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

Systemic Inflammation Predicts Alzheimer Pathology in Community Samples without Dementia

Neuroinflammation and oxidative stress (OS) are implicated in the pathophysiology of Alzheimer’s disease (AD). However, it is unclear at what stage of the disease process inflammation first becomes manifest. The aim of this study was to investigate the associations between specific plasma markers of inflammation and OS, tau, and Amyloid-β 38, 40, and 42 levels in cognitively unimpaired middle-age and older individuals. Associations between inflammatory states identified through principal component analysis and AD biomarkers were investigated in middle-age (52–56 years, n = 335, 52% female) and older-age (72–76 years, n = 351, 46% female) participants without dementia. In middle-age, a component reflecting variation in OS was most strongly associated with tau and to a lesser extent amyloid-β levels. In older-age, a similar component to that observed in middle-age was only associated with tau, while another component reflecting heightened inflammation independent of OS, was associated with all AD biomarkers. In middle and older-age, inflammation and OS states are associated with plasma AD biomarkers

High "Normal" blood glucose is associated with decreased brain volume and cognitive performance in the 60s: the PATH through Life Study

Context:Type 2 diabetes is associated with cerebral atrophy, cognitive impairment and dementia. We recently showed higher glucose levels in the normal range not to be free of adverse effects and to be associated with greater hippocampal and amygdalar atrophy in older community-dwelling individuals free of diabetes.Objective:This study aimed to determine whether blood glucose levels in the normal range

Development of a novel scheme for long-term body temperature monitoring: a review of benefits and applications

