Christophe Delaloye

Combined analysis of grey matter voxel-based morphometry and white matter tract-based spatial statistics in late-life bipolar disorder.

BACKGROUND Previous magnetic resonance imaging (MRI) studies in young patients with bipolar disorder indicated the presence of grey matter concentration changes as well as microstructural alterations in white matter in various neocortical areas and the corpus callosum. Whether these structural changes are also present in elderly patients with bipolar disorder with long-lasting clinical evolution remains unclear. METHODS We performed a prospective MRI study of consecutive elderly, euthymic patients with bipolar disorder and healthy, elderly controls. We conducted a voxel-based morphometry (VBM) analysis and a tract-based spatial statistics (TBSS) analysis to assess fractional anisotropy and longitudinal, radial and mean diffusivity derived by diffusion tensor imaging (DTI). RESULTS We included 19 patients with bipolar disorder and 47 controls in our study. Fractional anisotropy was the most sensitive DTI marker and decreased significantly in the ventral part of the corpus callosum in patients with bipolar disorder. Longitudinal, radial and mean diffusivity showed no significant between-group differences. Grey matter concentration was reduced in patients with bipolar disorder in the right anterior insula, head of the caudate nucleus, nucleus accumbens, ventral putamen and frontal orbital cortex. Conversely, there was no grey matter concentration or fractional anisotropy increase in any brain region in patients with bipolar disorder compared with controls. LIMITATIONS The major limitation of our study is the small number of patients with bipolar disorder. CONCLUSION Our data document the concomitant presence of grey matter concentration decreases in the anterior limbic areas and the reduced fibre tract coherence in the corpus callosum of elderly patients with long-lasting bipolar disorder.

Longitudinal analysis of cognitive performances and structural brain changes in late-life bipolar disorder.

Cross‐sectional studies in bipolar disorder (BD) suggested the presence of cognitive deficits and subtle magnetic resonance imaging (MRI) changes in limbic areas that may persist at euthymic stages. Whether or not cognitive and MRI changes represent stable attributes of BD or evolve with time is still matter of debate. To address this issue, we performed a 2‐year longitudinal study including detailed neuropsychological and magnetic resonance imaging (MRI) analyses of 15 euthymic older BD patients and 15 controls.

Do age differences between young and older adults in inhibitory tasks depend on the degree of activation of information

Three inhibition/interference tasks (Stroop colour, Negative priming embedded within the Stroop colour, and Hayling) were administered to young and older adults, with two main objectives, each of which embedded within a developmental perspective: First manipulate the level of activation of the irrelevant information, and second, assess the number of individuals presenting a reliable effect rather than analyse the results only at the group level. For each task, two versions were used, corresponding to two levels at which the irrelevant information was likely to be activated. Analyses were conducted on relative difference scores rather than on raw response times. Results indicated that age differences in the magnitude of an interference effect were small and even null in the Negative priming task, independently of the salience of the irrelevant information. A bootstrap procedure showed that whereas the majority of both young and older adults presented a reliable interference effect in the Stroop colour and in the Hayling tasks, it was not the case in the Negative priming task. Moreover, correlations between the indices of interference/inhibition were very weak questioning the dimensionality of inhibition. Altogether these findings suggest that highly activated versions of the inhibitory tasks used do not really influence age-related differences in inhibitory control. It is also recommended to use bootstrap procedures more frequently instead of restricting analyses at a group level.

Cognitive features in euthymic bipolar patients in old age

OBJECTIVES Studies of cognition in bipolar disorder (BD) have reported impairments in processing speed, working memory, episodic memory, and executive function, but they have primarily focused on young and middle-aged adults. In such studies, the severity of cognitive deficits increases with the duration of illness. Therefore, one would expect more pronounced deficits in patients with longstanding BD. The first aim of the present study was to determine the pattern and the magnitude of cognitive impairment in older euthymic BD patients. The second aim was to explore the interrelationship between these cognitive deficits and determine whether they reflect a single core impairment or the co-occurrence of independent cognitive deficits. METHODS Twenty-two euthymic elderly BD patients and 22 controls, matched for gender, age, and education, underwent a comprehensive neuropsychological assessment. RESULTS Compared to controls, BD patients had significantly reduced performance in processing speed, working memory, verbal fluency, and episodic memory, but not in executive function. Hierarchical regression analyses showed that verbal fluency and working memory impairments were fully mediated by changes in processing speed. This was not the case for the episodic memory dysfunction. CONCLUSION The cognitive profile in older euthymic BD cases is similar to the one described in younger BD cohorts. Our results further suggest that impaired processing speed plays a major role in the cognitive changes observed in BD patients except for deficits in episodic memory, thus providing strong evidence that processing speed and episodic memory are two core deficits in elderly BD patients.

Neuroanatomical and Neuropsychological Features of Euthymic Patients with Bipolar Disorder

OBJECTIVE Previous studies reported that the severity of cognitive deficits in euthymic patients with bipolar disorder (BD) increases with the duration of illness and postulated that progressive neuronal loss or shrinkage and white matter changes may be at the origin of this phenomenon. To explore this issue, the authors performed a case-control study including detailed neuropsychological and magnetic resonance imaging analyses in 17 euthymic elderly patients with BD and 17 healthy individuals. METHODS Neuropsychological evaluation concerned working memory, episodic memory, processing speed, and executive functions. Volumetric estimates of the amygdala, hippocampus, entorhinal cortex, and anterior cingulate cortex were obtained using both voxel-based and region of interest morphometric methods. Periventricular and deep white matter were assessed semiquantitatively. Differences in cognitive performances and structural data between BD and comparison groups were analyzed using paired t-test or analysis of variance. Wilcoxon test was used in the absence of normal distribution. RESULTS Compared with healthy individuals, patients with BD obtained significantly lower performances in processing speed, working memory, and episodic memory but not in executive functions. Morphometric analyses did not show significant volumetric or white matter differences between the two groups. CONCLUSIONS Our results revealed impairment in verbal memory, working memory, and processing speed in euthymic older adults with BD. These cognitive deficits are comparable both in terms of affected functions and size effects to those previously reported in younger cohorts with BD. Both this observation and the absence of structural brain abnormalities in our cohort do not support a progressively evolving neurotoxic effect in BD.

