated to distinguish DLB from vascular dementia.
  • Patients with vascular dementia often have white matter lesions on MRIs, whereas patients with DLB do not.
  • MRI is superior to CT scanning in identifying hippocampal atrophy.
  • Patients with DLB usually have less hippocampal atrophy than patients with Alzheimer’s disease (but more than control subjects). Whether this difference is clinically useful is under investigation, as is the diagnostic utility of functional imaging.
  • Single-photon emission CT scanning or positron emission tomography scanning may show decreased occipital lobe blood flow or metabolism in DLB but not in Alzheimer’s disease.
  • Reduced dopamine transporter activity in the basal ganglia is seen with positron emission tomography scanning or single-photon emission CT scanning.
  • PET imaging with Pittsburgh Compound B showed that amyloid deposition in the clinically diagnosed patients with DLB was similar to that in the patients with Alzheimer’s disease. However, amyloid binding was less in patients with dementia in Parkinson’s disease.
  • Until disease-modifying therapies that are specific to DLB or Alzheimer’s disease are developed, metabolic imaging studies to enhance accuracy of the diagnosis are rarely needed.

Other Tests

  • In certain circumstances, neuropsychological testing is helpful to differentiate DLB from Alzheimer’s disease and to establish a baseline for future comparison.
  • Patients with DLB may have changes on electroencephalography earlier than patients with Alzheimer’s disease, but whether this difference is diagnostically useful is not clear.
  • CSF examination is not required in routine cases.
    • Patients with Alzheimer’s disease have higher levels of tau protein in their CSF than patients with DLB.
    • Patients with both LBV-AD have intermediate values.
    • CSF levels of beta-amyloid are lower than normal in DLB, Alzheimer’s disease, and LBV-AD. However, CSF beta-amyloid levels in DLB, LBV-AD, and Alzheimer’s disease do not differ from each other.

Histologic Findings

The characteristic lesion is the LB, an eosinophilic (hematoxylin and eosin staining), round inclusion found in the cytoplasm of substantia nigra cells and in the nucleus basalis of Meynert, locus ceruleus, dorsal raphe, and the dorsal motor nucleus of cranial nerve X. LBs are found in nonpyramidal cells in layers V and VI of the cortices (especially limbic and transitional cortex). Other findings are minimal atrophy, occasional vacuolization in deep layers of the temporal cortex, and abnormal neurites in cells of CA2/3 of the hippocampus and various brainstem nuclei. The primary constituent of LBs is alpha-synuclein, a presynaptic protein, the function of which is unknown. Neurofilament proteins and ubiquitin are other important constituents of LBs. Numerous neurotransmitters, including ACh, are diminished in DLB. The decrease in ACh may be more severe than in Alzheimer’s disease.

Treatment

Medical Care

  • Double-blinded, placebo-controlled studies have demonstrated that rivastigmine may decrease psychiatric symptoms associated with dementia with Lewy bodies (DLB), particularly apathy, anxiety, hallucinations, and delusions. These studies also demonstrate that patients with DLB treated with cholinesterase inhibitors do better on neuropsychological tests than subjects treated with placebo. Open-label studies suggest that donepezil and galantamine also are effective.
  • For the treatment of agitation and hallucinations associated with DLB, acetylcholinesterase inhibitors should be tried first in most instances.
  • In a small minority of patients, motor features are worsened with cholinesterase inhibitors.
  • Levodopa/carbidopa may improve motor function in some patients with DLB; however, in many patients this combination has no effect and may exacerbate psychiatric symptoms or confusion.
  • Hallucinations and agitation are especially troublesome in DLB. When these symptoms are mild, no medical treatment may be necessary.
    • Acetylcholinesterase inhibitors should usually be tried first.
    • Most experts recommend atypical neuroleptics such as clozapine, quetiapine, or aripiprazole when cholinesterase inhibitors are ineffective.
    • Avoid standard neuroleptics such as haloperidol because of neuroleptic sensitivity.
  • Depression is frequent in DLB patients and may result from damage in the dorsal raphe and locus ceruleus and/or as a psychological response to impaired function. Selective serotonin reuptake inhibitors are the drugs of choice.
  • A few case reports have reported exacerbation of fluctuations with memantine.
  • Some experts try antiepileptic drugs to treat agitation and hallucinations, but clinical data supporting their use is lacking.

