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Anxiety as a Predictor for Cognitive Decline and Dementia: A Systematic Review and Meta-Analysis

  • Bernice Gulpers
    Correspondence
    Send correspondence and reprint requests to Dr. Bernice Gulpers, Regional Institute for Mental Health Care in Outpatients, RIAGG Maastricht, Parallelweg 45-47, 6221BD Maastricht, The Netherlands.
    Affiliations
    Regional Institute for Mental Health Care in Outpatients, RIAGG Maastricht, Maastricht, The Netherlands

    Department of Psychiatry and Psychology / MUMC, School for Mental Health and Neuroscience (MHeNS) / Alzheimer Centre Limburg, Maastricht University Medical Center, Maastricht, The Netherlands
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  • Inez Ramakers
    Affiliations
    Department of Psychiatry and Psychology / MUMC, School for Mental Health and Neuroscience (MHeNS) / Alzheimer Centre Limburg, Maastricht University Medical Center, Maastricht, The Netherlands
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  • Renske Hamel
    Affiliations
    Department of Psychiatry and Psychology / MUMC, School for Mental Health and Neuroscience (MHeNS) / Alzheimer Centre Limburg, Maastricht University Medical Center, Maastricht, The Netherlands
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  • Sebastian Köhler
    Affiliations
    Department of Psychiatry and Psychology / MUMC, School for Mental Health and Neuroscience (MHeNS) / Alzheimer Centre Limburg, Maastricht University Medical Center, Maastricht, The Netherlands
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  • Richard Oude Voshaar
    Affiliations
    Center for Psychiatry & Interdisciplinary Center of Psychopathology of Emotion Regulation (ICPE), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
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  • Frans Verhey
    Affiliations
    Department of Psychiatry and Psychology / MUMC, School for Mental Health and Neuroscience (MHeNS) / Alzheimer Centre Limburg, Maastricht University Medical Center, Maastricht, The Netherlands
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      Background

      Because anxiety is postulated as a risk factor for dementia, we performed a systematic review and meta-analysis to investigate whether anxiety predicts cognitive decline and/or dementia, taking the stage of cognitive decline as well as setting into account.

      Methods

      A systematic literature search up to January 2015 was performed to identify all longitudinal studies on the association between anxiety and cognition. Data extraction and methodological quality assessment were conducted independently by two authors. Where possible, pooled relative risks were calculated to examine anxiety as a possible risk factor for cognitive decline cognitive impairment and dementia in community studies (objective 1), as well as for conversion to dementia patients referred to memory clinics (objective 2).

      Results

      Twenty studies met inclusion criteria. Data on cognitive decline were too heterogeneous for meta-analysis. Anxiety predicted incident cognitive impairment (4 studies, relative risk [RR]: 1.77, 95% confidence interval [CI]: 1.38–2.26, z = 4.50, p < 0.001) and dementia (6 studies, RR: 1.57, 95% CI: 1.02–2.42, z = 2.05, p = 0.040) in the community, the latter driven by studies with a mean age of 80 years or above. Among clinical mild cognitive impairment samples, anxiety did not predict conversion to dementia (RR: 1.21, 95% CI: 0.90–1.63, z = 1.28, p = 0.200).

      Conclusions

      Anxiety is associated with an increased risk for cognitive impairment and dementia in the community. Stronger associations were driven by higher age, suggesting that it is a prodromal symptom. Causal biological pathways have also been described, which could explain the risk for incident cognitive impairment in the community. Future studies should include mediating mechanism when studying anxiety as a predictor for cognitive decline and/or dementia.

      Key Words

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