Dementia with Lewy bodies

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Dementia with Lewy bodies
Lewy Koerperchen.JPG
Lewy bodies are the pathomorphological characteristic of the disease
Classification and external resources
Specialty Neurology
ICD-10 G31.8
ICD-9-CM 331.82
OMIM 127750
DiseasesDB 3800
eMedicine neuro/91
Patient UK Dementia with Lewy bodies
MeSH D020961
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Dementia with Lewy bodies (DLB), also known as Lewy body dementia (LBD), diffuse Lewy body disease, cortical Lewy body disease, and senile dementia of Lewy type, is a type of progressive neurodegenerative dementia closely associated with Parkinson's disease primarily affecting older adults. Its primary feature is cognitive decline, which can lead to hallucinations, as well as varied attention and alertness when compared to a person's baseline function.[1]

Persons with LBD display an inability to plan or a loss of analytical or abstract thinking and show markedly fluctuating cognition. Wakefulness varies from day to day, and alertness and short-term memory rise and fall. Persistent or recurring visual hallucinations with vivid and detailed pictures are often an early diagnostic symptom. The disorder is characterized anatomically by the presence of Lewy bodies, clumps of alpha-synuclein and ubiquitin protein in neurons, detectable in post mortem brain histology.[medical citation needed]

Signs and symptoms

While the specific symptoms in a person with LBD will vary, core features of LBD are: fluctuating cognition with great variations in attention and alertness from day to day and hour to hour, recurrent visual hallucinations (observed in 75% of people with LBD), and motor features of Parkinson's. Suggestive symptoms are rapid eye movement (REM)-sleep behavior disorder and abnormalities detected in PET or SPECT scans.[2] REM sleep behavior disorder (RBD) is a symptom often first recognized by the patient's caretaker. RBD includes vivid dreaming, with persistent dreams, purposeful or violent movements, and falling out of bed.[3] Benzodiazepines, anticholinergics, surgical anesthetics, some antidepressants, and OTC cold remedies can cause acute confusion, delusions, and hallucinations.

Parkinsonian 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 LBD than in Parkinson's disease.[4] LBD patients also often experience problems with orthostatic hypotension, including repeated falls, syncope (fainting), and transient loss of consciousness. Sleep-disordered breathing, a problem in multiple system atrophy, can also be a problem.[5]

One of the most critical and distinctive clinical features is hypersensitivity to neuroleptic and antiemetic medications that affect dopaminergic and cholinergic systems.[medical citation needed] In the worst cases, a patient treated with these medications could become catatonic, lose cognitive function and/or develop life-threatening muscle rigidity. Some commonly used medications which should be used with great caution, if at all, for people with LBD are chlorpromazine, haloperidol, or thioridazine.[6]

Visual hallucinations in people with LBD most commonly involve perception of people or animals that are not there, and may reflect Lewy bodies and/or AD pathology in the temporal lobe.[7][8] Delusions may include reduplicative paramnesia and other elaborate misperceptions or misinterpretations.[medical citation needed] These hallucinations are not necessarily disturbing and in some cases, the person with LBD may have insight into the hallucinations and even be amused by them or conscious they are not really there. People with LBD may also have problems with vision, including double vision[6] and misinterpretation of what they see, for example, mistaking a pile of socks for snakes or a clothes closet for the bathroom.[9]

Cause

The major cause of LBD is not yet well understood, but a genetic link with the PARK11 gene has been described.[10] As with Alzheimer's disease and Parkinson's disease, most cases of LBD appear sporadically and LBD is not thought to have a strong hereditary link.[11] As with Alzheimer's disease, the LBD risk is heightened with inheritance of the ε4 allele of the apolipoprotein E (APOE).[12]

In LBD, loss of cholinergic (acetylcholine-producing) neurons is thought to account for degeneration of cognitive function (similar to Alzheimer's), while the death of dopaminergic (dopamine-producing) neurons appears to be responsible for degeneration of motor control (similar to Parkinson's) – in some ways, therefore, LBD resembles both disorders.

