Prefrontal-Parietal White Matter Volumes in Healthy Elderlies Are Decreased in Proportion to the Degree of Cardiovascular Risk and Related to Inhibitory Control Deficits.

Cardiovascular risk (CVR) factors may be associated with poor cognitive functioning in elderlies and impairments in brain structure. Using MRI and voxel-based morphometry (VBM), we assessed regional white matter (WM) volumes in a population-based sample of individuals aged 65-75 years (n = 156), subdivided in three CVR subgroups using the Framingham Risk Score. Cognition was assessed using the Short Cognitive Performance Test. In high-risk subjects, we detected significantly reduced WM volume in the right juxtacortical dorsolateral prefrontal region compared to both low and intermediate CVR subgroups. Findings remained significant after accounting for the presence of the APOEε4 allele. Inhibitory control performance was negatively related to right prefrontal WM volume, proportionally to the degree of CVR. Significantly reduced deep parietal WM was also detected bilaterally in the high CVR subgroup. This is the first large study documenting the topography of CVR-related WM brain volume deficits. The significant association regarding poor response inhibition indicates that prefrontal WM deficits related to CVR are clinically meaningful, since inhibitory control is known to rely on prefrontal integrity.

Relationship between Brain Age-Related Reduction in Gray Matter and Educational Attainment.

Inter-subject variability in age-related brain changes may relate to educational attainment, as suggested by cognitive reserve theories. This voxel-based morphometry study investigated the impact of very low educational level on the relationship between regional gray matter (rGM) volumes and age in healthy elders. Magnetic resonance imaging data were acquired in elders with low educational attainment (less than 4 years) (n = 122) and high educational level (n = 66), pulling together individuals examined using either of three MRI scanners/acquisition protocols. Voxelwise group comparisons showed no rGM differences (p<0.05, family-wise error corrected for multiple comparisons). When within-group voxelwise patterns of linear correlation were compared between high and low education groups, there was one cluster of greater rGM loss with aging in low versus high education elders in the left anterior cingulate cortex (p<0.05, FWE-corrected), as well as a trend in the left dorsomedial prefrontal cortex (p<0.10). These results provide preliminary indication that education might exert subtle protective effects against age-related brain changes in healthy subjects. The anterior cingulate cortex, critical to inhibitory control processes, may be particularly sensitive to such effects, possibly given its involvement in cognitive stimulating activities at school or later throughout life.

Framingham Coronary Heart Disease Risk Score Can be Predicted from Structural Brain Images in Elderly Subjects.

Recent literature has presented evidence that cardiovascular risk factors (CVRF) play an important role on cognitive performance in elderly individuals, both those who are asymptomatic and those who suffer from symptoms of neurodegenerative disorders. Findings from studies applying neuroimaging methods have increasingly reinforced such notion. Studies addressing the impact of CVRF on brain anatomy changes have gained increasing importance, as recent papers have reported gray matter loss predominantly in regions traditionally affected in Alzheimer's disease (AD) and vascular dementia in the presence of a high degree of cardiovascular risk. In the present paper, we explore the association between CVRF and brain changes using pattern recognition techniques applied to structural MRI and the Framingham score (a composite measure of cardiovascular risk largely used in epidemiological studies) in a sample of healthy elderly individuals. We aim to answer the following questions: is it possible to decode (i.e., to learn information regarding cardiovascular risk from structural brain images) enabling individual predictions? Among clinical measures comprising the Framingham score, are there particular risk factors that stand as more predictable from patterns of brain changes? Our main findings are threefold: (i) we verified that structural changes in spatially distributed patterns in the brain enable statistically significant prediction of Framingham scores. This result is still significant when controlling for the presence of the APOE 4 allele (an important genetic risk factor for both AD and cardiovascular disease). (ii) When considering each risk factor singly, we found different levels of correlation between real and predicted factors; however, single factors were not significantly predictable from brain images when considering APOE4 allele presence as covariate. (iii) We found important gender differences, and the possible causes of that finding are discussed.

Depression in medical students: cluster symptoms and management.