Body temperature is a health or disease marker that has been in clinical use for centuries. The threshold currently applied to define fever, with small variations, is 38 °C. However, current approaches do not provide a full picture of the thermoregulation process and its correlation with disease. This paper describes a new non-invasive body temperature device that improves the understanding of the pathophysiology of diseases by integrating a variety of temperature data from different body locations. This device enables to gain a deeper insight into fever, endogenous rhythms, subject activity and ambient temperature to provide anticipatory and more efficient treatments. Its clinical use would be a big step in the overcoming of the anachronistic febrile/afebrile dichotomy and walking towards a system medicine approach to certain diseases. This device has already been used in some clinical applications successfully. Other possible applications based on the device features and clinical requirements are also described in this paper.Cuesta Frau, D.; Varela Entrecanales, M.; Valor Pérez, R.; Vargas, B. (2015). Development of a novel scheme for long-term body temperature monitoring: a review of benefits and applications. Journal of Medical Systems. 39(4):1-7. doi:10.1007/s10916-015-0209-3S17394Gai, M., Merlo, I., Dellepiane, S., Cantaluppi, V., Leonardi, G., Fop, F., Guarena, C., Grassi, G., and Biancore, L., Glycemic pattern in diabetic patients on hemodialysis: Continuous Glucose Monitoring (CGM) analysis. Blood Purif. 38(1):68–73 , 2014.Kondziella, D., Friberg, C.K., Wellwood, I., Reiffurth, C., Fabricius, M., and Dreier, J.P.: Continuous EEG monitoring in aneurysmal subarachnoid hemorrhage: A systematic review. Neurocrit. Care (2014)Ciccone, A., Celani, M.G., Chiaramonte, R., Rossi, C., and Righetti, E., Continuous versus intermittent physiological monitoring for acute stroke. Cochrane Database Syst. Rev. 31, 2013.Kushimoto, S., Yamanouchi, S., Endo, T., Sato, T., Nomura, R., Fujita, M., Kudo, D., Omura, T., Miyagawa, N., and Sato, T., Body temperature abnormalities in non-neurological critically ill patients: A review of the literature. J. Intensive Care 2, 2014.Mc Callum, L., and Higgings, D., Measuring body temperature. Nursing Times 108:20–22, 2012.Varela, M., Ruiz-Esteban, R., Martinez-Nicolas, A., Cuervo-Arango, A., Barros, C., and Delgado, E.G., Catching the spike and tracking the flow: Holter-temperature monitoring in patients admitted in a general internal medicine ward. Int. J. Clin. Pract. 65(12):1283–1288, 2011.Lopes, F., Peres, D., Bross, A., Melot, C., and Vincent, J.L., Serial evaluation of the SOFA score to predict outcome in critically ill patients. J. Am. Med. Assoc. 286:1754–1758, 2001.Vincent, J.L., and Moreno, R., Clinical review: Scoring systems in the critically ill. Crit. Care, 14, 2010.Sund-Levander, M., and Grodzinsky, E., Time for a change to assess and evaluate body temperature in clinical practice. Int. J. Nurs. Pract. 15:241–249, 2009.Cuesta-Frau, D., Varela, M., Aboy, M., and Miro, P., Description of a portable wireless device for body temperature acquisition and analysis. Sensors 9(10):7648–7663, 2009.Varela, M., Cuesta-Frau, D., Madrid, J.A., Churruca, J., Miro-Matinez, P., Ruiz, R., and Marinez, C., Holter monitoring of central peripheral temperature: Possible uses and feasibility study in outpatient settings. J. Clin. Monit. Comput. 4(23):209–216, 2009.Jordan, J., Miro, P., Cuesta-Frau, D., Varela, M., and Vargas B.: Aplicacion de analisis multivariante para la deteccion de estados prefebriles en pacientes ingresados (in Spanish), XXXIV Congreso Nacional de Estadistica e Investigacion Operativa, Castellon (Spain) (2013)Richman, J., and Moorman, J.R., Physiological time-series analysis using approximate entropy and sample entropy. Am. J. Physiol. Heart Circ. Physiol. 278(6):H2039–2049, 2000.Young, P., Saxena, M., Eastwood, G.M., Bellomo, R., and Beasley, R., Fever and fever management among intensive care patients with known or suspected infection: A multicentre prospective cohort study. Crit. Care Resusc. 13:97–102 , 2011.Drewry, A.M., Fuller, B.M., Bailey, T.C., and Hotchkiss, R.S., Body temperature patterns as a predictor of hospital-acquired sepsis in afebrile adult intensive care unit patients: A case-control study. Crit. Care,17, 2013.Musher, D., Fainstein, V., Young, E., and Pruett, T., Fever patterns. Their lack of significance. Arch. Intern. Med. 139(11):1225–8, 1979.Varela, M., Calvo, M., Chana, M., Gomez-Mestre, I., Asensio, R., and Galdos, P., Clinical implications of temperature curve complexity in critically ill patients. Crit. Care Med. 33(12):2764–2771, 2005.Varela, M., Churruca, J., Gonzalez, A., Martin, A., Ode, J., and Galdos, P., Temperature curve complexity predicts survival in critically ill patients. Am. J. Respir. Crit. Care Med. 174(3):290–298, 2006.Cuesta-Frau, D., Varela, M., Miro, P., Galdos, P., Abasolo, D., Hornero, R., and Aboy, M., Predicting survival in critical patients by use of body temperature regularity measurement based on Approximate Entropy. Med. Biol. Eng. Computing 45:671–678, 2007.Mackiowak, P. Temperature regulation and the pathogenesis of fever, Principles and Practice of Infectious Diseases, pp. 765–778. New York: Churchill Livingston Elsevier, 2010.Cherbuin N., and Brinkman C., Cognition is cool: Can hemispheric activation be assessed by tympanic membrane thermometry? Brain Cogn. 54:228–231, 2004

High-normal blood glucose levels may be associated with decreased spatial perception in young healthy adults.

The negative effects of high normal glucose on cognitive function were previously reported in euglycemic individuals of middle age and the elderly population. This study aimed at examining the effect of baseline blood glucose levels on spatial ability, specifically verticality perception on the computerized rod and frame test (CRFT) in young healthy adults. 63 healthy male medical students (age range from 18-23 years), of whom 30 were non-fasting outside the month of Ramadan and 33 fasting during Ramadan of the year 2016, were recruited in order to create varying degrees of glycemia during which verticality perception was carried out. Baseline blood glucose reading was obtained prior to commencing the CRFT test. Blood glucose levels at the time of testing decreased as the duration between the last meal and testing increased. A blood glucose range of 62-117 mg/dl was achieved among participants for this study. Linear regression analysis showed that blood glucose level at testing correlated positively with all alignment spatial error parameters, indicating a probable reduction of spatial perception ability with higher blood glucose levels. These results are consistent with other cognitive studies in older healthy humans and emphasize the critical impact of early glucose dys-homeostasis on cognitive function. They also indicate that elevated blood glucose may affect cognitive functioning outside of the usual complications of diabetes

