Dementia With Lewy Bodies

Prevalence, Prognosis, and Definition

Dementia with Lewy bodies (DLB) is a neurodegenerative disease of the brain characterized clinically by dementia, fluctuating attention and alertness, visual hallucinations, rapid-eye movement (REM) sleep behavior disorder, and/or parkinsonism, and pathologically by Lewy body formation and abnormal alpha-synuclein metabolism. Parkinson’s disease dementia (PDD) is a clinical diagnosis of dementia occurring in someone who already has Parkinson’s disease diagnosed at least one year before the onset of dementia. Pathologically, the cognitive deficits in Parkinson’s disease dementia are usually due to Lewy bodies, although they may be due to other pathologies, such as Alzheimer’s disease. Lewy body dementia is the “umbrella” term for a clinical diagnosis of either DLB or PDD. Mild cognitive impairment with Lewy bodies is prodromal dementia with Lewy bodies, that is, similar to dementia with Lewy bodies but with preserved or minimally affected function. Parkinson’s disease mild cognitive impairment (PD-MCI) is a clinical diagnosis of mild cognitive impairment in someone who already has Parkinson’s disease. It may be a prodromal stage of either dementia with Lewy bodies or Parkinson’s disease dementia, depending upon how quickly the cognitive symptoms start after the diagnosis of Parkinson’s disease. Lastly, Lewy body disease refers to the pathologic state of Lewy bodies in the brain seen in both Lewy body dementia and Parkinson’s disease ( ). (See Table 8.1 .)

Does all this terminology seem a bit confusing? In practice, Parkinson’s disease mild cognitive impairment and Parkinson’s disease dementia are not difficult to diagnose because they are essentially the development of mild cognitive impairment and dementia, respectively, in a patient with established Parkinson’s disease. In this chapter, we will focus on understanding dementia with Lewy bodies and its prodromal state, mild cognitive impairment with Lewy bodies, so that these disorders can be distinguished from others that they are commonly confused with, including Alzheimer’s disease (see Chapter 4 ), progressive supranuclear palsy (see Chapter 12 ), corticobasal degeneration (see Chapter 13 ), and chronic traumatic encephalopathy (see Chapter 15 ).

Dementia with Lewy bodies is either the second or third most common neurodegenerative cause of dementia in the older adult after Alzheimer’s disease (see Chapter 4 ) or Alzheimer’s and limbic-predominant age-related TDP-43 encephalopathy (LATE) (see Chapter 6 ), depending upon the age range of those studied ( ). One meta-analysis found the incidence of new cases of dementia with Lewy bodies to be 3.8%, with a prevalence of about 4.2% in the community and 7.5% of all dementias in secondary care ( ). Another study found the incidence in a county in Minnesota was estimated at 5.9 per 100,000 ( ).

Although some studies have suggested that the prognosis of patients with dementia with Lewy bodies is similar to those with Alzheimer’s disease, other studies suggest that patients with dementia with Lewy bodies show a more rapid decline in function, leading to earlier nursing home placement and death. Our clinical experience is that most patients with dementia with Lewy bodies do progress more rapidly than those with Alzheimer’s disease. The combination of parkinsonism, dementia, and visual hallucinations typically leads to nursing home placement in 2 to 6 years, and death in 3 to 8 years. One study found median survival of patients with dementia with Lewy bodies to be 3.7 years ( ), and another found survival of patients with Parkinson’s disease dementia to be 4.5 years ( ). There are, however, exceptions of patients who show a much slower disease progression.

Note that many patients with dementia with Lewy bodies also meet clinical and pathological criteria for Alzheimer’s disease, with some studies suggesting an overlap of greater than 90% ( ). Thus many patients have a mixed dementia of Alzheimer’s disease and dementia with Lewy bodies.

