Comparison of language impairment in late-onset depression and Alzheimer`s disease

Objectives: Depression and dementia are highly prevalent in the elderly. Language impairment is an inherent component of Alzheimer`s disease (AD), which can also be encountered in depressed patients. The aim of this study wasto compare the profiles of language abilities in late-onset depression and mild AD groups. Methods: We studied 25 patients with late-onset depression (mean age 73.6 +/- 6.6 years; schooling 9.1 +/- 5.7 years) and 30 patients with mild AD (77.6 +/- 5.4 years; 7.5 +/- 7.1 years) using the Arizona Battery for Communication Disorders of Dementia (ABCD), compared to a group of 30 controls (73.8 +/- 5.8 years; 9.1 +/- 5.4 years). Cut-off scores to discriminate between Controls x Depression and Depression x AD were determined. Results: Depressed patients` scores were similar to AD in confrontation naming, concept definition, following commands, repetition and reading comprehension (sentence). Episodic memory and mental status subtests were useful in differentiating depressed patients from AD, a result that was reproduced when using analysis of covariance to control for the effect of age in the same subtests (p = 0.01 and 0.04, respectively). Conclusion: Language impairment resembling AD was found in the aforementioned language subtests of the ABCD in elderly depressed patients; the mental status and episodic memory subtests were useful to discriminate between AD and depression. The ABCD has proven to be a suitable tool for language evaluation in this population and should aid in the differentiation of AD and pseudodementia (as that of depression).

Stressful life events and neuroticism as predictors of late-life versus early-life depression.

BACKGROUND: The occurrence of depression in younger adults is related to the combination of long-standing factors such as personality traits (neuroticism) and more acute factors such as the subjective impact of stressful life events. Whether an increase in physical illnesses changes these associations in old age depression remains a matter of debate. METHODS: We compared 79 outpatients with major depression and 102 never-depressed controls; subjects included both young (mean age: 35 years) and older (mean age: 70 years) adults. Assessments included the Social Readjustment Rating Scale, NEO Personality Inventory and Cumulative Illness Rating Scale. Logistic regression models analyzed the association between depression and subjective impact of stressful life events while controlling for neuroticism and physical illness. RESULTS: Patients and controls experienced the same number of stressful life events in the past 12 months. However, in contrast to the controls, patients associated the events with a subjective negative emotional impact. Negative stress impact and levels of neuroticism, but not physical illness, significantly predicted depression in young age. In old age, negative stress impact was weakly associated with depression. In this age group, depressive illness was also determined by physical illness burden and neuroticism. CONCLUSIONS: Our data suggest that the subjective impact of life stressors, although rated as of the same magnitude, plays a less important role in accounting for depression in older age compared to young age. They also indicate an increasing weight of physical illness burden in the prediction of depression occurrence in old age.

Effects of childhood development on late-life mental disorders

Purpose of review To explore recent findings bridging childhood development and common late-life mental disorders in the elderly. Recent findings We addressed aging as a part of the developmental process in central nervous system, typical and atypical neurodevelopment focusing on genetic and environmental risk factors and their interplay and links between psychopathology from childhood to the elderly, unifying theoretical perspectives and preventive intervention strategies. Summary Current findings suggest that childhood development is strictly connected to psychiatric phenotypes across the lifespan. Although we are far from a comprehensive understanding of mental health trajectories, some initial findings document both heterotypic and homotypic continuities from childhood to adulthood and from adulthood to the elderly. Our review also highlights the urgent need for investigations on preventive interventions in individuals at risk for mental disorders.

Ascertaining late-life depressive symptoms in Europe: an evaluation of the survey version of the EURO-D scale in 10 nations. The SHARE project.

The reported prevalence of late-life depressive symptoms varies widely between studies, a finding that might be attributed to cultural as well as methodological factors. The EURO-D scale was developed to allow valid comparison of prevalence and risk associations between European countries. This study used Confirmatory Factor Analysis (CFA) and Rasch models to assess whether the goal of measurement invariance had been achieved; using EURO-D scale data collected in 10 European countries as part of the Survey of Health, Ageing and Retirement in Europe (SHARE) (n = 22,777). The results suggested a two-factor solution (Affective Suffering and Motivation) after Principal Component Analysis (PCA) in 9 of the 10 countries. With CFA, in all countries, the two-factor solution had better overall goodness-of-fit than the one-factor solution. However, only the Affective Suffering subscale was equivalent across countries, while the Motivation subscale was not. The Rasch model indicated that the EURO-D was a hierarchical scale. While the calibration pattern was similar across countries, between countries agreement in item calibrations was stronger for the items loading on the affective suffering than the motivation factor. In conclusion, there is evidence to support the EURO-D as either a uni-dimensional or bi-dimensional scale measure of depressive symptoms in late-life across European countries. The Affective Suffering sub-component had more robust cross-cultural validity than the Motivation sub-component.

