Causes and Correlates of Brain Atrophy: A population-based MRI study

Abstract

In 1906, Alois Alzheimer described for the first time a form of dementia that later became known as Alzheimer’s disease. At necropsy, he had observed that the brain of a 51-year-old woman with progressive cognitive decline was filled with –at that time still anonymous– amyloid plaques and neurofibrillary tangles. Since then, numerous investigators saw in patients with dementia the same pathological findings that Alzheimer had seen. Clinically, Alzheimer’s disease is recognized by a long period of progressive cognitive decline. Braak and Braak showed in the late eighties that the accumulation of plaques and tangles in the brain follows a predictable pattern over time that parallels this cognitive decline. In their now widely accepted staging system, they identify a long phase where the medial temporal lobe is the first area to be afflicted whereas only in the later disease stages the pathology involves the isocortices. However, recent pathological studies show that brains of elderly patients, unlike the middle–aged patient that Alzheimer had observed, who in life receive a diagnosis of Alzheimer’s disease have a rather mixed bag of brain pathology. Not only the traditionally recognized amyloid plaques and neurofibrillary tangles are observed but also cerebrovascular disease is found which could have contributed to the cognitive decline. The search for causes of Alzheimer’s disease is hampered by its long preclinical period and the pathological diversity that contribute to clinical symptoms of Alzheimer’s disease.