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Neural substrates of cognitive reserve in Alzheimer’s disease spectrum and normal aging

Medicine to treat Alzheimer’s disease is extremely difficult to develop, and global pharmaceutical companies have invested trillions of won in development to no avail. This is the reason why dementia medicine is currently only able to provide temporary relief from symptoms. The Korean government has recognized the alarming seriousness of dementia and aims to address it as a national agenda. The present study demonstrates that cognitive reserve varies among patients, and suggests that controlling of this difference in clinical drug trials and an individualized approach is required.

Development of a model to quantify cognitive reserve

Cognitive reserve is a concept that refers to the discrepancy between the severity of a patient’s neuropathological findings and actual clinical symptoms. It is an important protective factor that controls the influence of neuropathology on cognitive function in patients with dementia. However, few methods have been developed to quantify the concept, and it is usually measured indirectly using education, activity, and other approximations. The present study used the latest multimodal neuroimaging techniques such as MRI and PET to create a cognitive reserve model that incorporates amyloid, tau, and neurodegeneration, the main causes of Alzheimer’s disease. The model was indirectly validated using an existing model, and also examined to see whether it directly changes the relationship between neuropathology and cognitive function.

Potential targets for the treatment and prevention of Alzheimer’s disease

Professor Yong Jeong suggests that different methods should be used to approach the disease in different people because cognitive ability is affected by both genetic differences and environmental factors, and that “it is necessary to boost brain endurance (cognitive reserve).” Examinations of the brains of people with dementia show that some had serious pathological findings but minor dementia symptoms, while others had severe symptoms but few pathological findings in the brain autopsy. This difference is due to cognitive reserve, which should be increased. The present study developed a model to quantify cognitive reserve, incorporating all major causes of Alzheimer’s disease. In the future, the model will help to distinguish between people who are vulnerable to Alzheimer’s disease and those who are resistant. It will also help to predict the clinical prognosis of patients, or classify patients for clinical studies. Moreover, it suggests that the middle temporal pole may be a potential target in the treatment of Alzheimer’s disease or preventive treatment.

Prof. Yong Jeong
2018 KI Annual Report

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