Dementia with Lewy bodies (DLB) is the preferred term that encompasses several conditions including senile dementia of Lewy body type, Lewy body variant of Alzheimer’s disease, Lewy body dementia, diffuse Lewy body disease and cortical Lewy body disease. The use of the term DLB enables clinicians and researchers to refer to the same disease state.
DLB is clinical diagnosis, based on a progressive dementia with parkinsonism and a fluctuation in the level of attention and the severity of the cognitive deficits. Gait and balance are often abnormal and visual hallucinations may be a common feature. Delusions are often an associated feature. There is evidence that persons with DLB may be more susceptible to the parkinsonian side effects of antipsychotic medications. Clinical consensus criteria for DLB were published in 1996 (see Table 10), but have been fraught with limitations in sensitivity and positive predictive value, although their specificity is high. When the clinical criteria were evaluated with neuropathological confirmation, one study showed 83% sensitivity and 95% specificity. Other studies have shown poorer correlations, with the sensitivity less than 50%. It has been suggested that adding the presence of visual hallucinations as a core criteria for the diagnosis improves the sensitivity. Of course, the use of dopaminergic drugs to address parkinsonian symptoms may confound this, as they may produce visual hallucinations.
Depending on the criteria utilized, DLB may be the second most prevalent dementia subtype. The clinical or neuropathological criteria often place DLB after AD or vascular dementia in terms of prevalence, with the neuropathological criteria often finding DLB in up to 25% of neuropathological specimens from persons with dementia. Unlike AD, DLB is more likely to be seen in men than women. Prevalence rates for DLB range between 10-25% of neuropathological specimens referred for evaluation of dementia etiology in the USA or UK, but may be much lower in other countries for example southern India (6-12%), Hong Kong (2.9%) and Japan (0.1%). This discrepancy may reflect the clinical criteria used. For example, in one clinical prevalence study in North London, the prevalence rate in patients with dementia for probable and possible DLB was 34%, but 10.9% if only cases with probable DLB were included.
The pathogenesis of DLB is not clear, although the assumption is that the cortical and subcortical Lewy Bodies are somehow associated with the cognitive decline and psychotic symptoms. There is some neuropathological evidence that suggests that visual hallucinations are associated with quantity of Lewy bodies in the temporal lobes. There is also limited evidence that the pathogenesis of DLB may involve interaction between APP, Aß and a-synuclein.
There is no definitive laboratory test to make a diagnosis of DLB, thus the diagnosis is made clinically. APOE e4 is more common in DLB than the general population but the APOE e2 allele is not reduced. Homozygotesfor APOE e4 are less common in DLB compared to AD.
Neuropathological criteria for DLB require the presence of Lewy bodies in the cortical and subcortical structures. This is a distinguishing feature compared with Parkinson’s disease (PD), in which Lewy bodies are found in the substantia nigra. Lewy bodies, first identified in 1912 by Friederich Lewy, are eosinophilic, round or elongated, intracytoplasmic structures (see image 5 – cortical Lewy Body, and image 6 imunohistochemical staining for a synulcein). When found in the brain stem, they usually have a halo around a dense core and are stainable with hematoxylin-eosin. Cortical Lewy bodies are devoid of the halo. Lewy bodies are composed of ubiquitin or alpha-synuclein, which can be detected using immunohistochemical techniques.
15-25% of AD patients may have Lewy bodies on autopsy. They are found in the hippocampus, entorhinal cortex, cingulate, and frontal and parietal cortex. Alzheimer’s disease pathology does not preclude the diagnosis of DLB. AD patients with DLB pathology appear to have more severe cognitive deficits as the burden of Lewy bodies in the cortical structures increase. In addition to the neuropathological overlap of DLB with AD and PD, up to 31% of DLB cases have additional vascular pathology at autopsy. Neurochemical studies suggest a cholinergic deficit earlier in the course and a decrease of choline acetyltransferase activity in DLB compared with AD.
DLB must be differentiated from AD with psychotic symptoms and Parkinson’s disease with dementia. As these are all clinical diagnoses, and there may be overlap between syndromes, it is important to obtain a careful clinical history, focusing on the course of the symptoms, as well as performing a careful neurologic exam. DLB patients have more pronounced visuospatial deficits and psychomotor impairments compared to AD patients, but AD patients have more severe memory deficits. Computerized testing reveals worsened attention with increased variability across trials in DLB pts compared to those with AD. Although neuropsychological testing has shown differences between DLB, AD and Vascular dementia, the tests are not able to reliable discrimination between the dementia subtypes. Functional neuroimaging studies without neuropathologic confirmation have suggested the use of SPECT as an aide in the differential diagnosis of DLB, but further studies are needed. At this time, neuroimaging, like neuropsycholical testing is unable to reliably differentiate DLB from AD or PD.
The presence of Lewy bodies in AD portends a more malignant course. For example, in AD patients, the number of Lewy bodies is related to a more rapid cognitive decline. AD patients with parkinsonism and Lewy bodies have a more rapid rate of decline than those without Lewy bodies.
There is no specific treatment for DLB. Studies have been done with cholinesterase inhibitors, and although there is a concern that they may worsen the parkinsonian symptoms, trials to date have not borne that out. For example, rivastigmine, a cholinesterase inhibitor, improved the DLB patients’ performance on a behavioral measure and a computerized test of cognitive functioning compared with placebo in a trial of 120 DLB patients. Patients with DLB may be extremely sensitive to the extrapyramidal side effects of antipsychotic medications, and therefore very low doses of atypical antipsychotics are usually used to treat the psychotic symptoms associated with DLB dementia.