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Anxiety as a risk factor of Alzheimer's disease and vascular dementia

  • Eva Becker (a1), Claudia Lorena Orellana Rios (a2), Claas Lahmann (a3), Gerta Rücker (a4), Joachim Bauer (a5) and Martin Boeker (a6)...
  • Please note a correction has been issued for this article.
Abstract
Background

The aetiology of dementia is not yet fully understood. Stress can have a damaging effect on brain health. The prognostic effect of anxiety is still unclear regarding Alzheimer's disease as well as vascular dementia.

Aims

To explore the association between anxiety and future dementia.

Method

Medline, PsycINFO, CINAHL, Web of Science and ALOIS were searched for publications up to 12 January 2018. Longitudinal studies with a follow-up of at least 2 years were included, if the trait or state anxiety had been assessed at baseline. Studies with cognitive impairment at baseline were not included. We used a random effects model to calculate the pooled time to Alzheimer's disease and incidence of vascular dementia.

Results

Anxiety predicts risk of Alzheimer's disease (n = 26 193 out of seven studies, hazard ratio1.53, 95% CI 1.16–2.01, P < 0.01) and vascular dementia (n = 4916 out of two studies, odds ratio1.88, 95% CI 1.05–3.36, P < 0.01). The pooled hazard ratio regarding risk of Alzheimer's disease was still significant when excluding studies with critical risk of bias (n = 14 110 out of six studies, hazard ratio 1.35, 95% CI 1.08–1.70, P < 0.01).

Conclusions

Anxiety is a risk factor for both types of dementia. The temporal and functional relation between anxiety and dementia needs investigation in future studies. The protective value of treating anxiety should be explored further.

Declaration of interest

None.

