Neuroanatomical and neuropsychological features of elderly euthymic depressed patients with early- and late-onset

doi:10.1016/j.jns.2010.08.046

Journal of the Neurological Sciences

Volume 299, Issues 1–2, 15 December 2010, Pages 19-23

https://doi.org/10.1016/j.jns.2010.08.046 Get rights and content

Abstract

Background

Whether or not cognitive impairment and brain structure changes are trait characteristics of late-life depression is still disputed. Previous studies led to conflicting data possibly because of the difference in the age of depression onset. In fact, several lines of evidence suggest that late-onset depression (LOD) is more frequently associated with neuropsychological deficits and brain pathology than early-onset depression (EOD). To date, no study explored concomitantly the cognitive profile and brain magnetic resonance imaging (MRI) patterns in euthymic EOD and LOD patients.

Method

Using a cross-sectional design, 41 remitted outpatients (30 with EOD and 11 with LOD) were compared to 30 healthy controls. Neuropsychological evaluation concerned working memory, episodic memory, processing speed, naming capacity and executive functions. Volumetric estimates of the amygdala, hippocampus, entorhinal and anterior cingulate cortex were obtained using both voxel-based and region of interest morphometric methods. White matter hyperintensities were assessed semiquantitatively.

Results

Both cognitive performance and brain volumes were preserved in euthymic EOD patients whereas LOD patients showed a significant reduction of episodic memory capacity and a higher rate of periventricular hyperintensities compared to both controls and EOD patients.

Conclusion

Our results support the dissociation between EOD thought to be mainly related to psychosocial factors and LOD that is characterized by increasing vascular burden and episodic memory decline.

Introduction

Amongst patients who suffer from late-life depression, 30% to 50% display deficits across a wide range of cognitive domains [1]. Even more than in younger cohorts [2], some cognitive deficits in old age may represent trait characteristics of depression that persist despite the amendment of symptoms [3]. However, this viewpoint has been challenged by prospective studies showing that depression at baseline is not necessarily associated with an increased risk of subsequent cognitive decline [4]. These discrepancies might be partly explained by age differences relative to the onset of depression among elderly patients. Recent studies suggest that the patterns of both neuropsychological deficits and structural imaging changes vary substantially between late-onset depression (LOD) and early-onset depression (EOD) [1], [5], [6]. LOD has been traditionally associated with more frequent and rapid cognitive decline as well as more severe structural brain abnormalities compared to age-matched controls and EOD patients [1], [6]. In particular, literature reported executive dysfunction to be a characteristic of LOD whereas episodic memory dysfunction is present both in LOD and EOD [1]. Consistent with the presence of dysexecutive impairment in LOD, neuroimaging studies [7] revealed a frontostriatal disruption caused by subcortical, white matter and periventricular hyperintensities. In contrast, EOD cases display selective hippocampal volume loss [8] underlying the episodic memory impairment.

There are two main methodological limitations of these studies. Most of them explored separately structural changes and neuropsychological performances. Most importantly, they included acutely depressed patients and did not provide further insight into their persistent abnormalities. To address these issues, we performed a prospective group study (EOD, LOD and controls) including a detailed neuropsychological assessment and MRI investigation.

Section snippets

Participants

Thirty EOD patients (depression onset before 60), eleven LOD patients (depression onset after 60), and thirty healthy controls were included. The diagnosis of depression or the absence of a psychiatric condition was established using the Mini International Neuropsychiatric Inventory Interview. Euthymia was defined according to DSM-IV criteria, namely the absence of depressive symptoms for at least two months. In addition, all participants had to obtain a score below 5 on the 15 item Geriatric

Demographics and clinical characteristics

The demographic and clinical characteristics of the series are summarized in Table 1. Among the three groups there were no significant differences in gender, education and somatic comorbidity as assessed by the CCI. EOD patients were significantly younger than controls (U = 205.50, p < 0.001) and LOD patients (U = 22.00, p < 0.001). Patients were already under treatment at inclusion. We did not interfere with their medication as the treatment was prescribed naturalistically. 73% of LOD patients and 50%

Conclusion

The preservation of both cognition and brain structures in euthymic EOD patients, in particular episodic memory capacity and hippocampal volume, as well as the absence of deleterious effect of the duration of illness does not support the hypothesis of a progressive neurotoxic effect of depression [8]. Our results parallel several lines of evidence supporting the preservation of cognitive abilities in elderly patients with EOD after remission [4], [6]. In particular, Brodaty et al. [4] found no

Conflict of interest

This research was supported by the Swiss National Science Foundation (SNSF grant no 3200BO-112018). The SNSF had no further role in study design; in collection, analysis and interpretation of the data; in the writing of the report; and in the decision to submit the paper for publication. All authors declare that they have no conflict of interest.

