Clinical features and diagnosis of dementia with Lewy bodies

Author
Martin R Farlow, MD
Section Editor
Steven T DeKosky, MD, FAAN, FACP, FANA
Deputy Editor
April F Eichler, MD, MPH
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Dec 2015. &#124 This topic last updated: Mar 17, 2015.

INTRODUCTION — Dementia with Lewy bodies (DLB) is increasingly recognized clinically as the
second most common type of degenerative dementia after Alzheimer disease (AD). In addition to
dementia, distinctive clinical features include: visual hallucinations, parkinsonism, cognitive
fluctuations, dysautonomia, sleep disorders, and neuroleptic sensitivity.

First described in the 1960s, DLB has a varied clinical presentation that shares features with other
degenerative dementias. It was often overlooked pathologically because of the difficulty in identifying
cortical Lewy bodies. With the advent of immunohistochemical stains for some of the constituents of
Lewy bodies, the prevalence of this disorder began to be recognized. However, challenges remain in
defining this as a distinct entity differentiable from other degenerative dementias.

There is some clinical imperative to diagnose DLB, as optimal treatment choices - for best efficacy
and limitation of significant side effects - are specific to DLB. However, DLB continues to be under
recognized, and the clinical diagnostic criteria continue to be refined to improve specificity and
sensitivity.

This topic will describe the clinical and radiologic features and diagnosis of dementia with Lewy
bodies. The epidemiology, neuropathology, pathogenesis, prognosis, and treatment of this disorder
are discussed separately. (See "Epidemiology, pathology, and pathogenesis of dementia with Lewy
bodies" and "Prognosis and treatment of dementia with Lewy bodies".)

Other dementia syndromes are discussed separately. (See "Cognitive impairment and dementia in
Parkinson disease" and "Etiology, clinical manifestations, and diagnosis of vascular dementia" and
"Clinical features and diagnosis of Alzheimer disease" and "Frontotemporal dementia: Clinical
features and diagnosis".)

CLINICAL FEATURES — Consensus criteria for the diagnosis of Dementia with Lewy bodies (DLB)
were developed by the Consortium on Dementia with Lewy Bodies and have been successively
revised to improve sensitivity and specificity [1]. The Table outlines the clinical diagnostic criteria for
probable and possible DLB defined by the third report of the DLB consortium (table 1). Dementia is
essential to the diagnosis of DLB. Other clinical manifestations of DLB are organized into a hierarchy
of diagnostic specificity of core, suggestive, and supportive features.

Dementia — Cognitive dysfunction is often the presenting symptom in DLB, and dementia eventually
occurs in all cases. Unlike Alzheimer disease (AD), which typically presents with memory loss as its
first and most prominent cognitive deficit, DLB is characterized by early impairments in attention and
executive and visuospatial function, with memory affected later in the course of the disease [ 2-8].
Early symptoms include driving difficulty (eg, getting lost, misjudging distances, or failing to see stop
signs or other cars) and impaired job performance.

Bedside tests of cognitive function, eg, the Mini-Mental State Examination (MMSE) are not reliable to
differentiate among dementia types. However, the early appearance of impaired figure copying
(overlapping pentagons), clock drawing, and serial sevens (or spelling WORLD backward) is
suggestive of DLB, while AD patients generally show impaired short-term memory and orientation as
the earliest deficits on the MMSE [9,10]. In one study with neuropathologic confirmation, absence of
visuospatial impairments in the early stages of disease helped to exclude DLB with a negative
predictive value of 90 percent [7].

Early signs on neuropsychological testing may include deficiencies in tests of visuospatial and visuo-
perception [4,8,11,12]. Measures of executive function and attention (eg, Trail-Making Test,
Wisconsin Card-Sorting Test, letter and category verbal fluency tests) may also be impaired early on
[13]. When memory does become impaired in DLB, memory retrieval may be more affected than
acquisition [14]. Neuropsychological tests, while helpful in quantifying and qualifying neurologic
deficits, do not have clear discriminative ability for different dementia syndromes.

DLB patients with prominent AD pathology (eg, neurofibrillary tangles) may have a cognitive profile
that is more characteristic of AD.

Core clinical features — In addition to dementia, a patient with probable DLB must have at least two
of three of the so-called "core clinical features" of DLB: cognitive fluctuations, visual hallucinations,
and parkinsonism (table 1).

Fluctuations — Fluctuations in cognition and levels of alertness may occur early in the course of DLB
and are estimated to be a feature in 60 to 80 percent [15] of cases. The severity, duration, and type
of symptoms involved in fluctuations is quite varied, even for a given patient. Episodes can be subtle,
as in a brief decline in ability to perform an activity of daily living, or they may be dramatic enough to
raise the question of a stroke or seizure. Caregivers often describe episodes in which patients
appear to "blank out" or lose consciousness, become confused or behave in a bizarre manner, have
speech or motor arrest, or become excessively somnolent. These episodes can last seconds to
days, and they can be interspersed with periods of near-normal function,

This feature of DLB has been considered the most difficult of the core clinical features for
inexperienced clinicians to evaluate. Family members may not volunteer this history. At the same
time, questions to elicit this history, if too general, are likely to obtain false positive responses in
patients with other forms of dementia [16,17]. Structured questionnaires (eg, Clinical Assessment of
Fluctuation, One Day Fluctuation Assessment Scale) appear to more specifically elicit the symptoms
of fluctuations in DLB. These share, as a common feature, the solicitation of more than one example
of a fluctuation episode with specific descriptive details regarding symptoms, severity, and duration
[18].

