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Lewy body dementia

From Wikipedia, the free encyclopedia

Lewy body dementia (LBD) is an umbrella term for two similar and common subtypes of dementia:[1] dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD).[2][3][4][5] Both are characterized by changes in thinking, movement, behavior, and mood.[1] The two conditions have similar features and may have similar causes, and are believed to belong on a spectrum of Lewy body disease[2] that includes Parkinson's disease.[5] As of 2014, they were more often misdiagnosed than any other common dementia.[6]

The exact cause is unknown, but involves widespread deposits of abnormal clumps of protein that form in neurons of the diseased brain.[7] Known as Lewy bodies (discovered in 1912 by Frederic Lewy[8]) and Lewy neurites, these clumps affect both the central nervous system and the autonomic nervous system.[9] The fifth revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) gives Lewy body disease as the causative subtype of dementia with Lewy bodies, and Parkinson's disease as the causative subtype of Parkinson's disease dementia.[10] Dementia with Lewy bodies is marked by the presence of Lewy bodies primarily in the cortical regions, and Parkinson's disease dementia with Lewy bodies primarily in the subcortical basal ganglia.[11]

Classification

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Further information: Dementia with Lewy bodies § Classification

The synucleinopathies (dementia with Lewy bodies, Parkinson's disease dementia, and Parkinson's disease) are characterized by shared features of parkinsonism motor symptoms, neuropsychiatric symptoms, impaired cognition, sleep disorders, and visual hallucinations.[12][13] The Lewy body dementias—dementia with Lewy bodies (DLB), and Parkinson's disease dementia (PDD)—are distinguished by the timing when cognitive and motor symptoms appear.[14] The two Lewy body dementias are often considered to belong on a spectrum of Lewy body disease that includes Parkinson's disease.[2][5]

MeSH lists Lewy body disease in several categories: as a nervous system disease in two listings one as a basal ganglia Parkinsonian movement disorder and the other under brain disease as a dementia; as a neurodegenerative disorder listed as a synucleinopathy; and as a neurocognitive disorder listed with dementia.[15]

A genetic architecture that predisposes an individual to some disease phenotypes is found in Parkinson's disease and the Lewy body dementias. The presence of Lewy bodies is a link between these disorders; the term 'diseases with Lewy bodies' therefore may be more accurate than 'Lewy body disease'.[16]

Cause and mechanisms

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Further information: Dementia with Lewy bodies § Pathophysiology

Dementia with Lewy bodies and Parkinson's disease dementia are similar in many ways, suggesting there may be a common pathophysiological mechanism, with PDD and DLB at opposite ends of a Lewy body disease spectrum,[2] and a shared component of protein deposits in Lewy bodies and Lewy neurites.[17] Lewy bodies and neurites have been found to develop from the aggregation of misfolded alpha-synuclein, a protein thought to assist in neurotransmitter release and vesicle turnover; whether these misfolded proteins are responsible for the neurodegenerative effects remains unclear, and no definitive link between Lewy bodies and neurodegenerative effects has been found.[18] DSM-5 gives Lewy body disease as the causative subtype of DLB, and Parkinson's disease as the causative subtype of PDD.[10] DLB is marked by the presence of Lewy bodies primarily in the cortical regions, and PDD with Lewy bodies primarily in the subcortical basal ganglia.[11]

Despite differences in the timing of the appearance of symptoms, the two dementias "show remarkably convergent neuropathological changes at autopsy".[2] The relationship between Parkinson's disease dementia and dementia with Lewy bodies is unclear as of 2020, but there is likely to be genetic overlap, and the two conditions may represent different points on a continuum.[19]

Diagnosis

[edit]
Further information: Dementia with Lewy bodies § Diagnosis

Dementia with Lewy bodies and Parkinson's disease dementia have similar neuropathological features, but these features are highly variable and the conditions cannot be distinguished on pathological features alone.[18] Generally, dementia with Lewy bodies is distinguished from Parkinson's disease dementia by the time frame in which dementia symptoms appear relative to parkinsonian symptoms and is diagnosed when cognitive symptoms begin before or at the same time as parkinsonism. Parkinson's disease dementia is the diagnosis when Parkinson's disease is already well established before the dementia occurs.[13]

Epidemiology

[edit]
Further information: Dementia with Lewy bodies § Epidemiology

Between 5% and 25% of diagnosed dementias in older adults are due to one of the Lewy body dementias.[14][a] As of 2014, the Lewy body dementias affect about 1.3 million people in the US and 140,000 in the UK.[6]

LBD usually develops after the age of 50.[8] Men are more likely to be diagnosed than women.[8]