Consultations

Spouses, family members, and caregivers of patients with DLB frequently realize that the patient with DLB behaves differently than typical patients with Alzheimer’s disease. Primary caregivers (or neurologists not specializing in dementia) frequently are unable to adequately explain these differences. In such situations, referral to a dementia specialist can be helpful.

Diet

No dietary restrictions are indicated except for patients with severe disease who have swallowing impairment.

Activity

Physical therapy and exercise classes can be useful to maintain mobility. Additionally, advise families of potential problems faced by patients with DLB who drive.

Medication

As yet, no compelling data indicate that medications can decrease the rate of cognitive decline. Medication can be used to treat agitation and hallucinations, treat depression, and improve cognition and/or alertness. Regarding nonspecific partial glutamate antagonists, in the United States, memantine (Namemda) is approved for the treatment of moderate-to-severe Alzheimer’s disease (AD). It is not approved for the treatment of Parkinson’s disease (PD) or DLB. Although this class of drugs might be useful in DLB, as of October 2008, no results of double-blinded, placebo-controlled comparisons of the efficacy of memantine and placebo in the treatment of DLB have been published. A few case reports have reported that memantine may exacerbate fluctuations. Melatonin may be administered at 3 mg hs. For further discussion of possible treatment of motor features, see Parkinson Disease.

Centrally acting acetylcholinesterase inhibitors

Ach concentrations are decreased in the brains of patients with DLB. Patients with DLB are more likely than patients with AD to improve with cholinesterase inhibitor therapy. Fluctuations in cognition may decrease, alertness may increase, and memory may improve.

Donepezil (Aricept)

Noncompetitively inhibits centrally active acetylcholinesterase, which may increase concentrations of ACh available for synaptic transmission in CNS.

Adult

5 mg PO qhs (with snack) for 6 wk; if tolerated, can be increased to 10 mg qhs

Pediatric

Not established

Increases effects of succinylcholine, cholinesterase inhibitors, or cholinergic agonists; may counteract effects of anticholinergics used for bladder control (anticholinergics should not be used in DLB)
Documented hypersensitivity; theoretic concerns about worsening COPD and peptic ulcer disease because of increased cholinergic tone not clinically observed; case reports, but not systematic studies, describe worsening of motor features of PD, but most studies indicate no exacerbation of PD motor signs; bradycardia may be exacerbated in patients with sick sinus syndrome, but clinical data are lacking
Pregnancy

D – Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in seizures, asthma, sick sinus syndrome, or other supraventricular conduction abnormalities

Rivastigmine (Exelon)

Competitive and reversible inhibitor of acetylcholinesterase. Although mechanism of action unknown, may reversibly inhibit cholinesterase, which may, in turn, increase concentrations of ACh available for synaptic transmission in CNS and enhance cholinergic function. Effect may lessen as disease process advances and fewer cholinergic neurons remain functionally intact. No evidence indicates that acetylcholinesterase inhibitors alter the course of underlying dementia.

Adult

1.5 mg PO bid; increase by 1.5 mg q2wk as tolerated; take with food; therapeutic dose range usually 3-6 mg PO bid

Pediatric

Not established

May reduce effects of anticholinergics (anticholinergics should not be used in DLB); increases effects of cholinergic agonists and neuromuscular blockers; risk of bradycardia increases when administered concurrently with beta-blockers without ISA, calcium channel blockers (ie, diltiazem, verapamil), or digoxin
Documented hypersensitivity
Pregnancy

D – Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

May cause significant nausea, vomiting, anorexia, and weight loss (occurs frequently in women and during titration phase); if significant adverse effects occur, patient should discontinue treatment for several doses, then restart at same or next lower dose; if treatment stopped for several days, initiate treatment at lowest daily dose; caution in history of peptic ulcer disease, concurrent NSAID use, sick sinus syndrome, urinary obstruction, pulmonary conditions (eg, COPD, asthma), and bradycardia or supraventricular conduction conditions; theoretical concerns about worsening COPD and peptic ulcer disease because of increase in cholinergic tone not observed in clinical use; case reports, but not systematic studies, have described worsening of motor features of PD, but most studies indicate no exacerbation of PD motor signs; bradycardia may be exacerbated in sick sinus syndrome, but clinical data are lacking

Galantamine (Razadyne [previously called Reminyl])

Competitive and reversible inhibitor of acetylcholinesterase. Although mechanism of action unknown, may reversibly inhibit cholinesterase, which may, in turn, increase concentrations of ACh available for synaptic transmission in CNS and enhance cholinergic function. Effect may lessen as disease process advances and fewer cholinergic neurons remain functionally intact. No evidence indicates that acetylcholinesterase inhibitors alter the course of underlying dementia. Available in ER daily dosing and in IR form.

