Dementia with Lewy bodies
Type of progressive dementia From Wikipedia, the free encyclopedia
Type of progressive dementia From Wikipedia, the free encyclopedia
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.
| Dementia with Lewy bodies | |
|---|---|
| Other names | Diffuse Lewy body disease, dementia due to Lewy body disease |
 | |
| Microscopic image of a Lewy body (arrowhead) in a neuron of the substantia nigra; scale bar=20 microns (0.02 mm) | |
| Specialty | Neurology, psychiatry |
| Symptoms | Dementia, abnormal behavior during REM sleep, fluctuations in alertness, visual hallucinations, parkinsonism[1] |
| Usual onset | After the age of 50,[2] median 76[3] |
| Duration | Long term[4] |
| Causes | Unknown[4] |
| Diagnostic method | Based on symptoms and biomarkers[1] |
| Differential diagnosis | Alzheimer's, Parkinson's disease dementia, certain mental illnesses, vascular dementia[5] |
| Medication | Donepezil, rivastigmine and memantine;[6] melatonin[7] |
| Prognosis | Variable; average survival 4 years from diagnosis[8] |
| Frequency | About 0.4% of persons older than 65[9] |
REM sleep behavior disorder (RBD)—in which people lose the muscle paralysis (atonia) that normally occurs during REM sleep and act out their dreams—is a core feature. RBD may appear years or decades before other symptoms. Other core features are visual hallucinations, marked fluctuations in attention or alertness, and parkinsonism (slowness of movement, trouble walking, or rigidity). A presumptive diagnosis can be made if several disease features or biomarkers are present; the diagnostic workup may include blood tests, neuropsychological tests, imaging, and sleep studies. A definitive diagnosis usually requires an autopsy.
Most people with DLB do not have affected family members, although occasionally DLB runs in a family. The exact cause is unknown but involves formation of abnormal clumps of protein in neurons throughout the brain. Manifesting as Lewy bodies (discovered in 1912 by Frederic Lewy) and Lewy neurites, these clumps affect both the central and the autonomic nervous systems. Heart function and every level of gastrointestinal function—from chewing to defecation—can be affected, constipation being one of the most common symptoms. Low blood pressure upon standing can also occur. DLB commonly causes psychiatric symptoms, such as altered behavior, depression, or apathy.
DLB typically begins after the age of fifty,[2] and people with the disease have an average life expectancy, with wide variability, of about four years after diagnosis.[8] There is no cure or medication to stop the disease from progressing, and people in the latter stages of DLB may be unable to care for themselves. Treatments aim to relieve some of the symptoms and reduce the burden on caregivers. Medicines such as donepezil and rivastigmine can temporarily improve cognition and overall functioning, and melatonin can be used for sleep-related symptoms. Antipsychotics are usually avoided, even for hallucinations, because severe reactions occur in almost half of people with DLB,[10] and their use can result in death. Management of the many different symptoms is challenging, as it involves multiple specialties and education of caregivers.
Dementia with Lewy bodies (DLB) is a type of dementia, a group of diseases involving progressive neurodegeneration of the central nervous system.[11] It is one of the two Lewy body dementias, along with Parkinson's disease dementia.[12]
Dementia with Lewy bodies can be classified in other ways. The atypical parkinsonian syndromes include DLB, along with other conditions.[13] Also, DLB is a synucleinopathy, meaning that it is characterized by abnormal deposits of alpha-synuclein protein in the brain. The synucleinopathies include Parkinson's disease, multiple system atrophy, and other rarer conditions.[14]
The vocabulary of diseases associated with Lewy pathology causes confusion.[15] 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).[15] Because individuals with Alzheimer's disease (AD) are often found on autopsy to also have Lewy bodies, DLB has been characterized as an Alzheimer disease-related dementia; the term Lewy body variant of Alzheimer disease is no longer used because the predominant pathology for these individuals is related to Alzheimer's.[15] Even the term Lewy body disease may not describe the true nature of this group of diseases; a unique genetic architecture may predispose individuals to specific diseases with Lewy bodies, and naming controversies continue.[16]
DLB is dementia that occurs with "some combination of fluctuating cognition, recurrent visual hallucinations, rapid eye movement (REM) sleep behavior disorder (RBD), and parkinsonism", according to Armstrong (2019),[17] when Parkinson's disease is not well established before the dementia occurs.[1] DLB has widely varying symptoms and is more complex than many other dementias.[18][19] Several areas of the nervous system (such as the autonomic nervous system and numerous regions of the brain) can be affected by Lewy pathology,[lower-alpha 1] in which the alpha-synuclein deposits cause damage and corresponding neurologic deficits.[20]
In DLB, there is an identifiable set of early signs and symptoms; these are called the prodromal, or pre-dementia, phase of the disease.[21][22] These early signs and symptoms can appear 15 years or more before dementia develops.[21] The earliest symptoms are constipation and dizziness from autonomic dysfunction, hyposmia (reduced ability to smell), RBD, anxiety, and depression.[22][23] RBD may appear years or decades before other symptoms.[7] Memory loss is not always an early symptom.[24]
