Publications
243 results found
Zhao Y, Ray A, Broberg K, et al., 2023, Prediagnostic Blood Metal Levels and the Risk of Parkinson's Disease: A Large European Prospective Cohort., Mov Disord
BACKGROUND: Metals have been postulated as environmental concerns in the etiology of Parkinson's disease (PD), but metal levels are typically measured after diagnosis, which might be subject to reverse causality. OBJECTIVE: The aim of this study was to investigate the association between prediagnostic blood metal levels and PD risk. METHODS: A case-control study was nested in a prospective European cohort, using erythrocyte samples collected before PD diagnosis. RESULTS: Most assessed metals were not associated with PD risk. Cadmium has a suggestive negative association with PD (odds ratio [95% confidence interval] for the highest quartile, 0.70 [0.42-1.17]), which diminished among never smokers. Among current smokers only, lead was associated with decreased PD risk (0.06 [0.01-0.35]), whereas arsenic showed associations toward an increased PD risk (1.85 [0.45-7.93]). CONCLUSIONS: We observe no strong evidence to support a role of metals in the development of PD. In particular, smoking may confound the association with tobacco-derived metals. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Rolland Y, Sierra F, Ferrucci L, et al., 2023, Challenges in developing Geroscience trials., Nat Commun, Vol: 14
Geroscience is becoming a major hope for preventing age-related diseases and loss of function by targeting biological mechanisms of aging. This unprecedented paradigm shift requires optimizing the design of future clinical studies related to aging in humans. Researchers will face a number of challenges, including ideal populations to study, which lifestyle and Gerotherapeutic interventions to test initially, selecting key primary and secondary outcomes of such clinical trials, and which age-related biomarkers are most valuable for both selecting interventions and predicting or monitoring clinical responses ("Gerodiagnostics"). This article reports the main results of a Task Force of experts in Geroscience.
Zhao Y, Walker DI, Lill CM, et al., 2023, Lipopolysaccharide-binding protein and future Parkinson's disease risk: a European prospective cohort, Journal of Neuroinflammation, Vol: 20, ISSN: 1742-2094
INTRODUCTION: Lipopolysaccharide (LPS) is the outer membrane component of Gram-negative bacteria. LPS-binding protein (LBP) is an acute-phase reactant that mediates immune responses triggered by LPS and has been used as a blood marker for LPS. LBP has recently been indicated to be associated with Parkinson's disease (PD) in small-scale retrospective case-control studies. We aimed to investigate the association between LBP blood levels with PD risk in a nested case-control study within a large European prospective cohort. METHODS: A total of 352 incident PD cases (55% males) were identified and one control per case was selected, matched by age at recruitment, sex and study center. LBP levels in plasma collected at recruitment, which was on average 7.8 years before diagnosis of the cases, were analyzed by enzyme linked immunosorbent assay. Odds ratios (ORs) were estimated for one unit increase of the natural log of LBP levels and PD incidence by conditional logistic regression. RESULTS: Plasma LBP levels were higher in prospective PD cases compared to controls (median (interquartile range) 26.9 (18.1-41.0) vs. 24.7 (16.6-38.4) µg/ml). The OR for PD incidence per one unit increase of log LBP was elevated (1.46, 95% CI 0.98-2.19). This association was more pronounced among women (OR 2.68, 95% CI 1.40-5.13) and overweight/obese subjects (OR 1.54, 95% CI 1.09-2.18). CONCLUSION: The findings suggest that higher plasma LBP levels may be associated with an increased risk of PD and may thus pinpoint to a potential role of endotoxemia in the pathogenesis of PD, particularly in women and overweight/obese individuals.
Zheng B, Su B, Ahmadi-Abhari S, et al., 2023, Dementia risk in patients with type 2 diabetes: Comparing metformin with no pharmacological treatment., Alzheimers Dement
INTRODUCTION: Metformin has been suggested as a therapeutic agent for dementia, but the relevant evidence has been partial and inconsistent. METHODS: We established a national cohort of 210,237 type 2 diabetes patients in the UK Clinical Practice Research Datalink. Risks of incident dementia were compared between metformin initiators and those who were not prescribed any anti-diabetes medication during follow-up. RESULTS: Compared with metformin initiators (n = 114,628), patients who received no anti-diabetes medication (n = 95,609) had lower HbA1c and better cardiovascular health at baseline. Both Cox regression and propensity score weighting analysis showed metformin initiators had lower risk of dementia compared to those non-users (adjusted hazard ratio = 0.88 [95% confidence interval: 0.84-0.92] and 0.90 [0.84-0.96]). Patients on long-term metformin treatment had an even lower risk of dementia. DISCUSSION: Metformin may act beyond its glycemic effect and reduce dementia risk to an even lower level than that of patients with milder diabetes and better health profiles. HIGHLIGHTS: Metformin initiators had a significantly lower risk of dementia compared with patients not receiving anti-diabetes medication. Compared with metformin initiators, diabetes patients not receiving pharmacological treatment had better glycemic profiles at baseline and during follow-up. Patients on long-term metformin treatment had an even lower risk of subsequent dementia incidence. Metformin may act beyond its effect on hyperglycemia and has the potential of being repurposed for dementia prevention.
