Dementia with Lewy bodies
Encyclopedia
Dementia with Lewy bodies (DLB), also known under a variety of other names including Lewy body dementia, diffuse Lewy body disease, cortical Lewy body disease, and senile dementia of Lewy type, is a type of dementia
Dementia
Dementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging...

 closely allied to both Alzheimers and Parkinson's Disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...

s. It is characterized anatomically by the presence of Lewy bodies
Lewy body
Lewy bodies are abnormal aggregates of protein that develop inside nerve cells in Parkinson's disease , Lewy Body Dementia and some other disorders. They are identified under the microscope when histology is performed on the brain....

, clumps of alpha-synuclein
Alpha-synuclein
Alpha-synuclein is a protein that, in humans, is encoded by the SNCA gene. An alpha-synuclein fragment, known as the non-Abeta component of Alzheimer's disease amyloid, originally found in an amyloid-enriched fraction, is shown to be a fragment of its precursor protein, NACP, by cloning of the...

 and ubiquitin
Ubiquitin
Ubiquitin is a small regulatory protein that has been found in almost all tissues of eukaryotic organisms. Among other functions, it directs protein recycling.Ubiquitin can be attached to proteins and label them for destruction...

 protein in neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...

s, detectable in post-mortem brain biopsies.
Lewy Body dementia affects 1.3 million individuals in the United States alone.

Classification

Dementia with Lewy bodies overlaps clinically with Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...

 and Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...

, but is more associated with the latter. With DLB, the loss of cholinergic (acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...

-producing) neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...

s is thought to account for the degradation of cognitive functioning, as in Alzheimer's disease; while the loss of dopaminergic (dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

-producing) neurons is thought to account for the degradation of motor control, as in Parkinson's disease. Thus, DLB is similar in some ways to both the dementia resulting from Alzheimer's disease and the movement problems of Parkinson's disease. The overlap of neuropathologies and presenting symptoms (cognitive, emotional, and motor) can make an accurate differential diagnosis difficult. In fact, it is often confused in its early stages with Alzheimer's disease and/or vascular dementia (multi-infarct dementia
Multi-infarct dementia
Multi-infarct dementia is one type of vascular dementia. Vascular dementia is the second most common form of dementia after Alzheimer's disease in older adults. Multi-infarct dementia is thought to be an irreversible form of dementia, and its onset is caused by a number of small strokes or...

) although, where Alzheimer’s disease usually begins quite gradually, DLB often has a rapid or acute onset, with especially rapid decline in the first few months. DLB tends to progress more quickly than Alzheimer’s disease. Despite the difficulty, a prompt diagnosis of DLB is important because of the risks of sensitivity to neuroleptic
Antipsychotic
An antipsychotic is a tranquilizing psychiatric medication primarily used to manage psychosis , particularly in schizophrenia and bipolar disorder. A first generation of antipsychotics, known as typical antipsychotics, was discovered in the 1950s...

 drugs and because appropriate treatment of symptoms can improve life for both the person with DLB and their caregivers.

DLB is distinguished from the dementia that sometimes occurs in Parkinson's Disease by the time frame in which dementia symptoms appear relative to Parkinson symptoms. Parkinson's disease with dementia (PDD) would be the diagnosis when dementia onset is more than 1 year after the onset of Parkinson's. DLB is diagnosed when cognitive symptoms begin at the same time or within a year of Parkinson symptoms.

Signs and symptoms

While the specific symptoms in a person with DLB will vary, core features of DLB are: 1) fluctuating cognition with great variations in attention and alertness from day to day and hour to hour 2) recurrent visual hallucination
Hallucination
A hallucination, in the broadest sense of the word, is a perception in the absence of a stimulus. In a stricter sense, hallucinations are defined as perceptions in a conscious and awake state in the absence of external stimuli which have qualities of real perception, in that they are vivid,...

s (observed in 75% of people with DLB), and 3) motor features of Parkinson's. Suggestive symptoms are rapid eye movement(REM)-sleep behavior disorder
Rapid eye movement behavior disorder
Rapid eye movement sleep behaviour disorder is a sleep disorder that involves abnormal behaviour during the sleep phase with rapid eye movement . It was first described in 1986....

 and abnormalities detected in PET
Positron emission tomography
Positron emission tomography is nuclear medicine imaging technique that produces a three-dimensional image or picture of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide , which is introduced into the body on a...

 or SPECT scans.

