Age, neuropathology, and dementia

N Engl J Med. 2009 May 28;360(22):2302-9. doi: 10.1056/NEJMoa0806142.


Background: Research in Alzheimer's disease is focused mainly on younger old persons, whereas studies involving very old persons report attenuated relationships between the pathological features of Alzheimer's disease and dementia.

Methods: We assessed 456 brains donated to the population-based Medical Research Council Cognitive Function and Ageing Study from persons 69 to 103 years of age at death. We used a standard neuropathological protocol that included measures of the pathological features of Alzheimer's disease, cerebral atrophy, and cerebrovascular disease. Neuropathological variables were dichotomized to represent no burden or a mild burden of pathological lesions as compared with a moderate or severe burden. Logistic regression was used to estimate the effect of age on the relationship between neuropathological features and dementia.

Results: The difference in the prevalence of moderate and severe Alzheimer's-type pathological changes between persons with and those without dementia decreased with increasing age. The association between neocortical neuritic plaques and dementia was strong at 75 years of age (odds ratio, 8.63; 95% confidence interval [CI], 3.81 to 19.60) and reduced at 95 years of age (odds ratio, 2.48; 95% CI, 0.92 to 4.14), and similar attenuations with advancing age were observed in the association between other pathological changes related to Alzheimer's disease and dementia in all brain areas. In contrast, neocortical cerebral atrophy maintained a relationship with age in persons with dementia at both 75 years of age (odds ratio, 5.11; 95% CI, 1.94 to 13.46) and 95 years of age (odds ratio, 6.10; 95% CI, 2.80 to 13.28) and thus distinguished the cohort with dementia from the cohort without dementia.

Conclusions: The association between the pathological features of Alzheimer's disease and dementia is stronger in younger old persons than in older old persons. Age must be taken into account when assessing the likely effect of interventions against dementia on the population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Aging / pathology
  • Alzheimer Disease / pathology*
  • Atrophy / pathology
  • Autopsy
  • Brain / pathology*
  • Cerebrovascular Disorders / pathology
  • Dementia / pathology*
  • Female
  • Humans
  • Lewy Bodies / pathology
  • Male
  • Odds Ratio
  • Plaque, Amyloid / pathology