Lai HTM, Chang K, Sharabiani MTA, et al., 2023, Twenty-year trajectories of cardio-metabolic factors among people with type 2 diabetes by dementia status in England: a retrospective cohort study, European Journal of Epidemiology, Vol: 38, Pages: 733-744, ISSN: 0393-2990
To assess 20-year retrospective trajectories of cardio-metabolic factors preceding dementia diagnosis among people with type 2 diabetes (T2D). We identified 227,145 people with T2D aged > 42 years between 1999 and 2018. Annual mean levels of eight routinely measured cardio-metabolic factors were extracted from the Clinical Practice Research Datalink. Multivariable multilevel piecewise and non-piecewise growth curve models assessed retrospective trajectories of cardio-metabolic factors by dementia status from up to 19 years preceding dementia diagnosis (dementia) or last contact with healthcare (no dementia). 23,546 patients developed dementia; mean (SD) follow-up was 10.0 (5.8) years. In the dementia group, mean systolic blood pressure increased 16-19 years before dementia diagnosis compared with patients without dementia, but declined more steeply from 16 years before diagnosis, while diastolic blood pressure generally declined at similar rates. Mean body mass index followed a steeper non-linear decline from 11 years before diagnosis in the dementia group. Mean blood lipid levels (total cholesterol, LDL, HDL) and glycaemic measures (fasting plasma glucose and HbA1c) were generally higher in the dementia group compared with those without dementia and followed similar patterns of change. However, absolute group differences were small. Differences in levels of cardio-metabolic factors were observed up to two decades prior to dementia diagnosis. Our findings suggest that a long follow-up is crucial to minimise reverse causation arising from changes in cardio-metabolic factors during preclinical dementia. Future investigations which address associations between cardiometabolic factors and dementia should account for potential non-linear relationships and consider the timeframe when measurements are taken.
Aune D, Schlesinger S, Mahamat-Saleh Y, et al., 2023, Diabetes mellitus, prediabetes and the risk of Parkinson’s disease: a systematic review and meta-analysis of 15 cohort studies with 29.9 million participants and 86,345 cases, European Journal of Epidemiology, Vol: 38, Pages: 591-604, ISSN: 0393-2990
A diagnosis of diabetes mellitus and prediabetes has been associated with increased risk of Parkinson’s disease (PD) in several studies, but results have not been entirely consistent. We conducted a systematic review and meta-analysis of cohort studies on diabetes mellitus, prediabetes and the risk of PD to provide an up-to-date assessment of the evidence. PubMed and Embase databases were searched for relevant studies up to 6th of February 2022. Cohort studies reporting adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) for the association between diabetes, prediabetes and Parkinson’s disease were included. Summary RRs (95% CIs) were calculated using a random effects model. Fifteen cohort studies (29.9 million participants, 86,345 cases) were included in the meta-analysis. The summary RR (95% CI) of PD for persons with diabetes compared to persons without diabetes was 1.27 (1.20–1.35, I2 = 82%). There was no indication of publication bias, based on Egger’s test (p = 0.41), Begg’s test (p = 0.99), and inspection of the funnel plot. The association was consistent across geographic regions, by sex, and across several other subgroup and sensitivity analyses. There was some suggestion of a stronger association for diabetes patients reporting diabetes complications than for diabetes patients without complications (RR = 1.54, 1.32–1.80 [n = 3] vs. 1.26, 1.16–1.38 [n = 3]), vs. those without diabetes (pheterogeneity=0.18). The summary RR for prediabetes was 1.04 (95% CI: 1.02–1.07, I2 = 0%, n = 2). Our results suggest that patients with diabetes have a 27% increased relative risk of developing PD compared to persons without diabetes, and persons with prediabetes have a 4% increase in RR compared to persons with normal blood glucose. Further studies are warranted to clarify the specific role age
Sadlon A, Takousis P, Evangelou E, et al., 2023, Association of Blood MicroRNA Expression and Polymorphisms with Cognitive and Biomarker Changes in Older Adults, Journal of Prevention of Alzheimer's Disease, ISSN: 2274-5807
