Research report
Increased risk of developing dementia in patients with major affective disorders compared to patients with other medical illnesses

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Abstract

Background: The association between affective disorder and subsequent dementia is unclear. Our aim was to investigate whether patients with unipolar or bipolar affective disorder have an increased risk of developing dementia compared to patients with other chronic illnesses. Method: By linkage of the psychiatric and somatic nation-wide registers of all hospitalised patients in Denmark, 2007 patients with mania, 11,741 patients with depression, 81,380 patients with osteoarthritis and 69,149 patients with diabetes were identified according to diagnosis at first-ever discharge from a psychiatric or somatic hospital between 1 January 1977 and 31 December 1993. The risk of receiving a diagnosis of dementia on subsequent re-admission was estimated with the use of survival analyses. Results: Patients with unipolar or bipolar affective disorder had a greater risk of receiving a diagnosis of dementia than patients with osteoarthritis or diabetes. Differences in age and gender and the effect of alcohol- or drug-abuse did not explain these associations. Conclusion: Patients with unipolar or bipolar affective disorder seem to have an increased risk of developing dementia compared to patients with other illnesses. Limitation: The study includes only patients who have been hospitalised at least once. Clinical relevance: Patients with unipolar or bipolar affective disorder may be at increased risk of developing dementia.

Introduction

Jorm has recently concluded in a seminal review that there is sufficient evidence to take seriously the possibility that depression is a risk factor for dementia and cognitive decline (Jorm, 2000). Findings from several areas of research indicate that depression or depressive symptoms may be associated with an increased risk of eventually developing dementia. In retrospective studies of patients with Alzheimer’s disease, a history of depression has been found to be associated with late onset Alzheimer’s disease (Jorm et al., 1991, Speck et al., 1996, Steffens et al., 1997) and in prospective community studies, depressive mood at baseline has been found to be associated with an increased risk of incident dementia (Devanand et al., 1996, Schmand et al., 1997). Similarly, subgroups of patients with depression have been found to develop dementia in uncontrolled follow-up studies (Rabins et al., 1984, Pearlson et al., 1989, Alexopoulos et al., 1993, Stoudemire et al., 1993, Stoudemire et al., 1995). Only one controlled (historical) prospective long-term study of patients with affective disorder has been published, the study by our group (Kessing et al., 1999). We found that the risk of receiving a discharge diagnosis of dementia on re-admission was increased in patients previously discharged from psychiatric hospitals with a diagnosis of unipolar (single or recurrent depression) or bipolar affective disorder compared to patients with a diagnosis of neurosis and compared to the general population in Denmark.

The study had some limitations. Firstly, it can be argued that cognitive decline may be a consequence of the reduced activity and stimulation in daily life that is often associated with a chronic disease. It could be that such an effect is more pronounced in patients with recurrent affective disorders than in patients with neurosis and in the general population. No study has compared the risk of developing dementia in patients with affective disorder with the risk in suitable control groups of patients with other chronic diseases. Secondly, patients with affective disorders and controls included in our previous study may have been diagnosed with dementia in places outside psychiatric wards as only diagnoses given following admission to psychiatric wards were recorded. Thus, there is a need for replication of the findings in a study including diagnoses from both psychiatric and somatic wards and including patients with other chronic diseases as controls.

The present study compares the risk of receiving a diagnosis of dementia on re-admission in patients hospitalised at least once with a diagnosis of affective disorder, osteoarthritis or diabetes mellitus.

Osteoarthritis (also referred to as osteoarthritis deformans) is a progressive, degenerative joint disease, the most common form of arthritis, especially in elderly people. In the present study, patients with osteoarthritis were chosen as a control group because osteoarthritis is a chronic and progressive disease which does not affect brain function. Additionally, patients with osteoarthritis do not seem to present with a high degree of co-morbidity (Gabriel et al., 1999).

Patients with diabetes were chosen because diabetes is a serious chronic disease that requires continuous medication and surveillance as does affective disorder. The natures of diabetes and affective disorder are comparable as both diseases fluctuate in intensity. When well-medicated, the patients do not necessarily feel any symptoms of the illness. However, when the patients are free of medication the risk of relapse or recurrence of a new episode of the illness is increased. Diabetes has been shown to cause both diffuse and focal changes in the brain following many years with the disease (especially if the diabetes is inadequately regulated). This is possibly due to vascular disease and hypertension, and also to the effects of metabolic disturbances on neurons.

For both osteoarthritis and diabetes, treatment with traditional medication (NSAIDs and anti-diabetic drugs, including insulin) is not known to increase the risk of developing symptoms of affective episodes or cognitive dysfunction.

The aim of the present study was to compare the risk of receiving a diagnosis of dementia on a subsequent discharge from hospital, in patients previously discharged with a diagnosis of unipolar affective disorder, bipolar affective disorder, osteoarthritis or diabetes.

Only patients who had been hospitalised at least once on a psychiatric or somatic ward were included in the study and these patients thus represent the more severely affected patients. Data on treatment or out-patient status were not available.

Section snippets

The registers

In Denmark, all psychiatric admissions have been registered in a nation-wide register, The Danish Psychiatric Central Register (DPCR) (Munk-Jørgensen and Mortensen, 1997) from 1 April 1970 to 31 December 1993 using the Danish edition of ICD-8 (National Board of Health Denmark, 1971). Likewise, all somatic hospital admissions to day or night care have been recorded in a nation-wide register, The Danish National Hospital Register (DNHR; Andersen et al., 1999) from 1 January 1977 to 31 December

Results

In total, 164,385 patients were discharged with a diagnosis of affective disorder, osteoarthritis or diabetes in the period from 1977 to 1993. However, 108 patients were excluded due to miscoding (21 patients had insufficient data and 87 had overlapping episodes of admission). Thus, the study sample included 164,277 patients: 2007 patients with mania, 11,741 patients with depression, 81,380 patients with osteoarthritis and 69,149 patients with diabetes. Characteristics regarding gender, age at

Discussion

The present study showed that patients with unipolar and or bipolar affective disorder had an increased risk of receiving a diagnosis of dementia compared to patients with osteoarthritis or diabetes. The associations could not be explained by differences in age and gender between probands and controls or by an effect of alcohol/drug abuse.

Acknowledgements

The authors acknowledge the generous financial support of ‘The Theodore and Vada Stanley Foundation’.

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