Bipolar disorder in older men linked to increased risk of dementia

Last year I blogged about the increased risk of premature death in people with bipolar disorder. Although not all people with bipolar disorder will necessarily have poor long-term outcomes, it is clear that the disorder is associated with factors affecting longevity.

People with bipolar disorder experience:

Long-term usage of lithium or antipsychotic medication
Increased risk of suicide
Difficulty securing employment or maintaining positive social relationships
Long periods of either depression or manic episodes.

So can bipolar disorder increase your risk other health conditions?

Well, according to a sizeable portion of literature, the answer is yes. It appears that affective disorders may be a risk factor for dementia, as highlighted in a number of systematic reviews (da Silva 2013, Jorm 2002, Ownby 2006). These reviews were, however, limited due to the size of the included studies, the methods used for determining outcomes and a heavy focus on depression rather than bipolar disorder.

To investigate this association further, Almeida and colleagues (2016) carried out a study looking at the risk of dementia and mortality (including a number of causes) in people with bipolar disorder in the total population of older men living in Perth, Australia.

Do older Australian men with a diagnosis of bipolar disorder have a higher risk of developing dementia?

Methods

Population

Using the electoral register, the authors located 37,768 men aged 65-85 years in 1995 from the Perth metropolitan area.

Exposure and Outcomes

Exposure (previous diagnosis of bipolar disorder) and outcomes were obtained using the Western Australian Data Linkage System (WADSLD) which ‘links information for all contacts with out-patient and in-patient mental health services in Western Australia, hospital morbidity data, as well as cancer and death registries.’

The primary outcome was a diagnosis of dementia. In addition to the WASLD, the authors also scanned death records and looked for diagnoses of dementia using the words dementia, Alzheimer, Lewy and Pick.

The secondary outcome was cause of death. These were grouped into the following categories: suicide, accident, infection, cancer, diseases of the heart, diseases of the brain, vascular diseases (excluding stroke and heart conditions), diseases of the digestive system (including liver), diseases of the kidney, and other causes of death.

Other variables considered in the study were date of birth, alcohol and substance use disorders.

For diagnoses of bipolar disorder, the WADSLD was scanned from January 1966 to April 1996 (the study baseline). For outcomes, records were examined between April 1996 and June 2009.

Statistical analysis

To investigate the association between diagnoses of bipolar disorder and age, alcohol and substance use disorders, the authors calculated odds ratios using a series of logistic regressions.
To calculate the time to a dementia diagnosis and time to death between people with a diagnosis of bipolar disorder and those without, hazard ratios were estimated using Cox proportional hazards models, adjusted for age. Incident rates of dementia and death for people with and without bipolar disorder were also age standardised.
Age-adjusted Cox regressions were used to investigate the association between a diagnosis of bipolar disorder and different causes of death.
To explore the possibility of confounding factors, the authors re-analysed the risk of dementia and mortality in a sub-group of the sample for whom lifestyle and clinical data were available between 1996 and 1998. Two additional Cox regression models were run adjusting for the following factors: place of birth, marital status, education, physical activity, smoking, alcohol consumption, BMI, history of diabetes/hypertension, and previous heart attack or stroke.

Results

Overall 37,768 men aged 65-85 years were eligible to be included in the study. At study baseline, 256 (0.7%) had a diagnosis of bipolar disorder.

Bipolar disorder and dementia

There was an increased risk of dementia for men with bipolar disorder, compared with those without a diagnosis. During the study period 13% of the whole sample developed dementia, compared with 25.4% (n = 65) of the group of participants who had bipolar disorder
There was also evidence of a shorter time to a diagnosis of dementia in men with bipolar disorder when adjusted for age (HR = 2.58, 95% CI, 2.02 to 3.30)
This also held when adjusted for a history of alcohol and substance use (HR = 2.30, 95% CI, 1.80 to 2.94).

Bipolar disorder and mortality

Men with bipolar disorder also showed an increased risk of premature mortality. There was a 69.7% mortality rate per 1,000 person-years in men with bipolar disorder, compared with 49.4% in those without
There was also a shorter time to death, when adjusted for age, in those with bipolar disorder (HR = 1.51, 95% CI, 1.28 to 1.77)
As with dementia, adjusting for alcohol and substance use disorders had little effect on the estimate (HR = 1.32, 95% CI, 1.13 to 1.55).

