Pauline Anderson

July 24, 2017

LONDON – Depression that starts early in life increases the risk for Alzheimer's disease (AD), as demonstrated in findings from a large, longitudinal study that is the first to report this association.

This relationship has not been seen in earlier studies, Lena Johansson, PhD, Institute of Neuroscience and Physiology, Sahlgrenska Academy Center for Aging and Health, the University of Gothenburg, Sweden, told Medscape Medical News.

"Prior studies had shorter follow-up periods and were mainly done in late-life populations. The associations between depression and dementia could in those cases have been due to cognitive decline and mild cognitive impairment," she said.

Dr Lena Johansson

The current study suggests that "depression is not only a result of incipient dementia," said Dr Johansson.

The findings were presented here at the Alzheimer's Association International Conference (AAIC) 2017.

Potential Hypotheses

Numerous previous studies, systematic reviews, and meta-analyses have analyzed the relationship between dementia and depression, and almost all of this research has shown that the risk for dementia increases following depression.

However, because these studies were limited by short follow-up, the association between depression and dementia found in these studies can be a reverse correlation, Dr Johansson told conference delegates.

Several possible hypotheses may explain the association between depression and dementia, said Dr Johansson. For example, depression could be a prodromal state of dementia, or the two conditions could share an underlying pathophysiology.

It is possible that depression is a psychological reaction to cognitive decline. If depression affects levels of stress hormones and various neurotransmitters, including serotonin, dopamine, and glutamate, this might damage the brain and raise the risk for dementia.

The new study used data from the Prospective Population Study of Women in Gothenburg Sweden, which began almost 50 years ago. In 1968, the study sample included 800 women (mean age, 46 years), born between 1914 and 1930.

In the initial interview, participants were asked about current and past depression. The sample was followed up in 1974, 1980, 1992, 2000, 2009, and 2012. During these follow-up visits, participants were again asked about depression.

In addition to neuropsychiatric examinations, information on depression came from interviews with informants, medical records, and the Swedish Hospital Discharge Register.

Researchers used DSM-III criteria to establish a diagnosis of depression and to determine whether cases were of mild or major depression. They also determined the age of the patient at the first depressive episode.

About 67% of the study participants had met criteria for either mild or major depression one or more times. Of these patients, 44% experienced major depression.

The mean age of the patients at the time of the first depressive episode was 42 years.

Researchers used the DSM-III-R to determine diagnoses of dementia. Using criteria from the National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer's Disease and Related Disorders Association criteria, researchers identified 133 patients who had developed AD.

Using criteria from the International Workshop of the National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences, the researches concluded that 70 patients developed vascular and other types of dementia.

A Serious Condition

The investigators found that in comparison with women who did not have a history of depression, those who had experienced any depression during their life were at increased risk for AD (hazard ratio [HR], 1.75; 95% confidence interval [CI], 1.15 - 2.66) after adjusting for age, education, the presence of hypertension, and APOE4 genetic status.

The association was stronger for major depression than for mild depression.

The researchers found that compared to women who were without depression, those who experienced the onset of depression before age 20 years were three times more likely to develop AD (adjusted HR, 3.41; 95% CI, 1.78 - 6.54).

The risk was also increased for patients who experienced the onset of depression between the ages of 20 and 49 years (HR, 1.65), but not for those who experienced depression onset between the ages of 50 and 69 years (HR, 1.02). The risk increased after age 70 years (HR, 2.11).

There were no associations between depression and vascular and other types of dementia.

A limitation of the study was that it did not include information regarding treatment for depression.

"So we can't know if antidepressant medication or psychotherapy played any role," said Dr Johansson.

But because the study showed that major depression was associated with the highest risk for dementia, "it's probably important to avoid severe episodes of depression," she said.

Another limitation of the study is that the researchers did not have information on the number of depressive episodes.

"Further research should look at this and factors such as socioeconomic status, physical activity, and drug use to further untangle the associations," said Dr Johansson.

The main take-away message from this new research is that clinicians should consider depression as a serious condition and prescribe therapy, including conversational therapy or antidepressants, when needed, she added.

There is no reason to think that the association between long-term depression and dementia would be any different for men, noted Dr Johansson.

Following her presentation, a delegate asked Dr Johansson to explain the high prevalence of depression in the study sample – almost 70%.

She stressed that this represents a lifetime prevalence of depression and that the data are comparable with those from other epidemiologic research.

Another delegate was surprised that the study found no association between vascular dementia and depression.

Dr Johansson responded that this could be due to methodologic problems. The fact that few patients developed vascular dementia could have lessened statistical power.

"Depression may not affect vascular factors to the extent that it affects the brain," said Dr Johansson. "Further studies are need to analyse this association."

Dr Johansson has disclosed no relevant financial relationsihps.

Alzheimer's Association International Conference (AAIC) 2017. Abstract 17671, presented July 16, 2017.

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