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The symptom of low mood in the prodromal stage of mild cognitive impairment and dementia: a cohort study of a community dwelling elderly population
  1. B Caracciolo1,
  2. L Bäckman1,2,
  3. R Monastero3,
  4. B Winblad1,
  5. L Fratiglioni1,2
  1. 1Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden
  2. 2Stockholm Gerontology Research Center, Stockholm, Sweden
  3. 3Department of Clinical Neuroscience, Section of Neurology, University of Palermo, Palermo, Italy
  1. Correspondence to B Caracciolo, Aging Research Center, Karolinska Institutet, Gävlegatan 16, Stockholm 113 30, Sweden; barbara.caracciolo{at}


Objective To investigate the symptom of low mood as a predictor of mild cognitive impairment (MCI) and its progression to dementia, taking into account: (i) MCI severity, (ii) time of assessment and (iii) interaction with other factors.

Methods 764 cognitively healthy elderly subjects living in the community, from the Kungsholmen Project. Participants were assessed by direct interview to detect low mood. Subjects were then followed for 6 years to identify those who developed MCI. People with incident MCI were followed for a further 3 years to assess progression to dementia.

Results People with low mood at baseline had a 2.7-fold (95% CI 1.9 to 3.7) increased risk of developing MCI at follow-up. The association was stronger for amnestic MCI (aMCI: HR 5.8; 95% CI 3.1 to 10.9) compared with global cognitive impairment (other cognitive impairment no dementia, oCIND: HR 2.2; 95% CI 1.5 to 3.3). ApoE-ε4 interacted with low mood in a synergistic fashion, increasing the risk of aMCI, while no interaction with psychiatric, vascular, frailty related or psychosocial factors was observed. Low mood at baseline, as opposed to low mood co-occurring with MCI, was associated with a 5.3-fold (95% CI 1.2 to 23.3) increased risk of progression to dementia in aMCI. In contrast, no association was found in oCIND.

Conclusion Low mood was more strongly associated with aMCI than with global cognitive impairment. Progression towards dementia was predicted only by low mood manifest in the prodromal stage of MCI. These findings indicate that low mood is particularly prominent in the very early stages of cognitive decline.

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  • Funding This study was supported by grants from the Swedish Council for Working Life and Social Research, Regional Agreement on Medical Training and Clinical Research (ALF) between Stockholm County Council and Karolinska Institutet, and the Swedish Brain Power Initiative. Private funding from Stiftelsen Gamla Tjänarinnor and Gun and Bertil Stohnes Foundation was also provided.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the ethics committee of Karolinska Institutet, Stockholm, Sweden.

  • Provenance and peer review Not commissioned; externally peer reviewed.