Episodes that include at least three of the four following features: daytime drowsiness, daytime naps
lasting more than two hours, prolonged staring spells, and episodes of disorganized speech, are
more likely to occur in patients with DLB than with AD [16]. Fluctuations in AD are usually described
vaguely as "good days and bad days" and are often explained by external stressors. In DLB,
fluctuations are more often spontaneous and episodic, seemingly related to an interruption of
awareness or attention that impacts functional ability [17].

An objective measure of fluctuations in DLB using computerized assessments of reaction time and
vigilance has been shown to distinguish patients with DLB from Vascular Dementia and AD, but this
is not a generally available clinical assessment tool [19].

Visual hallucinations — Visual hallucinations occur in approximately two-thirds of patients with DLB,
and are relatively rare in AD [20-22]. These are also an early sign in DLB and may precede
parkinsonism. In one study with neuropathologic confirmation, visual hallucinations at presentation
was the most useful clinical feature to distinguish DLB from AD, with 83 percent positive predictive
value [7]. Among patients with DLB, those with visual hallucinations appear to have more severe
deficits in visual attention and executive function compared with those without visual hallucinations,
but similar degrees of visuospatial and visual-perceptual impairment [23].

Descriptions range from well-formed images of people or animals, to more abstract visions such as
shapes or colors. Patients have described such simple hallucinations as seeing something briefly out
of the corner of their eye, or extremely complex hallucinations, such as an ongoing dialog with a
deceased loved one. Patients may also describe visual misperceptions, in which an object seems to
move, zoom toward or away from the patient, or change shape.

If not specifically solicited, visual hallucinations are often under reported. Patients may or may not
have insight into the nature of the hallucinations or illusions, and reactions may vary from fear to
indifference to enjoyment. (See "Approach to the patient with visual hallucinations", section on
'Neurodegenerative disease'.)

Parkinsonism — Parkinsonian symptoms, brady- and akinesia, limb rigidity, and/or gait disorder, are
seen in approximately 70 to 90 percent of patients with DLB, and they can be as severe as in
idiopathic Parkinson disease (PD) [21,24]. However, parkinsonian features are usually more
bilaterally symmetric and milder than in PD in most, although not all, studies [25]. Tremor may also
occur, but it is much less common and less severe than in PD [26,27]. Despite these observed
clinical trends, no individual symptom characteristic reliably distinguishes the motor parkinsonism of
PD versus DLB. (See "Bradykinetic movement disorders in children", section on 'Parkinson disease'.)

Suggestive features — These features include REM sleep disorder, severe neuroleptic sensitivity,
and low dopamine transporter uptake in the basal ganglia on single photon emission computed
tomography (SPECT) or positron-emission tomography (PET) (table 1). The presence of one of
these in combination with one core clinical feature supports the diagnosis of probable DLB. The
presence of one or more suggestive features in the absence of a core clinical feature suggests
possible DLB.

REM sleep behavior disorder — Rapid eye movement (REM) sleep behavior disorder (RBD) is a
parasomnia characterized by dream enactment that emerges after a loss of REM sleep atonia.
Individuals have recurrent sleep-related vocalization and/orcomplex motor behaviors during REM
sleep, correlating with dream mentation. The movements of RBD are short in duration (less than 60
seconds) and appear purposeful, such as throwing a ball or flailing to protect oneself. They range in
severity from benign hand gestures to violent thrashing, punching, and kicking. Sleep-related injuries
can arise from jumping out of bed or striking a bed partner. (See "Rapid eye movement sleep
behavior disorder", section on 'Clinical features' and "Rapid eye movement sleep behavior disorder",
section on 'Diagnosis'.)

RBD is commonly associated with DLB, occurring in 85 percent of individuals, often early in the
course of the disease [28]. It can precede the clinical diagnosis of DLB by up to 20 years. Some data
suggests that it sufficiently common in DLB to be a core rather than a suggestive clinical feature [29].
It is also prevalent in other synucleinopathies and narcolepsy, and it can occur secondary to
structural lesions in the brainstem and medications, most notably the serotonergic antidepressants.
(See "Rapid eye movement sleep behavior disorder", section on 'Etiology' and "Rapid eye movement
sleep behavior disorder", section on 'Epidemiology'.)

All patients with RBD and their bed partners should be counseled on ways to alter the sleeping
environment to prevent injury. Most patients respond to treatment with melatonin or clonazepam.
(See "Rapid eye movement sleep behavior disorder", section on 'Treatment' and "Rapid eye
movement sleep behavior disorder", section on 'Epidemiology'.)

Other sleep disorders that may be seen with DLB include insomnia, daytime hypersomnolence, sleep
apnea (obstructive or central), periodic limb movements of sleep, and restless legs syndrome [30].
These are not diagnostic features of DLB, but are important to recognize as effective treatments
exist.

Neuroleptic sensitivity — Approximately 30 to 50 percent of individuals with DLB have severe

sensitivity to neuroleptics [31-33]. Acute reactions include severe, sometimes irreversible
parkinsonism and impaired consciousness, sometimes with other features suggestive of neuroleptic
malignant syndrome. This can occur in individuals without baseline parkinsonism. This is more
common with conventional agents, but reactions to newer drugs have also been described [ 34]. It is
not dose-related. Neuroleptic medications may also precipitate or worsen confusion or autonomic
dysfunction, and their use has been associated with a two to three-fold increase in mortality.

Severe reactions to neuroleptics are less common in patients with Parkinson disease (with or without
dementia), but have not been described in AD. Despite the high specificity of this finding, deliberate
pharmacologic challenge as a diagnostic strategy is obviously unwise. A history of neuroleptic
tolerance does not exclude DLB or future neuroleptic sensitivity.

