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Effects of drinking on late-life brain and cognition.
Alcohol consumption is common in Western countries and has been increasing in older adults. Latest figures from Great Britain suggest 75% of those over 65 years drink, an increase from 71% 10 years ago. Chronic heavy intake is a well-established cause of brain atrophy and dementia, with a recent long-term prospective study from the USA reporting a doubling of the odds of later severe memory impairment in those with a history of an alcohol use disorder. Drinking of moderate amounts has been reported to be protective for brain health in a number of epidemiological studies, including some claims of possibly reducing dementia risk. Rigorous recent research has questioned this belief, with new evidence of harmful associations in moderate drinkers compared with abstainers. This has raised suspicion that reported protective effects of moderate drinking were due to confounding by socioeconomic class and intelligence. Clinicians should look out for cognitive impairment in heavy drinkers, considering that abstinence may induce a degree of clinical improvement. Discussions with patients regarding moderate drinking should be informed by recent research. Health benefits of moderate drinking at least for cognitive function are questionable, and if they exist are probably limited to one unit of alcohol daily with respect to other body systems.
Mood disorders and cognitive impairment
In vivo methods of brain investigation have recently made it possible to extend research into psychosocial risk factors for mental disorders, such as post-traumatic stress, depressive and cognitive disorders, to the effect of behavioural risks on the brain. There are now theories explaining brain correlates of stress-related anxiety disorders, the effects of chronic stress on the brain and, at least partially, the organic brain changes found in cognitive and mood disorders. The concepts of chronic stress and allostatic load have been used to conceptualize such brain behaviour relationships. Research combining brain changes associated with chronic stress and allostatic load may also explain some of the commonalities of mood disorders and cognitive disorders, which make them risk factors for each other.
Exploring variability in basal ganglia connectivity with functional MRI in healthy aging.
Changes in functional connectivity (FC) measured using resting state fMRI within the basal ganglia network (BGN) have been observed in pathologies with altered neurotransmitter systems and conditions involving motor control and dopaminergic processes. However, less is known about non-disease factors affecting FC in the BGN. The aim of this study was to examine associations of FC within the BGN with dopaminergic processes in healthy older adults. We explored the relationship between FC in the BGN and variables related to demographics, impulsive behavior, self-paced tasks, mood, and motor correlates in 486 participants in the Whitehall-II imaging sub-study using both region-of-interest- and voxel-based approaches. Age was the only correlate of FC in the BGN that was consistently significant with both analyses. The observed adverse effect of aging on FC may relate to alterations of the dopaminergic system, but no unique dopamine-related function seemed to have a link with FC beyond those detectable in and linearly correlated with healthy aging.
Healthy minds 0-100 years: Optimising the use of European brain imaging cohorts ("Lifebrain").
The main objective of "Lifebrain" is to identify the determinants of brain, cognitive and mental (BCM) health at different stages of life. By integrating, harmonising and enriching major European neuroimaging studies across the life span, we will merge fine-grained BCM health measures of more than 5000 individuals. Longitudinal brain imaging, genetic and health data are available for a major part, as well as cognitive and mental health measures for the broader cohorts, exceeding 27,000 examinations in total. By linking these data to other databases and biobanks, including birth registries, national and regional archives, and by enriching them with a new online data collection and novel measures, we will address the risk factors and protective factors of BCM health. We will identify pathways through which risk and protective factors work and their moderators. Exploiting existing European infrastructures and initiatives, we hope to make major conceptual, methodological and analytical contributions towards large integrative cohorts and their efficient exploitation. We will thus provide novel information on BCM health maintenance, as well as the onset and course of BCM disorders. This will lay a foundation for earlier diagnosis of brain disorders, aberrant development and decline of BCM health, and translate into future preventive and therapeutic strategies. Aiming to improve clinical practice and public health we will work with stakeholders and health authorities, and thus provide the evidence base for prevention and intervention.
Meta-analysis of Magnetic Resonance Imaging Studies in Velocardiofacial Syndrome (VCFS)
Introduction:Velocardiofacial syndrome (VCFS) is a common genetic disorder due to a micro deletion on chromosome 22q11. This region includes several risk-associated genetic variants, including COMT, and VCFS is associated with a substantially increased risk for schizophrenia. As such, VCFS may serve as a valuable model for clarifying the neuroanatomical changes associated with genetic risk for psychosis.Methods:A systematic literature search was conducted. Studies were included if they presented original data and were published by March 2008, compared subjects with VCFS and healthy controls and reported measures of brain regions according to SI units as mean and standard deviation. Data extracted from the studies included diagnosis, demographic variables and IQ. Statistical analysis was conducted using STATA 8.0 supplemented by ‘Metan’ software.Results:Twenty studies were retrieved. All measures were expressed in volumes apart from the corpus callosum (area). Subjects with VCFS showed reduced total brain volume (N=156 versus N=138), ([ES]=1.04, 95% CI:1.40, -0.67), with no significant heterogeneity or publication bias. This reduction was reflected in total hemisphere grey and white matter. Prefrontal, parieto-occipital and temporal cortices appeared to be particularly affected. A number of sub-cortical areas also showed decreased volumes including the hippocampus and putamen. In contrast, callosal areas were increased in VCFS.Conclusion:In relation to controls, subjects with VCFS present with an overall reduction in brain volumes and specific abnormalities in multiple cortical and subcortical brain regions. These abnormalities may explain partly why VCFS is associated with a greatly increased risk of psychosis and other psychiatric disorders.
