ABSTRACT
The last decade has seen unprecedented progress in the elucidation of the mechanisms and pathophysiology of Alzheimer’s disease (AD). It appears increasingly clear that there is a cascade of events that act together to produce the neuropathology responsible for the disease. This chapter reviews the current evidence for the contribution of a variety of mechanisms to the pathogenetic cascade of AD. One theory of the neurobiology of AD is that it is rooted in the architectonic evolution of the human brain. Epidemiologically, there is evidence from numerous longitudinal retrospective studies and meta-analyses that the risk of AD is reduced among users of non-steroidal anti-inflammatory drugs. These medications may reduce the inflammatory process or prevent it. Several randomized clinical trials and observational cohort studies have demonstrated that there are links between midlife hypertension and AD. Dysregulated cerebral blood flow and hypoperfusion of brain regions due to arteriosclerosis of the cerebral vasculature might precede dementia symptoms by many years.