Pathophysiology

Photomicrographs of regions of substantia nigra in a patient showing Lewy bodies and Lewy neurites in various magnifications

Pathologically, LBD is characterized by the development of abnormal collections of (alpha-synuclein) protein within the cytoplasm of neurons (known as Lewy bodies). These intracellular collections of protein have similar structural features to "classical" Lewy bodies seen subcortically in Parkinson's disease. Additionally, those affected by LBD experience a loss of dopamine-producing neurons (in the substantia nigra) in a manner similar to that seen in Parkinson's disease. A loss of acetylcholine-producing neurons (in the basal nucleus of Meynert and elsewhere) similar to that seen in Alzheimer's disease is also known to occur in those with LBD. Cerebral atrophy also occurs as the cerebral cortex degenerates. Autopsy series have revealed the pathology of LBD 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, including senile plaques (deposited beta-amyloid protein), and granulovacuolar degeneration (grainy deposits within and a clear zone around hippocampal neurons). Neurofibrillary tangles (abnormally phosphorylated tau protein) are less common in LBD, although they are known to occur, and astrocyte abnormalities[vague] are also known to occur.[13][14][15][16] It is presently not clear whether LBD is an Alzheimer's variant or a separate disease entity.[17][18][19][20] Unlike Alzheimer's disease, the brain may appear grossly normal with no visible signs of atrophy.[21]

Diagnosis

LBD symptoms overlap clinically with Alzheimer's disease and Parkinson's disease, but are more commonly associated with the latter.[17] Because of this overlap, LBD in its early years is often misdiagnosed. The overlap of neuropathological and presenting symptoms (cognitive, emotional, and motor) can make an accurate differential diagnosis difficult. In fact, LBD is often confused in its early stages with Alzheimer's disease and/or vascular dementia (multi-infarct dementia), although, whereas Alzheimer’s disease usually begins gradually, LBD frequently has a rapid or acute onset, with especially rapid decline in the first few months. Thus, LBD tends to progress more rapidly than Alzheimer’s disease.[6] Despite the difficulty, a prompt diagnosis is important because of the risks of sensitivity to certain neuroleptic (antipsychotic) medications and because appropriate treatment of symptoms can improve life for both the person with LBD and the person's caregivers.[6]

LBD 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.[22] Parkinson's disease with dementia (PDD) would be the diagnosis when dementia onset is more than a year after the onset of Parkinson's. LBD is diagnosed when cognitive symptoms begin at the same time or within a year of Parkinson symptoms.

Management

There is no cure for LBD. Treatment may offer symptomatic benefit, but remains palliative in nature. Current treatment modalities 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. Motor symptoms appear to respond somewhat to the medications used to treat Parkinson's disease (e.g. levodopa) while cognitive issues may improve with medications for Alzheimer's disease such as donepezil. Medications used in the treatment of Attention deficit/hyperactivity disorder (e.g. methylphenidate) might improve cognition or daytime sleepiness; however, medications for both Parkinson's disease and ADHD increase levels of the chemical dopamine in the brain and so increase the risk of hallucinations with those classes of pharmaceuticals.[23]

Treatment of the movement and cognitive portions of the disease can worsen hallucinations and psychosis, while treatment of hallucinations and psychosis with anti-psychotics can worsen parkinsonian or ADHD symptoms in LBD such as tremor or rigidity and lack of concentration or impulse control.[24][25] Doctors may find the use of cholinesterase inhibitors represents the treatment of choice for cognitive problems and donepezil (Aricept), rivastigmine (Exelon) and galantamine (Reminyl) may be recommended as a means to help with these problems and to slow or prevent the decline of cognitive function.[6] Reports indicate Lewy body dementia may be more responsive to donepezil than Alzheimer's disease.[26] Memantine may also be useful.[27] Levocarb may help with movement problems, but in some cases, like dopamine agonists, may tend to aggravate psychosis in people with LBD. Clonazepam may help with rapid eye movement behavior disorder; table salt or antihypotensive medications may help with fainting and other problems associated with orthostatic hypotension. Botulinum toxin injections in the parotid glands may help with sialorrhea. Other medications, especially stimulants such as the ADHD drug methylphenidate (Ritalin) and modafinil, may improve daytime alertness but as with the anti-parkinsonian drug Levocarb, anti-hyperkinetics like Ritalin increase the risk of psychosis.[17] Experts advise extreme caution in the use of antipsychotic medication in people with LBD 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 increased slowly, and patients should be carefully monitored for adverse reactions to the medications.

Due to hypersensitivity to neuroleptics, prevention of LBD patients taking these medications is of great importance. People with LBD are at risk for neuroleptic malignant syndrome, a life-threatening illness, because of their sensitivity to these medications, especially the older typical antipsychotics, such as haloperidol. Other medications, including medications for urinary incontinence and the antihistamine medication diphenhydramine (Benadryl) can also worsen confusion.

