The feasibility of a multidomain dementia risk reduction randomised controlled trial for people experiencing cognitive decline: the Body, Brain, Life for Cognitive Decline (BBL-CD).

OBJECTIVES: To evaluate the feasibility of a proof-of-concept multidomain dementia risk reduction intervention. METHOD: An 8-week, parallel-group RCT, focused on increasing adherence to lifestyle domains of Mediterranean diet (MeDi), Physical Activity (PA), and Cognitive Engagement (CE). Feasibility was evaluated against the Bowen Feasibility Framework objectives of: Acceptability of the intervention, compliance with the protocol, and efficacy of the intervention to change behaviour in the three domains of interest. RESULTS: High acceptability of the intervention was demonstrated through a participant retention rate of 80.7% (Intervention: 84.2%; Control: 77.4%). Compliance to the protocol was strong with 100% of participants completing all educational modules and all MeDi and PA components, with 20% compliance for CE. Linear mixed models demonstrated efficacy to change behaviour through significant effects of adherence to MeDi (χ2 = 16.75, df = 3, p < .001) and CE (χ2 = 9.83, df = 3, p =.020), but not PA (χ2 = 4.48, df = 3, p =.211). CONCLUSION: Overall the intervention was shown to be feasible. Recommendations for future trials in this area are: The implementation of practical, one-on-one sessions as they are more effective than passive education at eliciting behaviour change; use of booster sessions to increase likelihood of lifestyle changes being sustained; and collection of qualitative data to identify barriers to change.

Cost-Effectiveness of Dementia Prevention Interventions.

BACKGROUND: Assessment of cost-effectiveness of interventions to address modifiable risk factors associated with dementia requires estimates of long-term impacts of these interventions which are rarely directly available and must be estimated using a range of assumptions. OBJECTIVES: To test the cost-effectiveness of dementia prevention measures using a methodology which transparently addresses the many assumptions required to use data from short-term studies, and which readily incorporates sensitivity analyses. DESIGN: We explore an approach to estimating cost-effective prices which uses aggregate data including estimated lifetime costs of dementia, both financial and quality of life, and incorporates a range of assumptions regarding sustainability of short- term gains and other parameters. SETTING: The approach is addressed in the context of the theoretical reduction in a range of risk factors, and in the context of a specific small-scale trial of an internet-based intervention augmented with diet and physical activity consultations. MEASUREMENTS: The principal outcomes were prices per unit of interventions at which interventions were cost-effective or cost-saving. RESULTS: Taking a societal perspective, a notional intervention reducing a range of dementia risk-factors by 5% was cost-effective at $A460 per person with higher risk groups at $2,148 per person. The on-line program costing $825 per person was cost-effective at $1,850 per person even if program effect diminished by 75% over time. CONCLUSIONS: Interventions to address risk factors for dementia are likely to be cost-effective if appropriately designed, but confirmation of this conclusion requires longer term follow-up of trials to measure the impact and sustainability of short-term gains.

Oxidative stress, inflammation and risk of neurodegeneration in a population sample.

BACKGROUND AND PURPOSE: Inflammation and oxidative stress (OS) have been clearly linked to neurodegeneration. However, studies investigating the associations between peripheral markers of inflammation and cognitive decline have produced mixed results. This is possibly due to the fact that markers are typically tested individually despite the fact that biologically they function interactively. Thus, the aim of this study was to investigate the association between a combination of OS/inflammation markers and outcomes including mild cognitive impairment (MCI) diagnosis, cognitive decline and hippocampal atrophy. METHODS: Oxidative stress/inflammation status was assessed in 380 older community-living individuals. Thirteen blood markers were assayed. Principal component analysis (PCA) of all markers was conducted to identify the more salient inflammatory components. Associations between significant principal components, MCI diagnosis, previous change in Mini-Mental State Examination (MMSE) score and hippocampal atrophy were investigated through logistic and linear multiple regression. RESULTS: Two factors (PC1 and PC2) reflecting predominantly broad pro-inflammatory activity and two factors (PC3 and PC4) reflecting predominantly OS activity were identified by PCA analysis. PC3 and PC4 were predictive of MCI. PC3 was also predictive of prior MMSE change. PC1, PC2 and PC3 were significantly associated with hippocampal atrophy. CONCLUSIONS: Combined analysis of complex and interacting biomarkers revealed a protective association between antioxidant activity and MCI that is consistent with lifestyle factors shown to reduce risk of cognitive decline. OS and broad systemic inflammation were also found to be associated with hippocampal atrophy further highlighting the benefits of the PCA methodology applied in this study.

