Evelyn Smith

A review of the association between obesity and cognitive function across the lifespan : implications for novel approaches to prevention and treatment

Recent research suggests that increased adiposity is associated with poor cognitive performance, independently of associated medical conditions. The evidence regarding this relationship is examined in this review article. A relatively consistent finding across the lifespan is that obesity is associated with cognitive deficits, especially in executive function, in children, adolescents and adults. However, as illustrated by contradictory studies, the relationship between obesity and cognition is uncertain in the elderly, partly because of inaccuracy of body mass index as a measure of adiposity as body composition changes with aging. This review further discusses whether obesity is a cause or a consequence of these cognitive deficits, acknowledging the possible bidirectional relationship. The possible effects of increased adiposity on the brain are summarized. Our investigations suggest that weight gain results, at least in part, from a neurological predisposition characterized by reduced executive function, and in turn obesity itself has a compounding negative impact on the brain via mechanisms currently attributed to low‐grade systemic inflammation, elevated lipids and/or insulin resistance. The possible role of cognitive remediation treatment strategies to prevent and/or treat obesity is discussed.

Inflammatory biomarkers predict depressive, but not anxiety symptoms during aging: The prospective Sydney Memory and Aging Study

This study addresses the paucity of research on the prospective relationship between a range of inflammatory markers and symptoms of depression and anxiety during aging. In the Sydney Memory and Aging Study, the relationships between remitted depression, current and first onset of symptoms of depression or anxiety (Geriatric Depression Scale and Goldberg Anxiety Scale (GDS, GAS), and markers of systemic inflammation (C-reactive protein (CRP), interleukins-1β, -6, -8, -10, -12, plasminogen activator inhibitor-1 (PAI-1), serum amyloid A, tumor necrosis factor-α, and vascular adhesion molecule-1) were investigated. The sample consists of N=1037 non-demented community-dwelling elderly participants aged 70-90 years assessed at baseline and after 2-years. All analyses were adjusted for gender, age, years of education, total number of medical disorders diagnosed by a doctor, cardiovascular disorders, endocrine disorders, smoking, body mass index, currently using anti-depressants, NSAIDS or statins and diabetes mellitus. The results show a significant linear relationship between increasing levels of IL-6 and depressive symptoms at baseline only, whereas IL-8 was associated with depressed symptoms at baseline and at 2 years follow-up. In addition, IL-8 was associated with first onset of mild to moderate depressive symptoms over 2 years. Logistic regression analyses showed that PAI-1 (OR=1.37, 95% CI=1.10-1.71, p=0.005) was associated with remitted depression. Results for anxiety symptoms were negative. The findings are suggestive of IL-6 and IL-8 being associated with current symptoms and IL-8 being associated with first onset of depressive symptoms, whereas PAI-1 could be regarded as a marker of remitted depression.

Arterial stiffness, the brain and cognition: a systematic review.

BACKGROUND Arterial stiffness is a known predictor of cardiovascular disease, and has also been associated with markers of cerebral small vessel disease as well as poor cognitive function and cognitive decline. The consistency of these associations and their relationship to each other are unclear. METHOD We conducted a systematic review of the evidence associating arterial stiffness with cognitive function and cognitive decline, and with makers of cerebral small vessel disease, specifically lacunar infarcts and white matter hyperintensities. RESULTS Thirteen cross-sectional studies examining arterial stiffness and white matter hyperintensities or lacunar infarctions reported a positive association between increased arterial stiffness and radiological findings of cerebral small vessel disease. Two longitudinal studies examining the relationship between arterial stiffness and white matter hyperintensities found increased pulse wave velocity to be an independent predictor of white matter hyperintensity volume. Fifteen cross-sectional and seven longitudinal studies examining arterial stiffness and cognition were identified. Fourteen of the fifteen cross-sectional studies associated increased arterial stiffness with lower cognitive function, and six of the seven longitudinal studies found arterial stiffness to be predictive of cognitive decline. CONCLUSION Arterial stiffness is associated with cerebral small vessel disease and decreased cognitive function. However methodological limitations such as differing covariates between studies and an over-reliance on the MMSE to measure cognition are a concern across much of the literature.

