A two decade dementia incidence comparison from the Cognitive Function and Ageing Studies I and II.

Dramatic global increases in future numbers of people with dementia have been predicted. No multicentre population-based study powered to detect changes over time has reported dementia incidence. MRC Cognitive Function and Ageing Study (CFAS) undertook baseline interviews in populations aged 65+ years in England and Wales (1989-1994). Three areas (CFAS I) were selected for new sampling two decades later (2008-2011) with same geographical boundaries, sampling and approach methods (CFAS II). At 2 years CFAS I interviewed 5,156 (76% response) with 5,288 interviewed in CFAS II (74% response). Here we report a 20% drop in incidence (95% CI: 0-40%), driven by a reduction in men across all ages above 65. In the UK we estimate 209,600 new dementia cases per year. This study was uniquely designed to test for differences across geography and time. A reduction of age-specific incidence means that the numbers of people estimated to develop dementia in any year has remained relatively stable.

Conversion to dementia in mild cognitive impairment diagnosed with DSM-5 criteria and with Petersen's criteria.

OBJECTIVE: In a background of revision of criteria for states of increased risk for progression to dementia, we compare the conversion rate to dementia and Alzheimer's disease (AD) of mild cognitive impairment (MCI) as diagnosed using DSM-5 (DSM-5-MCI) and Petersen's (P-MCI) criteria. METHOD: A population representative cohort of 4057 dementia-free individuals 55+ years of age was followed up at 2.5 and 4.5 years in Zaragoza, Spain (ZARADEMP). Using the Geriatric Mental State- AGECAT for assessment, research psychiatrists diagnosed DSM-5-MCI and P-MCI following operationalized criteria. 'Conversion rate' (CR), 'annual conversion rate' (ACR), and incidence rate (IR) were calculated along with incidence rate ratio (IRR) to compare the performance of the intermediate cognitive definitions. RESULTS: At 4.5-year follow-up, in individuals aged 65+ years, ACRs for non-cases, P-MCI, and DSM-5-MCI were 0.8, 1.9 and 3.4, respectively, for global dementia. The IRRs were 2.9 and 5.3 for P-MCI and DSM5-MCI, respectively, being the non-cases the reference category. The corresponding values were slightly lower for AD. CONCLUSION: Conversion rate to dementia and AD was higher using DSM-5-MCI criteria than using Petersen's criteria. However, prediction of the construct still has some way to go, as most MCI individuals did not convert at 4.5-year follow-up.

Lower weight loss expectations and healthier eating attitudes in older overweight and obese women attempting weight loss.

Weight loss outcomes in overweight and obese individuals may be influenced by individual weight loss expectations (WLEs). Research on these phenomena in older women is lacking. This cross-sectional study compared groups of younger and older women on their WLEs and related attitudes (body dissatisfaction and disordered eating). Twenty-six younger (18-38 years) and 33 older (60-78 years) overweight and obese women were recruited from a weight loss clinic, prior to treatment. Disordered eating attitudes and body dissatisfaction were assessed using validated questionnaires and a pictorial figure-choice scale. Participants reported 10 WLEs categorized according to personal, lifestyle and social factors. Overall, women with a higher body mass index had greater WLEs. Older women reported lower WLEs than younger women (-14.5 kg vs. -22.4 kg) in all categories except past weight. Older women perceived that career success would necessitate the greatest level of weight loss (-18.5 kg), whereas younger women derived their greatest WLEs from mass media (-28.5 kg). Both older and younger groups perceived that their families would be supportive of the smallest amount of weight loss (-8.4 and -17.6 kg, respectively). The groups did not differ on body dissatisfaction, but younger women's disordered eating attitudes were significantly higher (p < .001). Older overweight and obese women have lower WLEs than younger women but experience similar levels of body dissatisfaction and healthier eating attitudes. The attitudinal constructs underlying these differences may be useful in clinical practice to tailor age-specific weight loss interventions.

Weight loss expectations and body dissatisfaction in young women attempting to lose weight.