BACKGROUND: Rates of depression among medical students have been shown to be high and related to year of study and other factors. We report on cluster of symptoms related to depression and their association with other difficulties in specific domains. METHODS: 481 (Response rate=79.8%) medical students completed a questionnaire about areas of difficulty in the medical school (studies, leisure, colleagues, professors, and patients), and Beck Depression Inventory (BDI). We studied correlation among areas of difficulty and clusters of BDI along with year in the course. RESULTS: Two areas which contributed most difficulty were studies and leisure. The significant associations for studies were seen between somatic cluster of depressive symptoms and the level of the course. Difficulties associated with leisure activities and with colleagues were correlated with the affective cluster of symptoms of depression. Activities related to clinical matters especially working with patients in the internship year were associated with somatic clusters. The different associations confirmed that rather than relying on scores emphasis should be placed on clusters of symptoms. LIMITATIONS: Sample from a single medical school. CONCLUSIONS: Although the clusters are associated with specific difficulties, it is important that educators and health professionals are aware of streesors the medical students face. The correlations if confirmed in future studies with qualitative factors could guide the development of more specific therapeutic or curriculum interventions.

Cardiovascular risk in cognitively preserved elderlies is associated with glucose hypometabolism in the posterior cingulate cortex and precuneus regardless of brain atrophy and apolipoprotein gene variations.

Cardiovascular risk factors (CVRF) possibly contribute to the emergence of Alzheimer's disease (AD). Fluorodeoxyglucose-positron emission tomography (FDG-PET) has been widely used to demonstrate specific patterns of reduced cerebral metabolic rates of glucose (CMRgl) in subjects with AD and in non-demented carriers of the apolipoprotein ε4 (APOE ε4) allele, the major genetic risk factor for AD. However, functional neuroimaging studies investigating the impact of CVRF on cerebral metabolism have been scarce to date. The present FDG-PET study investigated 59 cognitively preserved elderlies divided into three groups according to their cardiovascular risk based on the Framingham 10-year risk Coronary Heart Disease Risk Profile (low-, medium-, and high-risk) to examine whether different levels of CVRF would be associated with reduced CMRgl, involving the same brain regions affected in early stages of AD. Functional imaging data were corrected for partial volume effects to avoid confounding effects due to regional brain atrophy, and all analyses included the presence of the APOE ε4 allele as a confounding covariate. Significant cerebral metabolism reductions were detected in the high-risk group when compared to the low-risk group in the left precuneus and posterior cingulate gyrus. This suggests that findings of brain hypometabolism similar to those seen in subjects with AD can be detected in association with the severity of cardiovascular risk in cognitively preserved individuals. Thus, a greater knowledge about how such factors influence brain functioning in healthy subjects over time may provide important insigths for the future development of strategies aimed at delaying or preventing the vascular-related triggering of pathologic brain changes in the AD.

Does ragging play a role in medical student depression - cause or effect?

BACKGROUND: Medical students experience a lot of stress what may contribute to symptoms of depression. In this study we set out to look at the environmental factors which may be contributing in one medical school in Brazil. METHODS: We assessed depressive symptoms using Beck's Depression Inventory in 465 and 267 medical students in 2001 and 2006 respectively. We explored possible social and environmental causes using qualitative data. RESULTS: Nearly 15% scored above the cut off for depression in both the samples. Males in the pre-clinical stage in 2006 showed an increase in depressive symptoms than males in the same cycle in 2001 (aOR=7.36 [95% CI=0.85-63.5] p=0.07). Qualitative data confirmed that factors such as ragging and low social involvement were correlated with depressive symptoms in pre-clinical stage males. LIMITATIONS: The sample size was small both for quantitative and qualitative aspects of the study. CONCLUSIONS: It appears that ragging plays an important role in the genesis of depressive symptoms in medical students.

Perceptions of and attitudes toward antidepressants: stigma attached to their use--a review.

The aim of this study was to ascertain whether there is any evidence of stigma related to the use of antidepressants. Using the PubMed and MEDLINE databases, we searched for the terms stigma, antidepressants, and depression. A protocol was developed to extract information from the papers, which were identified and explored further. Thirty-two papers were identified. We found that the stigma against depression differs from stigma against the use of antidepressants. Stigma against depression does not impact on therapeutic adherence to antidepressant use. Stigma related to antidepressant use appears to be linked with perceived emotional weakness, severity of illness, an inability to deal with problems, and a lack of belief in the therapeutic efficacy of antidepressants. Stigma against medication can be a useful target for interventions, just like the stigma related to depression. However, clinicians must be careful in avoiding the medicalization of symptoms.

Subtle gray matter changes in temporo-parietal cortex associated with cardiovascular risk factors.

