Lewy body dementia

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Lewy body dementia 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]

Contents

The exact cause is unknown, but involves widespread deposits of abnormal clumps of protein that form in neurons of the diseased brain. Known as Lewy bodies (discovered in 1912 by Frederic Lewy [7] ) and Lewy neurites, these clumps affect both the central nervous system and the autonomic nervous system. [8] 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. [9] 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. [10]

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. [11] [12] 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. [13] 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. [14]

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'. [15]

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 Lewy body disease spectrum, [2] and a shared component of protein deposits in Lewy bodies and Lewy neurites. [16] 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. [17] DSM-5 gives Lewy body disease as the causative subtype of DLB, and Parkinson's disease as the causative subtype of PDD. [9] 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. [10]

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. [18]

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. [17] 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. [12]

Epidemiology

Between 5% and 25% of diagnosed dementias in older adults are due to one of the Lewy body dementias. [13] [lower-alpha 1] 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. [7] Men are more likely to be diagnosed than women. [7]

Prognosis

Life expectancy of people with one of the LBD is reduced; following diagnosis it ranges on average from five to eight years. [21]

Society and culture

Advocacy and awareness

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

Robin Williams (shown in 2011): his widow said he was diagnosed on autopsy with Lewy bodies. Robin Williams 2011a.jpg
Robin Williams (shown in 2011): his widow said he was diagnosed on autopsy with Lewy bodies.

Robin Williams, the American actor and comedian, died on August 11, 2014. Before his suicide, he had been diagnosed with Parkinson's disease, [22] and according to his widow, Susan Schneider Williams, he experienced depression, anxiety, and increasing paranoia. [23] Upon autopsy, his widow said he was found to have diffuse Lewy body disease, [22] [23] [24] while the autopsy used the term diffuse Lewy body dementia. [25] The vocabulary associated with Lewy pathology causes confusion. [26] 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). [26] 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. [25] 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." [25] Ian G. McKeith, professor and researcher of Lewy body dementias, commented that Williams' symptoms and autopsy findings were explained by dementia with Lewy bodies. [27]

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 . [28] Sahlas said his death was "variously ascribed to Alzheimer disease, Parkinson disease, or postencephalitic parkinsonism". [28] 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. [28]

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 , [29] Nicholas King, a US actor and horticulturist, [30] actress Dina Merrill, [31] Donald Featherstone, who created the plastic pink flamingo, [32] American radio and television host Casey Kasem, [33] Canadian singer Pierre Lalonde, [34] [35] graphic artist/film set designer Ron Cobb, [36] American actor Frank Bonner, [37] and Canadian musician and actor André Gagnon. [38]

Individuals from industry or government who have or died from LBD include Seymour Berry, US Director of the Bureau of Engraving and Printing, [39] Los Angeles Times publisher Otis Chandler, [40] Philip J. Rock, a US Democratic politician of the Illinois Senate, [41] U.S. media mogul and philanthropist Ted Turner, [42] and Indian-born British billionaire S. P. Hinduja. [43]

Arnold R. Hirsch, an American historian who taught at the University of New Orleans, [44] and Jessie Isabelle Price, an American veterinary microbiologist, [45] died from LBD.

In the sports realm, Jerry Sloan, American professional basketball player and coach, died from LBD. [46] Major League Baseball players Tom Seaver, [47] Andy Carey, [48] and Bill Buckner died of LBD. [49] Stan Mikita, Canadian ice hockey player, was diagnosed with possible LBD, [50] but a post-mortem brain autopsy found that he had chronic traumatic encephalopathy. [51]

Robin's Wish , a documentary exploring Robin Williams's Lewy body disease and how it contributed to his death, was released in September 2020. [52] [53] [54]

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. [55]

Notes

  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." [19] The NINDS (2020) says that Lewy body dementia "is one of the most common causes of dementia, after Alzheimer's disease and vascular disease." [7] Hershey (2019) says, "DLB is the third most common of all the neurodegenerative diseases behind both Alzheimer's disease and Parkinson's disease". [20]

Related Research Articles

<span class="mw-page-title-main">Dementia</span> Long-term brain disorders causing impaired memory, thinking and behavior

Dementia is a syndrome associated with many neurodegenerative diseases, which is characterized by a general decline in cognitive abilities that impacts a person's ability to perform everyday activities. This typically involves problems with memory, thinking, behavior, and motor control. Aside from memory impairment and a disruption in thought patterns, the most common symptoms include emotional problems, difficulties with language, and decreased motivation. The symptoms may be described as occurring in a continuum over several stages. Dementia ultimately has a significant effect on the individual, caregivers, and on social relationships in general. A diagnosis of dementia requires the observation of a change from a person's usual mental functioning and a greater cognitive decline than what is caused by normal aging.