Manifestations of DLB can be divided into essential, core, and supportive features.[1] Dementia is the essential feature and must be present for diagnosis, while core and supportive features are further evidence in support of diagnosis (see diagnostic criteria below).[25]
A dementia diagnosis is made after cognitive decline progresses to a point of interfering with normal daily activities, or social or occupational function.[25] While dementia is an essential feature of DLB, it does not always appear early on, and is more likely to be present as the condition progresses.[25][26]
While specific symptoms may vary, the core features of DLB are fluctuating cognition, alertness or attention; REM sleep behavior disorder; one or more of the cardinal features of parkinsonism, not due to medication or stroke; and repeated visual hallucinations.[1]
The 2017 Fourth Consensus Report of the DLB Consortium determined these to be core features based on the availability of high-quality evidence indicating they are highly specific to the condition.[25]
Fluctuations in cognitive function are the most characteristic feature of the Lewy body dementias.[27][28] They are the most frequent symptom of DLB, and are often distinguishable from those of other dementias by concomitant fluctuations of attention and alertness,[29] described by Tsamakis and Mueller (2021) as "spontaneous variations of cognitive abilities, alertness, or arousal".[30] They are further distinguishable by a "marked amplitude between best and worst performances", according to McKeith (2002).[31] These fluctuations vary in severity, frequency and duration; episodes last anywhere from seconds to weeks,[28][29] interposed between periods of more normal functioning.[29] When relatively lucid periods coincide with medical appointments, cognitive testing may inaccurately reflect disease severity,[29] with subsequent assessments of cognition showing improvements from baseline.[32]
Unlike the deficits in memory and orientation that are characteristic of Alzheimer disease,[25] the distinct impairments in cognition seen in DLB are most commonly in three domains: attention, executive function, and visuospatial function.[33][34] These fluctuating impairments are present early in the course of the disease.[25] Individuals with DLB may be easily distracted, have a hard time focusing on tasks,[35] or appear to be "delirium-like", "zoning out", or in states of altered consciousness[25][36] with spells of confusion, agitation or incoherent speech.[37] They may have disorganized speech and their ability to organize their thoughts may change during the day.[5][25]
Executive function describes attentional and behavioral controls, memory and cognitive flexibility that aid problem solving and planning.[38] Problems with executive function surface in activities requiring planning and organizing.[9] Deficits can manifest in impaired job performance, inability to follow conversations, difficulties with multitasking, or mistakes in driving, such as misjudging distances or becoming lost.[39]
The person with DLB may experience disorders of wakefulness or sleep disorders (in addition to REM sleep behavior disorder) that can be severe.[7] These disorders include daytime sleepiness, drowsiness or napping more than two hours a day, insomnia, periodic limb movements, restless legs syndrome and sleep apnea.[7]
"REM sleep behavior disorder (RBD) has been studied more thoroughly in correlation with DLB and is now considered a core feature. ... Basically, dementia in the presence of polysomnogram-confirmed RBD suggests possible DLB."
—B. Tousi (2017), Diagnosis and Management of Cognitive and Behavioral Changes in Dementia With Lewy Bodies[40]
REM sleep behavior disorder (RBD) is a parasomnia in which individuals lose the paralysis of muscles (atonia) that is normal during rapid eye movement (REM) sleep, and consequently act out their dreams or make other abnormal movements or vocalizations.[41] About 80% of those with DLB have RBD.[42] Abnormal sleep behaviors may begin before cognitive decline is observed,[25] and may appear decades before any other symptoms, often as the first clinical indication of DLB and an early sign of a synucleinopathy.[43]
On autopsy, 94 to 98% of individuals with polysomnography-confirmed RBD have a synucleinopathy—most commonly DLB or Parkinson's disease[44][45] in about equal proportions.[46] More than three out of four people with RBD are diagnosed with a neurodegenerative condition within ten years,[47] but additional neurodegenerative diagnoses may emerge up to 50 years after RBD diagnosis.[45] RBD may subside over time.[25]
Individuals with RBD may not be aware that they act out their dreams.[48] RBD behaviors may include yelling, screaming, laughing, crying, unintelligible talking, nonviolent flailing, or more violent punching, kicking, choking, or scratching.[49][50] The reported dream enactment behaviors are frequently violent,[51] and involve a theme of being chased or attacked.[44] People with RBD may fall out of bed or injure themselves or their bed partners,[25][44][50] which may cause bruises, fractures, or subdural hematomas.[52] Because people are more likely to remember or report violent dreams and behaviors—and to be referred to a specialist when injury occurs—recall or selection bias may explain the prevalence of violence reported in RBD.[53]
Parkinsonism is a clinical syndrome characterized by slowness of movement (called bradykinesia), rigidity, postural instability, and tremor;[54][55] it is found in DLB and many other conditions like Parkinson's disease, Parkinson's disease dementia, and others.[55] Parkinsonism occurs in more than 85% of people with DLB, who may have one or more of these cardinal features,[25] although tremor at rest is less common.[56]
