Vascular Disease, Depression, and Dementia

he coexistence of depression with cognitive impairment (CI) in late life has been a source for hypothesis development on the mechanisms underlying mood and cognitive syndromes. An early hypothesis postulated that depression with first onset in late life is a heterogeneous syndrome that encompasses patients whose depression is caused by neurological disorders that may or may not be clinically evident when the depression first appears. This hypothesis was supported by findings suggesting that patients with late-onset depression have more cognitive and neuroradiological abnormalities, greater disability, lower familial prevalence of mood disorders, and less personality dysfunction than elderly people with early-onset depression. 1 However, some studies failed to identify differences between lateand early-onset depression, perhaps because of the heterogeneity in both syndromes. Indeed, early-onset depression does not protect patients from developing brain abnormalities similar to those of late-onset depression. If anything, early-onset depression may predispose to such abnormalities. Although research on the late-onset hypothesis did not identify the exact mechanisms of depressive and cognitive symptoms, it yielded findings suggesting that related neurobiological processes contribute to depressive and cognitive symptoms. Late-onset depression was initially viewed as a condition caused by progressive or static neurological disorders, but basic research led to the realization that neurobiological changes occurring during depressive states may interfere with neurogenesis and contribute to neuronal changes that promote depression and CI. Such processes are operative in lateand early-onset depression. Therefore, the path to geriatric depression in most patients may involve an interaction between the pathophysiological changes of depression and neurological changes initiated through other mechanisms. The vascular depression hypothesis exemplifies these interactions. The vascular depression hypothesis postulates that cerebrovascular disease predisposes, precipitates, or perpetuates a depressive syndrome in some elderly patients. 1,2 Vascular depression encompasses depressive syndromes with diverse vascular impairments. Because the definition of vascular depression is still evolving, the vascular depression hypothesis cannot be directly tested, but it has provided the conceptual background for studies of the role of cerebrovascular disease in the development of depressive and cognitive symptoms. In this issue of the Journal of the American Geriatrics Society, the paper by Fuhrer and her colleagues of the PAQUID Study documented that depressive symptoms increase the risk of developing dementia during an 8-year follow-up period, 3 but this effect was noted only in men. Moreover, the risk for dementia was 50% higher in depressed hypertensive men than in nonhypertensive men. Hypertension did not increase the risk for dementia in women. Finally, elders who developed vascular dementia had more depressive symptoms than persons without dementia or with Alzheimer’s disease (AD). These findings suggest that, in some men, vascular disease leads to depressive symptoms, and a subgroup of those who develop depression progress into dementia. The path from vascular disease to depression to dementia may not be direct and sequential (Figure 1). Vascular disease and depression have a reciprocal relationship. There is evidence that vascular disease promotes development of depression. Patients with hypertension, coronary artery disease, myocardial infarction (MI), and vascular dementia often have high prevalence of depression. 4 One in five patients has major depression at the time of diagnostic cardiac catheterization 5 or after acute MI. 6 Another one in five has minor depression at these times. Approximately one in three patients develops major depression at some time during the 12 months after an MI. 7 Depression is a common complication of stroke. Stroke with neurological signs occurs in a small number of older people with depression, but silent stroke without neurological signs is common in elderly depressed populations. Silent stroke was documented in approximately 25% of older depressed Caucasian patients 8 and in 80% of Japanese patients. 9 Although vascular disease increases the risk of depression, the opposite sequence is also true (i.e., depression may increase the risk for vascular diseases). Approximately 50% of patients with coronary heart disease and major depression have had one or more prior episodes of major depression. 6 Depression exacerbates vascular morbidity and increases mortality from vascular diseases. 7 Depression may contribute to development of vascular dementia and perhaps to dementias of other etiologies. Depressive symptoms occurring long before the onset of dementia increase the likelihood for later development of AD. 10 Moreover, longitudinal studies of community-residing From the Weill Medical College of Cornell University, New York Presbyterian Hospital; and Cornell Institute of Geriatric Psychiatry, White Plains, New York.