Caregiving

Because LBD gradually renders people incapable of tending to their own needs, caregiving is very important and must be carefully managed over the course of the disease. Caring for people with LBD involves adapting the home environment, schedule, activities, and communications to accommodate declining cognitive skills and Parkinsonian symptoms.[9]

People with LBD may swing dramatically between good days—high alertness and few cognitive or movement problems—and bad days, and the level of care they require thus may vary widely and unpredictably. Sharp changes in behavior may be due to the day-to-day variability of LBD, 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 a person with LBD may not be able to convey to caregivers. Potential physical problems should always be checked out when an individual with LBD becomes agitated.

As hallucinations and delusions are not dangerous or troubling to the person with LBD, it may be best for caregivers not to disabuse patients of them. Often the best approach is benign neglect - acknowledging, but not encouraging or agreeing. Trying to talk the LBD 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 antipsychotics, such as quetiapine, for psychosis and agitation in LBD. A small clinical trial found that about half of LBD 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, such as excessive daytime sleepiness or orthostatic hypotension.[22]

Changes in the schedule or environment, delusions, hallucinations, misperceptions, and sleep problems may also trigger behavior changes. It can help people with LBD 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 LBD.[12]

Epidemiology

Currently, an estimated 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 (Picks Disease), alcoholic dementia, pure vascular dementia, etc. LBD is slightly more prevalent in men than women.[12]

Lewy body dementia affects about 1 million individuals in the United States alone.[citation needed]

History

Frederic Lewy (1885–1950) was first to discover the abnormal protein deposits ("Lewy body inclusions") in the early 1900s.[28] Dementia with Lewy bodies was first described by Japanese psychiatrist and neuropathologist Kenji Kosaka in 1976.[29] LBD only started to be diagnosed in the mid-1990s after the discovery of alpha-synuclein staining first highlighted Lewy bodies in the cortex of post mortem brains of a subset of dementia patients.[11] Because it was only recently discovered, LBD 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. It is in DSM-5 (published in 2013) as "Major or Mild Neurogocognitive Disorder with Lewy Bodies".

Notable sufferers

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  • Otis Chandler, the publisher of The Los Angeles Times from 1960 to 1980, who led a large expansion of the newspaper and its ambitions, died from the disease on February 27, 2006.[30]
  • Artist Donald Featherstone, creator of the Plastic Pink Flamingo, died from the disease in 2015.[31]
  • The actress Estelle Getty, best known for her role in the television series The Golden Girls, suffered from Lewy Body dementia in her later years.[32]
  • American radio and television disc jockey and host Casey Kasem died from the disease on June 15, 2014. He had previously been diagnosed with Parkinson's disease.[33]
  • Canadian ice hockey player Stan Mikita was diagnosed with the disease in January 2015.[34]
  • British author Mervyn Peake was diagnosed as having died (in 1968) from DLB in a 2003 study published in JAMA Neurology.[35]
  • American actor and comedian Robin Williams died by suicide on August 11, 2014. Upon autopsy it was discovered that he had diffuse Lewy Body dementia. Williams had been diagnosed with Parkinson's disease prior to his death; he had also been suffering from depression, anxiety, and increasing paranoia (all symptoms of DLB).[36][37][38]

See also

References

  1. ↑ http://www.lbda.org/node/14
  2. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  3. ↑ Lewy Body Dementia Association (lbda.org)
  4. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  5. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  6. ↑ 6.0 6.1 6.2 6.3 6.4 Lua error in package.lua at line 80: module 'strict' not found.
  7. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  8. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  9. ↑ 9.0 9.1 Lua error in package.lua at line 80: module 'strict' not found.
  10. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  11. ↑ 11.0 11.1 Lua error in package.lua at line 80: module 'strict' not found.
  12. ↑ 12.0 12.1 12.2 Lua error in package.lua at line 80: module 'strict' not found.
  13. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  14. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  15. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  16. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  17. ↑ 17.0 17.1 17.2 Lua error in package.lua at line 80: module 'strict' not found.
  18. ↑ Uchikado H, Lin WL, DeLucia MW, Dickson DW Lua error in package.lua at line 80: module 'strict' not found.
  19. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  20. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  21. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  22. ↑ 22.0 22.1 Lua error in package.lua at line 80: module 'strict' not found.
  23. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  24. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  25. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  26. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  27. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  28. ↑ Lewy body dementia at Who Named It?
  29. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  30. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  31. ↑ [1]
  32. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  33. ↑ Lua error in package.lua at line 80: module 'strict' not found. Comments about disease aired around 9:41 p.m. EDT; comments about purpose at the end of the interview.
  34. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  35. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  36. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  37. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  38. ↑ Lua error in package.lua at line 80: module 'strict' not found.

External links

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