BACKGROUND: Unrealistic weight loss expectations (WLEs) and greater body dissatisfaction may be associated with the poor long-term outcomes of dietary and lifestyle weight loss treatments. We evaluated the association between body size, WLEs and body dissatisfaction in young women attempting to lose weight. METHODS: Forty-four young healthy women [age range 18-35 years, body mass index (BMI) range 23-40 kg/m2] were recruited. Women were classified as obese (BMI ≥ 30.0 kg/m2) and non-obese (BMI <30.0 kg/m2). The Body Dissatisfaction scale of the Eating Disorder Inventory-2 and the Body Image Assessment for Obesity silhouette charts were used to assess body dissatisfaction. WLEs were categorised according to personal (ideal, happiness, satisfaction, weight history), lifestyle (fitness) and social (career, family acceptance, peer acceptance, mass media, social pressure) factors. Individual WLEs were compared with recommended clinical targets (5%, 10% and 20%) for weight loss. RESULTS: Body dissatisfaction was lower in non-obese subjects and was directly associated with BMI (P < 0.05). WLEs were directly associated with BMI and the obese group reported greater expectations. Five non-obese subjects (23%) desired to lose more than 20% of their body weight, whereas the proportion was significantly higher in the obese group (17 subjects; 74%). Subjects derived the greatest WLEs from mass media, whereas they perceived that family and friends were supportive of a lesser degree of weight loss. CONCLUSIONS: We observed a mismatch between clinical and personal expectations, and social pressure and interpersonal relationships appear to have a prominent role with respect to influencing the association.

The association between social stress and global cognitive function in a population-based study: the European Prospective Investigation into Cancer (EPIC)-Norfolk study.

BACKGROUND: Stress is thought to exert both positive and negative effects on cognition, but the precise cognitive effects of social stress and individuals' response to stress remain unclear. We aimed to investigate the association between different measures of social stress and cognitive function in a middle- to older-aged population using data from the European Prospective Investigation into Cancer (EPIC)-Norfolk study. METHOD: Participants completed a comprehensive assessment of lifetime social adversity between 1993 and 1997 and the short form of the Mini Mental State Examination (SF-MMSE), an assessment of global cognitive function, during the third health check between 2004 and 2011 (a median of 10.5 years later). A low MMSE score was defined as a score in the bottom quartile (20-26). RESULTS: Completed MMSE scores and stress measures were available for 5129 participants aged 48-90 years. Participants who reported that their lives had been more stressful over the previous 10 years were significantly more likely to have low MMSE scores [odds ratio (OR) 1.14, 95% confidence interval (CI) 1.04-1.24 per unit increase in perceived stress], independently of sociodemographic factors, physical and emotional health. The effects were restricted to the highest level of stress and the association was stronger among participants with a lower educational level. Adaptation following life event experiences also seemed to be associated with MMSE scores after adjusting for sociodemographic factors, but the association was attenuated with further adjustment. CONCLUSIONS: In this generally high-functioning population, individuals' interpretations and responses to stressful events, rather than the events themselves, were associated with cognitive function.

Sarcopenic obesity: A Critical appraisal of the current evidence.

Sarcopenic obesity (SO) is assuming a prominent role as a risk factor because of the double metabolic burden derived from low muscle mass (sarcopenia) and excess adiposity (obesity). The increase in obesity prevalence rates in older subjects is of concern given the associated disease risks and more limited therapeutic options available in this age group. This review has two main objectives. The primary objective is to collate results from studies investigating the effects of SO on physical and cardio-metabolic functions. The secondary objective is to evaluate published studies for consistency in methodology, diagnostic criteria, exposure and outcome selection. Large between-study heterogeneity was observed in the application of diagnostic criteria and choice of body composition components for the assessment of SO, which contributes to the inconsistent associations of SO with cardio-metabolic outcomes. We propose a metabolic load:capacity model of SO given by the ratio between fat mass and fat free mass, and discuss how this could be operationalised. The concept of regional fat distribution could be incorporated into the model and tested in future studies to advance our understanding of SO as a predictor of risk for cardio-metabolic diseases and physical disability.

Ageing, adiposity indexes and low muscle mass in a clinical sample of overweight and obese women.