Supportive features — The following clinical features are common in DLB but do not have clear
diagnostic specificity (table 1).

Repeated falls — Recurrent falls occur in up to a third of patients with DLB and may be among the
earliest symptoms [35]. Falls may seem to occur with or without provocation and may be related to
parkinsonism, to cognitive fluctuations, or to orthostatic hypotension.
Syncope or transient loss of consciousness — Episodes of altered or loss of consciousness are
commonly described. Patients may transiently lose consciousness, or they may be awake but mute
and staring blankly. Episodes may even resemble cataplexy, in which patients develop sudden
atonia and fall to the floor.

These can occur as a result of orthostatic hypotension, which has been reported in 28 to 50 percent
of patients, and which can be severe enough to mimic multiple systems atrophy [36,37]. In one
series, 6 of 20 patients with DLB followed for three years required medication for blood pressure
maintenance [37]. Carotid sinus sensitivity has also been described in association with DLB and may
underlie episodes of syncope, or may be a general marker of autonomic dysfunction [38].

Episodes may also represent an extreme cognitive fluctuation or may be analogous to the motor
"freezing" seen in idiopathic PD. Other etiologies such as seizures, stroke, transient ischemic attack,
or cardiac arrhythmia should also be ruled out.

Autonomic dysfunction — In addition to orthostatic hypotension and neurocardiovascular instability

discussed above, autonomic dysfunction in DLB may include urinary incontinence or retention,
constipation and other gastrointestinal symptoms, and impotence [36,37,39]. Autonomic symptoms
are more prevalent and severe than in PD, but less than in multiple systems atrophy [ 37]. Urinary
incontinence occurs at late stages of AD when dementia is severe but is often an early sign in DLB
[40,41].

Some small case series suggest that tests of autonomic dysfunction (eg, sympathetic sweat
responses, skin vasomotor reflexes, head-up tilt, ventilatory response to hypercapnia, and heart rate
variability) are likely to be markedly abnormal in patients with DLB and may help differentiate these
patients from individuals with other neurodegenerative dementias [42,43]. However, this diagnostic
approach requires independent, prospective validation.

Hallucinations in other modalities — In addition to visual hallucinations, patients with DLB may also
experience hallucinations in other modalities. Auditory hallucinations may be well formed, such as
hearing identifiable speech or music, or they may be less distinct, such as having the impression of
hearing a television, voice, or telephone ringing in another room. Olfactory hallucinations can be
pleasant (eg, flowers or food) or unpleasant (eg, burning rubber). Patients have described tactile
hallucinations such as the feeling of insects on their skin, or a cat brushing against their leg. The
presence of these hallucinations may also prompt a workup for partial seizures, psychotic disorders,
or substance intoxication or withdrawal.

Systematized delusions — Delusions (false, fixed beliefs) occur commonly in DLB (in as many as 75
percent of cases) and may be elaborate, specific, and systematic [44]. They are often rooted in
hallucinations or visual misperceptions that the patient has experienced. Common themes include:
the spouse or caregiver is an impostor, the house is not their home, or people in the television or
mirror are speaking to them or following them.

Somatoform disorder (characterized by a high frequency of medically unexplained symptoms) is a

related but distinct psychiatric syndrome that may be observed in patients with DLB. In one study, 12
percent (15 of 124) of patients with DLB exhibited symptoms of somatization [45]. The observed
symptoms often took on delusional qualities (body deformation, requests for invasive medical
procedures) and were associated with motor catatonic signs in eight patients.

Depression — Most patients with DLB experience depressive symptoms at some point in their
illness, and up to 40 percent have a major depressive episode. This is similar to the rate in PD [ 46],
but higher in one study than the rate seen in AD [47]. Depression is less likely than other features of
DLB to persist over time [44].

RADIOLOGIC FEATURES — Radiologic features are not essential to the diagnosis of DLB, but may
provide supporting evidence (table 1).

Magnetic resonance imaging — While generalized atrophy and white matter lesions are nonspecific
findings in dementia, magnetic resonance imaging (MRI) may identify patterns of regional atrophy
that are more specific to DLB. In particular, MRI coronal sections through the hippocampi usually
show a greater degree of hippocampal atrophy in Alzheimer disease (AD) compared with DLB
(image 1) [48-50]. In one study, volumetric analysis of MRI scans found that patients with DLB had
more pronounced cortical atrophy than did patients with Parkinson disease dementia (PDD) [ 51].
However, it seems unlikely that this observation is sufficiently sensitive and specific to aid in
diagnosis of DLB versus PDD in individual patients [52].

Volumetric analyses of MRI scans have also suggested atrophy of the putamen and dorsal
mesopontine gray matter in DLB compared with AD [50,53]. Despite the changes in the occipital
lobe on functional imaging discussed below, regional occipital atrophy is generally not observed on
MRI in DLB. However, one study did report that a finding of reduced fractional anisotropy in the
parieto-occipital white matter tracts on diffusion tensor imaging was associated with DLB and not AD
[54].

SPECT and PET studies — Single-photon emission computed tomography (SPECT) and positron
emission tomography (PET) scans show generalized decreased perfusion and metabolism,
respectively, which is most noticeable in the occipital areas [55-61]. The changes in the occipital
lobe appear, at least in small series, to have potential diagnostic utility in DLB, with a sensitivity and
specificity for SPECT of 65 and 87 percent and for PET of 90 and 80 percent [ 56,62]. This requires
independent validation.

