Late-onset depressive disorders: a preventable variant of cerebrovascular disease?

Abstract

The severe depressive disorders of late life are associated with high rates of medical morbidity and mortality, cognitive impairment, suicide, disability, complex treatment regimens, institutionalization and high costs to the community (Murphy, 1983; Murphy et al. 1988; Bruce & Leaf, 1989; NIH Consensus Development Panel, 1992; Alexopoulos et al. 1993a, b; Brodaty et al. 1993; Bruce et al. 1994; Forsell et al. 1994; Hickie et al. 1995; Blazer, 1996). Those disorders that are accompanied by cognitive impairment and/or concurrent medical morbidity have a particularly poor outcome (Bruce & Leaf, 1989; Alexopoulos et al. 1993b; Hickie et al. 1995, 1997a). Although psychosocial models of late-life depression place considerable importance on age-related psychological and social risk factors, those who survive into later life may actually be characterized by psychological resilience (Henderson, 1994; Blazer, 1997).Current aetiological research in late-life depression, therefore, places particular emphasis on the potential role of biological risk factors. The potential importance of vascular risk factors is receiving renewed attention and may provide opportunities for specific prevention and intervention strategies in high-risk populations. This emphasis on possible vascular risk factors, and the wider importance of vascular pathologies in late-life neuropsychiatric disorders, mirrors the emphasis of much earlier clinico-pathological studies (Binswanger, 1894; Alzheimer, 1895). The specific focus on the importance of small progressive changes within the subcortical white matter, as distinct from more discrete cortical infarcts (Olszewski, 1962), is now supported by the emerging neuroimaging literature and theoretical constructs in late-life depression (Krishnan, 1991, 1993; Hickie et al. 1996, 1997b; Krishnan et al. 1997).

Autonomous Neurobiological Pathways to Late-Life Major Depressive Disorder Clinical and Pathophysiological Implications

“…The apparent link of these lesions to vascular disease has led to speculation that the presence of these lesions suggests an underlying etiology that is predominantly vascular in origin (O'Brien et al 1996;Krishnan et al 1997;Hickie and Scott 1998) The neuropathological correlates of high-intensity lesions are diverse and include areas of white matter ischemia, edema, demyelination, and perivascular spaces in the neocortical and subcortical areas of the brain (Awad et al 1986;Braffman et al 1988;Drayer 1988;Spangler et al 1994;Ylikoski et al 1995). Our data indicate that vascular and nonvascular comorbidity contribute to these lesions.…”

A fully automated method for quantifying and localizing white matter hyperintensities on MR images

“…A number of previous studies have shown that white matter hyperintensities (WMH), also called leuokoaraiosis, commonly seen on T2-weighted FLAIR MR images, are associated with neuropsychiatric disorders, including vascular dementia (van Gijn 1998), Alzheimer's disease (Mirsen, et al 1991), and late-onset late-life depression (Hickie and Scott 1998;Thomas, et al 2004). Two analysis strategies have been used to evaluate WMHs on MR brain images: (1) semi-quantitative rating systems and (2) quantitative volumetric analyses.…”

Do the Genetic or Environmental Determinants of Anxiety and Depression Change with Age? A Longitudinal Study of Australian Twins

“…Hence, a new illness entity of "vascular depression" has been proposed (Alexopoulos et al, 1997a;Alexopoulos et al, 1997b;Krishnan et al, 1997;Krishnan, 2002) and is thought to be particularly prevalent among persons who develop depression for the first time after 50 years of age. Not only does such a concept have important treatment and prognostic implications, but also raises the prospect of novel methods for prevention based on this more basic understanding of its pathophysiology (Hickie & Scott, 1998).…”