Causes of death

There was a statistically significant increased risk of death for people with bipolar disorder due to the following causes:

Suicide (HR = 13.43, 95% CI, 5.35 to 33.73)
Accident (HR = 2.78, 95% CI, 1.14 to 6.75)
Pneumonia or influenza (HR = 3.66, 95% CI, 1.81 to 7.40)
Liver and digestive diseases (HR = 2.02, 95% CI, 1.00 to 4.06)

For the following causes of death, the risk was higher in people with bipolar disorder compared with the total sample, however, the differences were not significant: infection, cancer, diseases of the brain, vascular diseases, kidney diseases and other causes. There was a very small reduced risk of diseases of the heart and respiratory diseases as causes of death, however these differences were not significant.

Adjusting for confounding factors

When adjusting for a series of lifestyle and clinical factors in a sub-sample of 12,147 men, the authors reported an increased hazard for dementia (HR = 2.52, 95% CI, 1.54 to 4.15) and for mortality (HR = 1.40, 95% CI, 1.01 to 1.95) in men with bipolar disorder.

Elderly men with bipolar disorder have a higher risk of dementia and premature death, when compared to elderly men without bipolar disorder.

Conclusions

The authors concluded that:

The results showed that dementia and death accrue with greater frequency among older men with than without bipolar disorder. The diagnosis of bipolar disorder was associated with more than double the risk of dementia over 13 years and with a 50% increase in mortality. This excess risk could not be attributed to confounding due to age or use of substances.

Strengths and limitations

The main strength of this study is the availability of data for the entire population of older men living in Perth. However, despite the large number of included participants, only a relatively small number of participants had a diagnosis of bipolar disorder (n = 256).

Another strength lies in the use of information for outcomes from inpatient and outpatient mental health service records, hospital morbidity records, and cancer and death registries. Information about past diagnoses of bipolar disorder was only available from 1966 onwards, which may have potentially missed some men who’d had a diagnosis prior to this date. However, due to the long-term nature of bipolar disorder this is quite unlikely.

This study is somewhat limited in the analysis of confounding factors as data were only available for approximately a third of the sample, and collected via self-report questionnaires. It is unclear whether the other two thirds of participants were also asked for this extra information and did not respond.

Additionally, it would have been interesting to know if men with bipolar disorder were more frequently in contact with health services compared with men without the disorder. Should this have been the case, it may have potentially overestimated the risk of dementia; a diagnosis of dementia may have been more likely due to better monitoring of older men with bipolar disorder compared with those without.

How can we optimise the care provided for older people with a bipolar diagnosis?

Summary

This study was well conducted and included a large sample (of men!), increasing our confidence in the findings. Overall, older men with bipolar disorder were found to have an increased risk of dementia and mortality, even when controlling for alcohol and substance use disorders. Whilst the association between affective disorders and dementia is not a new finding, this study provides good evidence to support this link, specifically in older men with bipolar disorder.

What can we do to help ageing men with bipolar disorder?

Unfortunately this study does not answer this question, as the underlying mechanism for this association is still unknown. Possible reasons include the long-term usage of medication or the negative impact of episodes of depression and mania on cognitive functions.

Further research is needed to clarify this link with the aim of optimising treatment and care for older men with bipolar disorder who show significant reductions in cognitive function.

Women were excluded from this study, so will have to wait and see if other studies can answer this question for them.

Links

Primary paper

Almeida OP, McCaul K, Hankey GJ, Yeap BB, Golledge J, Flicker L. (2016) Risk of dementia and death in community-dwelling older men with bipolar disorder. Br J Psychiatry. 2016;209(2):121-6. doi: 10.1192/bjp.bp.115.180059 [PubMed abstract]

Other references

Jorm AF. (2001) History of depression as a risk factor for dementia: an updated review. Aust N Z J Psychiatry. 2001;35(6):776-81. [PubMed abstract]

da Silva J, Gonçalves-Pereira M, Xavier M, Mukaetova-Ladinska EB. (2012) Affective disorders and risk of developing dementia: systematic review. Br J Psychiatry. 2012;202(3):177-86. [PubMed abstract]

Ownby RL, Crocco E, Acevedo A, John V, Loewenstein D. (2006) Depression and risk for Alzheimer disease: systematic review, meta-analysis, and meta-regression analysis. Arch Gen Psychiatry. 2006;63:530–8. [PubMed abstract]