Microvascular changes in late-life schizophrenia and mood disorders: stereological assessment of capillary diameters in anterior cingulate cortex.

AIMS: Previous neuroimaging reports described morphological and functional abnormalities in anterior cingulate cortex (ACC) in schizophrenia and mood disorders. In earlier neuropathological studies, microvascular changes that could affect brain perfusion in these disorders have rarely been studied. Here, we analysed morphological parameters of capillaries in this area in elderly cases affected by these psychiatric disorders. METHODS: We analysed microvessel diameters in the dorsal and subgenual parts of the ACC in eight patients with schizophrenia, 10 patients with sporadic bipolar disorder, eight patients with sporadic major depression, and seven age- and gender-matched control cases on sections stained with modified Gallyas silver impregnation using a stereological counting approach. All individuals were drug-naïve or had received psychotropic medication for less than 6 months, and had no history of substance abuse. Statistical analysis included Kruskal-Wallis group comparisons with Bonferroni correction as well as multivariate regression models. RESULTS: Mean capillary diameter was significantly decreased in the dorsal and subgenual parts of areas 24 in bipolar and unipolar depression cases, both in layers III and V, whereas schizophrenia patients were comparable with controls. These differences persisted when controlling for age, local neuronal densities, and cortical thickness. In addition, cortical thickness was significantly smaller in both layers in schizophrenia patients. CONCLUSIONS: Our findings indicate that capillary diameters in bipolar and unipolar depression but not in schizophrenia are reduced in ACC. The significance of these findings is discussed in the light of the cytoarchitecture, brain metabolism and perfusion changes observed in ACC in mood disorders.

Neurocognitive deficits and personality traits among euthymic patients with mood disorders in late life.

BACKGROUND: Previous studies revealed that acute depressive episodes are associated with both cognitive deficits and modified personality patterns in late life. Whether or not these psychological changes are present after remission remains a matter of debate. To date, no study provided concomitant assessment of cognition and psychological functions in this particular clinical setting. METHOD: Using a cross-sectional design, 58 remitted outpatients (36 with unipolar early-onset depression (EOD) and 22 with bipolar disorder (BD)) were compared to 62 healthy controls. Assessment included detailed neurocognitive measures and evaluation of the five factor personality dimensions (NEO-Personality Inventory). RESULTS: Group comparisons revealed significant slower processing speed, working and episodic memory performances in BD patients. EOD patients showed cognitive abilities comparable to those of elderly controls. In NEO PI assessment, both BD and EOD patients displayed higher Depressiveness facet scores. In addition, the EOD but not BD group had lower Extraversion factor, and Warmth and Positive Emotion facet scores than controls. CONCLUSIONS: After remission from acute affective symptoms, older BD patients show significant impairment in several cognitive functions while neuropsychological performances remained intact in elderly patients with EOD. Supporting a long-lasting psychological vulnerability, EOD patients are more prone to develop emotion-related personality trait changes than BD patients.

Coping, depressive feelings and gender differences in late life widowhood

The study investigated the relationship between depressive feelings and coping amongst older widowed men and women. Participants were interviewed about their affective experiences of widowhood and completed two depression questionnaire assessments, the Symptoms of Anxiety and Depression Scale ( SAD) and the Hospital Anxiety and Depression Scale ( HADS). Participants were assessed as either coping or not coping. The results showed that both measures were effective at differentiating those who coped (Copers) from those who did not (Non-Copers) in the sample as a whole. Amongst the widows the HADS significantly differentiated the two groups. Amongst men, neither measure significantly distinguished Copers from Non-Copers. However, an examination of the interviews suggested that widowers reported depressive feelings significantly more often than widows. The results suggest that depressive feelings are associated with non-coping in older widowed people. There is also evidence to suggest that widows and widowers respond differentially to assessment measures.