Use of Antihypertensives, Blood Pressure, and Estimated Risk of Dementia in Late Life: An Individual Participant Data Meta-Analysis

Importance: The utility of antihypertensives and ideal blood pressure (BP) for dementia prevention in late life remains unclear and highly contested. Objectives: To assess the associations of hypertension history, antihypertensive use, and baseline measured BP in late life (age >60 years) with dementia and the moderating factors of age, sex, and racial group. Data Source and Study Selection: Longitudinal, population-based studies of aging participating in the Cohort Studies of Memory in an International Consortium (COSMIC) group were included. Participants were individuals without dementia at baseline aged 60 to 110 years and were based in 15 different countries (US, Brazil, Australia, China, Korea, Singapore, Central African Republic, Republic of Congo, Nigeria, Germany, Spain, Italy, France, Sweden, and Greece). Data Extraction and Synthesis: Participants were grouped in 3 categories based on previous diagnosis of hypertension and baseline antihypertensive use: healthy controls, treated hypertension, and untreated hypertension. Baseline systolic BP (SBP) and diastolic BP (DBP) were treated as continuous variables. Reporting followed the Preferred Reporting Items for Systematic Review and Meta-Analyses of Individual Participant Data reporting guidelines. Main Outcomes and Measures: The key outcome was all-cause dementia. Mixed-effects Cox proportional hazards models were used to assess the associations between the exposures and the key outcome variable. The association between dementia and baseline BP was modeled using nonlinear natural splines. The main analysis was a partially adjusted Cox proportional hazards model controlling for age, age squared, sex, education, racial group, and a random effect for study. Sensitivity analyses included a fully adjusted analysis, a restricted analysis of those individuals with more than 5 years of follow-up data, and models examining the moderating factors of age, sex, and racial group. Results: The analysis included 17 studies with 34 519 community dwelling older adults (20 160 [58.4%] female) with a mean (SD) age of 72.5 (7.5) years and a mean (SD) follow-up of 4.3 (4.3) years. In the main, partially adjusted analysis including 14 studies, individuals with untreated hypertension had a 42% increased risk of dementia compared with healthy controls (hazard ratio [HR], 1.42; 95% CI 1.15-1.76; P = .001) and 26% increased risk compared with individuals with treated hypertension (HR, 1.26; 95% CI, 1.03-1.53; P = .02). Individuals with treated hypertension had no significant increased dementia risk compared with healthy controls (HR, 1.13; 95% CI, 0.99-1.28; P = .07). The association of antihypertensive use or hypertension status with dementia did not vary with baseline BP. There was no significant association of baseline SBP or DBP with dementia risk in any of the analyses. There were no significant interactions with age, sex, or racial group for any of the analyses. Conclusions and Relevance: This individual patient data meta-analysis of longitudinal cohort studies found that antihypertensive use was associated with decreased dementia risk compared with individuals with untreated hypertension through all ages in late life. Individuals with treated hypertension had no increased risk of dementia compared with healthy controls

Determinants of cognitive performance and decline in 20 diverse ethno-regional groups: A COSMIC collaboration cohort study

