Dementia with Lewy bodies

Diagnostic workup
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By Ann Marie Hake MD

Currently there is no single test to diagnose dementia with Lewy bodies; essentially it becomes a diagnosis of exclusion. Clinically, dementia with Lewy bodies is characterized by progressive cognitive impairment with fluctuating course, recurrent visual hallucinations, and parkinsonism. Although formal clinical criteria have been proposed, there is a pronounced clinical and neuropathologic overlap with Alzheimer disease as well as Parkinson disease with dementia. Four items of interest in the patient history suggesting dementia with Lewy bodies would be (1) acute-subacute onset, (2) early parkinsonism, (3) early hallucinations, and (4) early onset of urinary incontinence (Del Ser et al 2001). The relationship of dementia with Lewy bodies and Parkinson disease is an area of considerable controversy, particularly because dementia frequently occurs in Parkinson disease. Many investigators believe that a spectrum of Lewy body disorders exists. An arbitrary 1-year rule is used to distinguish dementia with Lewy bodies from Parkinson disease with dementia. If parkinsonism has been present for 12 months or longer before cognitive impairment is detected, the disorder is called Parkinson disease with dementia; otherwise, it is called dementia with Lewy bodies (Boeve 2004). Evaluation should begin with a complete medical history, including the patient's general health, past medical history, and family history. A possible diagnosis of dementia with Lewy bodies is more likely if the patient reports repeated falls, fainting, brief losses of consciousness, delusions, or is sensitive to antipsychotic drugs that are given to control hallucinations and other psychiatric symptoms. Blood tests may be done to rule out other causes of the dementia, such as vitamin B12 deficiency, thyroid deficiency, syphilis, or human immunodeficiency virus (HIV). Signs of inflammation may suggest infection, or certain biomarkers may suggest cancer, an autoimmune disorder, or possibly Creutzfeldt-Jakob disease (Knopman et al 2001). Cerebrospinal fluid should be sent for the 14-3-3 and tau proteins if a prion disease is suspected (Coulthart et al 2011). A mental status evaluation should evaluate for deficits in orientation, attention, memory, and visuospatial function, which are common. Neuropsychological testing will be especially helpful in trying to detect dementia at an early stage and typically can quantify a specific pattern of deficits that is supportive of a diagnosis of dementia with Lewy bodies. These include deficits of attention, executive function, memory (especially retrieval), and visuospatial processing. These differences can be elucidated even in the mild cognitive impairment stage of disease with careful testing, where individuals with amnestic deficits are more likely to progress to Alzheimer’s dementia and those with nonamnestic patterns with deficits in attention and/or visuospatial function are more likely to develop Lewy body dementia; the likelihood of Lewy body disease is increased if there is daytime sleepiness, subtle parkinsonism, or restless legs syndrome (Ferman et al 2013, Graff-Radford et al 2014). Neuroimaging will help in ruling out structural causes of dementia. Specifically, CT or MRI should be used for ruling out abscess, normal pressure hydrocephalus, tumor, stroke, and subdural hematoma. MRI will often show cortical atrophy, but the extent of hippocampal atrophy is less than that seen in Alzheimer disease. Perfusion SPECT or PET scanning with [18F]fluorodeoxyglucose (FDG) may detect temporal, parietal, and occipital hypoperfusion or hypometabolism that can help in the diagnosis of dementia with Lewy bodies (Vander Borght et al 1997; McKeith et al 2007). The pattern is similar to that seen in Alzheimer disease and Parkinson disease with dementia, but on average there is greater occipital hypometabolism seen in dementia with Lewy bodies than in Alzheimer disease. In those patients with dementia with Lewy bodies who do demonstrate posterior hypometabolism on FDG PET, the posterior congulate is often relatively spared compared to the precuneus and cuneus, the so-called “cingulate island sign” (Graff-Radford et al 2014). SPECT brain imaging with the ligand (123)I-2beta-carbometoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane ((123)I-FP-CIT) or PET scanning with (+)-[11C]dihydrotetrabenazine may show reduced striatal binding compared to Alzheimer disease and more symmetrical nigrostriatal uptake of dopamine than in Parkinson disease (Koeppe et al 2008). Quantitative electroencephalography (QEEG) may show slowing (less than 8 Hz) and variability (greater than 15Hz) of the dominant frequency even in the mild cognitive impairment phase although these abnormalities are typically not seen in those with Alzheimer disease without Lewy bodies or in Parkinson disease without dementia (Bonanni et al 2014). Polysomnography may show an increase in electromyography tone associated with dream enactment behavior during REM sleep to support a diagnosis of REM sleep behavior disorder or may identify evidence of periodic limb movements of sleep (Boeve et al 2004). The symptoms of REM sleep behavior disorder may precede the other symptoms of Lewy body disease by many years, or even decades (Claassen et al 2010). There may be evidence of orthostatic hypotension or other autonomic dysfunction on formal testing; in particular, low heart rate variability, decreased uptake on (123)I-metaiodobenzylguanidine myocardial (MIBG) scintigraphy, and decreased ventilatory response to hypercapnia (Tateno et al 2008; Mizukami et al 2009; Treglia et al 2010).

