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Lewy Body Dementia

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Lewy Body Dementia Dementia with Lewy Bodies Victor W. Henderson, MD, MS Departments of Health Research & Policy (Epidemiology) and of Neurology & Neurological Sciences Stanford University Director, Stanford Alzheimer’s Disease Research Center A Lewy body is an abnormal, round structure dementia, and here the pathological changes found inside nerve cells and composed largely are due to stroke and to related changes that of a protein called alpha-synuclein (Figure). impair blood circulation in the brain. DLB is Lewy bodies are associated with two the third most common cause. Changes of all important brain disorders, Parkinson's disease three disorders can occur in the same brain. and dementia with Lewy bodies (DLB). DLB Dementia can be defined as cognitive (mental) is classified as a neurodegenerative disease, decline that has an adverse impact on daily because it involves the progressive function or independence. The term mild impairment and loss of nerve cells. cognitive impairment is used to describe lesser cognitive decline that is not explained by age alone, but the decline does not impair daily function or affects function only minimally. Although DLB is a type of dementia, Lewy bodies can cause milder symptoms that might be better characterized as mild cognitive impairment. Clinical criteria for dementia with Lewy bodies The dementia of DLB differs from that of Alzheimer's disease. In Alzheimer's disease, trouble remembering recent events is often an Figure. Cortical Lewy body. A single Lewy body (arrow) is shown within a pyramidal nerve cell in the early, prominent symptom. In DLB, memory cerebral cortex. H&E stain. Image courtesy of Dr. is often good early in the course of the illness. Edward D. Plowey, Stanford University. Instead, there can be confusion, mental slowness, visual problems, trouble with spatial Dementia and mild cognitive relations, and difficulty with problem solving. impairment The Dementia with Lewy Bodies Consortium DLB is one of several causes of dementia. has recommended criteria for the diagnosis of The most common cause is Alzheimer's probable DLB (Table 1). The consortium disease, which is an entirely separate used the word "probable" to indicate that a neurodegenerative disease. Vascular dementia definite diagnosis of DLB usually requires is the second most common cause of documentation of Lewy bodies during a brain Stanford ADRC | Page 1 | Supported by the NIH AG046366 V W Henderson / Dementia with Lewy Bodies autopsy. There are four "core features" of own and is occasionally seen with other brain DLB, and the diagnosis of DLB requires at disorders. least two of these features, plus dementia. DLB and Parkinson's disease overlap in One core feature is "fluctuating cognition." several ways, and the final core clinical This term refers to periods of confusion or feature of DLB is abnormal movement. In lack of alertness that come and go. A person Parkinson's disease, there are three cardinal with DLB may be drowsy off and on during types of abnormal movements, and any one of the daytime, stare off into space (zone out), or these qualifies as a core feature of DLB. speak in a disorganized manner. These three are bradykinesia (slowness), The second core feature is visual tremor (shaking), and rigidity (stiffness). hallucinations. These also come and go. Bradykinesia refers to slowness in facial Often, the hallucinations are of people or expression, moving the arms and legs, or animals. Even though these can be realistic, walking. It also refers to small movements, the patient sometimes knows quite well that such as separating the hands less than usual these cannot be real. when clapping. Another key feature is tremor, Although not a core feature, some people with especially when resting quietly and not DLB have other mental problems. These otherwise moving. The final key feature of include delusions (fixed, false beliefs like Parkinson's disease is stiffness, which is not paranoia), illusions (misperceptions), or a painful and contributes to slowness. To test false sense of presence or passage. (Presence for rigidity, the doctor might first ask the refers to the experience that someone is person to relax. The doctor should be able to nearby when no one is actually there. Passage move a relaxed arm or leg freely, with very refers to a fleeting, vague image of someone little resistance. When there is rigidity, the or something moving off to the side.) movement will feel stiff and have a ratchet quality. The third core feature is called REM sleep behavior disorder. REM stands for rapid eye Specialized laboratory tests can also be used movements, the stage of sleep during which to help meet consortium criteria for probable dreams occur. During REM sleep, only the DLB. eyes move; the arms and legs are still. In Table. Clinical criteria for probable dementia REM sleep behavior disorder, dreaming and with Lewy bodies staying still are disconnected. A person with A. Dementia, established by clinical examination this disorder