Criteria and Diagnosis

The most important features of dementia with Lewy bodies are dementia (which must of course always be present), rapid-eye movement (REM) sleep behavior disorder, fluctuating cognition, visual hallucinations, and parkinsonism ( Fig. 8.1 ). Criteria for mild cognitive impairment with Lewy bodies have been published ( ). Although technically for research, they are immediately useful, as patients with mild cognitive impairment, preserved independent function, and features of dementia with Lewy bodies commonly present to the clinic. See Boxes 8.1–8.3 for a summary of the current clinical diagnostic criteria (see Chapter 3 for the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition general criteria for major and mild neurocognitive disorder). Regarding the parkinsonism, note that up to 25% of patients with autopsy-proven dementia with Lewy bodies showed no signs of parkinsonism during life, perhaps due to having mainly cortical and little brainstem pathology. Note that biomarkers can now be used in support of a probable dementia with Lewy bodies diagnosis, namely reduced dopamine transporter uptake in basal ganglia demonstrated by single photon emission computed tomography (SPECT) or positron emission tomography (PET) imaging, abnormal (low uptake) ¹²³ iodine–meta-iodobenzylguanidine (MIBG) myocardial scintigraphy, and polysomnographic confirmation of REM sleep without atonia.

Regarding the characteristics of the dementia, it may appear identical to Alzheimer’s disease, with memory problems being prominent, or memory may be relatively normal with major difficulties present in attention, executive function, and visuospatial ability. If the dementia appears quite similar to that of Alzheimer’s disease, it is reasonable to presume that (as is common in patients with dementia with Lewy bodies) Alzheimer’s pathology of senile plaques and neurofibrillary tangles is likely present along with Lewy bodies and abnormal alpha-synuclein metabolism. Patients with dementia with Lewy bodies can, however, have prominent memory problems without Alzheimer’s pathology ( ).

Determining whether “fluctuating cognition” is present is quite difficult for most clinicians, for the simple reason that all dementing illnesses produce waxing and waning, with some days and times of day better than others. In our experience, the key aspect of fluctuating cognition to look for is relative dramatic fluctuations of alertness and/or attention that impact functional abilities ( ). In one patient we cared for, this manifested rather dramatically: the patient literally fell asleep during dinner and could not be awakened. Quite reasonably, the family was concerned that he had suffered a stroke or other catastrophic medical illness, and he was taken by ambulance to the hospital. By the time he reached the hospital he had awakened, and was back to baseline (the work-up, including magnetic resonance imaging [MRI], electroencephalogram [EEG], and laboratory studies, was unrevealing). Other patients who we have cared for have had similar, although less dramatic, alterations in alertness.

Visual hallucinations are perhaps the most definitive criteria for dementia with Lewy bodies, and are related to the degree of pathology ( ). In our experience actual well-formed hallucinations of people or animals are simply not present in other disorders (see below for discussion). The hallucinations are usually visual, and are almost always of people or animals, although they are sometimes described as large “bugs.” These hallucinations are remarkable in several ways. First, patients with mild dementia may be fully or partially aware that they are having hallucinations. We have had many patients who can both describe in detail their hallucinations and also know, at least some of the time, that they are not real (i.e. they do not always have a delusional component). During a consultation, one patient said that he could see a man curled up under the desk, but knew that this could not be real. In other cases, the hallucinations can be incredibly realistic, and typically as the dementia progresses there is usually no ability of the patient to separate them from reality. One patient asked his wife why she was not serving dinner to the other people sitting at the table. Another patient thought she was petting an imaginary dog in the waiting room. And another patient used to see little children playing in the corner of the room. This last patient was thought initially to be suffering from a psychotic depression (she had lost a child) until the correct diagnosis was made. Unfortunately, she had already received several courses of electroconvulsive therapy that may have exacerbated her hallucinations and dementia. The cause of visual hallucinations in Lewy body dementia is unknown. One study found an association between the concentration of Lewy bodies in the temporal lobe and well-formed visual hallucinations ( ). However, the hallucinations may also relate to sleep disturbances, as discussed below. Although less common, hallucinations may be in other sensory modalities, including auditory, olfactory, and tactile. Visual hallucinations may also be preceded by prodromal symptoms of seeing things fleetingly “out of the corner of one’s eye” and/or a feeling of a presence (without an abnormal visual perception).