Biomarkers and Risk Factors of Dementia

Dementia is a devastating disease that is common in elderly people. The prevalence increases from almost 1% at age 65 to over 40% of people older than 90 years.1 Because the population is aging, the number of people living with dementia world- wide is expected to double every 20 years with an expected number of 81 million people with dementia in 2040.2 Currently, dementia is still a clinical diagnosis of disturbances in cognitive functions that interfere with normal daily functioning.3,4 The major subtype of dementia is Alzheimer disease, which based on a clinical diag- nosis, accounts for around 70% of all dementia. The second most common subtype is vascular dementia, which is diagnosed in about 15% of dementia cases.1 Nowadays, however, we know that most patients with dementia have a mix of the neurodegen- erative changes that typically occur in Alzheimer disease, vascular pathology and other pathological signs, like Lewy bodies.5,6 In addition, vascular risk factors have repeatedly been associated with not only vascular dementia, but also with Alzheim- er disease,7 supporting the neuropathological findings of mixed brain pathologies. Although many risk factors for dementia have been identified in the past decades, the exact mechanisms that lead to dementia are still unclear. When the clinical di- agnosis of dementia is made, the actual neuropathological processes that have lead to dementia have already been ongoing for many years. Biomarkers that can detect these processes before a clinical diagnosis can be made are strongly needed in order to identify persons who will develop dementia, to gain more insight in the pathogen- esis of dementia and ultimately to help find new therapeutic agents that may alter or stop the disease. Currently, the most explored biomarkers are imaging markers and the proteins β-Amyloid (Aβ)-42 and tau that are altered in the cerebrospinal fluid of patients with Alzheimer disease early in the disease process.8,9 A lumbar puncture, required to obtain cerebrospinal fluid, is a relative invasive procedure that is not easily performed on large numbers of patients or in the general population, and imaging methods such as PET are not routinely available in all clinical settings. Less invasive biomarkers of dementia are therefore wanted.

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