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Education and Income Show Heterogeneous Relationships to Lifespan Brain and Cognitive Differences Across European and US Cohorts.
Higher socio-economic status (SES) has been proposed to have facilitating and protective effects on brain and cognition. We ask whether relationships between SES, brain volumes and cognitive ability differ across cohorts, by age and national origin. European and US cohorts covering the lifespan were studied (4-97 years, N = 500 000; 54 000 w/brain imaging). There was substantial heterogeneity across cohorts for all associations. Education was positively related to intracranial (ICV) and total gray matter (GM) volume. Income was related to ICV, but not GM. We did not observe reliable differences in associations as a function of age. SES was more strongly related to brain and cognition in US than European cohorts. Sample representativity varies, and this study cannot identify mechanisms underlying differences in associations across cohorts. Differences in neuroanatomical volumes partially explained SES-cognition relationships. SES was more strongly related to ICV than to GM, implying that SES-cognition relations in adulthood are less likely grounded in neuroprotective effects on GM volume in aging. The relatively stronger SES-ICV associations rather are compatible with SES-brain volume relationships being established early in life, as ICV stabilizes in childhood. The findings underscore that SES has no uniform association with, or impact on, brain and cognition.
Vascular risk factors and depression in later life: a systematic review and meta-analysis.
Reports of the association between cardiovascular risk factors and depression in later life are inconsistent; to establish the nature of their association seems important for prevention and treatment of late-life depression. We searched MEDLINE, EMBASE, and PsycINFO for relevant cohort or case control studies over the last 22 years; 1097 were retrieved; 26 met inclusion criteria. Separate meta-analyses were performed for Risk Factor Composite Scores (RFCS) combining different subsets of risk factors, Framingham Stroke Risk Score, and single factors. We found a positive association (odds ratio [OR]: 1.49; 95% confidence interval [CI]: 1.27-1.75) between RFCS and late-life depression. There was no association between Framingham Stroke Risk Score (OR: 1.25; 95% CI: .99-1.57), hypertension (OR: 1.14; 95% CI: .94-1.40), or dyslipidemia (OR: 1.08; 95% CI: .91-1.28) and late-life depression. The association with smoking was weak (OR: 1.35; 95% CI: 1.00-1.81), whereas positive associations were found with diabetes (OR: 1.51; 95% CI: 1.30-1.76), cardiovascular disease (OR: 1.76; 95% CI: 1.52-2.04), and stroke (OR: 2.11; 95% CI: 1.61-2.77). Moderate to high heterogeneity was found in the results for RFCS, smoking, hypertension, dyslipidemia, and stroke, whereas publication bias was detected for RFCS and diabetes. We therefore found convincing evidence of a strong relationship between key diseases and depression (cardiovascular disease, diabetes, and stroke) and between composite vascular risk and depression but not between some vascular risk factors (hypertension, smoking, dyslipidemia) and depression. More evidence is needed to be accumulated from large longitudinal epidemiological studies, particularly if complemented by neuroimaging.
Diffusion tensor imaging in parkinsonian syndromes: a systematic review and meta-analysis.
OBJECTIVES: We performed a systematic review to assess alterations in measures of diffusion tensor imaging (DTI) in parkinsonian syndromes, exploring the potential role of DTI in diagnosis and as a candidate biomarker. METHODS: We searched EMBASE and Medline databases for DTI studies comparing parkinsonian syndromes or related dementias with controls or another defined parkinsonian syndrome. Key details for each study regarding participants, imaging methods, and results were extracted. Estimates were pooled, where appropriate, by random-effects meta-analysis. RESULTS: Of 333 results, we identified 43 studies suitable for inclusion (958 patients, 764 controls). DTI measures detected alterations in all parkinsonian syndromes, with distribution varying differentially with disease type. Nine studies were included in a meta-analysis of the substantia nigra in Parkinson disease. A notable effect size was found for lowered fractional anisotropy in the substantia nigra for patients with Parkinson disease vs controls (-0.639, 95% confidence interval -0.860 to -0.417, p < 0.0001). CONCLUSION: DTI may be a promising biomarker in parkinsonian syndromes and have a future role in differential diagnosis. Larger cohort studies are required to investigate some encouraging preliminary findings. Given the complexity of the parkinsonian syndromes, it is likely that any potential DTI biomarker would be used in combination with other relevant biomarkers.
