Predictors of progression from mild cognitive impairment to Alzheimer disease

Neurology. 2007 May 8;68(19):1596-602. doi: 10.1212/01.wnl.0000260968.92345.3f.


Objective: To determine the occurrence of neuropsychiatric symptomatology and the relation to future development of Alzheimer disease (AD) in persons with and without mild cognitive impairment (MCI).

Method: We followed 185 persons with no cognitive impairment and 47 with MCI (amnestic and multidomain), ages 75 to 95, from the population-based Kungsholmen Project, Stockholm, Sweden, for 3 years. Three types of neuropsychiatric symptoms were assessed at baseline: mood-related depressive symptoms, motivation-related depressive symptoms, and anxiety-related symptomatology. AD at 3-year follow-up was diagnosed according to Diagnostic and Statistical Manual for Mental Disorders-III-R criteria.

Results: Psychiatric symptoms occurred more frequently in persons with MCI (36.2% mood, 36.2% motivation, and 46.8% anxiety symptoms) than in cognitively intact elderly individuals (18.4% mood, 13.0% motivation, and 24.9% anxiety). Of persons with both MCI and anxiety symptoms, 83.3% developed AD over follow-up vs 6.1% of cognitively intact persons and 40.9% persons who had MCI without anxiety. Among persons with MCI, the 3-year risk of progressing to AD almost doubled with each anxiety symptom (relative risk [RR] = 1.8 [1.2 to 2.7] per symptom). Conversely, among cognitively intact subjects, only symptoms of depressive mood were related to AD development (RR = 1.9 [1.0 to 3.6] per symptom).

Conclusions: The predictive validity of mild cognitive impairment (MCI) for identifying future Alzheimer disease (AD) cases is improved in the presence of anxiety symptoms. Mood-related depressive symptoms (dysphoria, suicidal ideation, etc.) in preclinical AD might be related to the neuropathologic mechanism, as they appear preclinically in persons both with and without MCI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / epidemiology
  • Alzheimer Disease / psychology
  • Anxiety Disorders / diagnosis
  • Anxiety Disorders / psychology
  • Cognition Disorders / diagnosis*
  • Cognition Disorders / epidemiology
  • Cognition Disorders / psychology
  • Cohort Studies
  • Depressive Disorder / diagnosis
  • Depressive Disorder / psychology
  • Disease Progression
  • Female
  • Humans
  • Male
  • Mood Disorders / diagnosis*
  • Mood Disorders / epidemiology
  • Mood Disorders / psychology
  • Neuropsychological Tests / standards*
  • Neuropsychological Tests / statistics & numerical data*
  • Predictive Value of Tests
  • Prevalence
  • Risk Factors