Meta-analysis of Magnetic Resonance Imaging Studies in Bipolar Disorder and Schizophrenia [P01-175]
Introduction:Several MRI studies have identified structural abnormalities in association with bipolar disorder. The literature is however heterogeneous and there is remaining uncertainty about the brain areas pivotal to the pathogenesis of the condition. The aim of this study was to identify, appraise and summarise volumetric MRI studies of brain regions comparing bipolar disorder with an unrelated control group and/or patients with schizophrenia.Methods:A systematic review and random-effects meta-analysis was carried out to identify key areas of structural abnormality in bipolar disorder and whether the pattern of affected areas separated bipolar disorder from schizophrenia. Excessive variability was explored using meta-regression analyses.Results:Seventy two reports met inclusion criteria. Subjects with bipolar disorder showed significant whole brain and prefrontal lobe volume reductions, and also increases in the volume of the globus pallidus. Enlargement of the lateral ventricles in bipolar disorder was confirmed, although the magnitude of enlargement was smaller than in schizophrenia. Subjects with schizophrenia, but not bipolar disorder, showed significant reductions in right amygdala volumes. Heterogeneity was statistically significant for many of the analyses and could amongst others be explained by age, duration of illness and year of publication.Conclusion:There appear to be robust changes in brain volume in bipolar disorder compared with healthy volunteers. Age and duration of illness appear to be key issues in determining the magnitude of observed effect sizes.
Reduced in vivo binding to the serotonin transporter in the cerebral cortex of MDMA ('ecstasy') users
Background: The use of MDMA ('ecstasy') is common among young people in Western countries. Animal models of MDMA toxicity suggest a loss of serotonergic neurons, and potentially implicate it in the development of significant psychiatric morbidity in humans. Aims: To test whether long-term use of MDMA can produce abnormalities in cerebral serotonin, but not dopamine, transporter binding measured by single photon emission computed tomography (SPECT). Method: Ten male regular ecstasy users and 10 well- matched controls recruited from the same community sources participated in SPECT with the serotonin transporter (SERT) ligand [123I]β-CIT. Dopamine transporter binding was determined from scans acquired 23 hours after injection of the tracer. Results: Ecstasy users showed a cortical reduction of SERF binding, particularly prominent in primary sensory-motor cortex, with normal dopamine transporter binding in lenticular nuclei. Conclusions: This cross-sectional association study provides suggestive evidence for specific, at least temporary, serotonergic neurotoxicity of MDMA in humans. Declaration of interest: Funded by the Wellcome Trust and the Medical Research Council.
A systematic review and meta-analysis of structural magnetic resonance imaging studies investigating cognitive and social activity levels in older adults.
Population aging has prompted considerable interest in identifying modifiable factors that may help protect the brain and its functions. Collectively, epidemiological studies show that leisure activities with high mental and social demands are linked with better cognition in old age. The extent to which socio-intellectual activities relate to the brain's structure is, however, not yet fully understood. This systematic review and meta-analysis summarizes magnetic resonance imaging studies that have investigated whether cognitive and social activities correlate with measures of gray and white matter volume, white matter microstructure and white matter lesions. Across eighteen included studies (total n = 8429), activity levels were associated with whole-brain white matter volume, white matter lesions and regional gray matter volume, although effect sizes were small. No associations were found for global gray matter volume and the evidence concerning white matter microstructure was inconclusive. While the causality of the reviewed associations needs to be established, our findings implicate socio-intellectual activity levels as promising targets for interventions aimed at promoting healthy brain aging.
Cognition and mobility show a global association in middle- and late-adulthood: Analyses from the Canadian Longitudinal Study on Aging.
BACKGROUND: Given our aging population, there's great interest in identifying modifiable risk factors for cognitive decline. Studies have highlighted the relationship between aspects of mobility and cognitive processes. However, cognition and mobility are both multifaceted concepts and their interrelationships remain to be well defined. RESEARCH QUESTION: Here, we firstly aimed to replicate cross-sectional associations between objective measures of mobility and cognition. Second, we tested whether these associations remained after the consideration of multiple age-related confounders. Finally, to test the hypothesis that the association between mobility and cognition is stronger in older adults, we examined the moderating effect of age in the association between mobility and cognition. METHODS: In the Canadian Longitudinal Study on Aging, 28,808 community-dwelling adults (aged 45-87; 51% female) completed mobility (gait, balance and chair stands) and cognitive (memory, executive function and processing speed) assessments. General linear models were used to examine mobility-cognition relationships and the moderating effect of age. RESULTS: Cognitive measures were significantly associated with mobility measures (all p