The Clinical Obesity Maintenance Model: An Integration of Psychological Constructs including Mood, Emotional Regulation, Disordered Overeating, Habitual Cluster Behaviours, Health Literacy and Cognitive Function

Psychological distress and deficits in executive functioning are likely to be important barriers to effective weight loss maintenance. The purpose of this paper is twofold. First, in the light of recent evidence in the fields of neuropsychology and obesity, particularly on the deficits in the executive function in overweight and obese individuals, a conceptual and theoretical framework of obesity maintenance is introduced by way of a clinical obesity maintenance model (COMM). It is argued that psychological variables, that of habitual cluster Behaviors, emotional dysregulation, mood, and health literacy, interact with executive functioning and impact on the overeating/binge eating behaviors of obese individuals. Second, cognizant of this model, it is argued that the focus of obesity management should be extended to include a broader range of maintaining mechanisms, including but not limited to cognitive deficits. Finally, a discussion on potential future directions in research and practice using the COMM is provided.

Macrophage inhibitory cytokine‐1 is associated with cognitive impairment and predicts cognitive decline – the Sydney Memory and Aging Study

Higher levels of macrophage inhibitory cytokine‐1, also known as growth differentiation factor 15 (MIC‐1/GDF15), are associated with adverse health outcomes and all‐cause mortality. The aim of this study was to examine the relationships between MIC‐1/GDF15 serum levels and global cognition, five cognitive domains, and mild cognitive impairment (MCI), at baseline (Wave 1) and prospectively at 2 years (Wave 2), in nondemented participants aged 70–90 years. Analyses were controlled for age, sex, education, Framingham risk score, history of cerebrovascular accident, acute myocardial infarction, angina, cancer, depression, C‐reactive protein, tumor necrosis factor‐α, interleukins 6 and 12, and apolipoprotein ε4 genotype. Higher MIC‐1/GDF15 levels were significantly associated with lower global cognition at both waves. Cross‐sectional associations were found between MIC‐1/GDF15 and all cognitive domains in Wave 1 (all P < 0.001) and between processing speed, memory, and executive function in Wave 2 (all P < 0.001). Only a trend was found for the prospective analyses, individuals with high MIC‐1/GDF15 at baseline declined in global cognition, executive function, memory, and processing speed. However, when categorizing MIC‐1/GDF15 by tertiles, prospective analyses revealed statistically significant lower memory and executive function in Wave 2 in those in the upper tertile compared with the lower tertile. Receiver operating characteristics (ROC) analysis was used to determine MIC‐1/GDF15 cutoff values associated with cognitive decline and showed that a MIC‐1/GDF15 level exceeding 2764 pg/ml was associated with a 20% chance of decline from normal to MCI or dementia. In summary, MIC‐1/GDF15 levels are associated with cognitive performance and cognitive decline. Further research is required to determine the pathophysiology of this relationship.

The association between pulse wave velocity and cognitive function: the Sydney Memory and Ageing Study.

Objectives Pulse wave velocity (PWV) is a measure of arterial stiffness and its increase with ageing has been associated with damage to cerebral microvessels and cognitive impairment. This study examined the relationship between carotid-femoral PWV and specific domains of cognitive function in a non-demented elderly sample. Method Data were drawn from the Sydney Memory and Ageing Study, a cohort study of non-demented community-dwelling individuals aged 70–90 years, assessed in successive waves two years apart. In Wave 2, PWV and cognitive function were measured in 319 participants. Linear regression was used to analyse the cross-sectional relationship between arterial stiffness and cognitive function in the whole sample, and separately for men and women. Analysis of covariance was used to assess potential differences in cognition between subjects with PWV measurements in the top and bottom tertiles of the cohort. Covariates were age, education, body mass index, pulse rate, systolic blood pressure, cholesterol, depression, alcohol, smoking, hormone replacement therapy, apolipoprotein E ε4 genotype, use of anti-hypertensive medications, history of stroke, transient ischemic attack, myocardial infarction, angina, diabetes, and also sex for the whole sample analyses. Results There was no association between PWV and cognition after Bonferroni correction for multiple testing. When examining this association for males and females separately, an association was found in males, with higher PWV being associated with lower global cognition and memory, however, a significant difference between PWV and cognition between males and females was not found. Conclusion A higher level of PWV was not associated with lower cognitive function in the whole sample.

