Identifying those who are at risk of dementia, a type of neurodegenerative disease, is crucial for early treatment and development of new therapies, a new study suggests.
Dementia affected approximately 46.8 million people across the globe in 2015, and the number increased to close 50 million in 2017. By 2030, the number is expected to soar to 75 million. In Australia, dementia is considered the second leading cause of death, and in 2019, there are about 447,115 people living with dementia.
The researchers at the Brigham and Women’s Hospital aimed to identify biomarkers that can help identify people who are at higher risk of developing dementia, which can contribute to better treatment approaches for them. At present, interventions and therapies are limited to slow or even reverse the cognitive symptoms of dementia.
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In the study published in the journal Annals of Clinical and Translational, the team of researchers measured the circulating levels of insulin-like growth factor binding protein 2 (IGFBP-2), a promising new biomarker for dementia.
The levels of the biomarker have been tied to an increased risk of both all-cause dementia and the most common type, Alzheimer’s disease. If the measurement of IGFBP-2 protein biomarker is combined with a model of conventional risk factors for dementia, it can markedly improve dementia risk classification, which can help doctors predict dementia risk among patients.
The researchers explored the role of metabolic dysfunction and insulin resistance in the development of dementia. It has been studied that the insulin-like growth factor (IGF), a peptide hormone known to control glucose homeostasis, energy metabolism, and apoptosis, among others, play a role in neuroregeneration, neuronal survival, and proliferation. The IGFBP-2 hinders the IGF signaling, hence, preventing neuroprotection.
To arrive at their findings, the researchers measured plasma IGFBP-2 levels in more than 1500 healthy people from 1998 to 2001. Also, magnetic resonance imaging (MRI) brain scans and cognitive performance were added to the test.
Protein biomarker as a predictor of dementia
The researchers found that elevated circulating IGFBP-2 levels were linked to increased risk of both all-cause dementia and Alzheimer’s disease. Manipulation of IGFBP-2 shows promise as a therapeutic target for patients with dementia.
"Identifying biomarkers for dementia could improve our ability to predict a person's risk of dementia and his or her future outcomes," Dr Emer McGrath, an associate neurologist in the Brigham's Neurology Department, said in a statement.
"Novel biomarkers could also inform our understanding of complex biological pathways underlying the development of dementia, help to more accurately define disease subgroups and inform future clinical trials,” he added.
Increased levels of IGFBP-2 has also been associated with the development of tau pathology. In dementia and Alzheimer’s disease, along with other disorders called tauopathies, tau, which is critical to normal neuronal activity, is accumulated in intraneuronal tangles.
The researchers recommend further studies to explore the possibility of manipulating insulin sensitivity and IGF signaling in the brain. This way, scientists can develop new treatment approaches and promising therapeutics for dementia patients.
What is dementia?
Dementia isn’t a normal part of aging. In fact, it is a neurodegenerative disease that progresses over time. People with dementia experience the loss of cognitive functioning, including reasoning, remembering, and thinking. The symptoms are also accompanied with behavioral ability problems, to such as extent that the disease affects one’s daily life.
Mostly, people with dementia experience problems with memory, visual perception, language skills, self-management, problem solving, and the ability to concentrate.
McGrath, E., Himali, J., Levy, D., Conner, S., DeCarli, C., Pase, M., Courchesne, P., Satizabal, C., Vasan, R., Beiser, A., and Seshadri, S. (2019). Circulating IGFBP‐2: a novel biomarker for incident dementia. Annals of Clinical and Translational. https://onlinelibrary.wiley.com/doi/full/10.1002/acn3.50854