Patterns of Cognitive Decline Prior to Dementia in Persons with Mild Cognitive Impairment

J Alzheimers Dis. 2015;47(4):901-13. doi: 10.3233/JAD-142910.


Only a limited number of studies have investigated the decline of discrete cognitive domains as individuals progress from mild cognitive impairment (MCI) to dementia. Thus, the goal of this longitudinal study was to evaluate the cognitive changes underway during the years preceding a diagnosis of probable Alzheimer's disease (AD), and to compare these changes to those found in MCI participants who do not progress to dementia. Participants were compared as a function of whether they later converted to AD (n = 47) or not (n = 74). Cognitive change was assessed prior to the conversion year, using that year as a starting point. A combination of polynomial regression analyses and mixed ANOVAs assessed 1) the trajectory of cognitive decline for each domain and 2) the differences between non-progressors and those who had converted to AD. The different cognitive domains demonstrated very different patterns of decline in the group of MCI progressors. A quadratic function, i.e., many years of stable performance followed by a rapid decline just prior to diagnosis, was observed for delayed recall, working memory, and spatial memory. In contrast, a gradual linear decline was observed for immediate recall, executive function, and visuo-spatial abilities. Finally, language in progressors was impaired on all time periods relative to non-progressors, but there was no further change between the first assessments and conversion to AD. Individuals with MCI who progress to AD show abnormal cognition at least two years prior to their dementia diagnosis. The pattern of symptom change observed appears to depend upon the cognitive domain and thus, clinical studies should not assume similar rate of decline across domains. In contrast and, apart from verbal memory, the non-progressors present a performance similar to that of healthy older adults.

Keywords: Alzheimer’s disease; cognitive trajectory; mild cognitive impairment; natural history; retrospective study.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Allopurinol
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / psychology
  • Cognition*
  • Cognitive Dysfunction / diagnosis
  • Cognitive Dysfunction / psychology*
  • Disease Progression
  • Executive Function
  • Female
  • Follow-Up Studies
  • Humans
  • Language
  • Longitudinal Studies
  • Male
  • Memory, Short-Term
  • Mental Recall
  • Neuropsychological Tests
  • Retrospective Studies
  • Spatial Memory


  • Allopurinol