Definition

Dementia is the clinical syndrome characterized by acquired persistent impairment of cognitive and emotional abilities severe enough to interfere with daily functioning and quality of life.

Incidence and prevalence

Dementia occurs primarily late in life, the prevalence being about 1% at age 60 years, and it doubles every 5 years, reaching 30% to 50% by 85 years of age. Alzheimer’s disease is the most common of the progressive cortical dementias, accounting for about 70% of the dementias in persons older than 55 years of age.

Pathophysiology

Alzheimer’s disease is a progressive and ultimately fatal disorder in which certain types of nerve cells in particular areas of the brain degenerate and die for unknown reasons. Vulnerable brain regions include the amygdala as well as the hippocampus and areas around the hippocampus, and affected cell populations include cortical pathways involved in catecholaminergic, serotonergic, and cholinergic transmission. Advancing pathology is believed to underlie the classic clinical presentation of memory deficits followed by gradual erosion of judgment, reasoning ability, verbal fluency, and other cognitive skills.

A specific cause or pathologic process is not identified for dementia. The two “hallmark” Alzheimer’s lesions observable at autopsy are amyloid plaques and neurofibrillary tangles. Plaques are extracellular deposits of abnormally processed amyloid precursor protein, and tangles are intracellular accumulations of the cytoskeletal protein tau.

Development of plaques and tangles may represent a fairly late stage in the disease process that may or may not reflect the fundamental biochemical disruptions at work in Alzheimer’s disease. Although the “amyloid hypothesis,” which assigns a central causative role to abnormal amyloid processing, remains the most widely embraced theory, other active areas of research include tau, inflammation, disruptions of cell-signaling pathways, and cardiovascular risk factors.