Lewy Body Dementia
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Lewy Body Dementia

Lewy body dementia (LBD, or Lewy body disorder) is an umbrella term[1] that encompasses two similar dementias, both of which are characterized by abnormal deposits of the protein alpha-synuclein in the brain:

The two conditions have similar features, may have similar causes, and can be viewed as part of a spectrum. As of 2014, they were more often misdiagnosed than any other common dementia.

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.[5][6] The Lewy body dementias are considered to consist of the two related disorders, dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) that are distinguished by the timing when cognitive and motor symptoms appear.[7]

Cause and mechanisms

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 LBD spectrum, and a shared component of protein deposits in Lewy bodies and Lewy neurites.[8] Lewy bodies and neurites have been found to develop from 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.[9] 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.[10]

Diagnosis

Dementia with Lewy bodies and Parkinson's disease dementia have similar neuropathological features, but these features are highly variable and the conditions should not be distinguished on pathological features alone.[9] Generally, DLB is distinguished from PDD dementia by the time frame in which dementia symptoms appear relative to parkinsonian symptoms. DLB is diagnosed when cognitive symptoms begin before or at the same time as parkinsonism, while PDD is the diagnosis when Parkinson's disease is well established before the dementia occurs.[6]

Epidemiology

As of 2014, the Lewy body dementias affect about 1.3 million people in the US and 140,000 in the UK.[11] LBD usually develops after the age of 50.[12] Between 5% and 25% of diagnosed dementias in older adults are due to Lewy body dementias.[7]

Society and culture

Advocacy and awareness

As of 2014, the Lewy body dementias were more often misdiagnosed than any other common dementia.[11] 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.[11] 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.[11] 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.[11] 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.[11]

Notable individuals

Robin Williams (shown in 2011): his widow said he was diagnosed on autopsy with Lewy bodies.[13][14]

Robin Williams, the American actor and comedian, died on August 11, 2014. Before his suicide, he had been diagnosed with Parkinson's disease,[13] and according to his widow, Susan Schneider Williams, he experienced depression, anxiety, and increasing paranoia.[14] Upon autopsy, his widow said he was found to have diffuse Lewy body disease,[13][14][15] while the autopsy used the term diffuse Lewy body dementia.[16] 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.[16] According to Dickson, "Lewy bodies are generally limited in distribution", while in dementia with Lewy bodies, "the Lewy bodies are spread widely throughout the brain, as was the case with Robin Williams."[16]Ian G. McKeith, professor and researcher of Lewy body dementias, commented that Williams' symptoms and autopsy findings were explained by dementia with Lewy bodies.[17]

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.[18] Sahlas said his death was "variously ascribed to Alzheimer disease, Parkinson disease, or postencephalitic parkinsonism".[18] 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.[18]

Other entertainers and artists who have or died from LBD include Estelle Getty, an actress known for her role in the television series The Golden Girls,[19]Nicholas King, a US actor and horticulturist,[20] actress Dina Merrill,[21]Donald Featherstone, who created the plastic pink flamingo,[22] American radio and television host Casey Kasem,[23] Canadian singer Pierre Lalonde,[24][25] and graphic artist/film set designer Ron Cobb.[26]

Individuals from industry or government who have or died from LBD are Seymour Berry, US Director of the Bureau of Engraving and Printing,[27]Los Angeles Times publisher Otis Chandler,[28]Philip J. Rock, a US Democratic politician of the Illinois Senate,[29] and U.S. media mogul and philanthropist Ted Turner.[30]

Arnold R. Hirsch, an American historian who taught at the University of New Orleans,[31] and Jessie Isabelle Price, an American veterinary microbiologist,[32] died from LBD.

In the sports realm, Jerry Sloan, American professional basketball player and coach, died from LBD.[33]Major League Baseball players Tom Seaver,[34]Andy Carey,[35] and Bill Buckner died of LBD.[36]Stan Mikita, Canadian ice hockey player, was diagnosed with possible LBD,[37] but a post-mortem brain autopsy found that he had chronic traumatic encephalopathy.[38]

In popular culture

Robin's Wish, a documentary exploring Williams' Lewy body disease and how it contributed to his death was released in September 2020.[39][40][41]

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.[42]