Manualised Cognitive Remediation Therapy for adult obesity: study protocol for a randomised controlled trial

BackgroundResearch has shown that obese individuals have cognitive deficiencies in executive function, leading to poor planning and impulse control, and decision-making difficulties. An intervention that could help reduce these deficits and in turn help weight loss maintenance is Cognitive Remediation Therapy for Obesity (CRT-O). We aim to examine the efficacy of manualised CRT-O, which is intended to improve executive function, enhance reflective practice and help weight loss maintenance.Methods/DesignA randomised controlled trial (registered with the Australian New Zealand Clinical Trials Registry) will be conducted. First, 90 obese adults (body mass index >30 kg/m2) in the community will receive three weekly sessions of a group Behaviour Weight Loss Treatment (BWLT), and then will be randomised either to receive CRT-O or to enter a no-treatment control group. CRT-O training will comprise twice-weekly sessions of 45 minutes over a 4 to 6 week period, for a total of eight sessions. Measurement points will be at baseline, post CRT-O (or 4 to 6 weeks after BWLT for the no-treatment control), 3 months post treatment and 1 year post treatment. The primary outcome will be executive function and secondary outcome measures will include participants’ body mass index, hip to waist ratio, eating behaviours and quality of life.DiscussionThis is the first study of its kind to examine the efficacy of Cognitive Remediation Therapy for obese adults through a randomised controlled trial.Trial RegistrationAustralian New Zealand Clinical Trials Registry number: 12613000537752. Date of registration: 14 May 2013.

Comparison of Attention Training and Cognitive Therapy in the Treatment of Social Phobia: A Preliminary Investigation

BACKGROUND Prominent models of social phobia highlight the role played by attentional factors, such as self-focused attention, in the development and maintenance of social phobia. Elevated self-focused attention is associated with increases in self-rated anxiety. Treatments that aim to modify and change attentional processes, specifically self-focused attention, will have a direct effect on social phobia symptoms. Thus, Attention Training targets attentional focus. AIM The present study aimed to investigate the efficacy of Attention Training in comparison to an established treatment for social phobia, Cognitive Therapy. METHOD Participants (Intention-to-treat = 45; completers = 30) were allocated to either 6 weeks of Attention Training or Cognitive Therapy. It was hypothesized that both treatments would be effective in reducing social phobia symptoms, but that Attention Training would work primarily by reducing levels of self-focused attention. RESULTS The results found an overall effectiveness of both treatment conditions in reducing social phobia symptoms. However, Attention Training significantly improved scores on the Self-Focused Attention questionnaire and the Brief Fear of Negative Evaluation questionnaire compared to Cognitive Therapy. CONCLUSION Attention Training seems to be a promising treatment for social phobia.

The Relationship of Serum Macrophage Inhibitory Cytokine – 1 Levels with Gray Matter Volumes in Community-Dwelling Older Individuals

Using circulating inflammatory markers and magnetic resonance imaging (MRI), recent studies have associated inflammation with brain volumetric measures. Macrophage Inhibitory Cytokine–1 (MIC-1/GDF15) is a divergent transforming growth factor – beta (TGF-β) superfamily cytokine. To uncover the underlying mechanisms of the previous finding of a negative association between MIC-1/GDF15 serum levels and cognition, the present study aimed to examine the relationship of circulating MIC-1/GDF15 levels with human brain gray matter (GM) volumes, in a community-dwelling sample aged 70–90 years over two years (Wave 1: n = 506, Wave 2: n = 327), of which the age-related brain atrophy had been previously well defined. T1-weighted MRI scans were obtained at both waves and analyzed using the FMRIB Software Library and FreeSurfer. The results showed significantly negative associations between MIC-1/GDF15 serum levels and both subcortical and cortical GM volumes. GM volumes of the whole brain, cortex, temporal lobe, thalamus and accumbens showed significant mediating effects on the associations between MIC-1/GDF15 serum levels and global cognition scores. Increases in MIC-1/GDF15 serum levels were associated with decreases in cortical and subcortical GM volume over two years. In conclusion, MIC-1/GDF15 serum levels were inversely associated with GM volumes both cross-sectionally and longitudinally.

Adiposity estimated using dual energy X-ray absorptiometry and body mass index and its association with cognition in elderly adults.

To determine whether obesity, estimated according to body mass index (BMI), waist circumference, and body fat and abdominal fat assessed using dual‐energy X‐ray absorptiometry (DEXA), was associated with cognitive performance.