Adult

8 mg PO qd for 4 wk; increase by 8 mg q4wk, not to exceed 24 mg/d

Pediatric

Not established

Coadministration with other cholinesterase inhibitors (eg, succinylcholine) may increase toxicity; CYP2D6 or CYP3A4 inhibitors (eg, cimetidine, ketoconazole, ritonavir, paroxetine, erythromycin) may decrease elimination and increase serum levels; may counteract effects of anticholinergics used for bladder control (anticholinergics should not be used in DLB)
Documented hypersensitivity; severe renal dysfunction (ie, <10 mL/min CrCl)
Pregnancy

D – Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Decrease dose in moderate renal insufficiency or moderate-to-severe hepatic impairment; caution in asthma; may cause bradycardia or AV block; syncope may occur with doses >24 mg/d; caution in sick sinus syndrome or other supraventricular conduction; theoretical concerns about worsening COPD and peptic ulcer disease because of increase in cholinergic tone not observed in clinical use; case reports, but not systematic studies, have described worsening of motor features of PD, but most studies indicate no exacerbation of PD motor signs; bradycardia may be exacerbated in sick sinus syndrome, but clinical data are lacking

Rivastigmine transdermal patch (Exelon patch)

Competitive and reversible acetylcholinesterase inhibitor. While mechanism of action unknown, may reversibly inhibit cholinesterase, which may, in turn, increase concentrations of acetylcholine available for synaptic transmission in CNS and thereby enhance cholinergic function. Effect may lessen as disease process advances and fewer cholinergic neurons remain functionally intact. Available as 5-cm2 patch containing 9 mg (releases 4.6 mg/24 h) and 10-cm2 patch containing 18 mg (releases 9.5 mg/24 h). Indicated for dementia of Alzheimer disease and for dementia associated with Parkinson disease.

Adult

Apply patch to upper or lower back, upper arm, or chest Initiating patch therapy (not switching from oral therapy): 4.6 mg/24 h patch (5 cm2) applied qd initially; if well tolerated and after minimum of 4 wk, increase to 9.5 mg/24 h patch (10 cm2) applied qd Switching from oral administration to patch therapy: Apply first patch on day following last oral dose Total daily oral dose <6 mg/d: Switch to 4.6 mg/24 h patch Total daily oral dose 6-12 mg/d: Switch to 9.5 mg/24 h patch

Pediatric

Not indicated

May reduce effects of anticholinergics; increases effects of cholinergic agonists and neuromuscular blockers; risk of bradycardia increases when administered concurrently with beta-blockers without ISA, the calcium channel blockers diltiazem or verapamil, and digoxin
Documented hypersensitivity
Pregnancy

B – Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Apply patch to clean, dry, and hairless area of back, upper arm, or chest; area where patch is applied must be free of powder, oil, moisturizer, lotion, or other substances that would keep patch from adhering properly to skin; also, apply to areas free of cuts, rashes, or other irritation; may cause significant nausea, vomiting, anorexia, and weight loss if taken in doses higher than recommended; if significant adverse effects occur, patient should discontinue treatment for several doses, then restart at lowest dose; extrapyramidal symptoms may occur or be exacerbated (especially tremor); caution in history of peptic ulcer disease, sick sinus syndrome, urinary obstruction, pulmonary conditions (eg, COPD, asthma), and bradycardia or supraventricular conduction conditions

Atypical neuroleptics

Patients with DLB frequently have hallucinations that can cause them to engage in unsafe behavior. Thus, they require treatment. Standard neuroleptics exacerbate parkinsonian motor features and, therefore, are contraindicated.

Clozapine (Clozaril)

Associated with risk of agranulocytosis when used at doses required for treatment of schizophrenia with symptoms refractory to standard neuroleptics; in the United States, weekly dosing and weekly CBC counts required to dispense; discontinuing therapy at first sign of leukopenia decreases but does not eliminate risk of agranulocytosis; whether agranulocytosis is associated with low doses in treating elderly patients and those with dementia not clear.