Prognosis

[edit]
Further information: Dementia with Lewy bodies § Prognosis

Life expectancy of people with one of the LBD is reduced; following diagnosis it ranges on average from five to eight years.[22]

Society and culture

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Advocacy and awareness

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As of 2014, the Lewy body dementias were more often misdiagnosed than any other common dementia.[6] Most people with DLB had not heard of the condition prior to diagnosis; general awareness about LBD lags well behind that of Parkinson's and Alzheimer's diseases, even though LBD is the second most common dementia, after Alzheimer's.[6] It is not only frustrating for families and caregivers to find that few people, including many healthcare professionals, are knowledgeable about LBD; lack of knowledge can have significant health consequences because people with LBD have severe sensitivity to antipsychotics often used to treat the symptoms.[6] The Lewy Body Dementia Association (LBDA) and the UK Lewy Body Society promote awareness and provide support that helps society, by reducing costly use of healthcare, and families with LBD, by reducing stress.[6] These organizations, and others in Argentina, Australia and Japan, help raise knowledge and help families with LBD become advocates to raise awareness about the disease.[6]

Notable individuals

[edit]
Further information: List of people diagnosed with Parkinson's disease
Robin Williams (shown in 2011): his widow said he was diagnosed on autopsy with Lewy bodies.[23][24]

Robin Williams, the American actor and comedian, died on August 11, 2014. Before his suicide, he had been diagnosed with Parkinson's disease,[23] and according to his widow, Susan Schneider Williams, he experienced depression, anxiety, and increasing paranoia.[24] Upon autopsy, his widow said he was found to have diffuse Lewy body disease,[23][24][25] while the autopsy used the term diffuse Lewy body dementia.[26] The vocabulary associated with Lewy pathology causes confusion.[27] Lewy body dementia (the umbrella term that encompasses the clinical diagnoses of dementia with Lewy bodies and Parkinson's disease dementia) differs from Lewy body disease (the term used to describe pathological findings of Lewy bodies on autopsy).[27] Dennis Dickson, a spokesperson for the Lewy Body Dementia Association, clarified the distinction by stating that diffuse Lewy body dementia is more commonly called diffuse Lewy body disease and refers to the underlying disease process.[26] According to Dickson, "Lewy bodies are generally limited in distribution" in early Parkinson's disease, while in dementia with Lewy bodies, "the Lewy bodies are spread widely throughout the brain, as was the case with Robin Williams."[26] Ian G. McKeith, professor and researcher of Lewy body dementias, commented that Williams' symptoms and autopsy findings were explained by dementia with Lewy bodies.[28]

The British author and poet Mervyn Peake died in 1968 and was diagnosed posthumously as a probable case of DLB in a 2003 paper published in JAMA Neurology.[29] Sahlas said his death was "variously ascribed to Alzheimer disease, Parkinson disease, or postencephalitic parkinsonism".[29] Based on signs in his work and letters of progressive deterioration, fluctuating cognitive decline, deterioration in visuospatial function, declining attention span, and visual hallucinations and delusions, his may be the earliest known case where DLB was found to have been the likely cause of death.[29]

Other entertainers and artists who have or died from LBD include Estelle Getty, the actress known for her role as Sophia on the television series The Golden Girls,[30] Nicholas King, a US actor and horticulturist,[31] actress Dina Merrill,[32] Donald Featherstone, who created the plastic pink flamingo,[33] American radio and television host Casey Kasem,[34] Canadian singer Pierre Lalonde,[35][36] graphic artist/film set designer Ron Cobb,[37] American actor Frank Bonner,[38] and Canadian musician and actor André Gagnon.[39]

Individuals from industry or government who have or died from LBD include Seymour Berry, US Director of the Bureau of Engraving and Printing,[40] Los Angeles Times publisher Otis Chandler,[41] Philip J. Rock, a US Democratic politician of the Illinois Senate,[42] U.S. media mogul and philanthropist Ted Turner,[43] and Indian-born British billionaire S. P. Hinduja.[44]

Arnold R. Hirsch, an American historian who taught at the University of New Orleans,[45] and Jessie Isabelle Price, an American veterinary microbiologist,[46] died from LBD.