Vascular changes and brain plasticity: a new approach to neurodegenerative diseases.
The world's population is aging, which will result in an increasing prevalence of neurodegenerative diseases, such as dementia. Observations from functional brain imaging that older brains can be more active than their younger counterparts challenge stereotypical ideas of aging. In those aging successfully, brain activation is more anterior, less lateralized and more coordinated than in those at risk of, or suffering from, cognitive impairment. Several theories have been proposed to explain these findings. One of the most enticing is the scaffolding theory, which posits that the older brain is a plastic homeostatic organ, able to compensate for its deteriorating structure. However, with aging also come diffuse vascular changes and the resulting white matter damage. This decreases the compensatory capacity, and dementia can ensue. This and alternative hypotheses will be discussed, along with potential methodological problems of this genre of study and with their clinical implications.
A systematic review and meta-analysis of magnetic resonance imaging studies in late-life depression.
Gray matter abnormalities within frontal-subcortical and limbic networks are hypothesized to play a key role in the pathophysiology of late-life depression. In this work, gray matter abnormalities in late-life depression are examined in a systematic review and meta-analysis of magnetic resonance imaging studies. In the systematic review, 27 articles were identified that compared participants with late-life depression with comparison group participants, and 17 studies were suitable for inclusion in meta-analyses of volumes of the whole brain, orbitofrontal cortex, caudate, hippocampus, putamen, and thalamus. Volume reductions were detected in 7 of 15 comparisons of the hippocampus and a meta-analysis revealed a significant, but small, effect size. Although examined by fewer studies, meta-analyses also revealed significant volume reductions in the orbitofrontal cortex, putamen, and thalamus. A more systematic and comprehensive analysis of the global distribution of gray matter abnormalities, and an examination of subcortical abnormalities were identified as key areas for future research.
Early diagnosis beneficial in Alzheimer's disease.
GPs should consider a diagnosis of dementia when a patient presents with functional impairment in addition to at least two changes in cognitive function e.g. short-term memory, language, reasoning, spatial orientation, or personality change. The patient, friends, family or professional carers should have noticed these changes for at least six months. Patients should be referred to a memory clinic to make a formal diagnosis of probable or possible Alzheimer's disease and to exclude other types of dementia. Key to assessment is a careful history of cognitive and functional changes, medical conditions and past psychiatric history. An objective cognitive assessment is important, and in primary care screening tools such as the General Practitioner Assessment of Cognition provide a useful adjunct to justify referral to specialist services. Patients should have a physical examination and a dementia screen to exclude treatable causes of cognitive impairment. Acetylcholinesterase inhibitors and memantine both slow the progression of cognitive decline and extend independence in activities of daily living. NICE recommends donepezil, rivastigmine or galantamine for mild to moderate Alzheimer's disease, and memantine for severe disease. Primary care is optimally placed to screen for cognitive impairments, to provide essential longitudinal information that will make a diagnosis of dementia safer. Primary care also has a crucial role in primary and, particularly secondary, prevention programmes to tackle excessive weight, lack of activity, smoking, and other lifestyle risk factors for dementia, including Alzheimer's disease, as well as the treatment of medical conditions which increase dementia risk.
Use of self-administered instruments to assess psychiatric disorders in older people: validity of the General Health Questionnaire, the Center for Epidemiologic Studies Depression Scale and the self-completion version of the revised Clinical Interview Schedule.