Adult

25 mg tab, half the tab PO qd; may be increased to half the tab bid after 1-2 wk; dosage can be gradually increased further

Pediatric

Not established

Epinephrine and phenytoin may decrease effects; TCAs, neuroleptics, CNS depressants, guanabenz, and anticholinergics may increase effects
Documented hypersensitivity, WBC count <3500 cells/µL before or during therapy
Pregnancy

D – Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

May cause serious agranulocytosis; may worsen confusion and EPS; may increase lethargy and cause tachycardia, dizziness, and increased sweating; do not stop abruptly; perform WBC testing q2wk for duration of therapy

Quetiapine (Seroquel)

Atypical neuroleptic that may act by antagonizing dopamine and serotonin effects. Also used to treat insomnia.

Adult

Hallucinations: 25 mg PO bid; can be increased very gradually Insomnia: 12.5 mg PO hs

Pediatric

Not established

May antagonize levodopa and dopamine agonists; phenytoin, thioridazine, and other liver enzyme inducers may reduce levels; CYP450 3A inhibitors (eg, ketoconazole, fluconazole, erythromycin) increase serum concentrations
Documented hypersensitivity
Pregnancy

C – Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May induce orthostatic hypotension associated with dizziness, tachycardia, and syncope; neuroleptic malignant syndrome and tardive dyskinesia have been associated with treatment; hyperglycemia may occur and, in some cases, be extreme, resulting in ketoacidosis, hyperosmolar coma, or death; caution in hepatic impairment (decrease dose)

Aripiprazole (Abilify)

Improves positive and negative schizophrenic symptoms. Mechanism of action unknown, but is hypothesized to work differently than other antipsychotics. Thought to be partial dopamine (D2) and serotonin (5HT1A) agonist and to antagonize serotonin (5HT2A). Additionally, no QTc interval prolongation noted in clinical trials. Available as tab, orally disintegrating tab, or oral solution.

Adult

10-15 mg PO qd; if needed, may increase dose gradually q2wk, not to exceed 30 mg/d

Pediatric

Not established

CYP450 3A4 and 2D6 isoenzyme substrate, thus, inhibitors (ie, ketoconazole, quinidine, fluoxetine, paroxetine) or inducers (ie, carbamazepine) may increase or decrease serum levels, respectively
Documented hypersensitivity
Pregnancy

C – Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Common adverse effects include headache, anxiety, somnolence, or insomnia; rare reports of tardive dyskinesia and neuroleptic malignant syndrome; may cause orthostatic hypotension, seizure, dysphagia, or suicidal ideation; hyperglycemia may occur and, in some cases, be extreme, resulting in ketoacidosis, hyperosmolar coma, or death

Antidepressants

Depression is frequent in DLB. Antidepressants with little or no anticholinergic activity are desirable.

Venlafaxine (Effexor)

May treat depression by inhibiting neuronal serotonin and norepinephrine reuptake; in addition, causes beta-receptor down-regulation.

Adult

IR: 75 mg/d PO divided bid/tid with food; increase in 75-mg/d increments q4d to 225-375 mg/d ER: 75 mg/d PO with food; increase in 75-mg/d increments q4d to 225 mg/d

Pediatric

Not established

Cimetidine, MAOIs, sertraline, fluoxetine, class IC antiarrhythmics, TCAs, and phenothiazine may increase effects
Documented hypersensitivity; MAOIs within 14 d
Pregnancy

C – Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Patients may experience hypertension; fatal reaction may occur if taken concurrently with an MAOI; caution in patients with cardiovascular disorders

Paroxetine (Paxil)

Selectively inhibits presynaptic serotonin reuptake with minimal or no effect in reuptake of norepinephrine or dopamine.

Adult

10 mg/d PO initially; increase in 10-mg/d increments prn; dose changes should occur at intervals of at least 1 wk; usual dose range is 10-60 mg/d; not to exceed 60 mg/d

Pediatric

Not established

Phenobarbital and phenytoin decrease effects; alcohol, cimetidine, sertraline, phenothiazines, and warfarin increase toxicity Increases toxicity of diazepam and trazodone by decreasing their clearance; increases toxicity of highly protein-bound drugs
Documented hypersensitivity; MAOIs within 14 d
Pregnancy

C – Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution with history of seizures, mania, renal disease, cardiac disease, or hepatic impairment; discontinue MAOIs at least 14 d before initiating therapy

Sertraline (Zoloft)

Selectively inhibits presynaptic serotonin reuptake.

