Changing perspectives regarding late-life dementia

Nat Rev Neurol. 2009 Dec;5(12):649-58. doi: 10.1038/nrneurol.2009.175. Epub 2009 Nov 17.


Individuals over 80 years of age represent the most rapidly growing segment of the population, and late-life dementia has become a major public health concern worldwide. Development of effective preventive and treatment strategies for late-life dementia relies on a deep understanding of all the processes involved. In the centuries since the Greek philosopher Pythagoras described the inevitable loss of higher cognitive functions with advanced age, various theories regarding the potential culprits have dominated the field, ranging from demonic possession, through 'hardening of blood vessels', to Alzheimer disease (AD). Recent studies suggest that atrophy in the cortex and hippocampus-now considered to be the best determinant of cognitive decline with aging-results from a combination of AD pathology, inflammation, Lewy bodies, and vascular lesions. A specific constellation of genetic and environmental factors (including apolipoprotein E genotype, obesity, diabetes, hypertension, head trauma, systemic illnesses, and obstructive sleep apnea) contributes to late-life brain atrophy and dementia in each individual. Only a small percentage of people beyond the age of 80 years have 'pure AD' or 'pure vascular dementia'. These concepts, formulated as the dynamic polygon hypothesis, have major implications for clinical trials, as any given drug might not be ideal for all elderly people with dementia.

Publication types

  • Historical Article
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging*
  • Alzheimer Disease / complications
  • Atrophy / complications
  • Atrophy / pathology
  • Brain / pathology
  • Cognition Disorders / etiology*
  • Cognition Disorders / history
  • Cognition Disorders / psychology
  • Dementia / complications*
  • Dementia / etiology*
  • Dementia / history
  • Dementia / psychology
  • Environment
  • History, 20th Century
  • History, 21st Century
  • Humans
  • Risk Factors
  • Vascular Diseases / complications