The impact of type 2 diabetes and body mass index on cerebral structure is modulated by brain reserve.

BACKGROUND AND PURPOSE: Body mass index (BMI), hyperglycaemia and type 2 diabetes and their interactive effects are associated with brain volume atrophy in ageing. It remains to be established if these risk factors are particularly concerning in individuals with high or low brain volumes. METHODS: Demographics, venous blood and magnetic resonance imaging data were collected for 494 healthy community-living adults aged 53-78 (mean 65) years, as part of the Personality and Total Health Through Life study. Associations between BMI, blood glucose, diabetes status and brain volume (whole brain, grey matter, white matter and subcortical structures) were investigated using quantile regression. RESULTS: Quantile regression revealed vulnerability to BMI × glucose interactions particularly in lower volumes and significant main effects for type 2 diabetes particularly in higher volumes. Diabetes was most strongly associated with brain volumes. The association between BMI, blood glucose and diabetes was not consistent across the full range of brain volumes. CONCLUSION: Explicit investigation of the upper and lower boundaries of brain volume distributions was valuable. We found evidence of protective reserve from higher brain volumes and that a combination of high BMI and higher blood glucose was particularly concerning for individuals with lower brain volumes.

Combining Geospatial Analysis with Dementia Risk Utilising General Practice Data: A Systematic Review.

Geographical information systems (GIS) and geospatial analysis techniques will help to identify significant dementia risk clusters (hotspots) across communities and will enable policy makers to target prevention interventions to the right place. This review synthesises the published literature on geospatial analysis techniques for quantifying and mapping dementia risk, and reviews available dementia risk assessment tools. A systematic literature review was undertaken in four medical and life sciences databases (PubMed, Cochrane Central, Embase, and Web of Sciences) from their inception to March 2017 for all articles relating to dementia. The search terms included: 'dementia', 'Alzheimer's disease', 'general practice database', 'family physician', 'AD risk assessment tools', 'Geographical Information Systems' and 'geospatial analysis', 'geographical variation' and 'spatial variation'. To date, most geospatial studies on dementia have been carried out retrospectively using population based data. An alternative approach is utilisation of a rich source of general practice (family physician) databases to predict dementia risk based on available dementia risk assessment tools. In conclusion, the estimated risks of dementia can thus be geo-attributed and mapped at a small scale using geographical information systems and geospatial analysis techniques to identify dementia risk clusters across the communities and refine our understanding of the interaction between socio-demographic and environmental factors, and dementia risk clusters. .

Trajectories of BMI change impact glucose and insulin metabolism.

BACKGROUND AND AIMS: The aim of this study was to examine, in a community setting, whether trajectory of weight change over twelve years is associated with glucose and insulin metabolism at twelve years. METHODS AND RESULTS: Participants were 532 community-living middle-aged and elderly adults from the Personality and Total Health (PATH) Through Life study. They spanned the full weight range (underweight/normal/overweight/obese). Latent class analysis and multivariate generalised linear models were used to investigate the association of Body Mass Index (BMI, kg/m2) trajectory over twelve years with plasma insulin (µlU/ml), plasma glucose (mmol/L), and HOMA2 insulin resistance and beta cell function at follow-up. All models were adjusted for age, gender, hypertension, pre-clinical diabetes status (normal fasting glucose or impaired fasting glucose) and physical activity. Four weight trajectories were extracted; constant normal (mean baseline BMI = 25; follow-up BMI = 25), constant high (mean baseline BMI = 36; follow-up BMI = 37), increase (mean baseline BMI = 26; follow-up BMI = 32) and decrease (mean baseline BMI = 34; follow-up BMI = 28). At any given current BMI, individuals in the constant high and increase trajectories had significantly higher plasma insulin, greater insulin resistance, and higher beta cell function than those in the constant normal trajectory. Individuals in the decrease trajectory did not differ from the constant normal trajectory. Current BMI significantly interacted with preceding BMI trajectory in its association with plasma insulin, insulin resistance, and beta cell function. CONCLUSION: The trajectory of preceding weight has an independent effect on blood glucose metabolism beyond body weight measured at any given point in time.