Background: With no effective treatments for cognitive decline or dementia, improving the evidence base for modifiable risk factors is a research priority. This study investigated associations between risk factors and late-life cognitive decline on a global scale, including comparisons between ethno-regional groups. Methods and findings: We harmonized longitudinal data from 20 population-based cohorts from 15 countries over 5 continents, including 48,522 individuals (58.4% women) aged 54–105 (mean = 72.7) years and without dementia at baseline. Studies had 2–15 years of follow-up. The risk factors investigated were age, sex, education, alcohol consumption, anxiety, apolipoprotein E ε4 allele (APOE*4) status, atrial fibrillation, blood pressure and pulse pressure, body mass index, cardiovascular disease, depression, diabetes, self-rated health, high cholesterol, hypertension, peripheral vascular disease, physical activity, smoking, and history of stroke. Associations with risk factors were determined for a global cognitive composite outcome (memory, language, processing speed, and executive functioning tests) and Mini-Mental State Examination score. Individual participant data meta-analyses of multivariable linear mixed model results pooled across cohorts revealed that for at least 1 cognitive outcome, age (B = −0.1, SE = 0.01), APOE*4 carriage (B = −0.31, SE = 0.11), depression (B = −0.11, SE = 0.06), diabetes (B = −0.23, SE = 0.10), current smoking (B = −0.20, SE = 0.08), and history of stroke (B = −0.22, SE = 0.09) were independently associated with poorer cognitive performance (p < 0.05 for all), and higher levels of education (B = 0.12, SE = 0.02) and vigorous physical activity (B = 0.17, SE = 0.06) were associated with better performance (p < 0.01 for both). Age (B = −0.07, SE = 0.01), APOE*4 carriage (B = −0.41, SE = 0.18), and diabetes (B = −0.18, SE = 0.10) were independently associated with faster cognitive decline (p < 0.05 for all). Different effects between Asian people and white people included stronger associations for Asian people between ever smoking and poorer cognition (group by risk factor interaction: B = −0.24, SE = 0.12), and between diabetes and cognitive decline (B = −0.66, SE = 0.27; p < 0.05 for both). Limitations of our study include a loss or distortion of risk factor data with harmonization, and not investigating factors at midlife. Conclusions: These results suggest that education, smoking, physical activity, diabetes, and stroke are all modifiable factors associated with cognitive decline. If these factors are determined to be causal, controlling them could minimize worldwide levels of cognitive decline. However, any global prevention strategy may need to consider ethno-regional differences

Adult Attention Deficit Hyperactivity Disorder and Violence in the Population of England: Does Comorbidity Matter?

It is unclear whether the association between Attention Deficit/Hyperactivity Disorder (ADHD) and violence is explained by ADHD symptoms or co-existing psychopathology. We investigated associations of ADHD and its symptom domains of hyperactivity and inattention, among individuals reporting violence in the UK population. Methods We report data from the Adult Psychiatric Morbidity Survey (2007), a representative sample of the household population of England. A randomly selected sample of 7,369 completed the Adult Self-Report Scale for ADHD and the self-reported violence module, including repetition, injury, minor violence, victims and location of incidents. All models were weighted to account for non-response and carefully adjusted for demography and clinical predictors of violence: antisocial personality, substance misuse and anxiety disorders. Results ADHD was moderately associated with violence after adjustments (OR 1.75, p = .01). Hyperactivity, but not inattention was associated with several indicators of violence in the domestic context (OR 1.16, p = .03). Mild and moderate ADHD symptoms were significantly associated with violence repetition, but not severe ADHD where the association was explained by co-existing disorders. Stratified analyses further indicated that most violence reports are associated with co-occurring psychopathology. Conclusions The direct effect of ADHD on violence is only moderate at the population level, driven by hyperactivity, and involving intimate partners and close persons. Because violence associated with severe ADHD is explained by co-existing psychopathology, interventions should primarily target co-existing disorders

Hippocampal Atrophy as a Quantitative Trait in a Genome-Wide Association Study Identifying Novel Susceptibility Genes for Alzheimer's Disease

With the exception of APOE ε4 allele, the common genetic risk factors for sporadic Alzheimer's Disease (AD) are unknown., which can be considered potential “new” candidate loci to explore in the etiology of sporadic AD. These candidates included EFNA5, CAND1, MAGI2, ARSB, and PRUNE2, genes involved in the regulation of protein degradation, apoptosis, neuronal loss and neurodevelopment. Thus, we identified common genetic variants associated with the increased risk of developing AD in the ADNI cohort, and present publicly available genome-wide data. Supportive evidence based on case-control studies and biological plausibility by gene annotation is provided. Currently no available sample with both imaging and genetic data is available for replication.Using hippocampal atrophy as a quantitative phenotype in a genome-wide scan, we have identified candidate risk genes for sporadic Alzheimer's disease that merit further investigation