The Outcome of Patients with Amyloid-Negative Amnestic Mild Cognitive Impairment

Sandra Cardoso, Dina Silva, Luisa Alves, Manuela Guerreiro, Alexandre de Mendonca

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Background: Patients with amnestic mild cognitive impairment (aMCI) are usually at an initial stage of Alzheimer's disease (AD). However, some patients with aMCI do not present biomarkers of amyloid pathology characteristic of AD. The significance of amyloid-negative aMCI is not presently clear. Objective: To know the etiology and prognosis of amyloid-negative aMCI. Methods: Patients who fulfilled criteria for aMCI and were amyloid negative were selected from a large cohort of non-demented patients with cognitive complaints and were followed with clinical and neuropsychological assessments. Results: Few amyloid-negative aMCI had evidence of neurodegeneration at the baseline, as reflected in cerebrospinal fluid elevated tau protein levels. About half of the patients remained essentially stable for long periods of time. Others manifested a psychiatric disorder that was not apparent at baseline, namely major depression or bipolar disorder. Remarkably, about a quarter of patients developed neurodegenerative disorders other than AD, mostly frontotemporal dementia or Lewy body disease. Conclusion: Amyloid-negative aMCI is a heterogeneous condition. Many patients remain clinically stable, but others may later manifest psychiatric conditions or evolve to neurodegenerative disorders. Prudence is needed when communicating to the patient and family the results of biomarkers, and clinical follow-up should be advised.

Original languageEnglish
Pages (from-to)629-640
JournalJournal Of Alzheimers Disease
Issue number2
Publication statusPublished - 22 Mar 2022


  • Amnestic mild cognitive impairment
  • amyloid-beta
  • amyloid-negative
  • biomarkers
  • dementia
  • follow-up


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