Body mass index is associated with cortical thinning with different patterns in mid- and late-life.

OBJECTIVE: High BMI at midlife is associated with increased risk of dementia as well as faster decline in cognitive function. In late-life, however, high BMI has been found to be associated with both increased and decreased dementia risk. The objective of this study was to investigate the neural substrates of this age-related change in body mass index (BMI) risk. METHODS: We measured longitudinal cortical thinning over the whole brain, based on magnetic resonance imaging scans for 910 individuals aged 44-66 years at baseline. Subjects were sampled from a large population study (PATH, Personality and Total Health through Life). After attrition and exclusions, the final analysis was based on 792 individuals, including 387 individuals aged 60-66 years and 405 individuals aged 44-49 years. A mixed-effects model was used to test the association between cortical thinning and baseline BMI, as well as percentage change in BMI. RESULTS: Increasing BMI was associated with increased cortical thinning in posterior cingulate at midlife (0.014 mm kg-1 m-2, confidence interval; CI=0.005, 0.023, P<0.05 false discovery rate (FDR) corrected). In late-life, increasing BMI was associated with reduced cortical thickness, most prominently in the right supramarginal cortex (0.010 mm kg-1 m-2, CI=0.005-0.016, P<0.05 FDR corrected), as well as frontal regions. In late-life, decreasing BMI was also associated with increased cortical thinning, including right caudal middle frontal cortex (0.014 mm kg-1 m-2 (CI=0.006-0.023, P<0.05 FDR corrected). CONCLUSIONS: The pattern of cortical thinning-in association with increasing BMI at both midlife and late-life-is consistent with known obesity-related dementia risk. Increased cortical thinning in association with decreasing BMI at late-life may help explain the 'obesity paradox', where high BMI in midlife appears to be a risk factor for dementia, but high BMI in late-life appears, at times, to be protective.

Eye lens radiation exposure of the medical staff performing interventional urology procedures with an over-couch X-ray tube.

The purpose of this work was to estimate the eye lens radiation exposure of the medical staff during interventional urology procedures. The measurements were carried out for six medical staff members performing 33 fluoroscopically-guided procedures. All procedures were performed with the X-ray tube positioned over the couch. The dose equivalents (Hp(0.07)) were measured at the eye level using optically stimulated luminescent (OSL) dosimeters and at the chest level with OSL dosimeters placed over the protective apron. The ratio of the dose measured close to the eye lens and on the chest was determined. The annual eye lens dose was estimated based on the workload in the service. For the physician and the instrumentalist nurse, the eye to chest dose ratios were 0.9±0.4 and 2.6±1.6 (k = 2), respectively. The average doses per procedure received by the eye lens were 78±24 µSv and 38±18 µSv, respectively. The eye lens dose per DAP was 8.4±17.5 µSv/(Gy·cm2) for the physician and 4.1±8.7 µSv/(Gy·cm2) for the instrumentalist nurse. The results indicate that the eye lens to chest dose ratio greatly varies according to the staff function and that the dose equivalent measured by the personal dosimeter worn on the chest may underestimate the eye lens dose of some medical staff members.

Being overweight is associated with hippocampal atrophy: the PATH Through Life Study.

BACKGROUND: The prevalence of obesity has increased dramatically in the past two decades, with major implications for individual well-being, population health and the economy. Of particular concern is the risk obesity presents for brain health and its consequences in an ageing population. These associations and their time course are not well understood, particularly after middle age. The aim of this study was to investigate whether being overweight/obese or having an increasing body weight is associated with hippocampal atrophy in early old age. METHODS: Participants were 420 unimpaired (Mini-Mental State Examination >26) individuals aged 60-64 years, living in the community and taking part in a large prospective study of ageing over an 8 year follow-up. Magnetic resonance imaging scans were collected at three assessments and the hippocampus was manually traced by expert neuroscientists. Multi-level analyses assessing the relationship between body mass index (BMI) and hippocampal atrophy over 8 years while controlling for important covariates were conducted. RESULTS: Analyses showed that BMI was negatively associated with left (coefficient: -10.65 mm(3); s.e. 4.81; P=0.027) and right (coefficient: -8.18 mm(3); s.e. 4.91; P=0.097) hippocampal volume at the first assessment. Over the follow-up period, those with a higher BMI experienced greater hippocampal atrophy and more so in the left (P=0.001) than in the right (P=0.058) hippocampus. CONCLUSIONS: The findings from this study provide important evidence indicating that being overweight or obese is associated with poorer brain health. These results are consistent with those of previous animal and human studies and further stress the importance of reducing the rate of obesity through education, population health interventions and policy.

