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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.
Diagnosing early cognitive decline-When, how and for whom?
Mild cognitive impairment (MCI) is a term used to describe cognitive impairment in one or more cognitive domains that is greater than any expected age-related changes, but not of the magnitude to warrant a diagnosis of dementia. This review considers how early cognitive decline is diagnosed, focusing on the use of neuropsychological tests and neuroimaging, as well as the differential diagnosis. Potential treatments, including secondary prevention, post-diagnostic support and self-help are discussed. Finally, medico-legal matters such as driving, lasting power of attorney and employment are outlined.
What can gait tell us about dementia? Review of epidemiological and neuropsychological evidence.
BACKGROUND: Cognitive impairment and gait disorders in people over the age of 65 represent major public health issues because of their high frequency, their link to poor outcomes and high costs. Research has demonstrated that these two geriatric syndromes are closely related. METHODS AND RESULTS: We aim to review the evidence supporting the relationship between gait and cognitive impairment, particularly focusing on epidemiological and neuropsychological studies in patients with Mild cognitive impairment, Alzheimer's disease and Vascular dementia. The review demonstrates that gait and cognition are closely related, but our knowledge of their interrelationship is limited. Emerging evidence shows that gait analysis has the potential to contribute to diagnosis and prognosis of cognitive impairment. CONCLUSIONS: An integrated approach for evaluating these major geriatric syndromes, based on their close relationship, will not only increase our understanding of cognitive-motor interactions, but most importantly may be used to aid early diagnosis, prognosis and the development of new interventions.
Moderate alcohol consumption as risk factor for adverse brain outcomes and cognitive decline: longitudinal cohort study.
Objectives To investigate whether moderate alcohol consumption has a favourable or adverse association or no association with brain structure and function.Design Observational cohort study with weekly alcohol intake and cognitive performance measured repeatedly over 30 years (1985-2015). Multimodal magnetic resonance imaging (MRI) was performed at study endpoint (2012-15).Setting Community dwelling adults enrolled in the Whitehall II cohort based in the UK (the Whitehall II imaging substudy).Participants 550 men and women with mean age 43.0 (SD 5.4) at study baseline, none were "alcohol dependent" according to the CAGE screening questionnaire, and all safe to undergo MRI of the brain at follow-up. Twenty three were excluded because of incomplete or poor quality imaging data or gross structural abnormality (such as a brain cyst) or incomplete alcohol use, sociodemographic, health, or cognitive data.Main outcome measures Structural brain measures included hippocampal atrophy, grey matter density, and white matter microstructure. Functional measures included cognitive decline over the study and cross sectional cognitive performance at the time of scanning.Results Higher alcohol consumption over the 30 year follow-up was associated with increased odds of hippocampal atrophy in a dose dependent fashion. While those consuming over 30 units a week were at the highest risk compared with abstainers (odds ratio 5.8, 95% confidence interval 1.8 to 18.6; P≤0.001), even those drinking moderately (14-21 units/week) had three times the odds of right sided hippocampal atrophy (3.4, 1.4 to 8.1; P=0.007). There was no protective effect of light drinking (1-<7 units/week) over abstinence. Higher alcohol use was also associated with differences in corpus callosum microstructure and faster decline in lexical fluency. No association was found with cross sectional cognitive performance or longitudinal changes in semantic fluency or word recall.Conclusions Alcohol consumption, even at moderate levels, is associated with adverse brain outcomes including hippocampal atrophy. These results support the recent reduction in alcohol guidance in the UK and question the current limits recommended in the US.
Depression is linked to dementia in older adults.
Depression and dementia are both common conditions in older people, and they frequently occur together. Late life depression affects about 3.0-4.5% of adults aged 65 and older. Depression occurs in up to 20% of patients with Alzheimer’s disease and up to 45% of patients with vascular dementia. Rather than a risk factor, depression with onset in later life is more likely to be either prodromal to dementia or a condition that unmasks pre-existing cognitive impairment by compromising cognitive reserve. Depression can be a psychological response to receiving a diagnosis of dementia. The distinction between depression and early dementia may be particularly difficult. Detailed histories obtained from patients and their relatives as well as longitudinal follow-up are important. Cognitive testing can be very helpful. It is preferable to use a neuropsychological test that is sensitive to subtle cognitive changes and assesses all cognitive domains, such as the Montreal Cognitive Assessment. Older people with depression are at raised risk of dementia and this risk is increased if they have had symptoms for a long time, if their symptoms are severe, where there are multiple (vascular) comorbidities, and where there are structural brain changes including hippocampal atrophy and white matter abnormalities.
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.
Diagnosis and management of autism in adults.
