MRI and neuropsychological differences in early- and late-life-onset geriatric depression

Abstract

We sought to determine whether geriatric patients with late-life-onset major depression have more subcortical hyperintensities on MRI and greater cognitive impairment than age-matched geriatric patients with early-life-onset major depression, suggesting that subcortical disease may be etiologic in late-life depression. Most negative studies of the clinical significance of subcortical hyperintensities on MRI in geriatric patients have sampled from a restricted range of subjects, have employed limited batteries of neuropsychological tests, or have not quantified MRI changes; the present study attempted to address these limitations. Thirty subjects from a geriatric psychiatry inpatient service who were over 60 years of age and presented with major depression were divided into groups with onset of first depression after age 60 (mean = 72.4 years, 15 women, 0 men), and onset of first depression before age 60 (mean = 35.8 years, 12 women, 3 men). Quantitative analysis of MRI yielded the volume of: periventricular hyperintensities (PVH) and deep white-matter hyperintensities (DWMH). Subjects were administered a neuropsychological battery and measures of depression by raters blind to age of onset. The late-onset group had significantly more PVH and DWMH. They were also more impaired on executive and verbal and nonverbal memory tasks. Discriminant analysis using the severity or subcortical signal hyperintensities on MRI, cognitive index, and depression scores correctly predicted late versus early onset of depression in 87% of the early-onset group and 80% of the late-onset group. These findings suggest that late-life-onset depression may be associated with an increased severity of subcortical vascular disease and greater impairment of cognitive performance.

Mapping Callosal Morphology in Early- and Late-Onset Elderly Depression: An Index of Distinct Changes in Cortical Connectivity

“…Several distinctions between these groups have been identified, and subjects with early-onset depression are more likely to have a family history of psychiatric illness (Brodaty et al, 2001), while subjects with late-onset depression have greater subcortical ischemic disease (Krishnan et al, 1988;Salloway et al, 1996;Taylor et al, 2004). In addition, late-onset depression has been associated with more pronounced temporal lobe atrophy (Greenwald et al, 1997;Kumar et al, 1998) and hippocampal volume reductions (Steffens et al, 2000;Hickie et al, 2005), with specific genotypes possibly mediating this effect (Taylor et al, 2005).…”

“…In addition, late-onset depression has been associated with more pronounced temporal lobe atrophy (Greenwald et al, 1997;Kumar et al, 1998) and hippocampal volume reductions (Steffens et al, 2000;Hickie et al, 2005), with specific genotypes possibly mediating this effect (Taylor et al, 2005). If these previous investigations are interpreted to be signs of different causes or risk factors for depression based on age at onset, greater splenium thinning in late-than early-onset depression might indeed point to more prominent atrophic or neurodegenerative processes in temporal connections, possibly reflecting higher risk for cognitive impairment and dementia conversion in the future (Geda et al, 2006;Salloway et al, 1996;Schweitzer et al, 2002;van Ojen et al, 1995). Indeed, regionally specific posterior callosal atrophy has been reported in mild Alzheimer's disease (Lyoo et al, 1997;Wang et al, 2006;Yamauchi et al, 2000).…”

“…This subgroup, frequently referred to as having late-onset depression, exhibits certain unique clinical, biological, and neuroimaging characteristics (Burvill et al, 1989;Heun et al, 2000;Krishnan et al, 1995Krishnan et al, , 1997Schweitzer et al, 2002), implying that late-onset depression may represent a distinct subtype of depression in the elderly. Along with observations of greater cognitive deficits (Salloway et al, 1996) and an increased risk of dementia conversion (Geda et al, 2006;Schweitzer et al, 2002), there is some evidence that patients with late-onset depression may have more pronounced atrophy in cortical and subcortical regions implicated in the pathophysiology of elderly depression (Almeida et al, 2002;Hickie et al, 2005;Steffens et al, 2000). Using traditional volumetric region of interest analyses and computational cortical mapping methods, we previously found complex structural changes in frontal and temporo-parietal brain regions, which may point to differential patterns of atrophic or neurodegenerative processes that may be influenced by age at illness onset (Ballmaier et al, 2004a, b, c).…”

Depressão vascular no idoso: resposta ao tratamento antidepressivo associado a inibidor das colinesterases

“…O primeiro episódio depressivo, quando ocorre tardiamente, está mais relacionado à má resposta terapêutica e ao pior prognóstico, o que pode ser decorrente da associação com déficits cognitivos e o progressivo desenvolvimento de demência em alguns pacientes (Salloway et al, 1996). O risco familiar para depressão declina com o envelhecimento e os transtornos de início tardio podem ser conseqüência de doenças cuja incidência aumenta com a idade, como as doenças vasculares e neurodegenerativas (Novaretti et al, 2001).…”

Mood, cognition and in vivo protein imaging: the emerging nexus in clinical neuroscience

“…The putative link between high intensity lesions and MRI lesions has been interpreted as support for a vascular basis to depression in late-life (Krishnan et al, 1997;Kumar et al, 2002a). The high intensity lesions may account for some, though not all of the cognitive deficits observed in patients with late-life MDD Salloway et al, 1996;O'Brien et al, 1998;Kramer-Ginsberg et al, 1999;Nebes et al, 2001b). It is important to remember that while AD is not typically conceptualized as a vascular dementia, mixed vascular-degenerative dementias are increasingly recognized both clinically and neuropathologically.…”