References

  1. ^ 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 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 (7): 84. doi:10.3390/brainsci7070084. PMC 5532597. PMID 28714891.
  4. ^ Galasko D (May 2017). "Lewy Body Disorders". Neurol Clin. 35 (2): 325-38. doi:10.1016/j.ncl.2017.01.004. PMC 5912679. PMID 28410662.
  5. ^ Velayudhan L, Ffytche D, Ballard C, Aarsland D (September 2017). "New Therapeutic Strategies for Lewy Body Dementias". Curr Neurol Neurosci Rep (Review). 17 (9): 68. doi:10.1007/s11910-017-0778-2. PMID 28741230.
  6. ^ a b McKeith IG, Boeve BF, Dickson DW, et al. (July 2017). "Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium". Neurology (Review). 89 (1): 88-100. doi:10.1212/WNL.0000000000004058. PMC 5496518. PMID 28592453.
  7. ^ 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.
  8. ^ 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.
  9. ^ a b Latimer CS, Montine TJ. "Epidemiology, pathology, and pathogenesis of dementia with Lewy bodies". UpToDate, Inc. Retrieved 2019.
  10. ^ 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. PMID 31519472.
  11. ^ a b c d e f 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.
  12. ^ "Lewy body dementia: Hope through research". National Institute of Neurological Disorders and Stroke. US National Institutes of Health. December 8, 2017. Retrieved 2018.
  13. ^ 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 2018.
  14. ^ 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.
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  16. ^ 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 2018.
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  20. ^ McLellan D (April 23, 2012). "Nicholas King dies at 79; actor helped preserve the Watts Towers". The Los Angeles Times. Retrieved 2018.
  21. ^ Dangremond S (May 23, 2017). "Actress and philanthropist Dina Merrill dies at 93". Town and Country Magazine. Retrieved 2018.
  22. ^ Woo E (June 24, 2015). "Don Featherstone dies at 79; creator of the plastic pink flamingo". Los Angeles Times. Retrieved 2018.
  23. ^ Caffrey J (April 18, 2016). "Casey Kasem and a lesson about end-of-life care". CNN. Retrieved 2018.
  24. ^ Papineau P (June 23, 2016). "L'idole d'une génération s'éteint" (in French). Le Devoir. Retrieved 2018.
  25. ^ Belanger C (June 22, 2016). "Pierre Lalonde souffrait aussi de la démence à corps de Lewy" (in French). Le Journal de Montréal. Retrieved 2018.
  26. ^ 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 2020.
  27. ^ "Seymour Berry, 86; Headed U.S. Agency". Washington Post. December 27, 2008. Retrieved 2018.
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  29. ^ "Philip Rock, ex-Senate leader known for mentoring and bipartisanship, dies". Chicago Sun-Times. January 29, 2016. Archived from the original on February 1, 2016. Retrieved 2018.
  30. ^ Deerwester J (September 28, 2018). "Ted Turner has Lewy Body Dementia". USA Today. Retrieved 2018.
  31. ^ O'Donnell M (March 26, 2018). "Arnold R. Hirsch dies; analyzed Chicago segregation in influential book". Chicago Sun Times. Retrieved 2018.
  32. ^ "Jessie Isabelle Price Dies On November 12". The Southampton Press. November 23, 2015. Retrieved 2018.
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  34. ^ Canova D (September 2, 2020). "Tom Seaver, Mets' star who won 3 Cy Young awards and 311 games, dead at 75". Fox News. Retrieved 2020.
  35. ^ Weber B (January 7, 2012). "Andy Carey, Third Baseman for 1950s Yankees, Dies at 80". The New York Times. p. A26. Retrieved 2018.
  36. ^ Kelly M (May 27, 2019). "Batting champ, All-Star Buckner dies at 69". MLB.com. Retrieved 2019.
  37. ^ Kuc C (June 15, 2015). "For Stan Mikita, all the Blackhawks memories are gone". Chicago Tribune. Archived from the original on June 16, 2015. Retrieved 2018.
  38. ^ "Study shows hockey Hall of Famer Stan Mikita suffered from CTE". USA Today. Associated Press. September 13, 2019. Retrieved 2020.
  39. ^ Huff L (August 6, 2020). "Robin Williams' final days detailed in touching trailer for new documentary Robin's Wish". Entertainment Weekly. Retrieved 2020.
  40. ^ Boone J. "Robin Williams' Struggles on Final Film Set Detailed by His Director". Entertainment Tonight. Retrieved .
  41. ^ VanHoose B. "Robin Williams' Final Days Revealed in Touching New Documentary Robin's Wish". People.com. Retrieved .
  42. ^ "Sleepwalk with Me: Comedian's sleep disorder experience comes to film". American Academy of Sleep Medicine. January 26, 2012. Retrieved 2018.

External links

Classification

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