Small delays in onset of Alzheimer's Disease are predicted to reduce its global burden, but we need to better understand factors that increase the risk-and methods to reduce it.
The clinical syndrome of dementia refers to a pattern of cognitive deficits characterized by impairment in memory and at least one other cognitive domain (e.g., language, executive functions, visuospatial abilities) that is sufficiently severe to impact behavior and interfere with social or occupational functioning (American Psychiatric Association, 2000). Dementia may be progressive, static, or remitting, and its onset and course of symptoms are a function of underlying neuropathology from various causes. For example, dementia because of a neurodegenerative process tends to involve an insidious onset with gradual progressive cognitive impairment. In contrast, dementia from vascular or acquired brain injury tends to involve an abrupt onset of clinical symptoms that may remain static or show stepwise cognitive decline that corresponds to episodes of cerebrovascular accidents.
The most common causes of dementia are neuropathologically distinguished on the basis of the presence of beta-amyloid (Aβ) plaques and neurofibrillary tangles (e.g., Alzheimer's Disease); multiple or strategically placed infarctions, ischemic injury, or hemorrhagic lesions (e.g., vascular dementia); cell loss and the deposition of Lewy bodies in sub-cortical, limbic, and neocortical regions (e.g., dementia with Lewy bodies); and prominent frontal and temporal lobar atrophy (frontotemporal dementia). Dementia can also be found in the context of other neurological, infectious, or metabolic conditions, such as Parkinson's Disease, Huntington's Disease, human immunodeficiency virus, or traumatic brain injury.
Despite recent advances in amyloid imaging and cerebral spinal fluid analysis, neuropathological changes are often only accurately assessed at autopsy. This makes definitive diagnosis during an individual's lifetime difficult. Effectively differentiating between forms of dementia or normal aging requires reliance on the neuropsychological definition of a specific pattern of cognitive deficits.
Epidemiology and Neurobiology of Alzheimer's Disease
Alzheimer's Disease is the leading cause of dementia in elders and accounts for 60 percent to 80 percent of all dementia cases. An estimated 5.3 million Americans have Alzheimer's Disease. Reports indicate the disease is the seventh leading cause of death in the United States, and deaths because of Alzheimer's Disease are on the rise, with an increase of 46 percent between 2000 and 2006. Given the advancing age of the baby boom generation, by 2050, 14 million older Americans and 81 million adults worldwide are expected to have the disease (Alzheimer's Association, 2010a).
Alzheimer's Disease is an age-related degenerative brain disorder characterized by the abnormal accumulation of extracellular fibrillar amyloid deposits and intra-neuronal neurofibrillary tangles in the brain. These characteristics lead to neuronal atrophy and synapse loss in medial temporal lobe limbic structures that are critical for episodic memory and extend to the association cortices of the frontal, temporal, and parietal lobes with disease progression (Braak and Braak, 1991). Consistent with these widespread neuropathological changes, the primary clinical manifestation of Alzheimer's Disease is a progressive global dementia syndrome that usually begins in later life.
It is generally agreed that the pathological cascade of brain changes occurs gradually in Alzheimer's Disease, beginning with the very early accrual of Aβ plaques in the brain, and is followed by a variable lag time after which neuronal dysfunction and neurodegeneration become the leading pathological process (Jack et al., 2010). Although Aβ neuropathology is thought to be causal, clinical symptoms are more closely related to neurofibrillary tangles than amyloid deposition. …