Adult

50 mg tab, half the tab PO qd; gradually increase dose, not to exceed 200 mg (however, in most patients with DLB, not to exceed 100 mg)

Pediatric

Not established

Increases toxicity of MAOIs, diazepam, tolbutamide, and warfarin
Documented hypersensitivity, concurrent MAOIs
Pregnancy

C – Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May increase confusion and agitation; may increase sleepiness or conversely cause insomnia; may be associated with weight gain or weight loss; discontinue MAOIs at least 14 d before initiating therapy

Fluoxetine (Prozac)

Selectively inhibits presynaptic serotonin reuptake with minimal or no effect in the reuptake of norepinephrine or dopamine. May cause more gastrointestinal adverse effects than other SSRIs now currently available, which is the reason it is not recommended as a first choice. May be given as a liquid and a capsule. May give as 1 dose or divided doses. Presence of food does not appreciably alter levels of the medication. May take up to 4-6 weeks to achieve steady state levels of the medication as it has longest half-life (72 h). Long half-life is both an advantage and a drawback. If it works well, an occasional missed dose is not a problem; if problems occur, eliminating all active metabolites takes a long time. The choice depends on adverse effects and drug interactions. Adverse effects of SSRIs seem to be quite idiosyncratic; thus, relatively few reasons exist to prefer one over another at this point if dosing is started at a conservative level and advanced as tolerated.

Adult

20 mg/d PO qam; increase after several wk by 20 mg/d; not to exceed 80 mg/d

Pediatric

<18 years: Not established

Inhibits CYP450 isoenzymes 2C9, 2C19, 2D6, and 3A4; increases toxicity of diazepam and trazodone by decreasing clearance; also increases toxicity of MAO inhibitors, and highly protein bound drugs; serotonin syndrome (ie, myoclonus, rigidity, confusion, nausea, hyperthermia, autonomic instability, coma, eventual death) occurs with simultaneous use of other serotonergic agents (eg, anorectic agents, tramadol, buspirone, trazodone, clomipramine, nefazodone, tryptophan), discontinue other serotonergic agents at least 2 wk prior to SSRIs
Documented hypersensitivity; concurrently taking MAO inhibitors or took them in the last 2 wk; coadministration with thioridazine
Pregnancy

C – Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Known or suspected history of mania or hypomania; caution in hepatic impairment and history of seizures; MAO inhibitors should be discontinued at least 14 d before initiating fluoxetine therapy

Benzodiazepines

By binding to specific receptor-sites, these agents appear to potentiate the effects of GABA and facilitate inhibitory GABA neurotransmission and other inhibitory transmitters.

Clonazepam (Klonopin)

Long-acting benzodiazepine that increases presynaptic GABA inhibition and reduces monosynaptic and polysynaptic reflexes. Suppresses muscle contractions by facilitating inhibitory GABA neurotransmission and other inhibitory transmitters. Has multiple indications, including suppression of myoclonic, akinetic, or petit mal seizure activity and focal or generalized dystonias (eg, tardive dystonia). Reaches peak plasma concentration at 2-4 h after oral or rectal administration. In patients who are dependent, used in a manner similar to phenobarbital to smoothly wean patients from short-acting benzodiazepines. General principle is that sedatives with longer half-lives have less severe withdrawal symptoms. Various schemes are used to individualize dose to the patient. If symptoms are severe enough to require inpatient treatment, intravenous lorazepam or diazepam is used.

Adult

0.25 mg PO hs

Pediatric

Not established

Phenytoin and barbiturates may reduce effects; coadministration of CNS depressants increases toxicity
Documented hypersensitivity; severe liver disease and acute narrow-angle glaucoma
Pregnancy

D – Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in chronic respiratory disease or impaired renal function; withdrawal symptoms can result from abrupt discontinuation

Dopamine precursors

Patients with DLB have impaired dopaminergic tone due to disease in the substantia nigra and possibly other dopaminergic nuclei. Efficacy of the treatment of motor features in DLB depends on where the patient is on the PD-DLB spectrum. Whether or not levodopa influences cognition positively or negatively remains controversial, and its effect on cognition is probably modest.