Parkinson's features could include shuffling gait, reduced arm-swing during walking, blank expression (reduced range of facial expression), stiffness of movements, ratchet-like cogwheeling movements; low speech volume, sialorrhea and difficulty swallowing. Tremors are less common in DLB than in Parkinson's disease. DLB patients also often experience problems with orthostasis, including repeated falls, syncope
Syncope (medicine)
Syncope , the medical term for fainting, is precisely defined as a transient loss of consciousness and postural tone characterized by rapid onset, short duration, and spontaneous recovery due to global cerebral hypoperfusion that most often results from hypotension.Many forms of syncope are...

 (fainting), and transient loss of consciousness.

One of the most critical and distinctive clinical features is hypersensitivity to neuroleptic and antiemetic
Antiemetic
An antiemetic is a drug that is effective against vomiting and nausea. Antiemetics are typically used to treat motion sickness and the side effects of opioid analgesics, general anaesthetics, and chemotherapy directed against cancer....

 medications that affect dopaminergic and cholinergic systems. In the worst cases, a patient treated with these drugs could become catatonic, lose cognitive function and/or develop life-threatening muscle rigidity. Some commonly used drugs which should be used with great caution, if at all, for people with DLB are chlorpromazine
Chlorpromazine
Chlorpromazine is a typical antipsychotic...

, haloperidol
Haloperidol
Haloperidol is a typical antipsychotic. It is in the butyrophenone class of antipsychotic medications and has pharmacological effects similar to the phenothiazines....

, or thioridazine
Thioridazine
Thioridazine is a piperidine typical antipsychotic drug belonging to the phenothiazine drug group and was previously widely used in the treatment of schizophrenia and psychosis...

.

Visual hallucinations in people with DLB most commonly involve perception of people or animals that aren't there. Delusions may include reduplicative paramnesia
Reduplicative paramnesia
Reduplicative paramnesia is the delusional belief that a place or location has been duplicated, existing in two or more places simultaneously, or that it has been 'relocated' to another site...

 and other elaborate misperceptions or misinterpretations. These hallucinations are not necessarily disturbing and in some cases, the person with DLB may have insight into the hallucinations and even be amused by them or conscious that they are not really there. People with DLB may also have problems with vision, including double vision and misinterpretation of what they see, for example, mistaking a pile of socks for snakes or a clothes closet for the bathroom.

Causes

The causes are not yet well understood, but a genetic link with the PARK11
PARK11
PARK11 is a gene that has been associated with Parkinson's disease and dementia with Lewy bodies....

 gene has been described. As with Alzheimer's and Parkinson's diseases, most cases of DLB appear sporadically and DLB is not thought to be a strongly hereditary disease. As with Alzheimer's Disease, DLB risk is heightened with inheritance of the ε4 allele
Allele
An allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation...

 of the apolipoprotein E
Apolipoprotein E
Apolipoprotein E is a class of apolipoprotein found in the chylomicron and IDLs that binds to a specific receptor on liver cells and peripheral cells. It is essential for the normal catabolism of triglyceride-rich lipoprotein constituents.-Function:...

 (APOE).

Pathophysiology

Pathologically, DLB is characterized by the development of abnormal proteinaceous (alpha-synuclein
Alpha-synuclein
Alpha-synuclein is a protein that, in humans, is encoded by the SNCA gene. An alpha-synuclein fragment, known as the non-Abeta component of Alzheimer's disease amyloid, originally found in an amyloid-enriched fraction, is shown to be a fragment of its precursor protein, NACP, by cloning of the...

) cytoplasmic inclusions, called Lewy bodies
Lewy body
Lewy bodies are abnormal aggregates of protein that develop inside nerve cells in Parkinson's disease , Lewy Body Dementia and some other disorders. They are identified under the microscope when histology is performed on the brain....