Acknowledgments

The authors thank Abba Moussa, Corina Meiler-Mititelu, Karsten Ebbing, Montserrat Mendez Rubio, Françoise Lanet and Reto Meuli for their contribution to this work. This work was also supported by the Center for Biomedical Imaging (CIBM) of the Geneva-Lausanne Universities and the EPFL.

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In the realm of cognitive screening, the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) are widely utilized for detecting cognitive deficits in patients with late-life depression (LLD), However, the interindividual variability in neuroimaging biomarkers contributing to individual-specific symptom severity remains poorly understood. In this study, we used a connectome-based predictive model (CPM) approach on resting-state functional magnetic resonance imaging data from patients with LLD to establish individualized prediction models for the MoCA and the MMSE scores.
We recruited 135 individuals diagnosed with first-episode LLD for this research. Participants underwent the MMSE and MoCA tests, along with resting-state functional magnetic resonance imaging scans. Functional connectivity matrices derived from these scans were utilized in CPM models to predict MMSE or MoCA scores. Predictive precision was assessed by correlating predicted and observed scores, with the significance of prediction performance evaluated through a permutation test.
The negative model of the CPM procedure demonstrated a significant capacity to predict MoCA scores (r = −0.309, p = 0.002). Similarly, the CPM procedure could predict MMSE scores (r = −0.236, p = 0.016). The predictive models for cognitive test scores in LLD primarily involved the visual network, somatomotor network, dorsal attention network, and ventral attention network.
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Lateralized grey matter volume changes in adolescents versus adults with major depression: SDM-PSI meta-analysis
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The current study is the first meta-analysis to examine grey matter volume (GMV) changes in adolescents and across the lifespan in major depressive disorder (MDD). Seed-based d mapping–with permutation of subject images (SDM-PSI) has advantages over previous coordinate-based meta-analytical methods (CBMA), such as reducing bias (via the MetaNSUE algorithm) and including non-statistically significant unreported effects. SDM-PSI was used to analyze 105 whole-brain GMV voxel-based morphometry (VBM) studies comparing 6,530 individuals with MDD versus 6,821 age-matched healthy controls (HC). A laterality effect was observed in which adults with MDD showed lower GMV than adult HC in left fronto-temporo-parietal structures (superior temporal gyrus, insula, Rolandic operculum, and inferior frontal gyrus). However, these abnormalities were not statistically significant for adolescent MDD versus adolescent HC. Instead, adolescent MDD showed lower GMV than adult MDD in right temporo-parietal structures (angular gyrus and middle temporal gyrus). These regional differences may be used as potential biomarkers to predict and monitor treatment outcomes as well as to choose the most effective treatments in adolescents versus adults. Finally, due to the paucity of youth, older adult, and longitudinal studies, future studies should attempt to replicate these GMV findings and examine whether they correlate with treatment response and illness severity.
Neural substrates for late-life depression: A selective review of structural neuroimaging studies
2021, Progress in Neuro-Psychopharmacology and Biological Psychiatry
Citation Excerpt :
LLD can be classified into EOD and late-onset depression (LOD) according to the cut-off age which varies from 50 to 65 years (Aizenstein et al., 2016), and LOD is more strongly associated with CVD or cognitive impairment compared to EOD (Delaloye et al., 2010; Hashem et al., 2017). There have been reports that LOD was associated with more severe or greater volume of WMH compared to EOD in older adults (Delaloye et al., 2010; Feng et al., 2014; Madsen et al., 2012; Tupler et al., 2002). For example, Feng et al. classified older adults with depression into EOD (onset before 50 years), presenile-onset depression (POD, onset between 50 and 65 years) and LOD (onset after 65 years) and observed that patients with LOD showed significantly higher severity of periventricular and deep WMHs compared to EOD or POD (Feng et al., 2014).
