Approach

Dementia is defined as a progressive cognitive decline of sufficient magnitude to interfere with normal social or occupational functions, or with usual daily activities.[1] The diagnosis of DLB is based on clinical history and neurologic exam. Routine tests (laboratory and neuroimaging) are recommended in the evaluation of people with dementia. Other studies may be indicated depending on specific circumstances. Before confirming diagnosis, any medication that may be causing or exacerbating symptoms should be withdrawn (e.g., anticholinergics, dopamine agonists). Systemic causes such as infection, which can cause delirium on a repeated basis, should be excluded. 

Many cases of DLB are missed or misdiagnosed as Alzheimer disease (AD). DLB and AD pathologies may coexist in the same patient.[1][18] The Lewy Body composite risk score is a validated short structured questionnaire that has high discrimination between DLB and AD and mild cognitive impairment due to DLB and AD.[19][20] 

In the DSM-5-TR, DLB is classified as a major neurocognitive disorder with Lewy bodies.[3]​​

Clinical history

A history should be obtained both from the patient and from one or more informed family members, friends, and/or caregivers. A notable distinguishing feature of DLB compared with AD is attention and visuospatial abnormalities, in contrast to the prominent amnestic syndrome of most cases of AD.

Core clinical features

The core clinical features of DLB should be sought when assessing a patient with cognitive impairment. These are:[1]

  • Fluctuations in cognition, attention, and arousal

  • Recurrent visual hallucinations

  • Rapid eye movement (REM) sleep behavior disorder (RBD)

  • Spontaneous motor signs of parkinsonism.

Fluctuations in cognition, attention, and arousal that are typically delirium-like occur in patients with DLB.[21]​ They may include episodes of inconsistent behavior, alterations in attention, incoherent speech, or alterations to consciousness such as staring or zoning out. Questions about daytime drowsiness, lethargy, staring into space, and disorganized speech reliably discriminate DLB from AD. Fluctuations are observed earlier in DLB than in other dementias.[1][18]

Recurrent visual hallucinations are present in about 80% of patients with DLB.[1] These are typically complex and may include children or small animals. Emotional responses to hallucinations are variable.[1]

RBD is a common feature of DLB, occurring in up to 76% patients with the condition. It often occurs years before other features appear.[1][22] RBD manifests as excessive jerking and complex movements during REM sleep. Recurrent episodes of dramatic and violent behavior, including falling out of bed, kicking, punching, jumping up, and running, are also suggestive. Wounds and fractures have been reported in extreme cases; however, only a small proportion of RBD events involve violent dreams and behaviors.[23] Other characteristic signs include talking, yelling, and swearing. Duration is brief and patients regain full awareness when they wake up. Although vivid dreams are often reported during these episodes, they may be an adverse event associated with cholinesterase inhibitors. RBD is drug responsive and features should be sought in all patients with suspected DLB, including obtaining information from bed partners.[1] Up to 90% of patients diagnosed with idiopathic RBD eventually develop DLB or another synucleinopathy.[22][23]

The presence of one or more of the cardinal motor features of parkinsonism - bradykinesia, rest tremor, and rigidity - is a core clinical feature of DLB. Spontaneous motor signs are present in over 85% of patients with DLB.[1] Motor signs are diagnostically helpful when they occur early in the disease course. This can help differentiate from disorders such as AD.

The Mayo Fluctuations Scale, Unified Parkinson's Disease Rating Scale (UPDRS), and neuropsychiatric inventory (NPI) subscale for visual hallucinations can be useful in assessing core features of DLB.[21]​​[24][25] The presence of any of the core features should initiate clinical suspicion for the diagnosis.[26]

Supportive clinical features

Supportive clinical features are commonly present, sometimes early in the disease course. Although they lack diagnostic specificity, such features may indicate DLB in a patient with dementia, particularly when they persist over time and when several occur in combination. They are:[1]

  • Severe antipsychotic sensitivity

  • Hypersomnia

  • Hyposmia

  • Depression

  • Anxiety

  • Apathy

  • Delusions often associated with other neurobehavioral problems

  • Hallucinations in nonvisual modalities (e.g., auditory)

  • Severe autonomic disturbance, including postural hypotension, urologic disturbance, or constipation

  • Postural instability

  • Repeated falls

  • Syncope or other transient episodes of unresponsiveness.

