Dementia with Lewy bodies
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Dementia with Lewy bodies presents in older patients (onset typically in 50-70 years of age), and is sporadic 1,2,7.
It is the second most common neurodegenerative cause of dementia in older patients, after Alzheimer disease, accounting for 15-20% of cases 3,4,7.
Typically patients first present with a frontal-type dementia with little in the way of memory deficits early in the course of the disease. Core features include 2,4,7,14:
fluctuating cognitive impairment especially in executive function, attention and alertness
visuospatial impairment, including visual hallucinations (detailed and vivid)
concurrent parkinsonian symptoms may be present but are less common, more frequently occurring years after the onset of dementia
Gastrointestinal symptoms (constipation, gastroparesis, nausea) are also commonly reported due to enteric neuronal dysfunction secondary to the accumulation of Lewy bodies 14.
Dementia with Lewy bodies vs Parkinson disease dementia
There are three entities to be distinguished in this gamut:
Parkinson disease dementia
dementia with Lewy bodies
The relationship between Parkinson disease and dementia with Lewy bodies is controversial, with some authors believing they are different manifestations of the same disease, whereas others believe they are distinct entities 2. This notwithstanding, the main clinical distinction lies in the timing of symptoms.
In dementia with Lewy bodies, dementia precedes or accompanies parkinsonism (or at least becomes clinically evident within 12 months of presentation 5). Patients with Parkinson disease, on the other hand, will not infrequently also develop dementia. However, it typically occurs years after the onset of parkinsonian symptoms 1,2,5. Such cases are then referred to as Parkinson disease dementia (PDD); at least 12 months of Parkinsonism without dementia need to precede cognitive impairment 5,7.
Dementia with Lewy bodies vs Alzheimer disease
The prominent and fairly initially isolated memory disturbance seen early in the course of classical Alzheimer disease is the main distinguishing clinical feature 16. Posterior cortical atrophy variant of Alzheimer disease is harder to distinguish especially as it shares some clinical features. However, cortical atrophy of Lewy body dementia is less diffuse when compared to Alzheimer disease 15.
The characteristic feature of dementia with Lewy bodies is (not surprisingly) the accumulation of Lewy bodies throughout the brain. These intracellular inclusions result from the aggregation of misfolded α-synuclein 14.
Lewy bodies are seen in greatest concentrations in the midbrain, hypothalamus, basal ganglia, inferior olives, brainstem reticular formation, and dentate nuclei of the cerebellum 2.
Neurofibrillary tangles are also present, although unlike those found in Alzheimer disease, they lack an amyloid core 2.
MRI is the modality of choice to structurally image the brain, however, there are no easily identifiable features to specifically support the diagnosis of dementia with Lewy bodies. In contrast, functional imaging with SPECT/PET is in many ways more useful.
Unfortunately, the literature is replete with studies showing atrophy in various parts of the brain without a clearly identified unique pattern. Most helpful in distinguishing dementia with Lewy bodies from other entities resulting in dementia is the absence of features of other diseases.
Features reported include 1,2,7,12:
generalized decrease in cerebral volume most marked in
enlargement of the lateral ventricles
relatively focal atrophy of 4:
Although frontal and temporal hypoperfusion can be similar to that seen in Alzheimer disease, occipital hypoperfusion and the cingulate island sign (preserved metabolism of the posterior cingulate) on SPECT/PET 1 may aid in differentiation from other types of dementia, especially Alzheimer disease 8,9,13,14.
If the occipital lobe is not involved, DLB and AD cannot be distinguished on the basis of their metabolic signatures. Imaging with dopamine transporter agents can help distinguish DLB from AD when clinical and FDG PET findings are indeterminate.17
Findings of DLB include loss of dopaminergic neurons in the substantia nigra and related reduced striatal dopaminergic activity, therefore patients with DLB have abnormal striatal uptake on dopamine transporter scans.17
Treatment and prognosis
Unlike Parkinson disease, dementia with Lewy bodies respond less readily to L-dopa and also may have severe sensitivity reactions to neuroleptic drugs, such as rigidity, reduced consciousness, pyrexia, falling, postural hypotension and collapse 3.
Lewy body dementia also responds favourably to acetylcholinesterase inhibitors, even more so than Alzheimer disease 6.
History and etymology
Lewy body inclusions were first discovered in the early 1900s by the German-born, American neurologist Frederic Lewy 10. However, the association of dementia with Lewy bodies was first discovered in 1976 by Kenji Kosaka, a Japanese psychiatrist and neuropathologist 11.
It is important to realize that there is a significant overlap between many neurodegenerative diseases, and that a clear-cut distinction between entities is not always possible. In the case of dementia with Lewy bodies, this is particularly the case, with a strong overlap between:
clinical: may occasionally have a similar clinical presentation with a frontal type dementia or posterior cortical atrophy
imaging: prominent involvement of hippocampi on imaging
clinical: dementia is only a late feature, with parkinsonian symptoms having been present for many years 5
clinical: usually younger onset, absent parkinsonian features, absent visual hallucinations
imaging: more pronounced frontal/temporal atrophy; left-to-right asymmetry