BACKGROUND: Diagnosis of depressive disorder using interviewer-administered instruments is expensive and frequently impractical in large epidemiological surveys. The aim of this study was to assess the validity of three self-completion measures of depressive disorder and other psychiatric disorders in older people against an interviewer-administered instrument. METHOD: A random sample stratified by sex, age and social position was selected from the Whitehall II study participants. This sample was supplemented by inclusion of depressed Whitehall II participants. Depressive disorder and other mental disorders were assessed by the interviewer-administered structured revised Clinical Interview Schedule (CIS-R) in 277 participants aged 58-80 years. Participants also completed a computerized self-completion version of the CIS-R in addition to the General Health Questionnaire (GHQ) and the Center for Epidemiologic Studies Depression Scale (CES-D). RESULTS: The mean total score was similar for the interviewer-administered (4.43) and self-completion (4.35) versions of the CIS-R [95% confidence interval (CI) for difference -0.31 to 0.16]. Differences were not related to sex, age, social position or presence of chronic physical illness. Sensitivity/specificity of self-completion CIS-R was 74%/98% for any mental disorder and 75%/98% for depressive episode. The corresponding figures were 86%/87% and 78%/83% for GHQ and 77%/89% and 89%/86% for CES-D. CONCLUSIONS: The self-completion computerized version of the CIS-R is feasible and has good validity as a measure of any mental disorder and depression in people aged ≥ 60 years. GHQ and CES-D also have good criterion validity as measures of any mental disorder and depressive disorder respectively.
Review of treatment for late-life depression
Depressive disorder in those over the age of 60 has many clinical similarities to depression in younger adults, but biological changes related to ageing may necessitate a different approach to treatment. We present an evidence-based review of treatment for late-life depression, focusing on pharmacological approaches, including monotherapy, combination and augmentation strategies. Selective serotonin reuptake inhibitors such as sertraline and citalopram are well tolerated, have the advantage of a favourable side-effect profile, and are good options for first-line treatment. Second-line treatment options include combination therapy with a second antidepressant, or treatment augmentation with an antipsychotic or lithium. We also consider evidence for non-pharmacological treatment strategies, including psychological therapy and neurostimulation. Finally, we summarise evidence for treatment of depression in patients in dementia.
Use of self-administered instruments to assess psychiatric disorders in older people: Validity of the General Health Questionnaire, the Center for Epidemiologic Studies Depression Scale and the self-completion version of the revised Clinical Interview Schedule
Background Diagnosis of depressive disorder using interviewer-administered instruments is expensive and frequently impractical in large epidemiological surveys. The aim of this study was to assess the validity of three self-completion measures of depressive disorder and other psychiatric disorders in older people against an interviewer-administered instrument. Method A random sample stratified by sex, age and social position was selected from the Whitehall II study participants. This sample was supplemented by inclusion of depressed Whitehall II participants. Depressive disorder and other mental disorders were assessed by the interviewer-administered structured revised Clinical Interview Schedule (CIS-R) in 277 participants aged 58-80 years. Participants also completed a computerized self-completion version of the CIS-R in addition to the General Health Questionnaire (GHQ) and the Center for Epidemiologic Studies Depression Scale (CES-D). Results The mean total score was similar for the interviewer-administered (4.43) and self-completion (4.35) versions of the CIS-R [95% confidence interval (CI) for difference -0.31 to 0.16]. Differences were not related to sex, age, social position or presence of chronic physical illness. Sensitivity/specificity of self-completion CIS-R was 74%/98% for any mental disorder and 75%/98% for depressive episode. The corresponding figures were 86%/87% and 78%/83% for GHQ and 77%/89% and 89%/86% for CES-D. Conclusions The self-completion computerized version of the CIS-R is feasible and has good validity as a measure of any mental disorder and depression in people aged ≥ 60 years. GHQ and CES-D also have good criterion validity as measures of any mental disorder and depressive disorder respectively. © Cambridge University Press 2013.
CRP, IL-6 and depression: a systematic review and meta-analysis of longitudinal studies.