Recent neuroimaging studies have characterized the pathophysiology of late-life depression (LLD) as a dysfunction of the brain networks involved in the regulation of emotion, motivational behavior, cognitive control, executive function, and self-referential thinking. In this article, we reviewed LLD-associated structural neuroimaging markers such as white matter hyperintensity (WMH), white matter integrity measured by diffusion tensor imaging, cortical and subcortical volumes, and cortical thickness, which may provide a structural basis for brain network dysfunction in LLD. LLD was associated with greater severity or volumes of deep, periventricular, or overall WMH and with decreased white matter integrity in the brain regions belonging to the fronto-striatal-limbic circuits and reduced white matter tract integrity which connects these circuits, such as the cingulum, corpus callosum, or uncinate fasciculus. Decreased volumes or cortical thickness in the prefrontal cortex, orbitofrontal cortex, anterior and posterior cingulate cortex, several temporal and parietal regions, hippocampus, amygdala, striatum, thalamus, and the insula were associated with LLD. These structural neuroimaging findings were also associated with cognitive dysfunction, which is a prominent clinical feature in LLD. Several structural neuroimaging markers including the WMH burden, white matter integrity, and cortical and subcortical volumes predicted antidepressant response in LLD. These structural neuroimaging findings support the hypothesis that disruption of the brain networks involved in emotion regulation and cognitive processing by impaired structural connectivity is strongly associated with the pathophysiology of LLD.
Comparison of cognitive function between early- and late-onset late-life depression in remission
2020, Psychiatry Research
Citation Excerpt :
In addition, previous studies comparing multiple cognitive domains between LOD and EOD mostly included patients in a current depressed state; thus cognitive differences found in other studies may reflect depressive symptoms and their impact. As mentioned, apart from our investigation, we are only aware of one study comparing EOD/LOD groups for cognitive function in a euthymic state (Delaloye et al., 2010). In line with our finding, that study also found no group differences in processing speed and executive function, although these findings are in contrast to the results of a recent meta-analysis (Herrmann et al., 2007), which concluded greater reductions in processing speed and executive function in LOD compared to EOD, when considering patients with moderate to severe depression.
Differences in cognitive function have been suggested in people with late-life depression between those with early- (EOD) and late-onset (LOD), possibly reflecting different etiologies. The cutoff point for EOD and LOD was the first depressive episode before age 60 or later. However, depressive symptoms at the time of disorder are important confounders. The study aimed to compare cognitive function in older people with EOD and LOD in the euthymic state. A sample of 135 participants aged 60+ with a history of major depressive disorder in remission, received neuropsychological evaluation including tests of memory, attention, processing speed, visuospatial function, language, and executive function. Individual test scores and a derived composite score were investigated as dependent variables against age of onset using multiple linear regressions adjusted for potential confounders, including residual depressive symptoms. We found EOD (N = 67) and LOD (N = 68) groups did not differ significantly in overall composite cognitive scores after adjustment. Of individual test scores, only those for immediate recall were significantly lower in participants with EOD compared to LOD. In conclusion, the study found no associations between cognitive function and age of onset in this sample of people with depressive disorder in remission. Active or residual depressive symptoms might have confounded this relationship in previous research.
Depression related cerebral pathology and its relationship with cognitive functioning: A systematic review
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These papers included 62 cross-sectional studies, 22 longitudinal studies, and 13 treatment studies (Fig. 1). Within cross-sectional studies, 82% examined the this relationship within a clinical population, six of which compared the differences between EOD and LOD (Ballmaier et al., 2008; Delaloye et al., 2010; Lebedeva et al., 2015; Lesser et al., 1996; Murata et al., 2001; Weber et al., 2010), three studies examined remitted depression (Hou et al., 2010; Madsen et al., 2012; Matsuo et al., 2005), and five examined this relationship through a modifier gene or molecule (Benjamin et al., 2010; Charlton et al., 2018; Hou et al., 2010; Price et al., 2013; Sun et al., 2009). Eleven studies examined depressive symptoms in non-clinically depressed populations (Fujii et al., 2014; Fujishima et al., 2014; Krishnan et al., 2006; Lamar et al., 2010; Moon et al., 2011; Pink et al., 2017; Price et al., 2013; Ramakers et al., 2013; Sun et al., 2009; Sun et al., 2008; Tsuruga et al., 2014).