In the sports realm, Jerry Sloan, American professional basketball player and coach, died from LBD.[47] Major League Baseball players Tom Seaver,[48] Andy Carey,[49] and Bill Buckner died of LBD.[50] Stan Mikita, Canadian ice hockey player, was diagnosed with possible LBD,[51] but a post-mortem brain autopsy found that he had chronic traumatic encephalopathy.[52]

[edit]

Robin's Wish, a documentary exploring Robin Williams's Lewy body disease and how it contributed to his death, was released in September 2020.[53][54][55]

Sleepwalk with Me is a book, one-man comedy, and film about a young man with relationship problems and RBD, a precursor to synucleinopathy, including LBD.[56]

Notes

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  1. ^ Kosaka (2017) writes: "Dementia with Lewy bodies (DLB) is now well known to be the second most frequent dementia following Alzheimer disease (AD). Of all types of dementia, AD is known to account for about 50%, DLB about 20% and vascular dementia (VD) about 15%. Thus, AD, DLB, and VD are now considered to be the three major dementias."[20] The NINDS (2020) says that Lewy body dementia "is one of the most common causes of dementia, after Alzheimer's disease and vascular disease."[8] Hershey (2019) says, "DLB is the third most common of all the neurodegenerative diseases behind both Alzheimer's disease and Parkinson's disease".[21]

