Dementia with Lewy bodies

Dementia with Lewy bodies

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
MeSH D020961

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]

People 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.

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. 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. 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 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.

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

See also

References

  1. ↑ http://www.lbda.org/node/14
  2. ↑ Association Inc., Lewy Body Dementia (2007), "What is Lewy Body Dementia", Slideshare
  3. ↑ Lewy Body Dementia Association (lbda.org)
  4. ↑ Lennox, Graham; Lewy-net, Nottingham Medical School, Dementia with Lewy Bodies
  5. ↑ Presti MF, Schmeichel AM, Low PA, Parisi JE, Benarroch EE. (February 2014). "Degeneration of brainstem respiratory neurons in dementia with Lewy bodies". Sleep 37 (2): 373–8. doi:10.5665/sleep.3418. PMC 3900631.
  6. 1 2 3 4 5 Scotland, Alzheimer; Dementia, Action on, Dementia with Lewy Bodies
  7. ↑ Harding AJ1, Broe GA, Halliday GM (February 2002). "Visual hallucinations in Lewy body disease relate to Lewy bodies in the temporal lobe". Brai. 125(Pt 2): 391–403. PMID 11844739.
  8. ↑ Jacobson SA1, Morshed T2, Dugger BN3, Beach TG3, Hentz JG4, Adler CH4, Shill HA2, Sabbagh MN5, Belden CM3, Sue LI3, Caviness JN4, Hu C6; Arizona Parkinson's Disease Consortium. (September 2014). "Plaques and tangles as well as Lewy-type alpha synucleinopathy are associated with formed visual hallucinations.". Parkinsonism Relat Disord 20 (9): 1009–14. doi:10.1016/j.parkreldis.2014.06.018. PMID 25027359.
  9. 1 2 Ferman, Tanis J.; Assn, Lewy Body Dementia (2007), Behavioral Challenges in Dementia with Lewy Bodies, from "The Many Faces of Lewy Body Dementia" series at Coral Springs Medical Center, FL, YouTube
  10. ↑ Bogaerts V, Engelborghs S, Kumar-Singh S; et al. (September 2007), "A novel locus for dementia with Lewy bodies: a clinically and genetically heterogeneous disorder", Brain 130 (Pt 9): 2277–91, doi:10.1093/brain/awm167, PMID 17681982.
  11. 1 2 Stewart, Jonathan T.; Assn, Lewy Body Dementia (2007), Difficulties in Diagnosing Lewy Body Dementia, from "The Many Faces of Lewy Body Dementia" series at Coral Springs Medical Center, FL, YouTube
  12. 1 2 3 Crystal, Howard A. (2008), "Dementia with Lewy Bodies", E-Medicine from WebMD
  13. ↑ Hishikawa N, Hashizume Y, Yoshida M, Niwa J, Tanaka F, Sobue G.; Hashizume; Yoshida; Niwa; Tanaka; Sobue (April 2005), "Tuft-shaped astrocytes in Lewy body disease", Acta Neuropathol 109 (4): 373–80, doi:10.1007/s00401-004-0967-3, PMID 15668789
  14. ↑ Iseki E, Togo T, Suzuki K, Katsuse O, Marui W, de Silva R, Lees A, Yamamoto T, Kosaka K.; Togo; Suzuki; Katsuse; Marui; De Silva; Lees; Yamamoto; Kosaka (March 2003), "Dementia with Lewy bodies from the perspective of tauopathy", Acta Neuropathol. 105 (3): 265–70, doi:10.1007/s00401-002-0644-3 (inactive 2015-01-12), PMID 12557014
  15. ↑ Marla Gearing, PhD; Michael Lynn, MS; Suzanne S. Mirra, MD (February 1999), "Neurofibrillary Pathology in Alzheimer Disease With Lewy Bodies", Archives of Neurology 56 (2): 203–8, doi:10.1001/archneur.56.2.203, PMID 10025425
  16. ↑ Hiroshige Fujishiro, MD, PhD,1 Tanis J. Ferman, PhD,2 Bradley F. Boeve, MD,3 Glenn E. Smith, PhD,4 Neill R. Graff-Radford, MBBCh, FRCP,5 Ryan J. Uitti, MD,5 Zbigniew K. Wszolek, MD,5 David S. Knopman, MD,3 Ronald C. Petersen, MD,3 Joseph E. Parisi, MD,6 and Dennis W. Dickson, MD1 (July 2008), "Validation of the neuropathologic criteria of the third consortium for dementia with Lewy bodies for prospectively diagnosed cases.", J Neuropathol Exp Neurol. 67 (7): 649–56, doi:10.1097/NEN.0b013e31817d7a1d, PMC 2745052, PMID 18596548
