July 13, 2010

Published Date: 08 July 2010

"Having depression may nearly double the risk of developing dementia later in life," reported BBC news. It said that a 17-year study of nearly 1,000 elderly people, found that 22% of those who were depressed at the start went on to develop dementia, compared with 17% of those who were not depressed.
This is a well-designed study and was accurately reported by the BBC. It has several strengths and adds to the evidence of a link between the two conditions.

However, as the researchers say, this does not necessarily mean that depression causes de

mentia and the reason for the association between the two conditions is still unclear. It is unknown if depression is a risk factor for dementia, whether it is an early sign of cognitive decline or if certain changes in the brain are associated with both conditions. Also, certain lifestyle factors not measured by this study, such as poor diet, lack of physical activity and social interaction, may increase the risk of both depression and dementia.

Importantly, this study was in elderly people (average 79 years) and it is unknown if depression earlier in life would be associated with dementia in the same way. Further research is needed.


Where did the story come from?The study was carried out by researchers from the University of Massachusetts in Worcester, and Boston University in the US. It was funded by the US National Heart, Lung and Blood Institute, the National Institute on Aging and the National Institute of Neurological Disorders and Stroke. The study was published in the (peer-reviewed) medical journal Neurology.

The study was accurately reported on by the BBC, which was careful to explain that depression had not been proved to be a cause of dementia and that more research was needed to find out why the two conditions are linked. However, although the BBC mentions that the study was in elderly people, its story could be taken to imply that depression at any age is associated with dementia later. This study did not look at whether depression earlier in life is associated with later dementia.

The BBC also reported on another paper published in the same journal that found that the more times someone experienced depression, the higher their risk of dementia. This paper is not examined in this appraisal.


What kind of research was this?This was a prospective cohort study, which aimed to examine a possible association between depression and dementia. The participants were recruited from the Framingham Heart study, a long-running cohort study that began in 1948 and was initially set up to investigate risk factors for cardiovascular disease.

Cohort studies are useful for looking at potential risk factors for conditions because they are able to follow large groups of people for many years and to assess how certain events (in this case, depression) might impact their health later. As a prospective study, its results are more reliable than a retrospective study. This is because it tracks people forward in time and can establish any relevant information at the start of the study, as opposed to relying on previous medical records or personal recall. There is also added strength in that it ensured that participants were free from cognitive impairment at the time their depression was assessed.

The researchers point out that some, but not all previous studies have indicated a link between depression and cognitive impairment or dementia. Their research aimed to examine this possible association further over a longer follow-up period than previously achieved.


What did the research involve?This particular study began in 1990, when  1,166 members of the original Framingham cohort attended for assessment. A total of 949 attendees were identified to be free of dementia and were included in the study. Of these, about 64% were women and the average age was 79 years.

The participants were assessed for depressive symptoms, using a validated depression scale that has a score ranging from 0-60, with higher scores reflecting greater depressive symptoms. Based on established guidelines, a score of 16 or over was used to define depression. The researchers also recorded who was taking drug treatment for depression. Of the 949 participants, 125 (13.2%) were classified as depressed and a further 39 (4.1%) were taking anti-depressant medication.

The researchers followed up this group for up to 17 years (average follow up was eight years). Those participants that developed dementia were identified using regular examinations every two years. For this, a well-established questionnaire was used to screen for cognitive impairment, together with other relevant findings from the primary care physicians, medical records, observations from clinic staff and personal observations from the participant and their family. Those with possible dementia had further neurological tests and reviewed by a panel of specialists. Diagnoses of dementia were made using a validated diagnostic tool, and further assessments for Alzheimer’s disease made using established criteria.

The researchers used validated statistical methods to analyse any potential link between depression at the beginning of the study and the subsequent development of dementia. Their analyses also took into account many things that can affect the risk of dementia including age, sex, education, smoking habits, history of cardiovascular disease, diabetes and other relevant conditions.


What were the basic results?During the 17-year follow up, 164 participants developed dementia and 136 of these had. A total of 21.6% of participants assessed as depressed at the start of the study went on to develop dementia, compared with 16.6% of those who were not depressed.

Overall, a total 21.6% of depressed participants developed dementia compared to 16.6% of non-depressed participants. This was equivalent to a 72% increased risk of dementia if the person had depression (Hazard ratio [HR] 1.72, 95%, Confidence interval [CI] 1.04-2.84).

For each 10-point increase in depressive symptoms there was a 46% increase in the risk of dementia (HR 1.46, 95% CI 1.18-1.79) and a 39% increase in risk of Alzheimer’s disease (HR 1.39, 95% CI 1.11-1.75).

When the figures were further adjusted to take account of vascular risk factors such as stroke and diabetes, depressed participants were found to have double the risk of dementia (HR 2.01, 95% CI 1.20-3.31).


How did the researchers interpret the results?The researchers say that their findings support previous studies that have suggested depression is a risk factor for dementia and Alzheimer’s.


ConclusionThis is a well-designed study that has been reported on accurately by the BBC. It has numerous strengths including a large sample size, long duration of follow-up, and validated methods of diagnosing dementia at follow-up.

There are several points to take into consideration.

As the authors themselves say, it is difficult to establish causality. Although the participants were assessed and found to be free from dementia at the beginning of the study, it is possible that in some of the people classified as having depression, their de
pressive symptoms were actually an early sign of dementia. It is also possible that both depression and dementia cause similar pathological changes in the brain (e.g. inflammation), or that an unmeasured biological factor may predispose a person both to dementia and to depression.

When assessing the relationship between dementia risk and depression, the researchers adjusted for numerous possible confounders, and this increases the reliability of the results. However, there is a possibility that an unmeasured confounder could be having an effect on the risk of both dementia and depression. The authors themselves acknowledge that they did not take into account lifestyle factors such as exercise, diet and social interaction.

The study did not include diverse ethnic groups and did not have psychiatric documentation of depression. The researchers were also unable to look at how long depression lasted and response to or adherence to antidepressant medication or other treatments.

It should also be pointed out that study participants had an average age of 79 at the start of the study when their depression status was assessed. It is possible that the same relationship between depression and dementia would not be observed if a cohort of young or middle-aged people with depression were followed into old age.

Nevertheless, this study adds more evidence that there is an association between depression in elderly people and risk of dementia. However, the reasons for the observed link are not completely clear, and further research would be needed to better establish whether this was a cause-and-effect relationship, or whether there was a similar disease process or causative factor underlying both conditions