Using specific ligands for dopamine transporter, SPECT and PET studies have demonstrated low
dopaminergic activity in the striatum in DLB [63-70]. This is also seen in PD, multiple systems
atrophy, and progressive supranuclear palsy, but not in AD. A study in 326 patients with dementia
reported a sensitivity of 78 percent and a specificity of 90 percent of ioflupane I-123 dopamine
transporter SPECT imaging (DaTscan) for the diagnosis of DLB [71]. This test result is considered a
suggestive feature in the diagnosis of probable or possible DLB (see 'Suggestive features' above)
(table 1). However, this technique is not widely available for clinical use.

Myocardial scintigraphy — 123-I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy

demonstrates low uptake in DLB, representing reduced postganglionic sympathetic cardiac
innervation [72,73]. In small series, this test appears to have high sensitivity and specificity for DLB
[74], especially when distinguishing it from AD [75,76]. As an example, in one series, a heart to
mediastinum uptake ratio of <1.68 had a sensitivity, specificity, and positive predictive value of 100
percent in discriminating between 37 patients with DLB and 42 patients with AD [75]. Similar
abnormalities are also seen in PD, but not in multiple systems atrophy, progressive supranuclear
palsy, or corticobasal ganglionic degeneration.

DIFFERENTIAL DIAGNOSIS — The primary entity considered in the differential diagnosis for DLB is
Alzheimer disease (AD). Other considerations include Parkinson disease (PD), vascular dementia,
other degenerative dementias, and certain psychiatric disease [77]. The clinical features which are
useful in distinguishing among these disorders are discussed above (see 'Clinical features' above).

Parkinson disease dementia — The differentiation of Parkinson disease dementia (PDD) and
Dementia with Lewy bodies (DLB) is somewhat arbitrary [ 78]. In PDD, dementia occurs in the setting
of well established parkinsonism, while in DLB, dementia usually occurs concomitantly with or before
the development of parkinsonian signs. If parkinsonism is present for more than one year before the
onset of dementia, it is officially classified as PDD. This arbitrary "one-year rule" may be an artificial
distinction; the length of time that parkinsonism precedes other symptoms in otherwise similar
patients does not correlate with pathologic differences [77]. On the other hand, in one quantitative
morphometric MRI study, patients with DLB had more pronounced cortical atrophy compared with
patients with PDD, despite a similar severity of dementia in both groups [51]. Another study also
found that patients with PDD and DLB with similar severities of dementia could be distinguished by
patterns of fractional anisotropy on diffuse tensor imaging MRI [79]. In contrast, a positron emission
tomography study using dopaminergic and cholinergic tracers found that PDD and DLB appeared
similar [80].

Other features that may help distinguish between DLB and PDD are an older age of onset, faster
clinical decline, and decreased levodopa responsivity for DLB compared with PDD [81]. Other clinical
characteristics don't clearly distinguish well between DLB and PDD [22]. Parkinson disease
dementia is discussed separately. (See "Cognitive impairment and dementia in Parkinson disease".)
Other dementia syndromes — When superimposed on AD or other degenerative dementias, delirium
(from medication effects, systemic illness, or other metabolic abnormalities) may mimic some
symptoms of DLB, including fluctuations and hallucinations. Fluctuations in a demented individual
may be due to transient ischemic attack, seizure, or cardiac arrhythmia, rather than as a
manifestation of DLB. Similarly, extrapyramidal side effects of medications should be considered as
a potential cause of parkinsonism in patients with dementia. There is substantial clinical as well as
pathologic overlap between AD and DLB. (See "Epidemiology, pathology, and pathogenesis of
dementia with Lewy bodies", section on 'Clinical pathologic correlations'.)

Creutzfeldt-Jakob disease (CJD) and DLB can have similar presentations. Prominent visual
disturbances can present as an early sign in some forms of CJD, and myoclonus is sometimes a
feature of DLB. (See "Creutzfeldt-Jakob disease".)

Normal pressure hydrocephalus (NPH) presents with cognitive decline, urinary incontinence, and gait
disorder; all of these are features of DLB. Psychiatric symptoms, sleep disorder, and other
dysautonomic manifestations are absent in NPH. (See "Normal pressure hydrocephalus".)

DIAGNOSIS — The evaluation of a patient with dementia first establishes the presence of cognitive
impairment and provides a measure of its severity. Treatable conditions are excluded. In general,
this evaluation includes a cognitive assessment (Mini-Mental State Examination or formal
neuropsychological testing), a neuroimaging study (usually magnetic resonance imaging), and
laboratory evaluations (vitamin B12 level and thyroid function tests). This topic is discussed in more
detail elsewhere. (See "Evaluation of cognitive impairment and dementia".)

Other ancillary studies are not routinely indicated but may be needed depending on the clinical
picture. Electroencephalography (EEG) may be helpful if there is a question of seizures or of
Creutzfeldt-Jakob disease (CJD). In DLB, the tracing may appear normal or nonspecifically abnormal
with diffuse slowing, disorganization of the background rhythm, and temporal lobe transient sharp
waves; frontal intermittent rhythmic delta activity (FIRDA) has also been described [ 77,82]. Video-
monitored electroencephalogram (EEG) may be useful to rule out seizures in the evaluation of
cognitive fluctuations or staring spells. Polysomnography may be useful in evaluating sleep
disorders. Other tests to evaluate the possibility of transient ischemic attack or syncope may be
indicated in some patients with severe fluctuations or episodic loss of consciousness. (See "Initial
evaluation and management of transient ischemic attack and minor stroke" and "Evaluation of
syncope in adults".) SPECT scanning using the dopamine transporter ligand ioflupane I-123
(DaTscan) can provide support for the diagnosis of DLB in cases when the clinical features are
suggestive but not diagnostic [83]. (See 'SPECT and PET studies' above.)