Copyright
Corresponding author
Correspondence: Eva Becker, Department of Psychosomatic Medicine and Psychotherapy, Faculty of Medicine and Medical Center, University of Freiburg, Hauptstrasse 8, 79108 Freiburg, Germany. Email: eva.becker@neptun.uni-freiburg.de
References
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1Prince, M, Ali, GC, Guerchet, M, Yu-Tzu, W, Prina, M. The global prevalence of dementia. In World Alzheimer Report 2015 (eds G Rees, S Fletcher): 1029. Alzheimer's Disease International, 2015.
2O'Brien, JT, Thomas, A. Vascular dementia. Lancet 2015; 386: 1698–706.
3Fiest, KM, Roberts, JI, Maxwell, CJ, Hogan, DB, Smith, EE, Frolkis, A, et al. The prevalence and incidence of dementia due to Alzheimer's disease: a systematic review and meta-analysis. Can J Neurol Sci 2016; 43(Suppl 1): S5182.
4Rizzi, L, Rosset, I, Roriz-Cruz, M. Global epidemiology of dementia: Alzheimer's and vascular types. BioMed Res Int 2014; 2014: 18.
5Gulpers, B, Ramakers, I, Hamel, R, Kohler, S, Oude Voshaar, R, Verhey, F. Anxiety as a predictor for cognitive decline and dementia: a systematic review and meta-analysis. Am J Geriatr Psychiatry 2016; 24: 823–42.
6Machado, A, Herrera, AJ, de Pablos, RM, Espinosa-Oliva, AM, Sarmiento, M, Ayala, A, et al. Chronic stress as a risk factor for Alzheimer's disease. Rev Neurosci 2014; 25: 785804.
7Pary, R, Matuschka, PR, Lewis, S, Caso, W, Lippmann, S. Generalized anxiety disorder. South Med J 2003; 96: 581–6.
8Fuxe, K, Diaz, R, Cintra, A, Bhatnagar, M, Tinner, B, Gustafsson, J-A, et al. On the role of glucocorticoid receptors in brain plasticity. Cell Mol Neurobiol 1996; 16: 239–58.
9Dubois, B, Epelbaum, S, Santos, A, Di Stefano, F, Julian, A, Michon, A, et al. Alzheimer disease: from biomarkers to diagnosis. Rev Neurol 2013; 169: 744–51.
10Prenderville, JA, Kennedy, PJ, Dinan, TG, Cryan, JF. Adding fuel to the fire: the impact of stress on the ageing brain. Trends Neurosci 2015; 38: 1325.
11Moher, D, Liberati, A, Tetzlaff, J, Altman, DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009; 6: e1000097.
12Stroup, DF, Berlin, JA, Morton, SC, Olkin, I, Williamson, GD, Rennie, D, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000; 283: 2008–12.
13Higgins, JPT, Green, S (ed). Cochrane Handbook for Systematic Reviews of Interventions: Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011.
14American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. American Psychiatric Publishing, 2013.
15Sartorius, N. The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines: 4751. World Health Organization, 2016.
16Gough, D. Weight of evidence: a framework for the appraisal of the quality and relevance of evidence. Res Pap Educ 2007; 22: 213–28.
17Wells, GA, Shea, B, O'Connell, D, Peterson, J, Welch, V, Losos, M, et al. The Newcastle Ottawa Scale (NOS) for Assessing the Quality of Nonrandomized Studies in Meta-Analyses. Ottawa Hospital Research Institute, 2014. (http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp).
18Sterne, JA, Hernán, MA, Reeves, BC, Savović, J, Berkman, ND, Viswanathan, M, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ 2016; 355: i4919.
19Schwarzer, G, Carpenter, JR, Rücker, G. Chapter 2, Fixed effects and random effect meta-analysis. In Meta-Analysis with R: 2840. Springer International Publishing, 2015.
20Schwarzer, G, Carpenter, JR, Rücker, G. Chapter 2.6.1, meta-analysis with survival outcomes. In Meta-Analysis with R (eds R Gentleman, K Hornik, G Parmigiani): 46–8. Springer International Publishing, 2015.
21R Core Team. R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, 2017 (https://www.R-project.org/).
22Schwarzer, G. meta: an R package for meta-analysis. R News 2007; 7: 40–5.
23Burke, SL, Maramaldi, P, Cadet, T, Kukull, W. Neuropsychiatric symptoms and apolipoprotein E: associations with eventual Alzheimer's disease development. Arch Gerontol Geriatr 2016; 65: 231–8.
24Burke, SL, O'Driscoll, J, Alcide, A, Li, T. Moderating risk of Alzheimer's disease through the use of anxiolytic agents. Int J Geriatr Psychiatry 2017; 32: 1312–21.
25Bruijn, RF, Direk, N, Mirza, SS, Hofman, A, Koudstaal, PJ, Tiemeier, H, et al. Anxiety is not associated with the risk of dementia or cognitive decline: the Rotterdam Study. Am J Geriatr Psychiatry 2014; 22: 1382–90.
26Gallacher, J, Bayer, A, Fish, M, Pickering, J, Pedro, S, Dunstan, F, et al. Does anxiety affect risk of dementia? Findings from the Caerphilly Prospective Study. Psychosom Med 2009; 71: 659–66.
