This past year I faced a challenge as someone close to me suffered a rapid decline in mental health: we were initially concerned when she began forgetting events. It progressed to mood swings and her voicing confusion as to where she was, often thinking her home was a hotel. She began to appear with constant injuries from falling, which resulted in her breaking her hip, and we were baffled when she talked about a cat she saw in her hospital room. When we received a diagnosis of Dementia with Lewy Bodies (DLB), I immediately jumped to the computer to understand as much as I could about this disease I had never encountered.
DLB is an age-related, progressive neurodegenerative disorder caused by the biological disease process, resulting in physical, cognitive, and behavioral symptoms (LeBlanc, 2016). Lewy bodies are an abnormal build-up of alpha-synuclein, a protein involved in the regulation of neurotransmitters. Triggered by genetic mutation or cellular stressors, these clumps block cell paths, resulting in cell death: essentially clogging the transmitters “like hairs in a drain” (Outeiro et al., 2019). The spread of alpha-synuclein pathology through the brain proceeds like dominoes falling, with one abnormal a-synuclein configuration causing nearby molecules to adopt the abnormal configuration (LeBlanc, 2016). It suddenly made sense to me why this person went from forgetting her schedule to forgetting her family﹣as the abnormal a-synuclein set off a chain reaction, her cognitive functions began to degrade. A characteristic unique to DLB is hallucinations, and we understood where this cat no one could see was coming from.
DLB is not a rare disease: according to the State of Science regarding DLB, it is estimated to affect 1.4 million individuals in the United States and is the second most common dementia after Alzheimer's (LeBlanc, 2016). However, despite its commonality, there is little understood about DLB, and it is widely under-diagnosed. There is ongoing research in the area, and a multitude of assumed factors that are involved including genetic components, environmental risk factors, and the natural aging process that create susceptibility to DLB. Seeing the impact dementia has on someone first hand has drastically impacted my life, and emphasized the importance of continuing research for dementia so we can understand what causes these complex diseases and how we can stop them.
Outeiro, T. F., Koss, D. J., Erskine, D., Walker, L., Kurzawa-Akanbi, M., Burn, D., … McKeith, I. (2019). Dementia with Lewy bodies: an update and outlook. Molecular neurodegeneration, 14(1), 5. doi:10.1186/s13024-019-0306-8
LeBlanc, G. (2016). Lewy Body Dementia: The State of the Science [White paper]. Retrieved October 13, 2019, from Lewy Body Dementia Association:
Cindy,
ReplyDeleteI am sorry to hear that someone close to you is suffering from Lewy Body Dementia. I do not personally know anyone suffering from this disease, but your post reminded me of a patient with Lewy Body Dementia I saw while working in Family Practice. This patient had been misdiagnosed with Alzheimer’s Disease, and unfortunately the accurate diagnosis of Lewy Body Dementia was not found until the postmortem. Histology later revealed evidence of Lewy bodies. Upon recalling this particular patient, I began to wonder what caused this misdiagnosis. Lewy Body Dementia is frequently underdiagnosed clinically. It shares several clinical neurocognitive and psychological symptoms with Alzheimer’s disease which may explain these misdiagnoses (Nelson et al., 2010). Unfortunately, misdiagnosis is further complicated by the fact the both Lewy Body Dementia and Parkinson’s Disease have similar deficiencies in the dopamine and acetylcholine pathways in the brain (Klein et al., 2010). Although criteria for each neurodegenerative diagnosis has become more strict over the years, the number of misdiagnosed Lewy Body Dementia patients has increased (Nelson et al., 2010). It seems that the only accurate way to diagnose each of these neurodegenerative diseases is through a postmortem autopsy. Is there any way to diagnose these diseases more accurately antemortem?
It turns out, Diffusion Tensor Imaging (DTI) may be a promising solution. DTI works by tracing the diffusion of water in parallel bundles of axons and their myelin sheaths in the brain (Mori & Zhang, 2006). These white matter tracts can be identified and structural and functional abnormalities can be seen (Mori & Zhang, 2006). How does this help us identify Lewy Body Dementia in patients? Kantarci et al. (2010) found differences in water diffusion among different white matter tracts that distinguishes Lewy Body Dementia from Alzheimer’s Disease. Lewy body dementia is characterized by diffusion changes in the inferior longitudinal fasciculus which is the white matter tract that connects the amygdala to the temporal-occipital cortices; while Alzheimer’s Disease is characterized by diffusion changes in the white matter tracts that connect the hippocampus and parahippocampal gyrus (Kantarci et al., 2010). These findings indicate that DTI may be a promising tool for the diagnosis of neurodegenerative diseases. DTI is a fairly new technology with some limitations that are currently being addressed, and it is expensive. Therefore, it may still be a few years before DTI can be used as a diagnostic tool in clinical settings.
References
Kantarci, K., Avula, R., Senjem, M. L., Samikoglu, A. R., Zhang, B., Weigand, S. D., Przybelski, S. A., Edmonson, H. A., Vemuri, P., Knopman, D. S., Ferman, T. J., Boeve, B. F., Petersen, R. C., & Ferman, T. J. (2010). Dementia with Lewy bodies and Alzheimer disease: neurodegenerative patterns characterized by DTI. Neurology, 74(22), 1814-1821. doi: 10.1212/WNL.0b013e3181e0f7cf.
Klein, J. C., Eggers, C., Kalbe, E., Weisenbach, S., Hohmann, C., Vollmar, S., Baudrexel, S., Diederich, N. J., Heiss, W. D., & Hilker, R. (2010). Neurotransmitter changes in dementia with Lewy bodies and Parkinson disease dementia in vivo. Neurology, 74(11), 885-892. doi: https://doi.org/10.1212/WNL.0b013e3181d55f61
Mori, S., & Zhang, J. (2006). Principles of diffusion tensor imaging and its applications to basic neuroscience research. Neuron, 51(5), 527-539. https://doi.org/10.1016/j.neuron.2006.08.012
Nelson, P. T., Jicha, G. A., Kryscio, R. J., Abner, E. L., Schmitt, F. A., Cooper, G., Xu, L. O., Smith, C. D, & Markesbery, W. R. (2010). Low sensitivity in clinical diagnoses of dementia with Lewy bodies. Journal of neurology, 257(3), 359-366. doi: 10.1007/s00415-009-5324-y