Dementia with Lewy bodies (DLB) is a type of neurodegenerative disorder characterized by abnormal deposits of a protein called a-synuclein (1). The deposits, which are thought to disrupt chemical signaling in the brain, are called Lewy bodies after Fritz Heinrich Lewy, the German scientist who discovered them in 1912. Diseases that involve abnormal a-synuclein are listed as synucleinopathies and, while dementia with Lewy bodies is now starting to gain attention, the best known synucleinopathies are Parkinson’s disease and multiple system atrophy, which share much of DLBs’ pathology. Effects of the disease include, but are not limited to, changes in thinking and reasoning, confusion, motor problems, and difficulty processing sensory information (22). DLB is not an uncommon disease, affecting more than 1 million in the United States alone. In fact, the NIH estimates it to be one of the most common causes of dementia after Alzheimer’s disease (AD) and vascular disease (1). While DLB is more commonly diagnosed in those 50 and older, it can also affect younger people (1).
Figure 1. Some of the symptoms accompanying dementia with Lewy bodies are cognitive decline, problems sleeping, and difficulty moving, among others. Affected individuals may exhibit all symptoms, or a mix of different symptoms. Image Source: https://www.alzforum.org/news/conference-coverage/dementia-lewy-bodies-research-ready-clinical-trials
The protein involved in causing the disease, a-synuclein, is found abundantly in the brain, more precisely the presynaptic terminals of neurons. However, the actual function of the protein is still being investigated. Some suggest that it functions in maintaining a supply of synaptic vesicles. Still others propose that it’s involved in regulating release of the neurotransmitter dopamine, which controls involuntary and voluntary movement (2)(3). Either way, there is relatively little known on the protein. The deposits of a-synuclein draw parallels to Amyloid beta deposits in Alzheimer’s disease (AD). In addition, clinical signs of DLB are often observed in AD as well. This might include cognitive decline, hallucinations, depression, and sleep disorders (4). Due to the similarity in symptoms between the two diseases, dementia with Lewy bodies is often misdiagnosed as Alzheimer’s disease. A definitive diagnosis is performed pathologically, meaning by the actual detection of Lewy bodies in the brain (4). However, even so there is difficulty in defining the disease as it’s not uncommon to have it occur in combination with amyloid beta plaques (5).
Figure 2. In dementia with Lewy bodies (DLB), a-synuclein aggregates form in the neurons of the limbic system and cortical regions of the brain. The cortical regions of the brain function in processing sensory information and memory. The limbic system includes the amygdala and hippocampus, which play important roles in memory. The thalamus, also part of the limbic system, is involved in processing sensory information. This is why we see memory decline as well as confusion in patients with DLB. Source: http://www.doctorsbeyondmedicine.com/listing/the-limbic-system
There are currently no preventative measures or cures to the disease and treatments are used to target the individual symptoms rather than the underlying cause of the disease. Formulating treatments is rendered all the more challenging by how little is actually known on why/how the disease forms and the role of a-synuclein in the brain. Although relatively little is known about the native conformation of a-synuclein, there is a general consensus that a-synuclein accumulates in synaptic terminals as neurotoxic oligomers, which then propagate in a prion like fashion. This results is loss of synapses and cholinergic, glutamatergic, and dopaminergic neurons, which in turn promotes neurodegeneration and inflammation. Current therapeutic strategies aim to reduce a-synuclein deposition in patients (6).
Figure 3. Histology image of brain tissue containing Lewy bodies and stained with an antibody against a-synuclein. Black arrows point to Lewy bodies. Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5011129/
Most of the literature exploring dementia with Lewy bodies (DLB) look at this disease and Parkinson’s disease dementia (PDD) in combination as they share pathophysiology. In other words, they are both characterized by the aggregation of a-synuclein in the brain. The actual relationship between the two neurocognitive disorders is subject to debate, with some questioning whether they aren’t in fact the same disease (15). However, the two diseases can be differentiated by their individual timelines. In other words, they are differentiated by the sequence in which symptoms arise. DLB is diagnosed when dementia symptoms develop before Parkinson motor signs, whereas PDD is diagnosed when cognitive impairment develops after having established Parkinson’s disease. However, putting aside this difference, their clinical features are very similar and the cognitive domains of both disorders overlap. Due to similarities between neurodegenerative disorders, DLB is treated using medications commonly prescribed to individuals with PDD and/or AD. A common treatment is cholinesterase inhibitors, used primarily in AD, which function to increase levels of chemical messengers in the brain (1). Problems with movement are treated with the Parkinson’s disease medication carbidopa-levodopa. While both these treatments improve general functioning, they neither stop nor reverse the progression of the disease (6).
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