Late-onset minor and major depression: early evidence for common neuroanatomical substrates detected by using MRI

The purpose of our study was to examine the neuroanatomical correlates of late-onset minor and major depression and to compare them with similar measures obtained from nondepressed controls. Our study groups were comprised of 18 patients with late-onset minor depression, 35 patients diagnosed with late-onset major depression, and 30 nondepressed controls. All subjects were scanned by using a 1.5-tesla MRI scanner. Absolute whole brain volume and normalized measures of prefrontal and temporal lobe volumes were obtained and used for comparison among groups. Our findings indicate that patients with minor depression present with specific neuroanatomical abnormalities that are comparable with the major depression group but significantly different from the controls. Normalized prefrontal lobe volumes show a significant linear trend with severity of depression, with volumes decreasing with illness severity. Whole brain volumes did not differ significantly among groups. These findings have broad implications for the biology of late-life depression and suggest that there may be common neurobiological substrates that underlie all clinically significant forms of late-onset mood disturbances.

Brain hyperintensity location determines outcome in the triad of impaired cognition, physical health and depressive symptoms : A cohort study in late life

The authors would like to thank the participants of the Aberdeen 1936 Birth Cohort (ABC36). Image acquisition and image analysis for ABC36 were funded by the Alzheimer’s Research Trust (now Alzheimer’s Research UK). A.D.M., C.J.M., S.S., L.J.W., and R.T.S. have received grants from: Chief Scientist Office, Department of Health, Scottish Government; Biotechnology and Biological Sciences Research Council

Brain hyperintensity location determines outcome in the triad of impaired cognition, physical health and depressive symptoms : A cohort study in late life

The authors would like to thank the participants of the Aberdeen 1936 Birth Cohort (ABC36). Image acquisition and image analysis for ABC36 were funded by the Alzheimer’s Research Trust (now Alzheimer’s Research UK). A.D.M., C.J.M., S.S., L.J.W., and R.T.S. have received grants from: Chief Scientist Office, Department of Health, Scottish Government; Biotechnology and Biological Sciences Research Council

Prostatic Angiogenic Responses In Late Life: Antiangiogenic Therapy Influences And Relation With The Glandular Microenvironment In The Transgenic Adenocarcinoma Of Mouse Prostate (tramp) Model.

Aging is considered one of the main predisposing factors for the development of prostate malignancies. Angiogenesis is fundamental for tumor growth and its inhibition represents a promising therapeutic approach in cancer treatment. Thus, we sought to determine angiogenic responses and the effects of antiangiogenic therapy in the mouse prostate during late life, comparing these findings with the prostatic microenvironment in the Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) model. Male mice (52 week-old FVB) were submitted to treatments with SU5416 (6 mg/kg; i.p.) and/or TNP-470 (15 mg/kg; s.c.). Finasteride was administered (20 mg/kg; s.c.), alone or in association to both inhibitors. The dorsolateral prostate was collected for VEGF, HIF-1α, FGF-2 and endostatin immunohistochemical and Western Blotting analyses and for microvessel density (MVD) count. Senescence led to increased MVD and VEGF, HIF-1α and FGF-2 protein levels in the prostatic microenvironment, similarly to what was observed in TRAMP mice prostate. The angiogenic process was impaired in all the treated groups, demonstrating significantly decreased MVD. Antiangiogenic and/or finasteride treatments resulted in decreased VEGF and HIF-1α levels, especially following TNP-470 administration, either alone or associated to SU5416. The combination of these agents resulted in increased endostatin levels, regardless of the presence of finasteride. Prostatic angiogenesis stimulation during senescence favored the development of neoplastic lesions, considering the pro-angiogenic microenvironment as a common aspect also observed during cancer progression in TRAMP mice. The combined antiangiogenic therapy was more efficient, leading to enhanced imbalance towards angiogenic inhibition in the organ. Finally, finasteride administration might secondarily upregulate the expression of pro-angiogenic factors, pointing to the harmful effects of this therapy. Prostate 75: 484-499, 2015. © 2014 Wiley Periodicals, Inc.

