Dementia with Lewy bodies (DLB) is a type of dementia characterized by changes in sleep, behavior, cognition, movement, and regulation of automatic bodily functions. Unlike some other dementias, memory loss may not be 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.
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, and people with the disease have an average life expectancy, with wide variability, of about four years after diagnosis. 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. Medications 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 and life-threatening sensitivity reactions occur in almost half of people with DLB, and their use can result in death. Management of the many different symptoms is challenging, as it involves multiple specialties and education of caregivers.
Classification and terminology Dementia with Lewy bodies (DLB) is a type of dementia, a group of diseases involving progressive neurodegeneration of the central nervous system. It is one of the two Lewy body dementias, along with Parkinson's disease dementia.
Dementia with Lewy bodies can be classified in other ways. The atypical parkinsonian syndromes include DLB, along with other conditions. 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.
The vocabulary of diseases associated with Lewy pathology causes confusion. 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). 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 disease. 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.
Signs and symptoms 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), when Parkinson's disease is not well established before the dementia occurs. DLB has widely varying symptoms and is more complex than many other dementias. Several areas of the nervous system (such as the autonomic nervous system and numerous regions of the brain) can be affected by Lewy pathology, in which the alpha-synuclein deposits cause damage and corresponding neurologic deficits.
In DLB, there is an identifiable set of early signs and symptoms; these are called the prodromal, or pre-dementia, phase of the disease. These early signs and symptoms can appear 15 years or more before dementia develops. The earliest symptoms are constipation and dizziness from autonomic dysfunction, hyposmia (reduced ability to smell), RBD, anxiety, and depression. RBD may appear years or decades before other symptoms. Memory loss is not always an early symptom.
Manifestations of DLB can be divided into essential, core, and supportive features. 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).
Essential feature A dementia diagnosis is made after cognitive decline progresses to a point of interfering with normal daily activities, or social or occupational function. 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.
Core features 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.
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.
Fluctuating cognition and alertness Fluctuations in cognitive function are the most characteristic feature of the Lewy body dementias. They are the most frequent symptom of DLB, and are often distinguishable from those of other dementias by concomitant fluctuations of attention and alertness, described by Tsamakis and Mueller (2021) as "spontaneous variations of cognitive abilities, alertness, or arousal". They are further distinguishable by a "marked amplitude between best and worst performances", according to McKeith (2002). These fluctuations vary in severity, frequency and duration; episodes last anywhere from seconds to weeks, interposed between periods of more normal functioning. When relatively lucid periods coincide with medical appointments, cognitive testing may inaccurately reflect disease severity, with subsequent assessments of cognition showing improvements from baseline.
Unlike the deficits in memory and orientation that are characteristic of Alzheimer's disease, the distinct impairments in cognition seen in DLB are most commonly in three domains: attention, executive function, and visuospatial function. These fluctuating impairments are present early in the course of the disease. Individuals with DLB may be easily distracted, have a hard time focusing on tasks, or appear to be "delirium-like", "zoning out", or in states of altered consciousness with spells of confusion, agitation or incoherent speech. They may have disorganized speech and their ability to organize their thoughts may change during the day.
Executive function describes attentional and behavioral controls, memory and cognitive flexibility that aid problem solving and planning. Problems with executive function surface in activities requiring planning and organizing. 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.
The person with DLB may experience disorders of wakefulness or sleep disorders (in addition to REM sleep behavior disorder) that can be severe. These disorders include daytime sleepiness, drowsiness or napping more than two hours a day, insomnia, periodic limb movements, restless legs syndrome and sleep apnea.
REM sleep behavior disorder
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. About 80% of those with DLB have RBD. Abnormal sleep behaviors may begin before cognitive decline is observed, and may appear decades before any other symptoms, often as the first clinical indication of DLB and an early sign of a synucleinopathy.
On autopsy, 94 to 98% of individuals with polysomnography-confirmed RBD have a synucleinopathy—most commonly DLB or Parkinson's disease in about equal proportions. More than three out of four people with RBD are diagnosed with a neurodegenerative condition within ten years, but additional neurodegenerative diagnoses may emerge up to 50 years after RBD diagnosis. RBD may subside over time.
Individuals with RBD may not be aware that they act out their dreams. RBD behaviors may include yelling, screaming, laughing, crying, unintelligible talking, nonviolent flailing, or more violent punching, kicking, choking, or scratching. The reported dream enactment behaviors are frequently violent, and involve a theme of being chased or attacked. People with RBD may fall out of bed or injure themselves or their bed partners, which may cause bruises, fractures, or subdural hematomas. 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.
Parkinsonism Parkinsonism is a clinical syndrome characterized by slowness of movement (called bradykinesia), rigidity, postural instability, and tremor; it is found in DLB and many other conditions like Parkinson's disease, Parkinson's disease dementia, and others. Parkinsonism occurs in more than 85% of people with DLB, who may have one or more of these cardinal features, although tremor at rest is less common than in Parkinson's disease.
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. Presentation of motor symptoms is variable, but they are usually symmetric, presenting on both sides of the body. Only one of the cardinal symptoms of parkinsonism may be present, and the symptoms may be less severe than in persons with Parkinson's disease.
Visual hallucinations Up to 80% of people with DLB have visual hallucinations, typically early in the course of the disease. They are recurrent and frequent; may be scenic, elaborate and detailed; and usually involve animated perceptions of animals or people, including children and family members. 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".