OBJECTIVE: Ageing is associated with a progressive decline in the quantity (mass) and quality (function) of the muscular tissue. To assess the prevalence of low muscle mass (LMM) alone and in combination with high adiposity (LMM-HA) in a clinical representative sample of adult women and to determine how the prevalence of (LMM-HA) changes using different adiposity indexes. METHODS: 763 overweight and obese women (age range: 18-87 years) attending a weight loss clinic. Weight, height, and waist circumference (WC) were measured and BMI calculated. Bioelectrical impedance (BIA) was used to measure fat mass (FM). Skeletal muscle index (SMI) was used for the diagnosis of LMM. Adiposity indexes (BMI, WC, FM%, FM index) were combined with SMI to assess the prevalence of LMM-HA. RESULTS: The prevalence of LMM was 27.4% in women older than 60 years. Established cut-off scores for excess adiposity determined differences in the prevalence of LMM-HA. The lowest was observed using the BMI derived cut-off score (≥30 kg/m(2)), with FM% (≥35%) the most inclusive, classifying more than 90% of sarcopenia cases as LMM-HA. CONCLUSIONS: The prevalence of LMM-HA is different between anthropometric (BMI, WC) and bioimpedance measures (FM% and FMI) of adiposity. The sensitivity of the adiposity indexes for the diagnosis of sarcopenic obesity and its impact on the prediction of cardio-metabolic diseases remain to be tested.

The neuropathological profile of mild cognitive impairment (MCI): a systematic review.

Whether mild cognitive impairment (MCI) has a distinct neuropathological profile that reflects an intermediate state between no cognitive impairment and dementia is not clear. Identifying which biological events occur at the earliest stage of progressive disease and which are secondary to the neuropathological process is important for understating pathological pathways and for targeted disease prevention. Many studies have now reported on the neurobiology of this intermediate stage. In this systematic review, we synthesize current evidence on the neuropathological profile of MCI. A total of 162 studies were identified with varied definition of MCI, settings ranging from population to specialist clinics and a wide range of objectives. From these studies, it is clear that MCI is neuropathologically complex and cannot be understood within a single framework. Pathological changes identified include plaque and tangle formation, vascular pathologies, neurochemical deficits, cellular injury, inflammation, oxidative stress, mitochondrial changes, changes in genomic activity, synaptic dysfunction, disturbed protein metabolism and disrupted metabolic homeostasis. Determining which factors primarily drive neurodegeneration and dementia and which are secondary features of disease progression still requires further research. Standardization of the definition of MCI and reporting of pathology would greatly assist in building an integrated picture of the clinical and neuropathological profile of MCI.

Risk prediction models: a framework for assessment.

BACKGROUND: Medical risk prediction models estimate the likelihood of future health-related events. Many make use of information derived from analysis of the genome. Models predict health outcomes such as cardiovascular disease, stroke and cancer, and for some conditions several models exist. Although risk models can help decision-making in clinical medicine and public health, they can also be harmful, for example, by misdirecting clinical effort away from those who are most likely to benefit towards people with less need, thus exacerbating health inequalities. DISCUSSION: Risk prediction models need careful assessment before implementation, but the current approach to their development, evaluation and implementation is inappropriate. As a result, some models are pressed into use before it is clear whether they are suitable, while in other cases there is confusion about which model to use. This paper proposes an approach to the appraisal of risk-scoring models, based on a conference of UK experts. SUMMARY: By specifying what needs to be known before a model can be judged suitable for translation from research into practice, we can ensure that useful models are taken up promptly, that less well-proven ones undergo further evaluation and that resources are not wasted on ineffective ones.

Intentional weight loss in overweight and obese individuals and cognitive function: a systematic review and meta-analysis.

High adiposity in middle age is associated with higher dementia risk. The association between weight loss and cognitive function in older adults is still controversial. A meta-analysis was undertaken to estimate the effectiveness of intentional weight loss on cognitive function in overweight and obese adults. A structured strategy was used to search randomized and non-randomized studies reporting the effect of intentional and significant weight loss on cognitive function in overweight and obese subjects. Information on study design, age, nutritional status, weight-loss strategy, weight lost and cognitive testing was extracted. A random-effect meta-analysis was conducted to obtain summary effect estimates for memory and attention-executive domains. Twelve studies met inclusion criteria. Seven were randomized trials and the remaining five included a control group. A low-order significant effect was found for an improvement in cognitive performance with weight loss in memory (effect size 0.13, 95% CI 0.00-0.26, P=0.04) and attention/executive functioning (effect size 0.14, 95% CI 0.01-0.27, P<0.001). Studies were heterogeneous in study design, sample selection, weight-loss intervention and assessment of cognitive function. Weight loss appears to be associated with low-order improvements in executive/attention functioning and memory in obese but not in overweight individuals.

Measurement of in vivo nitric oxide synthesis in humans using stable isotopic methods: a systematic review.