Increased rates of white matter hyperintensities in late-onset bipolar disorder

Objectives: Magnetic resonance imaging (MRI) studies have reported an increased frequency of white matter hyperintensities (WMH) in association with late-onset (LO) depression, and this has supported the notion that vascular-related mechanisms may be implicated in the pathophysiology of LO mood disorders. Recent clinical studies have also suggested a link between LO bipolar disorder (LO-BD) and cerebrovascular risk factors, but this has been little investigated with neuroimaging techniques. In order to ascertain whether there could be a specific association between WMH and LO-BD, we directly compared WMH rates between LO-BD subjects (illness onset 60 years), early-onset BD subjects (EO-BD, illness onset < 60 years), and elderly healthy volunteers. Methods: T2-weighted MRI data were acquired in LO-BD subjects (n = 10, age = 73.60 +/- 4.09), EO-BD patients (n = 49, age = 67.78 +/- 4.44), and healthy subjects (n = 24, age = 69.00 +/- 7.22). WMH rates were assessed using the Scheltens scale. Results: There was a greater prevalence of WMH in LO-BD patients relative to the two other groups in the deep parietal region (p = 0.018) and basal ganglia (p < 0.045). When between-group comparisons of mean WMH scores were conducted taking account of age differences (ANCOVA), there were more severe scores in LO-BD patients relative to the two other groups in deep frontal and parietal regions, as well as in the putamen (p < 0.05). Conclusions: Our results provide empirical support to the proposed link between vascular risk factors and LO-BD. If extended in future studies with larger samples, these. findings may help to clarify the pathophysiological distinctions between bipolar disorder emerging at early and late stages of life.

Right Orbitofrontal Corticolimbic and Left Corticocortical White Matter Connectivity Differentiate Bipolar and Unipolar Depression

Objectives: The absence of pathophysiologically relevant diagnostic markers of bipolar disorder (BD) leads to its frequent misdiagnosis as unipolar depression (UD). We aimed to determine whether whole brain white matter connectivity differentiated BD from UD depression. Methods: We employed a three-way analysis of covariance, covarying for age, to examine whole brain fractional anisotropy (FA), and corresponding longitudinal and radial diffusivity, in currently depressed adults: 15 with BD-type I (mean age 36.3 years, SD 12.0 years), 16 with recurrent UD (mean age 32.3 years, SD 10.0 years), and 24 healthy control adults (HC) (mean age 29.5 years, SD 9.43 years). Depressed groups did not differ in depression severity, age of illness onset, and illness duration. Results: There was a main effect of group in left superior and inferior longitudinal fasciculi (SLF and ILF) (all F >= 9.8; p <= .05, corrected). Whole brain post hoc analyses (all t >= 4.2; p <= .05, corrected) revealed decreased FA in left SLF in BD, versus UD adults in inferior temporal cortex and, versus HC, in primary sensory cortex (associated with increased radial and decreased longitudinal diffusivity, respectively); and decreased FA in left ILF in UD adults versus HC. A main effect of group in right uncinate fasciculus (in orbitofrontal cortex) just failed to meet significance in all participants but was present in women. Post hoc analyses revealed decreased right uncinate fasciculus FA in all and in women, BD versus HC. Conclusions: White matter FA in left occipitotemporal and primary sensory regions supporting visuospatial and sensory processing differentiates BD from UD depression. Abnormally reduced FA in right fronto-temporal regions supporting mood regulation, might underlie. predisposition to depression in BD. These measures might help differentiate pathophysiologic processes of BD versus UD depression.

Long-term prognosis of geriatric major depression in relation to cognition and white matter integrity: follow up of two cases

INTRODUCTION: The geriatric depression (GD) represents one of the most frequent psychiatric disorders in outpatient services specialized in old-age treatment. OBJECTIVE: The course of two illustrative cases of GD is discussed, highlighting its clinical picture after antidepressant treatment and underlining variables related to disease prognosis, treatment effectiveness and conversion to major cognitive disorders such as vascular dementia (VD). METHODS: The cognitive performance, depressive symptoms, autonomy and brain structural measurements as white matter hyperintensities (WMH) and hippocampal size, and microstructural integrity of WM with diffusion tensor imaging were followed during four years. RESULTS: Case 1, with a severe degree of WMH, was associated with worsening cognition and increasing functional disability. Case 2, with mild WMH, an improvement of cognitive functioning could be seen. CONCLUSIONS: The existence of different subtypes of GD, as presented in this report, points a pathophysiological heterogeneity of GD, and suggests a possible continuum vascular depression (VaDp) and vascular cognitive impairment (VCI).

Vascular depression. An age-related mood disorder

Neuropathological and radiological evidences implicating cerebrovascular disease in the pathogenesis of certain types of geriatric depression have led to the relatively recent description of vascular depression, an age-related mood disorder. Its clinical and radiological presentation, the frequent coexistence of cognitive disorders including impairment in executive function and resistance to antidepressant therapy distinguish it from other types of depression. This article presents an overview of the existing literature on the epidemiology, pathophysiology, clinical features and therapeutic particularities of vascular depression. (C) 2010 Elsevier Masson SAS and European Union Geriatric Medicine Society. All rights reserved.