Personality traits are associated with acute major depression across the age spectrum

Objectives: Psychological predictors, such as personality traits, have aroused growing interest as possible predictors of late-life depression outcome in old age. It remains, however, unclear whether the cross-sectional relationship between personality traits and depression occurrence reported in younger samples is also present in the elderly. Methods: Comparisons amongst 79 outpatients with DSM-IV major depression and 102 healthy controls included assessment of the five-factor model of personality (NEO PI-R), socio-demographic variables, physical health status, as well as depression features. Two sub-groups were considered, defined as young (25–50 years) and old (60–85 years) patients. Results: Depressed patients showed significantly higher levels of Neuroticism and lower levels of Extraversion, Openness to Experience and Conscientiousness compared to controls. Sequential logistic regression models confirmed that the combination of increased physical burden, levels of dependency, and increased Neuroticism strongly predicts the occurrence of acute depressive symptoms. In contrast, the levels of Neuroticism did not allow for differentiating late-life from young age depression. Increased physical burden and decreased depression severity were the main predictors for this distinction. Conclusion: Our data indicate that personality factors and depression are related, independently of patients’ age. Differences in this relationship are mainly due to the intensity of depressive symptoms rather than the patients’ life period. They also stress the need to consider physical health, level of dependency and severity of symptoms when studying the relationship between personality traits and mood disorders.

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

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.

Magnetic resonance imaging determinants of intraindividual variability in the elderly: combined analysis of grey and white matter

Elderly individuals display a rapid age-related increase in intraindividual variability (IIV) of their performances. This phenomenon could reflect subtle changes in frontal lobe integrity. However, structural studies in this field are still missing. To address this issue, we computed an IIV index for a simple reaction time (RT) task and performed magnetic resonance imaging (MRI) including voxel based morphometry (VBM) and the tract based spatial statistics (TBSS) analysis of diffusion tensor imaging (DTI) in 61 adults aged from 22 to 88 years. The age-related IIV increase was associated with decreased fractional anisotropy (FA) as well as increased radial (RD) and mean (MD) diffusion in the main white matter (WM) fiber tracts. In contrast, axial diffusion (AD) and grey matter (GM) densities did not show any significant correlation with IIV. In multivariate models, only FA has an age-independent effect on IIV. These results revealed that WM but not GM changes partly mediated the age-related increase of IIV. They also revealed that the association between WM and IIV could not be only attributed to the damage of frontal lobe circuits but concerned the majority of interhemispheric and intrahemispheric corticocortical connections.

Volumetric MRI changes, cognition and personality traits in old age depression

BACKGROUND The presence of cognitive and structural deficits in euthymic elderly depressed patients remains a matter of debate. Integrative aetiological models assessing concomitantly these parameters as well as markers of psychological vulnerability such as persistent personality traits, are still lacking for this age group. METHODS Cross-sectional comparisons of 38 elderly remitted patients with early-onset depression (EOD) and 62 healthy controls included detailed neuropsychological assessment, estimates of brain volumes in limbic areas and white matter hyperintensities, as well as evaluation of the Five-Factor personality dimensions. RESULTS Both cognitive performances and brain volumes were preserved in euthymic EOD patients. No significant group differences were observed in white matter hyperintensity scores between the two groups. In contrast, EOD was associated with significant increase of Neuroticism and decrease of Extraversion facet scores. LIMITATIONS Results concern the restricted portion of EOD patients without psychiatric and physical comorbidities. Future longitudinal studies are necessary to determine the temporal relationship between the occurrence of depression and personality dimensions. CONCLUSIONS After remission from acute depressive symptoms, cognitive performances remain intact in elderly patients with EOD. In contrast to previous observations, these patients display neither significant brain volume loss in limbic areas nor increased vascular burden compared to healthy controls. Further clinical investigations on EOD patterns of vulnerability in old age will gain from focusing on psychological features such as personality traits rather than neurocognitive clues.

Cognitive Impairment in Late-Onset Depression

Background: While cognitive dysfunction in late-onset depression (LOD) is common, the nature and determinants of this impairment are heterogeneous. It has been suggested that neuropsychological decrements in LOD patients might result from a deficit in processing resources. In order to address this issue, we analyzed processing resources in LOD to see if their decrease explains higher-level cognition (episodic memory and naming capacity) deficits. Methods: Measures of processing speed, working memory, inhibition, episodic memory and naming capacity were administered to 14 LOD inpatients and 14 controls. Results: The LOD patients performed significantly worse than the controls in all domains except for inhibition. Hierarchical regression analyses showed that naming capacity impairment was totally mediated by processing speed and working memory, whereas episodic memory dysfunction was only partially mediated by working memory. Conclusion: The reduction in certain processing resources (working memory, processing speed) in late-onset depressed patients appears to mediate impairments in episodic memory and naming capacity. However, episodic memory impairment cannot only be explained by processing resource decrement in LOD patients, suggesting that a primary episodic memory dysfunction is present in this condition.