Neuropsychiatric predictors of progression from amnestic - Mild cognitive impairment to alzheimer's disease: The role of depression and apathy

Katie Palmer, Fulvia Di Iulio, Ambra Erika Varsi, Walter Gianni, Giuseppe Sancesario, Carlo Caltagirone, Gianfranco Spalletta

Research output: Contribution to journalArticlepeer-review


The aim of the study is to evaluate whether depression or apathy in patients with amnestic-mild cognitive impairment (MCI) increases the risk of progressing to Alzheimer's disease (AD). We investigated 131 consecutive memory-clinic outpatients with newly-diagnosed amnestic-MCI (mean age 70.8, SD=6.5). Psychiatric disorders were diagnosed at baseline according to the criteria for depression and apathy in AD. Neuropsychiatric symptoms were assessed with the Neuropsychiatric Inventory (NPI). Follow-up examinations were conducted after six months and annually for four years. Neurologists diagnosed AD at follow-up using NINCDS-ADRDA criteria. Cox proportional hazard models with 95% confidence intervals were used to test the hypothesis that apathy or depression increases the risk of developing AD. At baseline, 36.6% amnestic-MCI patients had a diagnosis of depression and 10.7} had apathy. Patients with both amnestic-MCI and an apathy diagnosis had an almost sevenfold risk of AD progression compared to amnestic-MCI patients without apathy (HR=6.9; 2.3-20.6), after adjustment for age, gender, education, baseline global cognitive and functional status, and depression. Furthermore, the risk of developing AD increased 30% per point on the NPI apathy item (HR=1.3; 1.1-1.4). There was no increased risk of developing AD in amnestic-MCI patients with either a diagnosis or symptoms of depression. In conclusion, apathy, but not depression, predicts which patients with amnestic-MCI will progress to AD. Thus, apathy has an important impact on amnestic-MCI and should be considered a mixed cognitive/psychiatric disturbance related to ongoing AD neurodegeneration.

Original languageEnglish
Pages (from-to)175-183
Number of pages9
JournalJournal of Alzheimer's Disease
Issue number1
Publication statusPublished - 2010


  • Cognitive deficits
  • dementia
  • early detection
  • MCI
  • neuropsychiatric symptoms

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Clinical Psychology


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