A systematic review and meta-analysis of cross-sectional studies examining the relationship between mobility and cognition in healthy older adults

Ageing is associated with declines in cognitive function and mobility. The extent to which this relationship encompasses the subdomains of cognition and mobility remains unclear, however. We searched MEDLINE and EMBASE databases for cross-sectional studies examining the association between objective mobility measures (gait, lower-extremity function, balance) and cognitive function (global, executive function, memory, processing speed) in healthy older adults. Of the 642 studies identified, 26 studies met the inclusion criteria, with a total of 26,355 participants. For each feature of physical mobility, the relation to each aspect of cognition was reviewed. In the context of each association, we summarised the results to date and performed random-effects meta-analyses of published data. Reviewed findings suggest that individuals with better mobility perform better on assessments of global cognition, executive function, memory and processing speed. Not all measures of mobility were equally associated with cognitive function, however. Although there was a larger number of gait and lower-extremity function studies, and this may have driven findings, most studies examining balance and cognition measures reported no significant results. Meta-analyses on reported associations supported results by revealing significant, albeit small, effect sizes in favour of a positive association between performance on mobility measures and cognitive assessments. Future research should aim to establish the mechanisms driving this relationship, as this may identify predictors of age-related impairments

Managing affect in learners' questions in undergraduate science

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2012 Society for Research into Higher Education.This article aims to position students' classroom questioning within the literature surrounding affect and its impact on learning. The article consists of two main sections. First, the act of questioning is discussed in order to highlight how affect shapes the process of questioning, and a four-part genesis to question-asking that we call CARE is described: the construction, asking, reception and evaluation of a learner's question. This work is contextualised through studies in science education and through our work with university students in undergraduate chemistry, although conducted in the firm belief that it has more general application. The second section focuses on teaching strategies to encourage and manage learners' questions, based here upon the conviction that university students in this case learn through questioning, and that an inquiry-based environment promotes better learning than a simple ‘transmission’ setting. Seven teaching strategies developed from the authors' work are described, where university teachers ‘scaffold’ learning through supporting learners' questions, and working with these to structure and organise the content and the shape of their teaching. The article concludes with a summary of the main issues, highlighting the impact of the affective dimension of learning through questioning, and a discussion of the implications for future research

Predicting cognitive resilience from midlife lifestyle and multi-modal MRI: A 30-year prospective cohort study

BACKGROUND: There is significant heterogeneity in the clinical expression of structural brain abnormalities, including Alzheimer's disease biomarkers. Some individuals preserve their memory despite the presence of risk factors or pathological brain changes, indicating resilience. We aimed to test whether resilient individuals could be distinguished from those who develop cognitive impairment, using sociodemographic variables and neuroimaging. METHODS: We included 550 older adults participating in the Whitehall II study with longitudinal data, cognitive test results, and multi-modal MRI. Hippocampal atrophy was defined as Scheltens Scores >0. Resilient individuals (n = 184) were defined by high cognitive performance despite hippocampal atrophy (HA). Non-resilient participants (n = 133) were defined by low cognitive performance (≥1.5 standard deviations (S.D.) below the group mean) in the presence of HA. Dynamic and static exposures were evaluated for their ability to predict later resilience status using multivariable logistic regression. In a brain-wide analysis we tested for group differences in the integrity of white matter (structural connectivity) and resting-state networks (functional connectivity). FINDINGS: Younger age (OR: 0.87, 95% CI: 0.83 to 0.92, p<0.001), higher premorbid FSIQ (OR: 1.06, 95% CI: 1.03 to 1.10, p<0.0001) and social class (OR 1 vs. 3: 4.99, 95% CI: 1.30 to 19.16, p = 0.02, OR 2 vs. 3: 8.43, 95% CI: 1.80 to 39.45, p = 0.007) were independently associated with resilience. Resilient individuals could be differentiated from non-resilient participants by higher fractional anisotropy (FA), and less association between anterior and posterior resting state networks. Higher FA had a significantly more positive effect on cognitive performance in participants with HA, compared to those without. CONCLUSIONS: Resilient individuals could be distinguished from those who developed impairments on the basis of sociodemographic characteristics, brain structural and functional connectivity, but not midlife lifestyles. There was a synergistic deleterious effect of hippocampal atrophy and poor white matter integrity on cognitive performance. Exploiting and supporting neural correlates of resilience could offer a fresh approach to postpone or avoid the appearance of clinical symptoms

Neurovascular unit dysfunction with blood-brain barrier hyperpermeability contributes to major depressive disorder: a review of clinical and experimental evidence

About one-third of people with major depressive disorder (MDD) fail at least two antidepressant drug trials at 1 year. Together with clinical and experimental evidence indicating that the pathophysiology of MDD is multifactorial, this observation underscores the importance of elucidating mechanisms beyond monoaminergic dysregulation that can contribute to the genesis and persistence of MDD. Oxidative stress and neuroinflammation are mechanistically linked to the presence of neurovascular dysfunction with blood-brain barrier (BBB) hyperpermeability in selected neurological disorders, such as stroke, epilepsy, multiple sclerosis, traumatic brain injury, and Alzheimer’s disease. In contrast to other major psychiatric disorders, MDD is frequently comorbid with such neurological disorders and constitutes an independent risk factor for morbidity and mortality in disorders characterized by vascular endothelial dysfunction (cardiovascular disease and diabetes mellitus). Oxidative stress and neuroinflammation are implicated in the neurobiology of MDD. More recent evidence links neurovascular dysfunction with BBB hyperpermeability to MDD without neurological comorbidity. We review this emerging literature and present a theoretical integration between these abnormalities to those involving oxidative stress and neuroinflammation in MDD. We discuss our hypothesis that alterations in endothelial nitric oxide levels and endothelial nitric oxide synthase uncoupling are central mechanistic links in this regard. Understanding the contribution of neurovascular dysfunction with BBB hyperpermeability to the pathophysiology of MDD may help to identify novel therapeutic and preventative approaches

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. © 2013 Society of Biological Psychiatry

Neuroimaging in dementia.

Over the last few years, advances in neuroimaging have generated biomarkers, which increase diagnostic certainty, provide valuable information about prognosis, and suggest a particular pathology underlying the clinical dementia syndrome. We aim to review the evidence for use of already established imaging modalities, along with selected techniques that have a great potential to guide clinical decisions in the future. We discuss structural, functional and molecular imaging, focusing on the most common dementias: Alzheimer's disease, fronto-temporal dementia, dementia with Lewy bodies and vascular dementia. Finally, we stress the importance of conducting research using representative cohorts and in a naturalistic set up, in order to build a strong evidence base for translating imaging methods for a National Health Service. If we assess a broad range of patients referred to memory clinic with a variety of imaging modalities, we will make a step towards accumulating robust evidence and ultimately closing the gap between the dramatic advances in neurosciences and meaningful clinical applications for the maximum benefit of our patients