title: Early symptoms and signs of cognitive deficits might not always be detectable in persons who develop Alzheimer's disease.
abstract: OBJECTIVE
  Clinical syndromes such as amnestic mild cognitive impairment (MCI) are highly predictive of future development of Alzheimer's disease (AD), but it is not known how many of the individuals that develop the disease can be identified with these syndromes. This study aims to determine how many individuals with AD show detectable symptoms or clinical signs of cognitive deficits three years before diagnosis.
  
  
  METHODS
  152 incident AD cases were identified in a dementia-free cohort of 1417 persons aged 75-95, after three-year follow-up from a prospective population-based study, the Kungsholmen Project. Symptoms of cognitive impairment including the subjective report of memory problems, and cognitive deficits were objectively measured with an extensive neuropsychological test battery at baseline. Incident AD was clinically diagnosed according to DSM-IIIR criteria at three-year follow-up.
  
  
  RESULTS
  Only half of future AD cases reported subjective memory problems three years before diagnosis. More than one-third of incident AD cases did not exhibit detectable deficits in any of the investigated specific cognitive domains. Only 38.3% had both subjective complaints and domain-specific cognitive deficits.
  
  
  CONCLUSIONS
  Symptoms and signs currently used to define MCI are not always present in persons who develop AD. Increasing the number of potentially identifiable and treatable preclinical AD cases is unfeasible unless more sensitive subjective and objective markers are identified. Furthermore, as only half of future AD cases report subjective memory problems three years before diagnosis, the number of persons coming to the attention of medical care is limited.
authors.affiliation: Aging Research Center, Karolinska Institutet, Stockholm, Sweden. katie.palmer@ki.se
authors.forename: Katie
authors.initials: K
authors.lastname: Palmer
authors.forename: Lars
authors.initials: L
authors.lastname: Bäckman
authors.forename: Bengt
authors.initials: B
authors.lastname: Winblad
authors.forename: Laura
authors.initials: L
authors.lastname: Fratiglioni
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000453:epidemiology*; D003072:Cognition Disorders / Q000175:diagnosis* / Q000453:epidemiology*; D003937:Diagnosis, Differential; D042241:Early Diagnosis; D006801:Humans; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D012720:Severity of Illness Index