Autism affects 1.1% of the adult population. The spectrum of symptoms is wide; some individuals have above average intelligence and are fully independent, while others have limited independence because of a learning disability. Developmental delay is a core feature, and autism is usually diagnosed in childhood. High-functioning individuals with autism, Asperger's syndrome, may remain undiagnosed until adulthood. Autism is a life-long condition characterised by problems in two core dimensions: difficulties with social communication and strongly repetitive behaviour, resistance to change or restricted interests.The history should identify early developmental and behavioural problems in different settings e.g. at home, in education or employment. Sensory and GI problems are very common, and should be asked about. The Autism-Spectrum Quotient (AQ-10) is a 10-item questionnaire for people with suspected autism. The advantage of using this in primary care is that it provides a time-efficient, structured way of ascertaining key symptoms and clearly signals those who should be referred for further assessment. Patients should be referred if autism is suspected clinically and a diagnosis of autism should be confirmed by a specialist multidisciplinary team. If a diagnosis of autism is made, clinicians should do a risk assessment and formulate risk and crisis management plans. These should include details of the roles and responsibilities of both the specialist team and primary care team in managing crisis situations. For adults with autism a group-based or an individual learning programme to improve social interaction is recommended. Adults with autism have high rates of unemployment, and employment programmes have been successfully used to support people
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.
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.
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.
Study protocol: The Whitehall II imaging sub-study.
BACKGROUND: The Whitehall II (WHII) study of British civil servants provides a unique source of longitudinal data to investigate key factors hypothesized to affect brain health and cognitive ageing. This paper introduces the multi-modal magnetic resonance imaging (MRI) protocol and cognitive assessment designed to investigate brain health in a random sample of 800 members of the WHII study. METHODS/DESIGN: A total of 6035 civil servants participated in the WHII Phase 11 clinical examination in 2012-2013. A random sample of these participants was included in a sub-study comprising an MRI brain scan, a detailed clinical and cognitive assessment, and collection of blood and buccal mucosal samples for the characterisation of immune function and associated measures. Data collection for this sub-study started in 2012 and will be completed by 2016. The participants, for whom social and health records have been collected since 1985, were between 60-85 years of age at the time the MRI study started. Here, we describe the pre-specified clinical and cognitive assessment protocols, the state-of-the-art MRI sequences and latest pipelines for analyses of this sub-study. DISCUSSION: The integration of cutting-edge MRI techniques, clinical and cognitive tests in combination with retrospective data on social, behavioural and biological variables during the preceding 25 years from a well-established longitudinal epidemiological study (WHII cohort) will provide a unique opportunity to examine brain structure and function in relation to age-related diseases and the modifiable and non-modifiable factors affecting resilience against and vulnerability to adverse brain changes.
Depression in older people is underdiagnosed.
Depression is more common in old age than dementia yet is underdiagnosed and undertreated. It is important to recognise that patients may not always present in a typical way, features that may indicate depression include anxiety, a preoccupation with somatic symptoms, and a change in function. The presence of understandable triggers and causes should not deter GPs from offering treatment, as long as symptoms are pervasive and continuously persist beyond two weeks. Age-related disabilities and changes to physical health are major risk factors for depression in older people. Vascular diseases, including stroke, MI and diabetes increase the risk of depression, both through direct effects on the brain and the psychological effects. Likewise, dementia is a risk factor for depression. Psychological factors such as loneliness and loss of a valued role, as well as social factors related to retirement, bereavement and reduced independence may also increase the risk. Patients with a previous history of depression and anxiety disorders are at increased risk of depression in later life. Assessment and diagnosis are largely based on a careful history. This should focus on eliciting current features of depression, which have been present for at least two weeks, and are associated with a significant change in function. It is important to exclude organic disorders including anaemia, B12 and folate deficiency, and hypothyroidism that may mimic symptoms of depressive disorder. Referral to specialist mental health services is indicated in the following cases: diagnostic difficulty, poor response to treatment, psychotic symptoms, significant psychiatric comorbidity or a risk of self-neglect or suicide.
Lifetime hypertension as a predictor of brain structure in older adults: cohort study with a 28-year follow-up.
BACKGROUND: Hypertension is associated with an increased risk of dementia and depression with uncertain longitudinal associations with brain structure. AIMS: To examine lifetime blood pressure as a predictor of brain structure in old age. METHOD: A total of 190 participants (mean age 69.3 years) from the Whitehall II study were screened for hypertension six times (1985-2013). In 2012-2013, participants had a 3T-magnetic resonance imaging (MRI) brain scan. Data from the MRI were analysed using automated and visual measures of global atrophy, hippocampal atrophy and white matter hyperintensities. RESULTS: Longitudinally, higher mean arterial pressure predicted increased automated white matter hyperintensities (P<0.002). Cross-sectionally, hypertensive participants had increased automated white matter hyperintensities and visually rated deep white matter hyperintensities. There was no significant association with global or hippocampal atrophy. CONCLUSIONS: Long-term exposure to high blood pressure predicts hyperintensities, particularly in deep white matter. The greatest changes are seen in those with severe forms of hypertension, suggesting a dose-response pattern.
Resilience and MRI correlates of cognitive impairment in community-dwelling elders.