<span class="mw-page-title-main">Parkinsonism</span> Medical condition

Parkinsonism is a clinical syndrome characterized by tremor, bradykinesia, rigidity, and postural instability. Both hypokinetic as well as hyperkinetic features are displayed by Parkinsonism.These are the four motor symptoms found in Parkinson's disease (PD) – after which it is named – dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD), and many other conditions. This set of symptoms occurs in a wide range of conditions and may have many causes, including neurodegenerative conditions, drugs, toxins, metabolic diseases, and neurological conditions other than PD.

<span class="mw-page-title-main">Dementia with Lewy bodies</span> Type of progressive dementia

Dementia with Lewy bodies (DLB) is a type of dementia characterized by changes in sleep, behavior, cognition, movement, and regulation of automatic bodily functions. Memory loss is not always an early symptom. The disease worsens over time and is usually diagnosed when cognitive impairment interferes with normal daily functioning. Together with Parkinson's disease dementia, DLB is one of the two Lewy body dementias. It is a common form of dementia, but the prevalence is not known accurately and many diagnoses are missed. The disease was first described on autopsy by Kenji Kosaka in 1976, and he named the condition several years later.

<span class="mw-page-title-main">Rapid eye movement sleep behavior disorder</span> Medical condition

Rapid eye movement sleep behavior disorder or REM behavior disorder (RBD) is a sleep disorder in which people act out their dreams. It involves abnormal behavior during the sleep phase with rapid eye movement (REM) sleep. The major feature of RBD is loss of muscle atonia during otherwise intact REM sleep. The loss of motor inhibition leads to sleep behaviors ranging from simple limb twitches to more complex integrated movements that can be violent or result in injury to either the individual or their bedmates.

<span class="mw-page-title-main">Lewy body</span> Spherical inclusion commonly found in damaged neurons

Lewy bodies are the inclusion bodies – abnormal aggregations of protein – that develop inside nerve cells affected by Parkinson's disease (PD), the Lewy body dementias, and some other disorders. They are also seen in cases of multiple system atrophy, particularly the parkinsonian variant (MSA-P).

<span class="mw-page-title-main">Multiple system atrophy</span> Neurodegenerative disorder

Multiple system atrophy (MSA) is a rare neurodegenerative disorder characterized by tremors, slow movement, muscle rigidity, and postural instability, autonomic dysfunction and ataxia. This is caused by progressive degeneration of neurons in several parts of the brain including the basal ganglia, inferior olivary nucleus, and cerebellum.

<span class="mw-page-title-main">Progressive supranuclear palsy</span> Medical condition

Progressive supranuclear palsy (PSP) is a late-onset neurodegenerative disease involving the gradual deterioration and death of specific volumes of the brain. The condition leads to symptoms including loss of balance, slowing of movement, difficulty moving the eyes, and cognitive impairment. PSP may be mistaken for other types of neurodegeneration such as Parkinson's disease, frontotemporal dementia and Alzheimer's disease. The cause of the condition is uncertain, but involves the accumulation of tau protein within the brain. Medications such as levodopa and amantadine may be useful in some cases.

Parkinson-plus syndromes (PPS) are a group of neurodegenerative diseases featuring the classical features of Parkinson's disease with additional features that distinguish them from simple idiopathic Parkinson's disease (PD). Parkinson-plus syndromes are either inherited genetically or occur sporadically.

