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.
Baseline depression predicts cognitive impairment
Rosenberg et al4 found depression to be associated with cognitive impairment in their evaluation of 436 women in their 70s; the women, who were participants in the Women’s Health and Aging Study, were evaluated for up to 9 years. To be included in the evaluation, subjects needed a Mini-Mental State Examination score of at least 24 points (out of 30 possible) and could not be impaired in more than one basic functional capacity: mobility and exercise tolerance, upper extremity, higher functioning (eg, shopping), and basic self-care). Baseline depressive symptoms were measured using the Geriatric Depression Scale.
Cognitive testing included Hopkins Verbal Learning Tests (for immediate and delayed word recall) and Trail Making Tests (for psychomotor speed and executive functioning). Those who were not impaired (ie, having a cognitive test score below the 10th percentile for age-adjusted norms) were followed with up to six examinations over the next 9 years.
Baseline depression was found to be highly associated with incident impairment in all cognitive areas, especially in executive functioning. For every point increase in the depression scale, a 6% to 7% increase was found in the annual risk of impairment in each cognitive domain.
DEPRESSION AND VASCULAR DISEASE LINKED
It is somewhat easier to assess the relationship between depression and vascular disease than between depression and cognitive impairment because of the availability of objective measures of cardiovascular function.
The International Stroke Study (INTERSTROKE),5 a case-control study in 22 countries with 3,000 cases of stroke and 3,000 age-, gender-, and ethnicity-matched controls, found nine risk factors that were correlated with 90% of ischemic stroke cases. Depression, with an odds ratio of 1.86, was found to be a more significant risk factor than physical activity, diet, or heavy drinking.
Paranthaman et al6 evaluated a number of measures of arterial anatomy and function in 25 subjects with depressive disorder and in 21 nondepressed controls (mean age, 72 years). They found that depressed subjects had significantly higher mean carotid intima media thickness, reduced dilation in response to acetyl choline in preconstricted small arteries, and more dilated Virchow-Robin spaces in the basal ganglia observed on magnetic resonance imaging. This study provides evidence that arterial structure and function may mediate the relationship between depression and vascular disease.
FUTURE DIRECTIONS
Future studies into depression as a risk factor should use very well-characterized cohorts that are controlled for blood pressure and other vascular risk factors. Finding biomarkers for depression would be useful, permitting its detection earlier and with more certainty than is now possible. Prospective studies to evaluate the relationship of depression to cognitive impairment and dementia are needed that start earlier than in middle or old age. The key question that needs study is whether treatment of depression can actually change the onset of cognitive impairment, Alzheimer disease, and vascular disease.