Interventions to Prevent Cognitive Decline and Dementia in Adults without Cognitive Impairment: A Systematic Review.

Without preventative strategies, the burden of dementia is likely to increase rapidly worldwide. Primary prevention approaches involve modifying risk factors before symptoms of cognitive impairment develop. This review systematically assesses Randomised Controlled Trials (RCTs) and reviews of RCTs for their effectiveness in primary prevention. We searched Medline, the Cochrane Library, Web of Science and Psych-Info for relevant studies using pre-determined keywords. Both non-pharmacological and pharmacological interventions were considered. Inclusion criteria were sample size greater or equal to 50, at least 6 months of follow-up, and participants with no cognitive impairment at baseline. Outcomes included dementia incidence, cognitive decline and cognitive function. Study quality was rated using the Jadad criteria. Thirty-nine studies, 17 non-pharmacological and 22 pharmacological, were included. Results were heterogeneous across interventions and studies, with few significant effects. Studies investigating physical activity and calcium channel blocker treatment demonstrated significant effects in preventing cognitive decline. There were no conclusive results demonstrating overall capacity of assessed interventions to reduce risk of dementia. The review provides an overview of the current literature, and identifies areas in need of further research.

Online memory screening--are older adults interested and can it work?

Subjective memory concerns are common in older adults and may prompt the use of web-based cognitive screening. Websites which purport to provide memory screening are numerous and can influence health behaviours; however there is currently limited evidence regarding their validity. The current research aims to assess potential user's attitudes and motivations regarding online cognitive screening and to evaluate the preliminary evidence for the feasibility and validity of two subjective online cognitive measures. The sample consisted of community-based older adults, 30 with, and 30 without, memory concerns. Participants rated their likelihood of their accessing online cognitive screening and gave rationales. Participants' performance on objective pen and paper measures of cognition was compared to performance on subjective online screening measures. The majority of participants indicated they would access online cognitive screening. A total of 100% of participants were able to use the online tools without assistance. None of the online measures was positively associated with the pen and paper screening measures. Anxiety and depression were significantly associated with subjective memory concerns. This study provided no supporting evidence for the validity of either subjective online screening measure assessed. Anxiety and depression were significantly associated with subjective cognition, indicating that, although they may not predict objective cognition, complaints about memory in older adults should be taken seriously by health professionals.

Body mass index in midlife and late-life as a risk factor for dementia: a meta-analysis of prospective studies.

The relationship between body mass index (BMI) (in midlife and late-life) and dementia was investigated in meta-analyses of 16 articles reporting on 15 prospective studies. Follow-ups ranged from 3.2 to 36.0 years. Meta-analyses were conducted on samples including 25 624 participants evaluated for Alzheimer's disease (AD), 15 435 participants evaluated for vascular dementia (VaD) and 30 470 followed for any type of dementia (Any Dementia). Low BMI in midlife was associated with 1.96 [95% confidence interval (CI): 1.32, 2.92] times the risk of developing AD. The pooled relative risks for AD, VaD and Any Dementia for overweight BMI in midlife compared with normal BMI were 1.35 (95% CI:1.19, 1.54), 1.33 (95% CI: 1.02, 1.75) and 1.26 (95% CI: 1.10, 1.44), respectively. The pooled relative risks of AD and Any Dementia for obese BMI in midlife compared to normal BMI were 2.04 (95% CI: 1.59, 2.62) and 1.64 (95% CI: 1.34, 2.00), respectively. Continuous BMI in late-life was not associated with dementia. Small numbers of studies included in pooled analyses reduce generalizability of findings, and emphasize the need for publication of additional findings. We conclude that underweight, overweight and obesity in midlife increase dementia risk. Further research evaluating late-life BMI and dementia is required.