Mild cognitive impairment (MCI) is a neurocognitive disorder which involves cognitive impairments beyond those expected based on an individual's age and education but which are not significant enough to interfere with instrumental activities of daily living. MCI may occur as a transitional stage between normal aging and dementia, especially Alzheimer's disease. It includes both memory and non-memory impairments. The cause of the disorder remains unclear, as well as both its prevention and treatment, with some 50 percent of people diagnosed with it going on to develop Alzheimer's disease within five years. The diagnosis can also serve as an early indicator for other types of dementia, although MCI may remain stable or even remit.

<span class="mw-page-title-main">Central nervous system disease</span> Disease of the brain or spinal cord

Central nervous system diseases or central nervous system disorders are a group of neurological disorders that affect the structure or function of the brain or spinal cord, which collectively form the central nervous system (CNS). These disorders may be caused by such things as infection, injury, blood clots, age related degeneration, cancer, autoimmune disfunction, and birth defects. The symptoms vary widely, as do the treatments.

<span class="mw-page-title-main">Alzheimer's disease</span> Progressive neurodegenerative disease

Alzheimer's disease (AD) is a neurodegenerative disease that usually starts slowly and progressively worsens, and is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems with language, disorientation, mood swings, loss of motivation, self-neglect, and behavioral issues. As a person's condition declines, they often withdraw from family and society. Gradually, bodily functions are lost, ultimately leading to death. Although the speed of progression can vary, the average life expectancy following diagnosis is three to twelve years.

<span class="mw-page-title-main">Parkinson's disease</span> Long-term degenerative neurological disorder

Parkinson's disease (PD), or simply Parkinson's, is a chronic degenerative disorder of the central nervous system that affects both the motor system and non-motor systems. The symptoms usually emerge slowly, and as the disease progresses, non-motor symptoms become more common. Early symptoms are tremor, rigidity, slowness of movement, and difficulty with walking. Problems may also arise with cognition, behaviour, sleep, and sensory systems. Parkinson's disease dementia is common in advanced stages.

Signs and symptoms of Parkinson's disease are varied. Parkinson's disease affects movement, producing motor symptoms. Non-motor symptoms, which include dysautonomia, cognitive and neurobehavioral problems, and sensory and sleep difficulties, are also common. When other diseases mimic Parkinson's disease, they are categorized as parkinsonism.

<span class="mw-page-title-main">Synucleinopathy</span> Medical condition

Synucleinopathies are neurodegenerative diseases characterised by the abnormal accumulation of aggregates of alpha-synuclein protein in neurons, nerve fibres or glial cells. There are three main types of synucleinopathy: Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Other rare disorders, such as various neuroaxonal dystrophies, also have α-synuclein pathologies. Additionally, autopsy studies have shown that around 6% of sporadic Alzheimer's Disease exhibit α-synuclein positive Lewy pathology, and are sub-classed as Alzheimer's Disease with Amygdalar Restricted Lewy Bodies (AD/ALB).

Early onset dementia is dementia in which symptoms first appear before the age of 65. The term favored until about 2000 was presenile dementia; young onset dementia is also used.

Parkinson's disease dementia (PDD) is dementia that is associated with Parkinson's disease (PD). Together with dementia with Lewy bodies (DLB), it is one of the Lewy body dementias characterized by abnormal deposits of Lewy bodies in the brain.

The Dementia with Lewy Bodies Consortium is an international multidisciplinary collaboration of researchers interested in the dementia with Lewy bodies. It first convened in Newcastle upon Tyne, England, in October 1995. Between 1995 and 2005, it issued three DLBC Consensus Reports on dementia with Lewy bodies.

Corticobasal syndrome (CBS) is a rare, progressive atypical Parkinsonism syndrome and is a tauopathy related to frontotemporal dementia. CBS is typically caused by the deposit of tau proteins forming in different areas of the brain.

Ian G. McKeith is a professor of Old Age Psychiatry at Newcastle University in Newcastle upon Tyne in the North-East of England. He is a Fellow of the Royal Society of Biology and a Fellow of the Academy of Medical Sciences.

The Lewy Body Dementia Association (LBDA) is a US nonprofit organization based in Lilburn, Georgia, and "dedicated to raising awareness of the Lewy body dementias (LBD), supporting people with LBD, their families and caregivers and promoting scientific advances".

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