Laboratory evaluation

The following tests should be routinely performed for all cases of suspected DLB in order to rule out reversible etiologies of cognitive impairment:

  • Thyroid-stimulating hormone (TSH), to rule out hyperthyroid- or hypothyroid-associated dementia

  • Serum vitamin B12, to rule out vitamin B12 deficiency-induced dementia.

Other laboratory tests that may be sought, based on individual evaluation and the context of presentation, include:

  • CBC, to rule out anemia

  • Basic metabolic panel including liver function tests and serum calcium, to assess for major organ failure

  • Folate, to rule out deficiency

  • Urine drug screen in suspected cases of drug abuse

  • Serologic testing for syphilis (Venereal Disease Research Laboratory), to rule out an infectious etiology

  • Urinalysis in cases of rapid cognitive decline or frequent fluctuations, to rule out urinary tract infection

  • HIV testing, to rule out HIV infection as a cause of dementia in people at risk.

Other tests may be added for patients with rapid dementia progression or early onset of dementia.

Imaging

Neuroimaging (computed tomography [CT] and magnetic resonance imaging, without intravenous contrast) is recommended at least once in the workup of all cases of dementia, including DLB.[1][6][27]​​​​ No specific structural imaging characteristic features are specific to DLB. The incidence of medial temporal lobe atrophy may be lower than in AD.[6]​​

The presence of the following imaging biomarkers aids with the diagnosis of DLB:

  • Single-photon emission CT (SPECT) or positron emission tomography (PET) studies may be helpful in distinguishing other dementias.[6]​​

    • Functional dopamine transporter imaging with ioflupane (I-FP-SPECT) may be performed if there is difficulty distinguishing between AD and DLB; it is typically normal in AD, but may show low striatal activity in DLB or Parkinson disease (however, DLB and AD may coexist in the same patient).[6]​ Reduced dopamine transporter uptake in basal ganglia demonstrated by SPECT or PET has a sensitivity of 78% and specificity of 90% relative to AD.[1][6]​​

    • Occipital hypometabolism on F-18-fluorodeoxyglucose PET correlates with visual cortex pathology in DLB at autopsy.[1][6]

    • The findings from amyloid PET/CT imaging in patients with DLB can overlap with findings typical of both AD and normal aging.[28]

  • Abnormal (low uptake) 123-iodine-metaiodobenzylguanidine (MIBG) myocardial scintigraphy has high sensitivity and specificity for DLB, especially when compared to mild AD.[1]

Other investigations

Additional investigations may be warranted if clinically indicated.

Quantitative EEG with evidence of prominent posterior slow-waves with periodic fluctuation in the pre-alpha/theta range has been proposed as a DLB biomarker.[1] It may distinguish from AD and may correlate with cognitive fluctuations. It may be seen when the patient has mild cognitive impairment.[29]

Neuropsychological assessment may help provide a clearer picture of cognitive deficits, and should include tests that cover the full range of cognitive domains that may be affected.[1][2] Attentional, executive function, and visual processing deficits are typical of DLB; memory impairment is less prominent than in AD, especially in the early stages.[1][23] 

Referral to a sleep specialist and polysomnography are recommended for diagnostic evaluation. REM sleep without atonia may be an indicative biomarker for DLB.

Cerebrospinal fluid analysis should be ordered for patients with atypical features in order to rule out infectious causes.

Genetic testing may be indicated if AD is suspected. However, there are no useful genetic or biochemical biomarkers for a diagnosis of DLB.[1][27]

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