Levodopa and carbidopa (Sinemet)

Large neutral amino acid absorbed in proximal small intestine by saturable carrier-mediated transport system; absorption decreased by meals that include other large neutral amino acids (but only patients with meaningful motor fluctuations need consider low-protein or protein-redistributed diet); half-life approximately 2 h. Provide at least 70-100 mg/d carbidopa; if more is required, substitute 25/100 tab for each 10/100 tab; when more levodopa is required, substitute 25/250 tab for 25/100 or 10/100 tab; CR formulation absorbed more slowly and provides more sustained levodopa levels than IR form; when initially required, CR form is as effective as IR form and may be more convenient; patients with dissipating motor fluctuations and no dyskinesia often benefit from prolongation of short-duration response when switched from IR to CR form; patients with meaningful fluctuations and dyskinesia often have increased dyskinesia when switched to CR form; doses and intervals for CR form may be increased or decreased to response. Most patients adequately treated with 2-8 tab/d in doses divided q4-8h when awake; >12 tab/d and 3 d between dose adjustments; may be administered as whole or half tab, which should not be crushed or chewed; motor symptoms and signs may or may not improve.

Adult

25/100 tab initially; half the tab PO bid; can be increased gradually; greater consistency of absorption when taken 1 h or longer after meals; some start with CR form

Pediatric

Not established

Follow-up

Deterrence/Prevention

Data are not available on deterrence or prevention of this condition.

Prognosis

  • Dementia with Lewy bodies (DLB) is a disorder of inexorable progression.
  • The rate of progression varies, and some investigators think that progression is faster than that of Alzheimer’s disease.
  • Patients eventually die from complications of immobility, poor nutrition, and swallowing difficulties.

Patient Education

  • Primary caregivers need information about the course of the disease and the management of symptoms such as agitation, hallucinations, and cognitive fluctuations.
  • Family members and physicians may mistake fluctuations for transient ischemic attacks.
  • Information concerning issues such as daycare and home health aides can be useful.
  • Children of patients with DLB may request information concerning genetic risks or neuroprotective treatment regimens.
  • For excellent patient education resources, visit eMedicine’s Dementia Center. In addition, see eMedicine’s patient education articles Dementia Overview, Dementia With Lewy Bodies, and Dementia Medication Overview.

Miscellaneous

Medicolegal Pitfalls

  • Family members should be made aware that DLB eventually affects job performance.
  • Depending on the patient’s occupation and level of dysfunction, medical leave of absence or early retirement may be advised.
  • Driving privileges need to be addressed by the patient, family, caregivers, primary care physician, and neurologist.

What is Lewy Body Dementia?

The following is extracted from the Lewy Body Dementia Association website:

Lewy body dementia (LBD) is a progressive brain disease and the second leading cause of degenerative dementia in the elderly. The clinical name, “dementia with Lewy bodies” (DLB), accounts for up to 20% of all dementia cases, or 800,000 patients in the US. Over 50% of Parkinson’s disease patients develop “Parkinson’s disease dementia” (PDD), which accounts for at least 750,000 patients. (PDD is also a Lewy body dementia.)

Other names for the Lewy body dementias are:

  • Lewy body disease (LBD)
  • Diffuse lewy body disease (DLBD)
  • Cortical Lewy body disease (CLBD)
  • Lewy body Variant of Alzheimer’s (LBV)(LBVA)
  • Parkinson’s disease with dementia (PDD)

In the early 1900’s, while researching Parkinson’s disease, the scientist Friederich H. Lewy discovered abnormal protein deposits that disrupt the brain’s normal functioning. These Lewy body proteins are found in an area of the brain stem where they deplete the neurotransmitter dopamine, causing Parkinsonian symptoms. In Lewy body dementia, these abnormal proteins are diffuse throughout other areas of the brain, including the cerebral cortex. The brain chemical acetylcholine is depleted, causing disruption of perception, thinking, and behavior. Lewy body dementia exists either in pure form, or in conjunction with other brain changes, including those typically seen in Alzheimer’s disease and Parkinson’s disease. 

Horn of Plenty

–Mark L. Madden

When a music student brought his French horn to my shop for repair, he complained that the instrument “felt stuffy” and he couldn’t blow air through it. It’s not unusual to find partial blockages in brass instruments if small items get lodged in the tubing, but when I tested the instrument, the horn was completely blocked. After much probing and prodding, a small tangerine dropped out of the bell. “Oh,” said the musician when I handed him the fruit. Seeing the bewildered look on my face, he explained, “My mom used the horn for a cornucopia in a Thanksgiving centerpiece.”

 

David

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