  17. 1 2 3 Van Gerpen, Jay A.; Assn, Lewy Body Dementia (2007), New Trends in Lewy Body Dementia, from "The Many Faces of Lewy Body Dementia" series at Coral Springs Medical Center, FL, YouTube
  18. ↑ Uchikado H, Lin WL, DeLucia MW, Dickson DW Uchikado, H; Lin, WL; Delucia, MW; Dickson, DW (2006), "Alzheimer disease with amygdala Lewy bodies: a distinct form of alpha-synucleinopathy", Journal of neuropathology and experimental neurology 65 (7): 685–97, doi:10.1097/01.jnen.0000225908.90052.07, PMID 16825955
  19. ↑ Kotzbauer PT, Trojanowsk JQ, Lee VM; Trojanowsk; Lee (2001), "Lewy body pathology in Alzheimer's disease", Journal of molecular neuroscience : MN 17 (2): 225–32, doi:10.1385/JMN:17:2:225, PMID 11816795
  20. ↑ "Dementia". A-Z Library. University of Oklahoma. Archived from the original on 2011-07-15. Retrieved 2014-06-10.
  21. ↑ S Love (2005-06-01). "Neuropathological investigation of dementia: a guide for neurologists - Love 76 (suppl 5): v8 - Journal of Neurology, Neurosurgery & Psychiatry". bmj.com. Retrieved 2014-06-10.
  22. 1 2 Weintraub, Daniel; Hurtig, Howard I. (2007), "Presentation and Management of Psychosis in Parkinson's Disease and Dementia with Lewy Bodies", American Journal of Psychiatry 164 (10): 1491–1498, doi:10.1176/appi.ajp.2007.07040715, PMC 2137166, PMID 17898337
  23. ↑ Carey RJ, Pinheiro-Carrera M, Dai H, Tomaz C, Huston JP (2014-05-14). "L-DOPA and psychosis:". Biological Psychiatry (NIH.gov) 38 (10): 669–76. doi:10.1016/0006-3223(94)00378-5. PMID 8555378. Retrieved 2014-06-10.
  24. ↑ "Secondary parkinsonism". MedlinePlus Medical Encyclopedia. NIH.gov. Retrieved 2014-06-10.
  25. ↑ Ellul, J (2006). "The effects of commonly prescribed drugs in patients with Alzheimer's disease on the rate of deterioration". Journal of Neurology, Neurosurgery and Psychiatry 78 (3): 233–239. doi:10.1136/jnnp.2006.104034 (inactive 2015-01-12).
  26. ↑ Neef, Doug; Walling, Anne D (2006-04-01), "Dementia with Lewy Bodies: an Emerging Disease", American Family Physician 73 (7): 1223–1229, PMID 16623209, retrieved 2010-01-29.
  27. ↑ Aarsland, D; Ballard, C; Walker, Z; Bostrom, F; Alves, G; Kossakowski, K; Leroi, I; Pozo-Rodriguez, F; et al. (2009), "Memantine in patients with Parkinson's disease dementia or dementia with Lewy bodies: a double-blind, placebo-controlled, multicentre trial", Lancet neurology 8 (7): 613–8, doi:10.1016/S1474-4422(09)70146-2, PMID 19520613
  28. ↑ Lewy body dementia at Who Named It?
  29. ↑ Kosaka K, Oyanagi S, Matsushita M, and Hori A. (1976), "Presenile dementia with Alzheimer-, Pick- and Lewy-body changes", Acta Neuropathol 36 (3): 221–233, doi:10.1007/bf00685366, PMID 188300
  30. ↑ Shaw, David; Mitchell Landsberg (February 27, 2006). "L.A. Icon Otis Chandler Dies at 78". The Los Angeles Times. Retrieved July 23, 2008.
  31. ↑
  32. ↑ Carlson, Michael (July 24, 2008). "Obituary: Estelle Getty". theguardian.com. Retrieved October 13, 2013.
  33. ↑ Kasem, Julie; Kasem, Kerri; Martin, Troy (2014-05-13). CNN Tonight. Interview with Bill Weir. CNN. Missing or empty |title= (help) Comments about disease aired around 9:41 p.m. EDT; comments about purpose at the end of the interview.
  34. ↑ Kuc, Chris (15 June 2015). "For Stan Mikita, all the Blackhawks memories are gone". Chicago Tribune. Retrieved 15 June 2015.
  35. ↑ Demetrios J. Sahlas (2003). "Dementia With Lewy Bodies and the Neurobehavioral Decline of Mervyn Peake". Arch. Neurology 60 (6): 889. doi:10.1001/archneur.60.6.889.
  36. ↑ "Robin Williams coroner’s report finds no illegal drugs or alcohol in system". New York Daily News. Retrieved 2014-11-10.
  37. ↑ "Robin Williams - Dementia Hallucinations Triggered Suicide". TMZ. Retrieved 2014-11-11.
  38. ↑ "Robin Williams' widow blames Lewy body dementia - CNN.com". CNN. Retrieved 2015-11-04.

External links

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