A positive diagnosis of DLB is primarily based upon clinical history and examination. Several
autopsy-confirmed studies have shown that clinical diagnostic criteria provide a high specificity (0.87
to 1.0), but low sensitivity (0.22 to 0.65) for the pathologic diagnosis of DLB [25,84-90]. An effort to
improve the sensitivity of the clinical diagnosis is represented by the revised criteria of the third report
of the DLB consortium (table 1). These have not been validated.

The clinical and radiologic features which distinguish DLB from AD and other dementias are most
useful earlier in the course of the disease. In late stages, the clinical features of most dementia
syndromes are more similar than different.

The biggest barrier to the diagnosis of DLB is a low index of suspicion. The cardinal features of DLB
which suggest the diagnosis may not be volunteered by patients or caregivers and often require
specific solicitation by the clinician.

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The
Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language,
at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might
have about a given condition. These articles are best for patients who want a general overview and
who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer,
more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading
level and are best for patients who want in-depth information and are comfortable with some medical
jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-
mail these topics to your patients. (You can also locate patient education articles on a variety of
subjects by searching on “patient info” and the keyword(s) of interest.)

●Basics topic (see "Patient information: Dementia with Lewy bodies (The Basics)")

●Beyond the Basics topic (see "Patient information: Dementia (including Alzheimer disease) (Beyond
the Basics)").

SUMMARY AND RECOMMENDATIONS — Dementia with Lewy bodies (DLB) is the second most
common form of degenerative dementia after Alzheimer disease.

●DLB is characterized clinically by deficits in attention and visuospatial function; fluctuating cognition;
recurrent visual hallucinations; and spontaneous motor features of parkinsonism. Other associated
symptoms include repeated falls, syncope, autonomic dysfunction, neuroleptic sensitivity, delusions,
hallucinations in other modalities, sleep disorders, and depression (table 1). (See 'Clinical features'
above.)

●The diagnosis of DLB requires a high index of suspicion and specific solicitation of cardinal
features, which may not be volunteered by patients or caregivers. (See 'Clinical features' above.)

●The differential diagnosis of DLB includes other degenerative dementias, especially if complicated
by superimposed delirium, medication toxicity, or seizures. (See 'Differential diagnosis' above.)

●The diagnosis of DLB is made primarily by clinical criteria (table 1). Radiologic features may also
aid in the diagnosis, but are not required. For any individual clinical feature, the specificity is greater
than the sensitivity for DLB. (See 'Diagnosis' above.)

●Additional testing (blood work, electroencephalogram) is frequently indicated to rule out delirium or
seizure as a cause or contributor to a patient's symptoms. (See 'Diagnosis' above.)

ACKNOWLEDGMENT — The editorial staff at UpToDate, Inc. would like to acknowledge Dr. Ann
Marie Hake, who contributed to an earlier version of this topic review.

Use of UpToDate is subject to the Subscription and License Agreement.