, throughout the brain. These inclusions have similar structural features to "classical" Lewy bodies seen subcortically in Parkinson's disease. Additionally, there is a loss of dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...

-producing neurons (in the substantia nigra
Substantia nigra
The substantia nigra is a brain structure located in the mesencephalon that plays an important role in reward, addiction, and movement. Substantia nigra is Latin for "black substance", as parts of the substantia nigra appear darker than neighboring areas due to high levels of melanin in...

) similar to that seen in Parkinson's disease, and a loss of acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...

-producing neurons (in the basal nucleus of Meynert and elsewhere) similar to that seen in Alzheimer's disease. Cerebral atrophy (or shrinkage) also occurs as the cerebral cortex
Cerebral cortex
The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...

 degenerates. Autopsy series have revealed that the pathology of DLB is often concomitant with the pathology of Alzheimer's disease. That is, when Lewy body inclusions are found in the cortex, they often co-occur with Alzheimer's disease pathology found primarily in the hippocampus
Hippocampus
The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...

, including: senile plaques (deposited beta-amyloid protein
Amyloid
Amyloids are insoluble fibrous protein aggregates sharing specific structural traits. Abnormal accumulation of amyloid in organs may lead to amyloidosis, and may play a role in various neurodegenerative diseases.-Definition:...

), and granulovacuolar degeneration (grainy deposits within, and a clear zone around hippocampal neurons). Neurofibrillary tangles (abnormally phosphorylated tau protein
Tau protein
Tau proteins are proteins that stabilize microtubules. They are abundant in neurons of the central nervous system and are less common elsewhere, but are also expressed at very low levels in CNS astrocytes and oligodendrocytes...

) are less common in DLB, although they are known to occur., It is presently not clear whether DLB is an Alzheimer's variant or a separate disease entity.,,

Management

There is no cure for DLB; available treatments offer relatively small symptomatic benefit but remain palliative
Palliative care
Palliative care is a specialized area of healthcare that focuses on relieving and preventing the suffering of patients...

 in nature. Current treatments can be divided into pharmaceutical, and caregiving.

Pharmaceutical

Pharmaceutical management, as with Parkinson's disease, involves striking a balance between treating the motor and emotive/cognitive symptoms.

Treatment of the movement portion of the disease can worsen hallucinations and psychosis, while treatment of hallucinations and psychosis can worsen parkinsonian symptoms. Doctors may find that the use of cholinesterase inhibitors represents the treatment of choice for cognitive problems and donepezil (Aricept), rivastigmine (Exelon
Exelon
Exelon Corporation is an electricity generating and distributing company headquartered in the Chase Tower in the Chicago Loop area of Chicago. It was created in October, 2000 by the merger of PECO Energy Company and Unicom, of Philadelphia and Chicago respectively. Unicom owned Commonwealth Edison...

) and galantamine (Reminyl) may be recommended as a means to help with these problems and to slow or prevent the decline of cognitive function. Reports indicate that Lewy body dementia may be more responsive to donepezil than Alzheimer's disease. Memantine may also be useful. Sinemet may help with movement problems, but in some cases may, like dopamine agonists, tend to aggravate psychosis in people with DLB. Clonazepam
Clonazepam
Clonazepamis a benzodiazepine drug having anxiolytic, anticonvulsant, muscle relaxant, and hypnotic properties. It is marketed by Roche under the trade name Klonopin in the United States and Rivotril in Australia, Brazil, Canada and Europe...

 may help with Rapid eye movement behavior disorder
Rapid eye movement behavior disorder
Rapid eye movement sleep behaviour disorder is a sleep disorder that involves abnormal behaviour during the sleep phase with rapid eye movement . It was first described in 1986....