will act out dreams and thrash B. Two or more of the following core features: about, and may even strike a bed partner. It is • Fluctuating cognition not uncommon for a spouse to move to a • Visual hallucinations separate bed to keep from being kicked or • REM sleep behavior disorder punched. Interestingly, REM sleep behavior • One or more cardinal feature of disorder sometimes appears years before other Parkinson's disease: bradykinesia problems of DLB. REM sleep behavior (slowness of movement), tremor at rest, or rigidity (stiffness) disorder is often associated with DLB or Parkinson's disease, but it can occur on its (after McKeith et al., 2017) Stanford ADRC | Page 2 | Supported by the NIH (AG047366) V W Henderson / Dementia with Lewy Bodies Relation between DLB, will have mild movement symptoms, or none Parkinson's disease, and at all. Parkinson's disease dementia Evaluation and diagnosis DLB, Parkinson's disease, and Parkinson's disease dementia are closely related. In each, In most instances, a diagnosis of DLB is made the main problem is with alpha-synuclein. or confirmed by a neurologist, geriatrician, or This is a protein is found inside nerve cells at geriatric psychiatrist. A neurologist is best sites where one nerve cell communicates with qualified to recognize and diagnose other the next. In each disorder, alpha-synuclein neurological conditions causing dementia or clumps to form abnormal fibers and larger, affecting movement and mimicking DLB. round Lewy bodies. It is not known why The physician's evaluation is directed towards clumping takes place. These clumps affect documentation of dementia, looking for nerve cells in the brainstem (in an area called changes in movement, and determining the the substantia nigra), the cerebral cortex, and underlying cause. The assessment includes a certain other regions of the nervous system. careful medical, neurological, and psychiatric Nerve cells in the substantia nigra use history; a family history to see whether close dopamine as a chemical transmitter, and family members have a similar or related damage and death of the dopamine nerve cells disorder; a general physical examination; and cause movement symptoms of Parkinson's a neurological examination. The physician disease. The main symptoms of Parkinson's reviews the use of prescription and over-the- disease are bradykinesia, tremor, and rigidity. counter medications. Many older adults take Nerve cells in the cerebral cortex use different multiple drugs, some of which can cause chemical transmitters, and damage and death confusion, impair mental function, and affect of these nerve cells contribute to the mental movement. symptoms of DLB. Nerve cells in the The neurological examination includes substantia nigra and cerebral cortex can be assessment of bradykinesia, tremor, rigidity, affected more or less separately, or they can ataxia (poor coordination), and walking be affected at the same time. balance. Lewy body dementia The evaluation also includes a mental status Lewy body dementia (LBD) is an umbrella examination of memory and other cognitive term for both DLB and Parkinson's disease abilities, sometimes supplemented by more dementia. This term — LBD — is detailed testing by a neuropsychologist. The confusingly similar to DLB. When dementia physician should consider the possibility of occurs in someone who already has depression and look for evidence of anxiety. Parkinson's disease, physicians speak of Laboratory tests depend on the individual Parkinson's disease dementia. DLB is circumstances but usually include a screening diagnosed when dementia occurs before blood test for kidney, liver, and related movement symptoms of Parkinson's disease, metabolic functions; a blood test for thyroid or at the same time. Some people with DLB function; a blood test to determine the level of Stanford ADRC | Page 3 | Supported by the NIH (AG047366) V W Henderson / Dementia with Lewy Bodies vitamin B12; and brain imaging. Brain Cardiac scintigraphy imaging with a CT (computed tomography) Parkinson's disease and DLB affect nerve cells scan or MRI (magnetic resonance imaging) outside the brain. 123Iodine- scan is used to evaluate brain structures and to metaiodobenzylguanidine (MIBG) is a help exclude stroke, tumor, and other less radioactively-labeled chemical. After it is common causes of dementia and abnormal injected into the blood, MIBG is stored in movement. None of these tests can prove the nerve cells that release norepinephrine. presence or absence of DLB. Norepinephrine, like dopamine, is a chemical messenger that travels a very short distance to Specialized laboratory tests activate a second nerve cell. In Parkinson's disease and DLB, the number of these second Specialized tests can help firm up a diagnosis nerve cells is often reduced in the heart. A of DLB when the extra information is needed scan (MIBG cardiac scintigraphy) showing for research. The Dementia with Lewy low levels of MIBG in the heart indicates a Bodies Consortium mentions tests that can be loss of nerve cells that receive norepinephrine.
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