 REFERENCES

McKeith IG, Dickson DW, Lowe J, et al. Diagnosis and management of dementia with Lewy
1
bodies: third report of the DLB Consortium. Neurology 2005; 65:1863.
Salmon DP, Galasko D, Hansen LA, et al. Neuropsychological deficits associated with
2
diffuse Lewy body disease. Brain Cogn 1996; 31:148.
Simard M, van Reekum R, Cohen T. A review of the cognitive and behavioral symptoms in
3
dementia with Lewy bodies. J Neuropsychiatry Clin Neurosci 2000; 12:425.
Ballard CG, Ayre G, O'Brien J, et al. Simple standardised neuropsychological assessments
4 aid in the differential diagnosis of dementia with Lewy bodies from Alzheimer's disease
and vascular dementia. Dement Geriatr Cogn Disord 1999; 10:104.
Aarsland D, Litvan I, Salmon D, et al. Performance on the dementia rating scale in
Parkinson's disease with dementia and dementia with Lewy bodies: comparison with
5
progressive supranuclear palsy and Alzheimer's disease. J Neurol Neurosurg Psychiatry
2003; 74:1215.
Calderon J, Perry RJ, Erzinclioglu SW, et al. Perception, attention, and working memory
6 are disproportionately impaired in dementia with Lewy bodies compared with Alzheimer's
disease. J Neurol Neurosurg Psychiatry 2001; 70:157.
Tiraboschi P, Salmon DP, Hansen LA, et al. What best differentiates Lewy body from
7
Alzheimer's disease in early-stage dementia? Brain 2006; 129:729.
Mondon K, Gochard A, Marqué A, et al. Visual recognition memory differentiates dementia
8 with Lewy bodies and Parkinson's disease dementia. J Neurol Neurosurg Psychiatry 2007;
78:738.
Ala TA, Hughes LF, Kyrouac GA, et al. Pentagon copying is more impaired in dementia
9 with Lewy bodies than in Alzheimer's disease. J Neurol Neurosurg Psychiatry 2001;
70:483.
10 Gnanalingham KK, Byrne EJ, Thornton A. Clock-face drawing to differentiate Lewy body
 and Alzheimer type dementia syndromes. Lancet 1996; 347:696.
Mori E, Shimomura T, Fujimori M, et al. Visuoperceptual impairment in dementia with
11
Lewy bodies. Arch Neurol 2000; 57:489.
Mosimann UP, Mather G, Wesnes KA, et al. Visual perception in Parkinson disease
12
dementia and dementia with Lewy bodies. Neurology 2004; 63:2091.
Bradshaw JM, Saling M, Anderson V, et al. Higher cortical deficits influence attentional
13 processing in dementia with Lewy bodies, relative to patients with dementia of the
Alzheimer's type and controls. J Neurol Neurosurg Psychiatry 2006; 77:1129.
Mormont E, Laurier-Grymonprez L, Baisset-Mouly C, Pasquier F. [The profile of memory
14 disturbance in early Lewy body dementia differs from that in Alzheimer's disease]. Rev
Neurol (Paris) 2003; 159:762.
McKeith IG, Galasko D, Kosaka K, et al. Consensus guidelines for the clinical and
15 pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on
DLB international workshop. Neurology 1996; 47:1113.
Ferman TJ, Smith GE, Boeve BF, et al. DLB fluctuations: specific features that reliably
16
differentiate DLB from AD and normal aging. Neurology 2004; 62:181.
Bradshaw J, Saling M, Hopwood M, et al. Fluctuating cognition in dementia with Lewy
17 bodies and Alzheimer's disease is qualitatively distinct. J Neurol Neurosurg Psychiatry
2004; 75:382.
Walker MP, Ayre GA, Cummings JL, et al. The Clinician Assessment of Fluctuation and the
18 One Day Fluctuation Assessment Scale. Two methods to assess fluctuating confusion in
dementia. Br J Psychiatry 2000; 177:252.
Walker MP, Ayre GA, Cummings JL, et al. Quantifying fluctuation in dementia with Lewy
19
bodies, Alzheimer's disease, and vascular dementia. Neurology 2000; 54:1616.
Ala TA, Yang KH, Sung JH, Frey WH 2nd. Hallucinations and signs of parkinsonism help
distinguish patients with dementia and cortical Lewy bodies from patients with Alzheimer's
20
disease at presentation: a clinicopathological study. J Neurol Neurosurg Psychiatry 1997;
62:16.
Strong C, Anderton BH, Perry RH, et al. Abnormally phosphorylated tau protein in senile
21 dementia of Lewy body type and Alzheimer disease: evidence that the disorders are
distinct. Alzheimer Dis Assoc Disord 1995; 9:218.
Galvin JE, Pollack J, Morris JC. Clinical phenotype of Parkinson disease dementia.
22
Neurology 2006; 67:1605.
Cagnin A, Gnoato F, Jelcic N, et al. Clinical and cognitive correlates of visual hallucinations
23
in dementia with Lewy bodies. J Neurol Neurosurg Psychiatry 2013; 84:505.
Aarsland D, Ballard C, McKeith I, et al. Comparison of extrapyramidal signs in dementia
24
with Lewy bodies and Parkinson's disease. J Neuropsychiatry Clin Neurosci 2001; 13:374.
Mega MS, Masterman DL, Benson DF, et al. Dementia with Lewy bodies: reliability and
25
validity of clinical and pathologic criteria. Neurology 1996; 47:1403.
Galasko D, Katzman R, Salmon DP, Hansen L. Clinical and neuropathological findings in
26
Lewy body dementias. Brain Cogn 1996; 31:166.
Burn DJ, Rowan EN, Allan LM, et al. Motor subtype and cognitive decline in Parkinson's
27 disease, Parkinson's disease with dementia, and dementia with Lewy bodies. J Neurol
Neurosurg Psychiatry 2006; 77:585.
Paparrigopoulos TJ. REM sleep behaviour disorder: clinical profiles and pathophysiology.
28
Int Rev Psychiatry 2005; 17:293.
Ferman TJ, Boeve BF, Smith GE, et al. Inclusion of RBD improves the diagnostic
29
classification of dementia with Lewy bodies. Neurology 2011; 77:875.
