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Original Investigation |

Long-term Risk of Dementia in Persons With Schizophrenia A Danish Population-Based Cohort Study

Anette Riisgaard Ribe, MD1; Thomas Munk Laursen, PhD2; Morten Charles, MD, PhD3; Wayne Katon, MD†4; Morten Fenger-Grøn, MSc1; Dimitry Davydow, MD, MPH4; Lydia Chwastiak, MD, MPH4; Joseph M. Cerimele, MD, MPH4; Mogens Vestergaard, MD, PhD1,3
[+] Author Affiliations
1Research Unit for General Practice, Department of Public Health, Aarhus University, Aarhus, Denmark
2National Centre for Register-Based Research, Department of Economics and Business, Aarhus University, Aarhus, Denmark
3Section for General Medical Practice, Department of Public Health, Aarhus University, Aarhus, Denmark
4Department of Psychiatry and Behavioral Sciences, School of Public Health, University of Washington, Seattle
JAMA Psychiatry. 2015;72(11):1095-1101. doi:10.1001/jamapsychiatry.2015.1546.
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Importance  Although schizophrenia is associated with several age-related disorders and considerable cognitive impairment, it remains unclear whether the risk of dementia is higher among persons with schizophrenia compared with those without schizophrenia.

Objective  To determine the risk of dementia among persons with schizophrenia compared with those without schizophrenia in a large nationwide cohort study with up to 18 years of follow-up, taking age and established risk factors for dementia into account.

Design, Setting, and Participants  This population-based cohort study of more than 2.8 million persons aged 50 years or older used individual data from 6 nationwide registers in Denmark. A total of 20 683 individuals had schizophrenia. Follow-up started on January 1, 1995, and ended on January 1, 2013. Analysis was conducted from January 1, 2015, to April 30, 2015.

Main Outcomes and Measures  Incidence rate ratios (IRRs) and cumulative incidence proportions (CIPs) of dementia for persons with schizophrenia compared with persons without schizophrenia.

Results  During 18 years of follow-up, 136 012 individuals, including 944 individuals with a history of schizophrenia, developed dementia. Schizophrenia was associated with a more than 2-fold higher risk of all-cause dementia (IRR, 2.13; 95% CI, 2.00-2.27) after adjusting for age, sex, and calendar period. The estimates (reported as IRR; 95% CI) did not change substantially when adjusting for medical comorbidities, such as cardiovascular diseases and diabetes mellitus (2.01; 1.89-2.15) but decreased slightly when adjusting for substance abuse (1.71; 1.60-1.82). The association between schizophrenia and dementia risk was stable when evaluated in subgroups characterized by demographics and comorbidities, although the IRR was higher among individuals younger than 65 years (3.77; 3.29-4.33), men (2.38; 2.13-2.66), individuals living with a partner (3.16; 2.71-3.69), those without cerebrovascular disease (2.23; 2.08-2.39), and those without substance abuse (1.96; 1.82-2.11). The CIPs (95% CIs) of developing dementia by the age of 65 years were 1.8% (1.5%-2.2%) for persons with schizophrenia and 0.6% (0.6%-0.7%) for persons without schizophrenia. The respective CIPs for persons with and without schizophrenia were 7.4% (6.8%-8.1%) and 5.8% (5.8%-5.9%) by the age of 80 years.

Conclusions and Relevance  Individuals with schizophrenia, especially those younger than 65 years, had a markedly increased relative risk of dementia that could not be explained by established dementia risk factors.

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Figure 1.
Incident Rate Ratios (IRRs) for Dementia in Persons With Schizophrenia Compared With Persons Without Schizophrenia

The IRRs were adjusted for age, sex, and calendar period and were stratified for age, sex, calendar period, civil status, medical comorbidity, or substance abuse. The estimates differed significantly when evaluated for age (P < .001), sex (P = .02), civil status (P < .001), cerebrovascular disease (P = .002), and substance abuse (P < .001). The vertical dotted line represents the overall estimate without stratification (IRR, 2.13). AF indicates atrial fibrillation or flutter; CHF, congestive heart failure; IHD, ischemic heart disease; IRR, incidence rate ratio; and PVD, peripheral vascular disease.

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Figure 2.
Cumulative Incidence Proportions of Risk of Dementia in Persons With and Without Schizophrenia as a Function of Age

The cumulative probability of dementia and corresponding 95% CIs (dashed lines) are presented as a function of age for persons with and without schizophrenia, taking competing risk of all-cause mortality into account. The 95% CIs are very narrow for persons without schizophrenia owing to the large sample size and thus are not discernible in this graph.

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