; table salt or antihypotensive medications may help with fainting and other problems associated with orthostasis. Botulinum toxin
Botulinum toxin
Botulinum toxin is a protein produced by the bacterium Clostridium botulinum, and is considered the most powerful neurotoxin ever discovered. Botulinum toxin causes Botulism poisoning, a serious and life-threatening illness in humans and animals...

 injections in the parotid glands may help with sialorrhea. Other medications, such as methylphenidate
Methylphenidate
Methylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult and obesity...

 and modafinil
Modafinil
Modafinil is an analeptic drug manufactured by Cephalon, and is approved by the U.S. Food and Drug Administration for the treatment of narcolepsy, shift work sleep disorder, and excessive daytime sleepiness associated with obstructive sleep apnea...

, may improve daytime alertness. Experts advise extreme caution in the use of anti-psychotic medication in people with DLB because of their sensitivity to these agents. When these medications must be used, atypical antipsychotics are preferred to typical antipsychotics; a very low dose should be tried initially and escalated only slowly; and patients should be carefully monitored for bad reactions to the drugs.

Due to hypersensitivity to neuroleptics prevention of DLB patients taking this drugs is of great importance. People with DLB are at risk for Neuroleptic Malignant Syndrome
Neuroleptic malignant syndrome
Neuroleptic malignant syndrome is a life- threatening neurological disorder most often caused by an adverse reaction to neuroleptic or antipsychotic drugs...

, a life-threatening illness, because of their sensitivity to these medications, especially the older Typical antipsychotic
Typical antipsychotic
Typical antipsychotics are a class of antipsychotic drugs first developed in the 1950s and used to treat psychosis...

s such as haloperidol
Haloperidol
Haloperidol is a typical antipsychotic. It is in the butyrophenone class of antipsychotic medications and has pharmacological effects similar to the phenothiazines....

. Other medications, including drugs for urinary incontinence and the antihistamine medication Benadryl
Benadryl
Benadryl is a brand name allergy medicine marketed over-the-counter by Johnson & Johnson subsidiary McNeil Consumer Healthcare. Prior to 2007, Benadryl was marketed by Pfizer Consumer Healthcare...

 can also exacerbate dementia.

Caregiving

Because DLB has no cure, it gradually renders people incapable of tending to their own needs. Caregiving is thus very important and must be carefully managed over the course of the disease. Caring for people with DLB involves adapting the home environment, schedule, activities, and communications to accommodate declining cognitive skills and parkinsonian symptoms.

People with DLB may swing dramatically between good days—high alertness and few cognitive or movement problems—and bad days, and the level of care they need may thus vary widely and unpredictably. Sharp changes in behavior may be due to the day-to-day variability of DLB, but they may also be triggered by changes in the schedule or home environment, or by physical problems, such as constipation, dehydration, bladder infection, injuries from falls and other problems that the person with DLB may not be able to convey to caregivers. Potential physical problems should always be checked out when a person with DLB becomes agitated.

Especially when hallucinations and delusions are not dangerous or troubling to the person with DLB, it may be best for caregivers not to disabuse patients of them. Often the best approach may be benign neglect—acknowledging, but not encouraging or agreeing. Trying to talk the DLB patient out of his delusion may be frustrating to caregivers and discouraging to patients, sometimes provoking anger or dejection. When misperceptions, hallucinations, and the behaviors stemming from these become troublesome, caregivers should try to identify and eliminate environmental triggers, and perhaps offer cues or "therapeutic white lies" to steer patients out of trouble. Doctors may prescribe low doses of atypical antipsychotic
Atypical antipsychotic
The atypical antipsychotics are a group of antipsychotic tranquilizing drugs used to treat psychiatric conditions. Some atypical antipsychotics are FDA approved for use in the treatment of schizophrenia...

s, such as quetiapine
Quetiapine
Quetiapine , is an atypical antipsychotic approved for the treatment of schizophrenia, and bipolar disorder....

 for psychosis and agitation in DLB. A small clinical trial found that about half of DLB patients treated with low doses of quetiapine experienced significant reduction in these symptoms. Unfortunately, several participants in the study had to discontinue treatment because of side-effects—excessive daytime sleepiness or orthostatic hypotension
Orthostatic hypotension
Orthostatic hypotension, also known as postural hypotension, orthostasis, and colloquially as head rush or dizzy spell, is a form of hypotension in which a person's blood pressure suddenly falls when the person stands up or stretches. The decrease is typically greater than 20/10 mm Hg, and may be...