Boeve BF, Silber MH, Ferman TJ. Current management of sleep disturbances in dementia.
30
Curr Neurol Neurosci Rep 2002; 2:169.
McKeith I, Fairbairn A, Perry R, et al. Neuroleptic sensitivity in patients with senile
31
dementia of Lewy body type. BMJ 1992; 305:673.
Aarsland D, Perry R, Larsen JP, et al. Neuroleptic sensitivity in Parkinson's disease and
32
parkinsonian dementias. J Clin Psychiatry 2005; 66:633.
Ballard C, Grace J, McKeith I, Holmes C. Neuroleptic sensitivity in dementia with Lewy
33
bodies and Alzheimer's disease. Lancet 1998; 351:1032.
34 Walker Z, Grace J, Overshot R, et al. Olanzapine in dementia with Lewy bodies: a clinical
 study. Int J Geriatr Psychiatry 1999; 14:459.
Barber R, Panikkar A, McKeith IG. Dementia with Lewy bodies: diagnosis and
35
management. Int J Geriatr Psychiatry 2001; 16 Suppl 1:S12.
Horimoto Y, Matsumoto M, Akatsu H, et al. Autonomic dysfunctions in dementia with Lewy
36
bodies. J Neurol 2003; 250:530.
Thaisetthawatkul P, Boeve BF, Benarroch EE, et al. Autonomic dysfunction in dementia
37
with Lewy bodies. Neurology 2004; 62:1804.
Kenny RA, Shaw FE, O'Brien JT, et al. Carotid sinus syndrome is common in dementia
38 with Lewy bodies and correlates with deep white matter lesions. J Neurol Neurosurg
Psychiatry 2004; 75:966.
Postuma RB, Gagnon JF, Pelletier A, Montplaisir J. Prodromal autonomic symptoms and
39
signs in Parkinson's disease and dementia with Lewy bodies. Mov Disord 2013; 28:597.
Del-Ser T, Munoz DG, Hachinski V. Temporal pattern of cognitive decline and incontinence
40 is different in Alzheimer's disease and diffuse Lewy body disease. Neurology 1996;
46:682.
Ransmayr GN, Holliger S, Schletterer K, et al. Lower urinary tract symptoms in dementia
41
with Lewy bodies, Parkinson disease, and Alzheimer disease. Neurology 2008; 70:299.
Akaogi Y, Asahina M, Yamanaka Y, et al. Sudomotor, skin vasomotor, and cardiovascular
42
reflexes in 3 clinical forms of Lewy body disease. Neurology 2009; 73:59.
Mizukami K, Homma T, Aonuma K, et al. Decreased ventilatory response to hypercapnia
43
in dementia with Lewy bodies. Ann Neurol 2009; 65:614.
Ballard CG, O'Brien JT, Swann AG, et al. The natural history of psychosis and depression
44 in dementia with Lewy bodies and Alzheimer's disease: persistence and new cases over 1
year of follow-up. J Clin Psychiatry 2001; 62:46.
Onofrj M, Bonanni L, Manzoli L, Thomas A. Cohort study on somatoform disorders in
45
Parkinson disease and dementia with Lewy bodies. Neurology 2010; 74:1598.
Klatka LA, Louis ED, Schiffer RB. Psychiatric features in diffuse Lewy body disease: a
46 clinicopathologic study using Alzheimer's disease and Parkinson's disease comparison
groups. Neurology 1996; 47:1148.
Ballard C, Holmes C, McKeith I, et al. Psychiatric morbidity in dementia with Lewy bodies:
47 a prospective clinical and neuropathological comparative study with Alzheimer's disease.
Am J Psychiatry 1999; 156:1039.
Burton EJ, Karas G, Paling SM, et al. Patterns of cerebral atrophy in dementia with Lewy
48
bodies using voxel-based morphometry. Neuroimage 2002; 17:618.
Barber R, Ballard C, McKeith IG, et al. MRI volumetric study of dementia with Lewy
49
bodies: a comparison with AD and vascular dementia. Neurology 2000; 54:1304.
Kantarci K, Ferman TJ, Boeve BF, et al. Focal atrophy on MRI and neuropathologic
50
classification of dementia with Lewy bodies. Neurology 2012; 79:553.
Beyer MK, Larsen JP, Aarsland D. Gray matter atrophy in Parkinson disease with dementia
51
and dementia with Lewy bodies. Neurology 2007; 69:747.
Seppi K, Rascol O. Dementia with Lewy bodies and Parkinson disease with dementia: can
52
MRI make the difference? Neurology 2007; 69:717.
Cousins DA, Burton EJ, Burn D, et al. Atrophy of the putamen in dementia with Lewy
53
bodies but not Alzheimer's disease: an MRI study. Neurology 2003; 61:1191.
Watson R, Blamire AM, Colloby SJ, et al. Characterizing dementia with Lewy bodies by
54
means of diffusion tensor imaging. Neurology 2012; 79:906.
Mirzaei S, Rodrigues M, Koehn H, et al. Metabolic impairment of brain metabolism in
55
patients with Lewy body dementia. Eur J Neurol 2003; 10:573.
Lobotesis K, Fenwick JD, Phipps A, et al. Occipital hypoperfusion on SPECT in dementia
56
with Lewy bodies but not AD. Neurology 2001; 56:643.
Pasquier J, Michel BF, Brenot-Rossi I, et al. Value of (99m)Tc-ECD SPET for the diagnosis
57
of dementia with Lewy bodies. Eur J Nucl Med Mol Imaging 2002; 29:1342.
Colloby SJ, Fenwick JD, Williams ED, et al. A comparison of (99m)Tc-HMPAO SPET
58 changes in dementia with Lewy bodies and Alzheimer's disease using statistical
parametric mapping. Eur J Nucl Med Mol Imaging 2002; 29:615.
59 Firbank MJ, Colloby SJ, Burn DJ, et al. Regional cerebral blood flow in Parkinson's disease
 with and without dementia. Neuroimage 2003; 20:1309.
Ceravolo R, Volterrani D, Gambaccini G, et al. Dopaminergic degeneration and perfusional
60
impairment in Lewy body dementia and Alzheimer's disease. Neurol Sci 2003; 24:162.
Okamura N, Arai H, Higuchi M, et al. [18F]FDG-PET study in dementia with Lewy bodies
61
and Alzheimer's disease. Prog Neuropsychopharmacol Biol Psychiatry 2001; 25:447.
Minoshima S, Foster NL, Sima AA, et al. Alzheimer's disease versus dementia with Lewy