Motor symptoms may include shuffling gait, problems with balance, falls, blank expression, reduced range of facial expression, and low speech volume or a weak voice.[2] Presentation of motor symptoms is variable, but they are usually symmetric, presenting on both sides of the body.[57] Only one of the cardinal symptoms of parkinsonism may be present,[1] and the symptoms may be less severe than in persons with Parkinson's disease.[58]
Up to 80% of people with DLB have visual hallucinations, typically early in the course of the disease.[25][59] They are recurrent and frequent; may be scenic, elaborate and detailed;[60] and usually involve animated perceptions of animals or people, including children and family members.[5] Examples of visual hallucinations "vary from 'little people' who casually walk around the house, 'ghosts' of dead parents who sit quietly at the bedside, to 'bicycles' that hang off of trees in the back yard".[61]
These hallucinations can sometimes provoke fear, although their content is more typically neutral.[5] In some cases, the person with DLB has insight that the hallucinations are not real.[62] Among those with more disrupted cognition, the hallucinations can become more complex, and they may be less aware that their hallucinations are not real.[63] Visual misperceptions or illusions are also common in DLB but differ from visual hallucinations. While visual hallucinations occur in the absence of real stimuli, visual illusions occur when real stimuli are incorrectly perceived;[63] for example, a person with DLB may misinterpret a floor lamp for a person.[5]
Supportive features of DLB have less diagnostic weight, but they provide evidence for the diagnosis.[25] Supportive features may be present early in the progression, and persist over time; they are common but they are not specific to the diagnosis. The supportive features are:[1]
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Partly because of loss of cells that release the neurotransmitter dopamine, people with DLB may have neuroleptic malignant syndrome, impairments in cognition or alertness, or irreversible exacerbation of parkinsonism including severe rigidity,[51] and dysautonomia from the use of antipsychotics.[67]
Dysautonomia (autonomic dysfunction) occurs when Lewy pathology affects the peripheral autonomic nervous system (the nerves dealing with the unconscious functions of organs such as the intestines, heart, and urinary tract).[20] The first signs of autonomic dysfunction are often subtle.[53] Manifestations include blood pressure problems such as orthostatic hypotension (significantly reduced blood pressure upon standing) and supine hypertension (significantly elevated blood pressure when lying horizontally);[68] constipation,[69] urinary problems,[70] and sexual dysfunction;[71] loss of or reduced ability to smell;[53][72] and excessive sweating, drooling, or salivation, and problems swallowing (dysphagia).[72][73]
Alpha-synuclein deposits can affect cardiac muscle and blood vessels.[74] "Degeneration of the cardiac sympathetic nerves is a neuropathological feature" of the Lewy body dementias, according to Yamada et al.[75] Almost all people with synucleinopathies have cardiovascular dysfunction, although most are asymptomatic.[76] Between 50 and 60% of individuals with DLB have orthostatic hypotension due to reduced blood flow, which can result in lightheadedness, feeling faint, and blurred vision.[74]
From chewing to defecation, alpha-synuclein deposits affect every level of gastrointestinal function.[77][78] Almost all persons with DLB have upper gastrointestinal tract dysfunction (such as gastroparesis, delayed gastric emptying) or lower gastrointestinal dysfunction (such as constipation and prolonged stool transit time).[78] Persons with Lewy body dementia almost universally experience nausea, gastric retention, or abdominal distention from delayed gastric emptying.[78] Problems with gastrointestinal function can affect medication absorption.[77] Constipation can present a decade before diagnosis,[79] and is one of the most common symptoms for people with Lewy body dementia.[77] Dysphagia is milder than in other synucleinopathies and presents later.[80] Urinary difficulties (urinary retention, waking at night to urinate, increased urinary frequency and urgency, and over- or underactive bladder) typically appear later and may be mild or moderate.[81] Sexual dysfunction usually appears early in synucleinopathies, and may include erectile dysfunction and difficulty achieving orgasm or ejaculating.[71]
Among the other supportive features, psychiatric symptoms are often present when the individual first comes to clinical attention and are more likely, compared to AD, to cause more impairment.[82] About one-third of people with DLB have depression, and they often have anxiety as well.[10] Anxiety leads to increased risk of falls,[83] and apathy may lead to less social interaction.[2]
Agitation, behavioral disturbances,[84] and delusions typically appear later in the course of the disease.[5] Delusions may have a paranoid quality, involving themes like a house being broken in to, infidelity,[5] or abandonment.[64] Individuals with DLB who misplace items may have delusions about theft.[5] Capgras delusion may occur, in which the person with DLB loses knowledge of the spouse, caregiver, or partner's face,[85] and is convinced that an imposter has replaced them.[5] Hallucinations in other modalities are sometimes present, but are less frequent.[64]
Sleep disorders (disrupted sleep cycles, sleep apnea, and arousal from periodic limb movement disorder) are common in DLB and may lead to hypersomnia.[86] Loss of sense of smell may occur several years before other symptoms.[23]
Like other synucleinopathies,[88] the exact cause of DLB is unknown.[89] No trigger for the build-up of alpha-synuclein deposits in the central nervous system has been conclusively identified.