BACKGROUND: Inflammatory markers are raised in cross-sectional studies of depressed patients and may represent an important mediating factor for behaviour, neural plasticity and brain structure. METHODS: We undertook a systematic review of longitudinal studies, investigating whether raised inflammatory markers indicate an increased risk of subsequent depressive symptoms. We searched three databases (1970-2012) for longitudinal studies with repeat data on CRP or IL-6 levels and subsequent depressive symptoms. We calculated effect sizes using a mixed-effects model, with separate meta-analyses for inflammatory markers and age groups. RESULTS: We identified eight papers for CRP (14,832 participants) and three for IL-6 (3695 participants). There was a significant association between increased CRP and depressive symptoms (weighted-mean effect size 'unadjusted r'=0.069, p<0.0005; 'adjusted r'=0.046, p<0.0005), with moderate heterogeneity between studies (Q=11.21, p=0.08, I(2)=46.5). For IL-6 the weighted-mean effect size was smaller ('unadjusted r'=0.045, p-value=0.007; 'adjusted r'=0.097, p-value=0.06). LIMITATIONS: The meta-analysis was based on a relatively small number of studies (particularly for IL-6) and only two inflammatory markers. There was moderate heterogeneity between studies and some evidence of publication bias. CONCLUSIONS: Raised inflammatory markers have a small but significant association with the subsequent development of depressive symptoms. This is a robust effect which remains significant after adjustment for age and a wide range of factors associated with risk for depression. Our results support the hypothesis that there is a causal pathway from inflammation to depression.
Prescribing selective serotonin reuptake inhibitors in older age.
Apart from commercial reasons, two motivations have led to the introduction of SSRIs to replace the first and second generation antidepressants already available. One was the search for a more rational treatment, based on specific mechanisms, the other the development of effective treatments with fewer side effects, particularly for older patients, who have a greater sensitivity to cardio-vascular and central nervous system effects. The first has been frustrated up to a point, in that SSRIs and other single mechanism drugs do not appear to be more effective than the earliest relatively non-specific antidepressants. The second has been fulfilled, in that SSRIs generally are better tolerated in older patients and in overdose. However, there is a spectrum of other side effects that are particularly relevant in older age and that need attention when treating depression in this particular patient group.
Mind over matter--what do we know about neuroplasticity in adults?
BACKGROUND: An increasing number of studies have examined the effects of training of cognitive and other tasks on brain structure, using magnetic resonance imaging. METHODS: Studies combining cognitive and other tasks training with longitudinal imaging designs were reviewed, with a view to identify paradigms potentially applicable to treatment of cognitive impairment. RESULTS: We identified 36 studies, employing training as variable as juggling, working memory, meditation, learning abstract information, and aerobic exercise. There were training-related structural changes, increases in gray matter volume, decreases, increases and decreases in different regions, or no change at all. There was increased integrity in white matter following training, but other patterns of results were also reported. CONCLUSIONS: Questions still to be answered are: Are changes due to use-dependent effects or are they specific to learning? What are the underlying neural correlates of learning, the temporal dynamics of changes, the relations between structure and function, and the upper limits of improvement? How can gains be maintained? The question whether neuroplasticity will contribute to the treatment of dementia will need to be posed again at that stage.
Cerebral hemodynamics in cerebral small vessel disease
Small vessel disease is an important frontier in neurology; about 25% of strokes are classified as small vessel, and SVD is the most common cause of vascular cognitive impairment. The risk of developing SVD increases with age, making this a growing concern for countries with aging populations. Despite this, there has been a paucity of information about its causes, diagnosis, prevention and treatment. This volume brings together contributions from leading international experts in the field and discusses pathogenesis, pathophysiology, clinical and radiologic manifestations, prevention and treatment modalities, and future directions for research and practice. Genetic forms of SVD are discussed, as well as the rapid development of neuroimaging techniques as tools for screening and treatment. This authoritative book is essential reading for neurologists, stroke physicians, geriatricians, and interventional neuroradiologists, as well as researchers in the fields of aging and dementia.
Parkinson's disease
Parkinson’s disease is a common neurological condition affecting movement, but also mental function. This review provides an introduction to the underlying pathology, clinical symptoms, diagnosis and treatment. More detailed discussion focusses on the use of neuroimaging to support clinical diagnosis, psychiatric co-morbidity and the cognitive changes associated with Parkinson’s disease.