References

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  1. ^ a b Walker Z, Possin KL, Boeve BF, Aarsland D (October 2015). "Lewy body dementias". Lancet (Review). 386 (10004): 1683–97. doi:10.1016/S0140-6736(15)00462-6. PMC 5792067. PMID 26595642.
  2. ^ a b c d e Gomperts SN (April 2016). "Lewy Body Dementias: Dementia With Lewy Bodies and Parkinson Disease Dementia". Continuum (Minneap Minn). 22 (2 Dementia): 435–63. doi:10.1212/CON.0000000000000309. PMC 5390937. PMID 27042903.
  3. ^ Pezzoli S, Cagnin A, Bandmann O, Venneri A (July 2017). "Structural and Functional Neuroimaging of Visual Hallucinations in Lewy Body Disease: A Systematic Literature Review". Brain Sci. 7 (12): 84. doi:10.3390/brainsci7070084. PMC 5532597. PMID 28714891.
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  6. ^ a b c d e f g Taylor A, Yardley C (2014). "Advocacy, education, and the role of not-for-profit organizations in Lewy body dementias". Alzheimers Res Ther (Review). 6 (5): 59. doi:10.1186/s13195-014-0059-0. PMC 4468791. PMID 26082807.
  7. ^ Spillantini, Maria Grazia; Crowther, R. Anthony; Jakes, Ross; Hasegawa, Masato; Goedert, Michel (1998-05-26). "α-Synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with Lewy bodies". Proceedings of the National Academy of Sciences. 95 (11): 6469–6473. doi:10.1073/pnas.95.11.6469. ISSN 0027-8424. PMC 27806. PMID 9600990.
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  10. ^ a b Diagnostic and statistical manual of mental disorders : DSM-5 (5th ed.). Arlington, VA: American Psychiatric Association. 2013. pp. 603–604. ISBN 9780890425541.
  11. ^ a b Diagnostic and statistical manual of mental disorders : DSM-5 (5th ed.). Arlington, VA: American Psychiatric Association. 2013. p. 619. ISBN 9780890425541.
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  14. ^ a b Connors MH, Quinto L, McKeith IG, et al. (August 2018). "Non-pharmacological interventions for Lewy body dementia: a systematic review". Psychol Med (Review). 48 (11): 1749–58. doi:10.1017/S0033291717003257. PMC 6088773. PMID 29143692.
  15. ^ "MeSH Browser". meshb.nlm.nih.gov. Retrieved 17 November 2020.
  16. ^ Menšíková K, Matěj R, Colosimo C, et al. (January 2022). "Lewy body disease or diseases with Lewy bodies?". npj Parkinson's Disease (Review). 8 (1): 3. doi:10.1038/s41531-021-00273-9. PMC 8748648. PMID 35013341. Material was copied from this source, which is available under a Creative Commons Attribution 4.0 International License
  17. ^ Weil RS, Lashley TL, Bras J, Schrag AE, Schott JM (2017). "Current concepts and controversies in the pathogenesis of Parkinson's disease dementia and Dementia with Lewy Bodies". F1000Res (Review). 6: 1604. doi:10.12688/f1000research.11725.1. PMC 5580419. PMID 28928962.
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  19. ^ Taylor JP, McKeith IG, Burn DJ, et al. (February 2020). "New evidence on the management of Lewy body dementia" (PDF). Lancet Neurol (Review). 19 (2): 157–69. doi:10.1016/S1474-4422(19)30153-X. hdl:10871/36535. PMC 7017451. PMID 31519472.
  20. ^ Kosaka K, ed. (2017). Dementia with Lewy bodies: clinical and biological aspects (1st ed.). Springer: Japan. doi:10.1007/978-4-431-55948-1. ISBN 978-4-431-55948-1. S2CID 45950966.
  21. ^ Hershey LA, Coleman-Jackson R (April 2019). "Pharmacological management of dementia with Lewy dodies". Drugs Aging (Review). 36 (4): 309–19. doi:10.1007/s40266-018-00636-7. PMC 6435621. PMID 30680679.
  22. ^ Haider A, Spurling BC, Sánchez-Manso JC (2021). "Lewy Body Dementia". StatPearls. PMID 29494048.
  23. ^ a b c Gallman S (November 4, 2015). "Robin Williams' widow speaks: Depression didn't kill my husband". CNN. Archived from the original on November 4, 2015. Retrieved April 6, 2018.
  24. ^ a b c Williams SS (September 2016). "The terrorist inside my husband's brain". Neurology. 87 (13): 1308–11. doi:10.1212/WNL.0000000000003162. PMID 27672165.
  25. ^ Robbins R (September 30, 2016). "How Lewy body dementia gripped Robin Williams". Scientific American. Retrieved April 9, 2018.
  26. ^ a b c "LBDA Clarifies Autopsy Report on Comedian, Robin Williams". Lewy Body Dementia Association. November 10, 2014. Archived from the original on August 12, 2020. Retrieved April 19, 2018.
  27. ^ a b Armstrong MJ (2021). "Advances in dementia with Lewy bodies". Ther Adv Neurol Disord (Review). 14: 17562864211057666. doi:10.1177/17562864211057666. PMC 8613883. PMID 34840608.
  28. ^ McKeith IG. "Robin Williams had dementia with Lewy bodies – so, what is it and why has it been eclipsed by Alzheimer's?". The Conversation. Archived from the original on November 4, 2016. Retrieved April 6, 2018.
  29. ^ a b c Sahlas DJ (June 2003). "Dementia with Lewy bodies and the neurobehavioral decline of Mervyn Peake". Arch. Neurol. 60 (6): 889–92. doi:10.1001/archneur.60.6.889. PMID 12810496.
  30. ^ Carlson M (July 24, 2008). "Obituary: Estelle Getty". theguardian.com. Archived from the original on September 2, 2013. Retrieved October 13, 2013.
  31. ^ McLellan D (April 23, 2012). "Nicholas King dies at 79; actor helped preserve the Watts Towers". The Los Angeles Times. Retrieved April 19, 2018.
  32. ^ Dangremond S (May 23, 2017). "Actress and philanthropist Dina Merrill dies at 93". Town and Country Magazine. Retrieved March 22, 2018.
  33. ^ Woo E (June 24, 2015). "Don Featherstone dies at 79; creator of the plastic pink flamingo". Los Angeles Times. Retrieved March 22, 2018.
  34. ^ Caffrey J (April 18, 2016). "Casey Kasem and a lesson about end-of-life care". CNN. Retrieved March 22, 2018.
  35. ^ Papineau P (June 23, 2016). "L'idole d'une génération s'éteint" (in French). Le Devoir. Retrieved April 9, 2018.
  36. ^ Belanger C (June 22, 2016). "Pierre Lalonde souffrait aussi de la démence à corps de Lewy" (in French). Le Journal de Montréal. Retrieved March 22, 2018.
  37. ^ Bartlett R, Parker R (September 21, 2020). "Ron Cobb, designer of the 'Alien' Ship and the 'Back to the Future' DeLorean, dies at 83". www.hollywoodreporter.com. Retrieved September 26, 2020.
  38. ^ Reid, Tony; Nakamura, Maglio (June 17, 2021). "Frank Bonner, 'WKRP in Cincinnati' Star, Dies at 79". TheWrap. Retrieved June 17, 2021.
  39. ^ "Pianist and composer Andre Gagnon, dead at 84, remembered as musical 'jack of all trades'". CTV News. December 3, 2020. Retrieved November 9, 2021.
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  43. ^ Deerwester J (September 28, 2018). "Ted Turner has Lewy Body Dementia". USA Today. Retrieved September 30, 2018.
  44. ^ "Indian-origin UK billionaire SP Hinduja dead at 87". 17 May 2023.
  45. ^ O'Donnell M (March 26, 2018). "Arnold R. Hirsch dies; analyzed Chicago segregation in influential book". Chicago Sun Times. Retrieved April 19, 2018.
  46. ^ "Jessie Isabelle Price Dies On November 12". The Southampton Press. November 23, 2015. Retrieved April 19, 2018.
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  52. ^ "Study shows hockey Hall of Famer Stan Mikita suffered from CTE". USA Today. Associated Press. September 13, 2019. Retrieved June 8, 2020.
  53. ^ Huff L (August 6, 2020). "Robin Williams' final days detailed in touching trailer for new documentary Robin's Wish". Entertainment Weekly. Retrieved August 7, 2020.
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