27Jessen, F, Wolfsgruber, S, Wiese, B, Bickel, H, Mosch, E, Kaduszkiewicz, H, et al. AD dementia risk in late MCI, in early MCI, and in subjective memory impairment. Alzheimers Dement 2014; 10: 7683.
28Lobo, A, Bueno-Notivol, J, de La Camara, C, Santabarbara, J, Marcos, G, Gracia-Garcia, P, et al. Clinically relevant anxiety and risk of dementia and Alzheimer's disease. J Psychosom Res 2017; 97: 158–9.
29Palmer, K, Berger, AK, Monastero, R, Winblad, B, Bäckman, L, Fratiglioni, L. Predictors of progression from mild cognitive impairment to Alzheimer disease. Neurology 2007; 68: 1588–602.
30Stewart, JC, Perkins, AJ, Hendrie, HC, Callahan, CM. Depression and anxiety screens as predictors of 8-year incidence of total dementia, Alzheimer's disease, and vascular dementia. Psychosom Med 2015; 77: A3.
31Terracciano, A, Sutin, AR, An, Y, O'Brien, RJ, Ferrucci, L, Zonderman, AB, et al. Personality and risk of Alzheimer's disease: new data and meta-analysis. Alzheimers Dement 2014; 10: 179–86.
32Wilson, RS, Begeny, CT, Boyle, PA, Schneider, JA, Bennett, DA. Vulnerability to stress, anxiety, and development of dementia in old age. Am J Geriatr Psychiatry 2011; 19: 327–34.
33Zilkens, RR, Bruce, DG, Duke, J, Spilsbury, K, Semmens, JB. Severe psychiatric disorders in mid-life and risk of dementia in late-life (age 65-84 years): a population based case-control study. Curr Alzheimer Res 2014; 11: 681–93.
34Dondu, A, Sevincoka, L, Akyol, A, Tataroglu, C. Is obsessive–compulsive symptomatology a risk factor for Alzheimer-type dementia? Psychiatry Res 2015; 225: 381–6.
35Diniz, BS, Butters, MA, Albert, SM, Dew, MA, Reynolds, CF III. Late-life depression and risk of vascular dementia and Alzheimer's disease: systematic review and meta-analysis of community-based cohort studies. Br J Psychiatry 2013; 202: 329–35.
36Tapiainen, V, Hartikainen, S, Taipale, H, Tiihonen, J, Tolppanen, A-M. Hospital-treated mental and behavioral disorders and risk of Alzheimer's disease: a nationwide nested case-control study. Eur Psychiatry 2017; 43: 92–8.
37Kuiper, JS, Zuidersma, M, Oude Voshaar, RC, Zuidema, SU, van den Heuvel, ER, Stolk, RP, et al. Social relationships and risk of dementia: a systematic review and meta-analysis of longitudinal cohort studies. Ageing Res Rev 2015; 22: 3957.
38Steunenberg, B, Twisk, JWR, Beekman, ATF, Deeg, DJH, Kerkhof, AJFM. Stability and change of neuroticism in aging. J Gerontol B Psychol Sci Soc Sci 2005; 60: P27–33.
39Beauquis, J, Vinuesa, A, Pomilio, C, Pavia, P, Galvan, V, Saravia, F. Neuronal and glial alterations, increased anxiety, and cognitive impairment before hippocampal amyloid deposition in PDAPP mice, model of Alzheimer's disease. Hippocampus 2014; 24: 257–69.
40Marchant, NL, Howard, RJ. Cognitive debt and Alzheimer's disease. J Alzheimers Dis 2015; 44: 755–70.
41Barulli, D, Stern, Y. Efficiency, capacity, compensation, maintenance, plasticity: emerging concepts in cognitive reserve. Trends Cogn Sci 2013; 17: 502–9.
42McEwen, BS. Stress, adaptation, and disease: allostasis and allostatic load. Ann N Y Acad Sci 1998; 840: 3344.
43de Lijster, JM, Dierckx, B, Utens, EMWJ, Verhulst, FC, Zieldorff, C, Dieleman, GC, et al. The age of onset of anxiety disorders. Can J Psychiatry 2017; 62: 237–46.
44Bruce, SE, Yonkers, KA, Otto, MW, Eisen, JL, Weisberg, RB, Pagano, M, et al. Influence of psychiatric comorbidity on recovery and recurrence in generalized anxiety disorder, social phobia, and panic disorder: a 12-year prospective study. Am J Psychiatry 2005; 162: 1179–87.
45Whalley, LJ, Dick, FD, McNeill, G. A life-course approach to the aetiology of late-onset dementias. Lancet Neurol 2006; 5: 8796.
46Watson, D, Clark, LA, Carey, G. Positive and negative affectivity and their relation to anxiety and depressive disorders. J Abnorm Psychol 1988; 97: 346–53.
47do Couto, FS, Lunet, N, Gino, S, Chester, C, Freitas, V, Maruta, C, et al. Depression with melancholic features is associated with higher long-term risk for dementia. J Affect Disord 2016; 202: 220–9.
48Remes, O, Brayne, C, van der Linde, R, Lafortune, L. A systematic review of reviews on the prevalence of anxiety disorders in adult populations. Brain Behav 2016; 6: e00497.
49Esler, M. Mental stress and human cardiovascular disease. Neurosci Biobehav Rev 2017; 74: 269–76.
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Anxiety as a risk factor of Alzheimer's disease and vascular dementia

  • Eva Becker (a1), Claudia Lorena Orellana Rios (a2), Claas Lahmann (a3), Gerta Rücker (a4), Joachim Bauer (a5) and Martin Boeker (a6)...
  • Please note a correction has been issued for this article.
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