Inflammation, Vascular Factors and Risk of Dementia

Abstract

Dementia is a common and devastating condition in the elderly. The prevalence ranges from approximately 1% in 60-year-old persons to more than 30% in persons over 85 years1 and the burden of disease is likely to rise as life expectancy increases. The clinical syndrome of dementia is characterized by a decline in memory and other cognitive functions, interfering with activities of daily living. Different subtypes of dementia are recognized, Alzheimer’s disease being the most common subtype followed by vascular dementia. It is likely that sporadic late onset dementia is a result of interplay of both genetic and environmental factors but the precise etiology is not yet known. Several mechanisms may cause brain pathology that ultimately causes the syndrome of dementia. Of particular interest are potentially modifiable mechanisms, including inflammatory and vascular mechanisms. Inflammation in the brain could contribute to or promote neuronal loss2 and also peripheral inflammation may contribute to the pathogenesis of dementia.3,4 Also, there is evidence for a prominent role of vascular disease and vascular factors in the development of dementia, both vascular dementia and Alzheimer’s disease.5,6 The association between vascular disease and dementia may be explained by overt cerebrovascular disease, such as stroke or cerebral small vessel disease,7 or result from cerebral hypoperfusion.5 Furthermore, inflammation has been linked to vascular disease and vascular risk factors and it is conceivable that both inflammatory and vascular mechanisms represent a similar pathway or interact in their association with dementia. Though associations of inflammatory and vascular factors with dementia have been reported, most existing evidence comes from cross-sectional studies or studies with a short follow-up period. Because it is likely that the neuropathology underlying the dementia process occurs many years before the clinical syndrome is recognized, it cannot be concluded from these studies that inflammatory and vascular factors actually cause dementia. Therefore, prospective studies with a long follow-up period are needed to establish whether inflammatory and vascular factors are actually causes and not consequences of the dementia process or simply unrelated co-existent disorders. Furthermore, a longterm follow-up study allows identification of markers in the extended period preceding the clinical syndrome of dementia. These preclinical markers may be useful for early detection of dementia. The main objective of the research described in this thesis was to examine the role of inflammatory and vascular factors in the pathogenesis of dementia using a long follow-up. A secondary objective was to identify markers that may be of help in early detection of dementia.