In 2003, the International Consortium on Dementia with Lewy Bodies revised the guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies.

Table 2. Guidelines for the Clinical Diagnosis of Dementia with Lewy Bodies

Central features (essential for the diagnosis of possible or probable dementia with Lewy bodies).

  • Dementia defined as progressive cognitive decline of significant magnitude to interfere with normal social or occupational function.
  • Prominent or persistent memory impairment may not necessarily occur in the early stages, but is usually evident with progression.
  • Deficits on tests of attention, executive function, or visuospatial ability may be especially prominent.

Core Features (2 core features are sufficient for the diagnosis of probable dementia with Lewy bodies, 1 for possible dementia with Lewy bodies.)

  • Fluctuating cognition with pronounced variation in attention and alertness.
  • Recurrent visual hallucinations that are typically well formed and detailed.
  • Spontaneous features of parkinsonism.

Suggestive features (If 1 or more of these is present in the presence of 1 or more core features, diagnosis of probable dementia with Lewy bodies can be made. Diagnosis of probable dementia with Lewy bodies should not be made on the basis of suggested features alone.)

  • REM sleep behavior disorder
  • Severe neuroleptic sensitivity
  • Low dopamine transporter uptake in the basal ganglia demonstrated by SPECT or PET imaging

Supportive features (commonly present but not proven to have diagnostic specificity)

  • Repeated falls and syncope
  • Transient unexplained loss of conscious
  • Severe autonomic dysfunction, eg, orthostatic hypotension, urinary incontinence
  • Hallucinations in other modalities
  • Systemized delusions
  • Depression
  • Relative preservation of medial temporal lobe structures on CT/MRI scan
  • Generalized low uptake on SPECT/PET perfusion scan with reduced occipital activity
  • Abnormal (low uptake) MIBG scintigraphy
  • Prominent slow-wave activity on EEG with temporal lobe transient sharp waves

Diagnosis of dementia with Lewy bodies is less likely:

  • In the presence of significant cerebrovascular disease–evident as focal neurologic signs or on brain imaging
  • In the presence of any other physical illness or brain disorder sufficient to account, in part or in total, for the clinical picture.
  • If parkinsonism appears only for the first time at a stage of severe dementia.

Temporal sequence of symptoms

Dementia with Lewy bodies should be diagnosed when dementia occurs before or concurrently with parkinsonism (if it is present). The term Parkinson disease dementia should be used to describe dementia that occurs in the context of well-established Parkinson disease. In a practice setting the term that is most appropriate to the clinical situation should be used and generic terms such as Lewy body disease are often helpful. In research studies in which distinction needs to be made between dementia with Lewy bodies and Parkinson disease dementia, the existing 1-year rule between the onset of dementia and parkinsonism dementia with Lewy bodies continues to be recommended (McKeith et al 2005).

Because the clinical presentation of dementia with Lewy bodies is so varied, the differential diagnosis remains quite broad even with the updated diagnostic criteria. It is important to maintain a high index of suspicion when evaluating individuals with any of the possible symptoms and to consider Lewy body disease in the differential diagnosis of any older person presenting with mental status changes, psychosis, parkinsonism, or autonomic symptoms.

In This Article

Introduction
Historical note and nomenclature
Clinical manifestations
Clinical vignette
Etiology
Pathogenesis and pathophysiology
Epidemiology
Prevention
Differential diagnosis
Diagnostic workup
Prognosis and complications
Management
Anesthesia
References cited
Contributors