Depression's relationship with cerebral abnormalities and cognitive decline is temporally dynamic. Despite clear clinical utility, understanding depression's effect on cerebral structures, cognitive impairment and the interaction between these symptoms has had limited consideration.
This review summarised studies examining a clinical depression diagnosis or validated scales measuring depressive symptoms, data concerning amyloid-beta (Aβ) levels, brain structure and function focusing on hippocampal alterations, or white matter hyperintensities (WMH), and at least one validated neuropsychological test. Online database searches of: PsycINFO, EMBASE, MEDLINE, and Scopus were conducted to identify potential articles.
While depression was consistently associated with cross-sectionally cognitive decline across multiple domains, the neuropathological basis of this dysfunction remained unclear. Hippocampal, frontal, and limbic dysfunction as well as cortical thinning, WMH, and Aβ burden all provide inconsistent findings, likely due to depression subtypes. The consistency of these findings additionally decreases when examining this relationship longitudinally, as these results are further confounded by pre-dementia states. The therapeutic interventions examined were more efficacious in the younger compared with the older samples, who were characterised by greater WMH and Aβ burden.
The limited number of longitudinal and interventional studies in addition to the heterogeneity of the samples restricts their generalisability.
Symptomatological differences between early-onset and late-onset depression (EOD and LOD) appear crucial in understanding whether late-life depression is the primary or secondary source of cerebral pathology. Though severe cognitive impairments and clearer neuropathological underpinnings are more characteristic of LOD than EOD, the inconsistency of valid biomarkers remains problematic.
Late-Life Depression, Hippocampal Volumes, and Hypothalamic-Pituitary-Adrenal Axis Regulation: A Systematic Review and Meta-analysis
2017, Biological Psychiatry
We systematically reviewed and meta-analyzed the association of late-life depression (LLD) with hippocampal volume (HCV) and total brain volume (TBV), and of cortisol levels with HCV, including subgroup analyses of depression characteristics and methodological aspects.
We searched PubMed and Embase for original studies that examined the cross-sectional relationship between LLD and HCV or TBV, and 46 studies fulfilled the inclusion criteria. Standardized mean differences (Hedges’ g) between LLD and control subjects were calculated from crude or adjusted brain volumes using random effects. Standardized Fisher transformations of the correlations between cortisol levels and HCVs were calculated using random effects.
We included 2702 LLD patients and 11,165 control subjects from 35 studies examining HCV. Relative to control subjects, patients had significantly smaller HCVs (standardized mean difference = –0.32 [95% confidence interval, –0.44 to –0.19]). Subgroup analyses showed that late-onset depression was more strongly associated with HCV than early-onset depression. In addition, effect sizes were larger for case-control studies, studies with lower quality, and studies with small sample size, and were almost absent in cohort studies and studies with larger sample sizes. For TBV, 2523 patients and 7880 control subjects from 31 studies were included. The standardized mean difference in TBV between LLD and control subjects was –0.10 (95% confidence interval, –0.16 to –0.04). Of the 12 studies included, higher levels of cortisol were associated with smaller HCV (correlation = –0.11 [95% confidence interval, –0.18 to –0.04]).
While an overall measure of LLD may be associated with smaller HCVs, differentiating clinical aspects of LLD and examining methodological issues show that this relationship is not straightforward.

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Neuroanatomical and neuropsychological features of elderly euthymic depressed patients with early- and late-onset

Abstract

Background

Method

Results

Conclusion

Introduction

Section snippets

Participants

Demographics and clinical characteristics

Conclusion

Conflict of interest

Acknowledgments

Am J Geriatr Psychiatry

J Psychiatr Res

J Neurol Sci

Biol Psychiatry

The cognitive neuropsychology of depression in the elderly

Psychol Med

A comparison of neurocognitive impairment in younger and older adults with major depression

Psychol Med

Neuropsychological performance and dementia in depressed patients after 25-year follow-up: a controlled study

Psychol Med

The pattern and course of cognitive impairment in late-life depression

Psychol Med