Depression: A shared risk factor for cardiovascular and Alzheimer disease
ABSTRACT
Depression has been linked to cardiovascular disease and cognitive impairment, including Alzheimer disease, but the exact nature of the relationship is poorly understood. Although depression seems to progress little after the onset of Alzheimer disease, depression in earlier life increases the risk of dementia and cognitive impairment many years in the future. Depression is also associated with reduced vascular function and is a poorly recognized but significant risk factor for stroke.
The associations among depression, cardiovascular disease, and cognitive impairment are well known. Inflammation is increasingly recognized as playing an important role as well. However, the nature of their relationships and which may actually cause the other is not well understood. This article reviews studies over the past year that link depression with dementia and vascular disease. Desirable directions for future work are also explored.
DEPRESSION AND ALZHEIMER DISEASE
Several studies have shown significant correlations between depression and the risk of developing Alzheimer disease; the frequency of depressive episodes appears to be an important factor. Despite the risk relationship, however, depression and Alzheimer disease may not share a common pathology.
No shared pathology
Wilson and colleagues1 analyzed data from the Chicago Health and Aging Project, a longitudinal cohort study of risk factors for Alzheimer disease that involved two groups of people aged 65 years and older; one group was composed of people who developed dementia during the study, while the other group had already developed dementia or had some degree of cognitive impairment. The investigators reasoned that if pathologic changes are common to depression and dementia, then there would be evidence of change in depressive symptoms along with the progression of dementia. They found only a barely perceptible increase in depressive symptoms among people who developed Alzheimer disease and concluded that there is no shared pathology between depression and Alzheimer disease.
Degree of depression signals risk
Depression has been associated with nearly double the risk of developing dementia and Alzheimer disease. Saczynski et al2 evaluated 949 people in the Framingham study, mean age 79 years, using the 60-point Center for Epidemiologic Studies Depression Scale (depression defined as > 16 points). Individuals who had depression at baseline were 1.7 times more likely to develop dementia over the 17-year evaluation period. Results were similar when adjusted for major vascular risk factors (smoking, diabetes, hypertension, and cardiovascular disease). The correlation was slightly lower but still significant when subjects taking antidepressant medications were included in the depressed group.
The study also found a continuous relationship between the level of depression and the likelihood of developing dementia and Alzheimer disease: for every 10-point increase on the depression scale, the risk of developing dementia increased by nearly 50%. This study supports depression as a risk factor for dementia. One could also argue that depression as a simple prodrome to dementia seems unlikely because of the long followup between baseline assessment and the development of dementia.
Multiple episodes of depression increase risk
Dotson et al3 analyzed data from 1,239 older adults from the Baltimore Longitudinal Study of Aging who did not have depression, dementia, or mild cognitive impairment at baseline. Every 1 to 2 years for about 25 years, cognitive status and mood of the subjects were evaluated. About 10% of the participants developed dementia during the course of the study. Of those who developed dementia, 35% had at least one episode of depression; among those who did not develop dementia, only 23% had a depressive episode. Findings were similar when investigators controlled for vascular risks and vascular dementia.
One episode of depression was associated with an 87% increase in risk of dementia; at least two episodes of depression more than doubled the risk (108%). Overall, each episode of depression conferred an additional 14% risk of developing dementia. Among subjects who had had two or more episodes of depression, the median age of developing dementia was 85 years versus 95 years for those without an episode of depression.
This study had the advantages of being prospective for both depression and dementia and of having a long followup period. A dose-effect relationship was observed, with the “dose” being the number of depressive episodes (rather than severity of depression). Because the definition of a depressive episode included subsyndromal depression (not likely to meet the criteria of clinical depression, but still clinically significant), the findings suggest that even minor depression increases the risk of dementia.
