Dementia series part 4 — Diagnostic Approaches to Dementia
Looxid Labs has developed the technology that analyzes EEG signals and eye-tracking data to assess cognitive performance. We are currently applying this technology to our in-home cognitive care solution, LUCY, designed to prevent dementia and spot the early signs of dementia in daily life. This dementia series aims to provide information on the basics of dementia and the latest digital technologies applied for early diagnosis, and last but not least, our technology and its use for early diagnosis of dementia through LUCY.
Written by Shannon H. Jeon
hyungsin.jeon@looxidlabs.com
Following the last article on dementia diagnosis, we would like to introduce the biomarkers of dementia examined for diagnosis. This article presents the importance of biomarkers in dementia research, examples of dementia biomarkers, and the insights these offer to the pathogenesis of dementia.
1. What is a Biomarker?
Our body is made up of numerous cells and neurons, and their activities with other cells and chemicals occur constantly. Their complex interactions also happen during pathological changes in our body. Understanding what is happening in our body is a crucial starting point in diagnosing and treating diseases. The biomarker concept is used to understand the underlying biological condition of disease and is applied for clinical diagnosis and treatment.
Biomarkers provide hints that help us understand our biological state. For example, a mutated gene called BCR-ABL and a fusion protein, p210, made from that mutation is often present in chronic myeloid leukemia (CML). Thus, their presence is considered a strong indicator for CML and examined to establish a diagnosis. In myocardial infarction (MI), elevated troponin levels can be used as an indicator for myocardial damage and are measured through blood tests during the diagnostic process.
Biomarkers hold promise both for use in diagnostics and also in the field of treatment. They allow health professionals to objectively identify and evaluate biological responses and their changes throughout the treatment of a disease. Using this information, clinicians and researchers can develop treatment plans and validate their efficacy. Therefore, identifying biomarkers is essential to understand the mechanisms of a disease and to develop effective treatment plans.
2. Biomarkers for Dementia
The most prominent biomarkers for dementia include amyloid-beta pathology, tau pathology, and neurodegeneration. These three are abbreviated as ATN and often as AT(N). These biomarkers are also helpful in researching subjective cognitive decline, mild cognitive impairment, and the preclinical stage of dementia. Since dementia is a condition that encompasses a broad set of neurological diseases and manifestations, its biomarkers are not only limited to ATN. The ongoing research in dementia biomarkers encompasses multiple biomarker candidates and searches for promising ones to improve diagnosis and treatment.
2.1 Amyloid-beta pathology (A)
The nerve cells in our body send and receive signals and communicate with other cells through pathways called synapses. When a protein called amyloid-beta, or short for amyloid, is abnormally accumulated in the bridges, it is more difficult for the neurons to exchange signals. If this condition persists, neurons cannot keep up to the signals, and eventually, the neuron loses its ability and starts to degenerate. Researchers believe that impaired signal communication due to abnormal accumulation of amyloid-beta promotes the degeneration of nerve cells, leading to dementia. According to a study published in The Journal of Neuroscience in 2020, among those who complain of subjective cognitive impairment, those who have amyloid-beta pathology (A+) developed mild cognitive impairment or dementia within three years, compared to their counterparts without the pathology (A-). The study reported that the risk of developing dementia was as high as 9.7 to 62.3 times. The study also stated that A+ people showed a sharper deterioration in cognitive function during the study period than A- individuals.
2.2 Tau pathology (T)
Although the amyloid-beta pathology received a lot of attention in dementia biomarker research, the treatment strategies targeting amyloid clumps have not yielded satisfactory results. Therefore, researchers started taking different approaches to find promising dementia biomarkers, and the tau pathology is one of these. Amyloid-beta accumulates in synapses between cells and interferes with neurotransmission, whereas tau proteins accumulate inside the cells and disrupt the cells’ ability to communicate with other cells, eventually causing cell death. Recent studies suggest that cognitive decline due to dementia may start before the abnormal accumulation of amyloid-beta. Many studies support the possibility that tau pathology may have more substantial clinical confidence than the amyloid-beta pathology in terms of early diagnosis of dementia.
One study from the University of California San Francisco showed that the tau pathology predicted brain atrophy at least one year earlier than the amyloid-beta pathology. This study also revealed that the brain tissue begins to deteriorate around the tau accumulation. As many researchers have accepted the tau pathology hypothesis, treatment strategies for dementia have started targeting abnormal formations of tau.
2.3 Neurodegeneration (N)
In AT(N), N refers to neurodegeneration such as neuronal injuries and brain atrophy. This can be assessed via neuroimaging tests such as PETs and MRIs. The structural evidence on brain atrophy or damage can help provide knowledge on the current and prospective state of the condition and identify possible treatment plans.
N is put in parentheses since it does not provide clarity and certainty as AT described above to determine the presence or absence of dementia only by neurodegeneration itself. Also, even if neurodegeneration is not present, it does not reach solid clinical confidence to rule out the possibility of dementia entirely. Because of this characteristic, parentheses are used to indicate that N in AT(N) is fundamentally different from the nature of AT biomarkers. However, when used together with AT, neurodegenerative evidence is beneficial in making a dementia diagnosis and prognosis.
2.4 Blood-brain barrier (BBB) damage
The blood-brain barrier (BBB) is a new biomarker on dementia that recent studies have suggested. The BBB is a gatekeeper that blocks harmful substances from entering our brain cells and selectively allows only beneficial nutrients to enter. Studies claim that BBB dysfunction or breakdown causes toxic substances to enter the brain cells, promoting cell damage. Especially when the loss of BBB integrity occurs in the hippocampus, an area responsible for memory and learning, rapid progressive cognitive decline is reported to occur. In addition, even if there are no clinical symptoms of cognitive impairment, the damaged BBB has been seen in people with genetic risk factors for dementia. Researchers believe that the damage to the blood-brain barrier can provide a crucial clue for the early diagnosis of dementia.
Closing
Biomarkers provide helpful knowledge in the diagnosis and treatment of dementia. The efficacy of current biomarkers and the discovery of new biomarkers are essential to conquer dementia. However, due to the cost and invasive nature of biomarker testing, it can be challenging to apply it in the early stage of dementia, especially when there are no clinical symptoms observed. For effective early diagnosis of dementia, alternatives to the above biomarkers are constantly searched and proposed. Scholars and health professionals try various approaches to this field of research, such as studying biosignals, unconditional reflexes, eye movement patterns, and changes in voice or behavior. Innovative digital tools, such as sensors that detect bodily movements and electronic signals or precise cameras that measure eye movement, are being designed and developed for this purpose.
Looxid Labs is developing a solution called LUCY to help prompt cognitive management by measuring and monitoring cognitive performance using virtual reality and biosignal data such as brainwaves and eye movement information. You can check your cognitive performance anytime, anywhere while playing games in LUCY. The patterns of brainwaves and eye movements during these games, designed for specific cognitive functions, may provide insights into your current cognitive ability. In a later article, we will introduce digital biomarkers related to dementia using various technologies and digital devices, along with their clinical evidence examples.
References
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