Stable isotopic methods are considered the "gold standard" for the measurement of rates of in vivo NO production. However, values reported for healthy human individuals differ by more than 1 order of magnitude. The reason for the apparent variability in NO production is unclear. The primary aim of this review was to evaluate and compare the rates of in vivo NO production in health and disease using stable isotope methods. Articles were retrieved using the PubMed electronic database. Information on concentrations, isotopic enrichments of fluxes, and conversion rates of molecules involved in the NO metabolic pathway was extracted from selected articles; 35 articles were included in the final analysis. Three protocols were identified, including the arginine-citrulline, the arginine-nitrate, and the oxygen-nitrate protocols. The arginine-citrulline protocol showed a wider variability compared to the arginine-nitrate and oxygen-nitrate protocols. The direction of the association between disease state and rate of NO production was essentially determined by the etiopathogenesis of the disorder (inflammatory, metabolic, vascular). Considerable variation in methodologies used to assess whole-body NO synthesis in humans exists. The precision of several aspects of the techniques and the validity of some assumptions made remain unknown, and there is a paucity of information about physiological rates of NO production from childhood over adolescence to old age.

First-borns have a higher metabolic rate and carry a higher metabolic risk in young women attending a weight loss clinic.

BACKGROUND: Birth order has been associated with variability in early life growth and subsequent obesity risk, but the consequent metabolic risks have not been assessed. OBJECTIVE: To quantify the metabolic risk in young adulthood of being first-born relative to those born second or subsequently. METHODS: Body composition, resting metabolic rate and metabolic risk were assessed in 383 women, aged 18-35 years, from a clinical setting in southern Italy. RESULTS: First-borns had increased body mass index, adiposity and metabolic risk (p<0.05) and increased resting metabolic rate adjusted for fat-free mass (p<0.05) in the Italian women. CONCLUSION: First-born status is associated with significantly elevated metabolic risk in a clinical population of overweight and obese young women attending a weight loss clinic. If these findings are confirmed in other studies, they may suggest that the prevalence of the metabolic syndrome worldwide may increase as a function of the trend to smaller family size.

Angiogenesis and biomarkers of cardiovascular risk in adults with metabolic syndrome.

OBJECTIVES: Metabolic syndrome (MetSyn) is associated with an increased risk of atherosclerosis and fatal cardiovascular events. Angiogenesis is thought to contribute to this risk as it might be involved in the progression of atherosclerotic plaques. We investigated the levels of circulating biomarkers of angiogenesis and cardiovascular risk in adults with MetSyn and assessed their association with established metabolic risk factors. DESIGN: The Genetic Park project is a highly inclusive cross-sectional survey (about 80% of residents) conducted in three isolated populations in Southern Italy. A total of 1000 men and women (age range: 18-98 years) were included in the analysis. Anthropometric and blood pressure measurements were recorded. Metabolic and cardiovascular biomarkers included glucose, triglycerides, total cholesterol, HDL, vascular endothelial growth factor, placental growth factor (PlGF), soluble fms-like tyrosine kinase-1, high-sensitivity C-reactive protein, high-sensitivity troponin T (hs-TnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP). RESULT: Subjects with MetSyn had higher levels of PlGF and NT-proBNP after adjustment for age, smoking and body mass index. Circulating levels of PlGF, hs-TnT and NT-proBNP were directly related to the number of criteria of MetSyn, and this association interacted with gender. There was a strong correlation between ageing and cardiovascular risk. CONCLUSIONS: The increase in circulating levels of biomarkers of angiogenesis and cardiac function in subjects with MetSyn mirrors the pathophysiological changes occurring in the cardiovascular system. Over time, these changes might accelerate the formation and progression of atherosclerotic plaques and contribute significantly to cardiovascular morbidity and mortality risk.

Increased fructose intake as a risk factor for dementia.

The transition in the world age demographic toward older age is associated with an increased risk of neurodegenerative diseases, such as Alzheimer's disease. Risk profiles for dementia may also be changing. Obesity and type 2 diabetes have increased in prevalence in the last half-century and have been associated with increased dementia risk. Specific changes in nutrition may also represent a direct risk. A diet transition in the United States has occurred in the intake of refined sugar, particularly high-fructose corn syrup (HFCS) from a yearly estimate of 8.1 kg/person at the beginning of the XIX century to a current estimate of 65 kg/person. This article considers the association between refined sugar intake, markers of cardiovascular disease risk, and the possible promotion of the development of dementia.