Vascular risk factors may play an important role in the pathophysiology of Alzheimer's disease (AD). While there is consistent evidence of gray matter (GM) abnormalities in earlier stages of AD, the presence of more subtle GM changes associated with vascular risk factors in the absence of clinically significant vascular events has been scarcely investigated. This study aimed to examine GM changes in elderly subjects with cardiovascular risk factors. We predicted that the presence of cardiovascular risk would be associated with GM abnormalities involving the temporal-parietal cortices and limbic structures. We recruited 248 dementia-free subjects, age range 66-75 years, from the population-based "São Paulo Ageing and Health Study", classified in accordance to their Framingham Coronary Heart Disease Risk (FCHDR) score to undergo an MRI scan. We performed an overall analysis of covariance, controlled to total GM and APOE4 status, to investigate the presence of regional GM abnormalities in association with FCHDR subgroups (high-risk, medium-risk, and low-risk), and followed by post hoc t-test. We also applied a co-relational design in order to investigate the presence of linear progression of the GM vulnerability in association with cardiovascular risk factor. Voxel-based morphometry showed that the presence of cardiovascular risk factors were associated with regional GM loss involving the temporal cortices bilaterally. Those results retained statistical significance after including APOE4 as a covariate of interest. We also observed that there was a negative correlation between FCHDR scores and rGM distribution in the parietal cortex. Subclinical cerebrovascular abnormalities involving GM loss may provide an important link between cardiovascular risk factors and AD.

Vascular diseases and old age mental disorders: an update of neuroimaging findings.

PURPOSE OF REVIEW: To review neuroimaging findings that have been reported in samples of patients with cardiovascular disorders and their association with the onset of Alzheimer's disease, vascular dementia, depression and bipolar disorder in the elderly and to highlight the implications of these findings to the knowledge about the pathophysiology of psychiatric disorders in old age, as well as their potential clinical implications. RECENT FINDINGS: Vascular risk factors, such as hypertension, diabetes, dyslipidemia, smoking habits and heart failure, have all been associated with signs of cerebrovascular dysfunction, including structural MRI findings of signal hyperintensities, lacunes and stroke and functional imaging findings of brain regional hypoperfusion and hypometabolism. Such brain abnormalities have been found to increase the risk of onset of psychiatric disorder (depression, bipolar and dementia) in old age. SUMMARY: As vascular risk factors are potentially modifiable when detected in midlife, the early characterization of brain changes associated with the presence of cardiovascular diseases holds promise to afford clinical applications in psychiatry, providing new perspectives for the prevention of old age psychiatric disorders.

Cardiac disorders as risk factors for Alzheimer's disease.

Vascular risk factors can play an important role in determining the onset of non-genetic Alzheimer's disease (AD). Most cases of AD are sporadic and late-onset, and a complex interaction between genetic predisposition and vascular risk factors has been proposed. Vascular risk factors for AD include stroke, hypertension, diabetes, homocysteine, smoking, hypercholesterolemia, heart failure and atrial fibrillation; it is possible that these can trigger cerebrovascular dysfunction and AD pathology. Explanations for these associations include the coincidence of common disorders in the elderly where vascular and cerebrovascular disease can precipitate AD, implying that the onset of dementia disease is determined by a synergistic combination of risk factors. In this paper we review the role of cardiovascular risk factors in the pathogenesis of AD and discuss the associated brain mechanisms that can underlie the onset of AD. Cardiovascular diseases are a promising avenue of AD research because they are potentially modifiable in early adult life and provide a new perspective for the prevention of dementia.

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 >or= 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.

Hypotension caused by therapeutic doses of venlafaxine: case report and proposed pathophysiological mechanisms.

Although venlafaxine is usually associated with modest increases in blood pressure and not so often clinical hypertension, there are a few reported cases of hypotension related to overdoses of this specific antidepressant. The case study of a young female patient with a history of Major Depressive Disorder who initiated treatment with venlafaxine 75 mg/day and developed hypotension when the dosage was titrated up to 225 mg/day is described. The patient did not present comorbid diseases nor use other medication. A temporal association and a dose-dependent relationship between the hypotension and the use of venlafaxine is shown. To the best of the knowledge of the authors,this is the first case report that specifically associates regular doses of venlafaxine with the presence of hypotension. A pathophysiological mechanism is proposed, involving the participation of presynaptic alpha2-adrenergic receptors and the presence of a possible genetic polymorphism of cytochrome P4502D6, which is associated with lower drug metabolization, to explain the relationship between venlafaxine in regular dosage and development of hypotension.