BACKGROUND: The contribution of education and intelligence to resilience against age-related cognitive decline is not clear, particularly in the presence of 'normal for age' minor brain abnormalities. METHOD: Participants (n = 208, mean age 69.2 years, s.d. = 5.4) in the Whitehall II imaging substudy attended for neuropsychological testing and multisequence 3T brain magnetic resonance imaging. Images were independently rated by three trained clinicians for global and hippocampal atrophy, periventricular and deep white matter changes. RESULTS: Although none of the participants qualified for a clinical diagnosis of dementia, a screen for cognitive impairment (Montreal Cognitive Assessment (MoCA) <26) was abnormal in 22%. Hippocampal atrophy, in contrast to other brain measures, was associated with a reduced MoCA score even after controlling for age, gender, socioeconomic status, years of education and premorbid IQ. Premorbid IQ and socioeconomic status were associated with resilience in the presence of hippocampal atrophy. CONCLUSIONS: Independent contributions from a priori risk (age, hippocampal atrophy) and resilience (premorbid function, socioeconomic status) combine to predict measured cognitive impairment.
Imaging
Exactly twenty years have passed since John Besson’s chapter on ‘Imaging’ in the previous edition of these seminars. There has been an amazing proliferation of imaging methods, but very little change in the clinical imaging protocols available to the average UK clinician. X-ray computed tomography still seems to be the mainstay of assessment in the standard psychiatric memory clinic. MRI tends to be available, but only as a ‘special treat’, often mediated by neurologists, and emission tomography, such as SPECT and PET, are only used in highly specialized cases outside a few academic centers. Apart from generic NHS austerity, ‘health without mental health’, and institutional ageism, what could be the reasons for this?
Neuroimaging
With dramatic developments in imaging technology over the past few decades, there has been a surge of neuroimaging research studies, particularly in old age psychiatry. Age-related brain changes, together with specific pathological abnormalities, have generated a host of case-control studies that illuminate the aetiology and pathophysiology of brain disease. However, little has as yet been translated into clinical practice. While cutting-edge imaging protocols have the potential to be translated into the clinical domain, they still lack a realistic estimation of sensitivity, specificity, and predictive power that typically comes from studying large-scale representative groups with a validated diagnosis. To cover this division of neuroimaging into scientific clinical enquiry and clinical routine, the first section of this chapter aims to provide a brief overview of the theory behind neuroimaging techniques and outline commonly used analysis methods. The second section will cover the current and future clinical applications of neuroimaging. Particular focus will be given to the role of neuroimaging in making a diagnosis, predicting outcome, and understanding illness mechanisms.
Association between gait and cognition in an elderly population based sample.
BACKGROUND: Gait is thought to have a cognitive component, but the current evidence in healthy elderly is mixed. We studied the association between multiple gait and cognitive measures in a cohort of older people. METHODS: One hundred and seventy-eight cognitively healthy participants from the Whitehall II Imaging Sub-study had a detailed clinical and neuropsychological assessment, as well as an MRI scan. Spatiotemporal and variability gait measures were derived from two 10 m walks at self-selected speed. We did a linear regression analysis, entering potential confounders with backwards elimination of variables with p ≥ 0.1. The remaining variables were then entered into a second regression before doing a stepwise analysis of cognitive measures, entering variables with p 0.05). CONCLUSIONS: No strong relationship between gait and non-motor cognition was observed in a cognitively healthy, high functioning sample of elderly. Nevertheless, we found some relationships with spatial, but not temporal gait which warrant further investigation. WMH made no independent contributionto gait.
Differential associations of anticipatory and consummatory anhedonia with depression and social anxiety symptoms: a network analysis of university students
Background: Depression and social anxiety are frequently co-occurring conditions that significantly impact young people. Anhedonia may be important to consider in early interventions for these conditions, but the roles of specific dimensions of anhedonia—anticipatory and consummatory—are not well understood. This study explored the symptom connectivity of depression and social anxiety in university students, focusing on how the two dimensions of anhedonia relate to symptoms of both conditions. Methods: We conducted a cross-sectional network analysis of data from 672 university students (19–24 years). A Gaussian Graphical Model was used to investigate the relationship between anticipatory and consummatory anhedonia and symptoms of depression and social anxiety. Results: Anticipatory anhedonia was distinctively connected with specific depression nodes (low mood, suicidal ideation) and social anxiety nodes (avoiding being the centre of attention, less fear of embarrassment). Consummatory anhedonia was related to a wider range of depression nodes (worthlessness/guilt, suicidal ideation, concentration problems, sleep problems) and all social anxiety nodes. Both dimensions of anhedonia demonstrated strong bridge expected influence, alongside worthlessness/guilt and avoiding being the centre of attention, highlighting their relevance to both social anxiety and depression nodes. Conclusions: The findings refine our understanding of the psychopathology of depressive and social anxiety symptoms in young people and exemplify the importance of distinguishing the dimensions of anhedonia. Given its transdiagnostic associations, anhedonia may be important to account for in early interventions for depression and social anxiety. Future research should incorporate clinical samples and longitudinal data.