62 bodies: cerebral metabolic distinction with autopsy confirmation. Ann Neurol 2001;
50:358.
Hu XS, Okamura N, Arai H, et al. 18F-fluorodopa PET study of striatal dopamine uptake in
63
the diagnosis of dementia with Lewy bodies. Neurology 2000; 55:1575.
Walker Z, Costa DC, Walker RW, et al. Differentiation of dementia with Lewy bodies from
64 Alzheimer's disease using a dopaminergic presynaptic ligand. J Neurol Neurosurg
Psychiatry 2002; 73:134.
Gilman S, Koeppe RA, Little R, et al. Striatal monoamine terminals in Lewy body dementia
65
and Alzheimer's disease. Ann Neurol 2004; 55:774.
Colloby SJ, O'Brien JT, Fenwick JD, et al. The application of statistical parametric mapping
66 to 123I-FP-CIT SPECT in dementia with Lewy bodies, Alzheimer's disease and Parkinson's
disease. Neuroimage 2004; 23:956.
Ceravolo R, Volterrani D, Gambaccini G, et al. Presynaptic nigro-striatal function in a
67 group of Alzheimer's disease patients with parkinsonism: evidence from a dopamine
transporter imaging study. J Neural Transm (Vienna) 2004; 111:1065.
Walker Z, Jaros E, Walker RW, et al. Dementia with Lewy bodies: a comparison of clinical
68 diagnosis, FP-CIT single photon emission computed tomography imaging and autopsy. J
Neurol Neurosurg Psychiatry 2007; 78:1176.
O'Brien JT, McKeith IG, Walker Z, et al. Diagnostic accuracy of 123I-FP-CIT SPECT in
69
possible dementia with Lewy bodies. Br J Psychiatry 2009; 194:34.
McCleery J, Morgan S, Bradley KM, et al. Dopamine transporter imaging for the diagnosis
70
of dementia with Lewy bodies. Cochrane Database Syst Rev 2015; 1:CD010633.
McKeith I, O'Brien J, Walker Z, et al. Sensitivity and specificity of dopamine transporter
71 imaging with 123I-FP-CIT SPECT in dementia with Lewy bodies: a phase III, multicentre
study. Lancet Neurol 2007; 6:305.
Yoshita M, Taki J, Yamada M. A clinical role for [(123)I]MIBG myocardial scintigraphy in
72 the distinction between dementia of the Alzheimer's-type and dementia with Lewy bodies.
J Neurol Neurosurg Psychiatry 2001; 71:583.
Taki J, Yoshita M, Yamada M, Tonami N. Significance of 123I-MIBG scintigraphy as a
73 pathophysiological indicator in the assessment of Parkinson's disease and related
disorders: it can be a specific marker for Lewy body disease. Ann Nucl Med 2004; 18:453.
Oda H, Ishii K, Terashima A, et al. Myocardial scintigraphy may predict the conversion to
74
probable dementia with Lewy bodies. Neurology 2013; 81:1741.
Yoshita M, Taki J, Yokoyama K, et al. Value of 123I-MIBG radioactivity in the differential
75
diagnosis of DLB from AD. Neurology 2006; 66:1850.
Treglia G, Cason E. Diagnostic performance of myocardial innervation imaging using MIBG
76 scintigraphy in differential diagnosis between dementia with lewy bodies and other
dementias: a systematic review and a meta-analysis. J Neuroimaging 2012; 22:111.
McKeith I, Mintzer J, Aarsland D, et al. Dementia with Lewy bodies. Lancet Neurol 2004;
77
3:19.
Lippa CF, Duda JE, Grossman M, et al. DLB and PDD boundary issues: diagnosis,
78
treatment, molecular pathology, and biomarkers. Neurology 2007; 68:812.
Lee JE, Park HJ, Park B, et al. A comparative analysis of cognitive profiles and white-
matter alterations using voxel-based diffusion tensor imaging between patients with
79
Parkinson's disease dementia and dementia with Lewy bodies. J Neurol Neurosurg
Psychiatry 2010; 81:320.
Klein JC, Eggers C, Kalbe E, et al. Neurotransmitter changes in dementia with Lewy bodies
80
and Parkinson disease dementia in vivo. Neurology 2010; 74:885.
Molloy S, McKeith IG, O'Brien JT, Burn DJ. The role of levodopa in the management of
81
dementia with Lewy bodies. J Neurol Neurosurg Psychiatry 2005; 76:1200.
82 Roks G, Korf ES, van der Flier WM, et al. The use of EEG in the diagnosis of dementia with
 Lewy bodies. J Neurol Neurosurg Psychiatry 2008; 79:377.
Kupsch AR, Bajaj N, Weiland F, et al. Impact of DaTscan SPECT imaging on clinical
management, diagnosis, confidence of diagnosis, quality of life, health resource use and
83
safety in patients with clinically uncertain parkinsonian syndromes: a prospective 1-year
follow-up of an open-label controlled study. J Neurol Neurosurg Psychiatry 2012; 83:620.
Luis CA, Barker WW, Gajaraj K, et al. Sensitivity and specificity of three clinical criteria for
84 dementia with Lewy bodies in an autopsy-verified sample. Int J Geriatr Psychiatry 1999;
14:526.
Holmes C, Cairns N, Lantos P, Mann A. Validity of current clinical criteria for Alzheimer's
85
disease, vascular dementia and dementia with Lewy bodies. Br J Psychiatry 1999; 174:45.
Verghese J, Crystal HA, Dickson DW, Lipton RB. Validity of clinical criteria for the
86
diagnosis of dementia with Lewy bodies. Neurology 1999; 53:1974.
Lopez OL, Litvan I, Catt KE, et al. Accuracy of four clinical diagnostic criteria for the
87
diagnosis of neurodegenerative dementias. Neurology 1999; 53:1292.
McKeith IG, Ballard CG, Perry RH, et al. Prospective validation of consensus criteria for the
88
diagnosis of dementia with Lewy bodies. Neurology 2000; 54:1050.
Hohl U, Tiraboschi P, Hansen LA, et al. Diagnostic accuracy of dementia with Lewy bodies.
89
Arch Neurol 2000; 57:347.
Lopez OL, Becker JT, Kaufer DI, et al. Research evaluation and prospective diagnosis of
90
dementia with Lewy bodies. Arch Neurol 2002; 59:43.