.

Changes in the schedule or environment, delusions, hallucinations, misperceptions, and sleep problems may also trigger behavior changes. It can help people with DLB to encourage exercise; simplify the visual environment; stick to a routine; and avoid asking too much (or too little) of them. Speaking slowly and sticking to essential information improves communication. The potential for visual misperception and hallucinations, in addition to the risk of abrupt and dramatic swings in cognition and motor impairment should put families on alert to the dangers of driving with DLB.

Epidemiology

Current estimates are that about 60 to 75% of diagnosed dementias are of the Alzheimer's and mixed (Alzheimer's and vascular dementia) type, 10 to 15% are Lewy body type, with the remaining types being of an entire spectrum of dementias including frontotemporal lobar degeneration
Frontotemporal lobar degeneration
-Further reading:*Hodges, John R. The Frontotemporal Dementia Syndromes. Cambridge University Press. 2007 ISBN 978-0-521-85477-1-External links:****Mayo Clinic - **...

, alcoholic dementia
Korsakoff's syndrome
Korsakoff's syndrome is a neurological disorder caused by the lack of thiamine in the brain. Its onset is linked to chronic alcohol abuse and/or severe malnutrition...

, pure vascular dementia, etc. It is slightly more prevalent in men than women.

History

Frederic Lewy
Frederic Lewy
Frederick Henry Lewey was a prominent neurologist. He is perhaps best known for the discovery of Lewy bodies, which are a characteristic indicator of Parkinson's disease and Dementia with Lewy bodies.-Other sources:* Holdorff B., Friedrich Heinrich Lewy and His Work...

 (1885–1950) was first to discover the abnormal protein deposits ("Lewy body inclusions") in the early 1900s. Dementia with Lewy bodies only started to be diagnosed in the mid-1990s after the discovery of alpha-synuclein
Alpha-synuclein
Alpha-synuclein is a protein that, in humans, is encoded by the SNCA gene. An alpha-synuclein fragment, known as the non-Abeta component of Alzheimer's disease amyloid, originally found in an amyloid-enriched fraction, is shown to be a fragment of its precursor protein, NACP, by cloning of the...

 staining first highlighted Lewy bodies in the cortex of post-mortem brains of a subset of dementia patients. Because it was only recently discovered, DLB is not a recognized diagnosis in DSM-IV, which was published in 1994. It is, however, briefly mentioned in the DSM-IV-TR (published in 2000) under Dementia Due to Other General Medical Conditions. In 1996, a consortium of scientists initially proposed and later revised diagnostic guidelines.

Attention was drawn to DLB following the 2008 death of actress Estelle Getty
Estelle Getty
Estelle Scher-Gettleman , better known by her stage name Estelle Getty, was an American actress, who appeared in film, television, and theatre...

, who had previously been diagnosed with both Parkinson's Disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...

 and Alzheimer's Disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...

 before her true condition was discovered. Fellow Golden Girls cast members noted that years earlier, Getty had severe trouble remembering her lines during the filming of the show.

Cultural reference

Kelsey Grammer
Kelsey Grammer
Allen Kelsey Grammer is an American actor and comedian. He is most widely known for his two-decade portrayal of psychiatrist Dr. Frasier Crane on the sitcoms Cheers and Frasier...

's lead character, mayor of Chicago
Mayor of Chicago
The Mayor of Chicago is the chief executive of Chicago, Illinois, the third largest city in the United States. He or she is charged with directing city departments and agencies, and with the advice and consent of the Chicago City Council, appoints department and agency leaders.-Appointment...

 Tom Kane in the television series Boss
Boss (TV series)
Boss is an American-Canadian political drama television series created by Farhad Safinia. The series stars Kelsey Grammer as Tom Kane, the mayor of Chicago, who has recently been diagnosed with a degenerative neurological disorder....

, suffers from early-stage Lewy body dementia.

External links

The source of this article is wikipedia, the free encyclopedia.  The text of this article is licensed under the GFDL.
 
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