Background: Identifying individuals before the onset of overt symptoms is key in the prevention of Alzheimer’s disease (AD). Objkectives: Investigate the use of miRNA as early blood-biomarker of cognitive decline in older adults. Design: Cross-sectional. Setting: Two observational cohorts (CHARIOT-PRO, Alzheimer’s Disease Neuroimaging Initiative (ADNI)). Participants: 830 individuals without overt clinical symptoms from CHARIOT-PRO and 812 individuals from ADNI. Measurements: qPCR analysis of a prioritised set of 38 miRNAs in the blood of individuals from CHARIOT-PRO, followed by a brain-specific functional enrichment analysis for the significant miRNAs. In ADNI, genetic association analysis for polymorphisms within the significant miRNAs’ genes and CSF levels of phosphorylated-tau, total-tau, amyloid-β42, soluble-TREM2 and BACE1 activity using whole genome sequencing data. Post-hoc analysis using multi-omics datasets. Results: Six miRNAs (hsa-miR-128-3p, hsa-miR-144-5p, hsa-miR-146a-5p, hsa-miR-26a-5p, hsa-miR-29c-3p and hsa-miR-363-3p) were downregulated in the blood of individuals with low cognitive performance on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The pathway enrichment analysis indicated involvement of apoptosis and inflammation, relevant in early AD stages. Polymorphisms within genes encoding for hsa-miR-29c-3p and hsa-miR-146a-5p were associated with CSF levels of amyloid-β42, soluble-TREM2 and BACE1 activity, and 21 variants were eQTL for hippocampal MIR29C expression. Conclusions: six miRNAs may serve as potential blood biomarker of subclinical cognitive deficits in AD. Polymorphisms within these miRNAs suggest a possible interplay between the amyloid cascade and microglial activation at preclinical stages of AD.
Middleton LT, Riboli E, 2023, Dietary Cholesterol and Dementia Risk, Journal of Prevention of Alzheimer's Disease, ISSN: 2274-5807
Middleton LT, Touchon J, Vellas B, 2023, Editorial: What Is Reasonable and Necessary for Alzheimer Patients from Randomized Clinical Trials to Clinical Practice?, J Prev Alzheimers Dis, Vol: 10, Pages: 331-332
Charpignon M-L, Vakulenko-Lagun B, Zheng B, et al., 2022, Causal inference in medical records and complementary systems pharmacology for metformin drug repurposing towards dementia., Nat Commun, Vol: 13
Metformin, a diabetes drug with anti-aging cellular responses, has complex actions that may alter dementia onset. Mixed results are emerging from prior observational studies. To address this complexity, we deploy a causal inference approach accounting for the competing risk of death in emulated clinical trials using two distinct electronic health record systems. In intention-to-treat analyses, metformin use associates with lower hazard of all-cause mortality and lower cause-specific hazard of dementia onset, after accounting for prolonged survival, relative to sulfonylureas. In parallel systems pharmacology studies, the expression of two AD-related proteins, APOE and SPP1, was suppressed by pharmacologic concentrations of metformin in differentiated human neural cells, relative to a sulfonylurea. Together, our findings suggest that metformin might reduce the risk of dementia in diabetes patients through mechanisms beyond glycemic control, and that SPP1 is a candidate biomarker for metformin's action in the brain.
Dobricic V, Schilling M, Farkas I, et al., 2022, Common signatures of differential microRNA expression in Parkinson's and Alzheimer's disease brains, BRAIN COMMUNICATIONS, Vol: 4
Vamos EP, Lai H, Sharabiani M, et al., 2022, Cardio-metabolic factors and risk of dementia in people with type 2 diabetes in England: a large retrospective cohort study, DUK, Publisher: SPRINGER, Pages: S402-S403, ISSN: 0012-186X
Lai H, Sharma A, Chang K, et al., 2022, COMPARISON OF SEX-SPECIFIC HISTORICAL CARDIOMETABOLIC TRAJECTORIES IN T2D PATIENTS BY DEMENTIA STATUS IN ENGLAND, DUK, Publisher: BMJ PUBLISHING GROUP, Pages: A1-A2, ISSN: 0143-005X
Zheng B, Udeh-Momoh C, Watermeyer T, et al., 2022, Practice effect of repeated cognitive tests among older adults: associations with brain amyloid pathology and other influencing factors., Frontiers in Neuroscience, Vol: 14, ISSN: 1662-453X
Background: Practice effects (PE), after repeated cognitive measurements, may mask cognitive decline and represent a challengein clinical and research settings. However, an attenuated practice effect may indicate the presence of brain pathologies. This studyaimed to evaluate practice effects on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scale, andtheir associations with brain amyloid status and other factors in a cohort of cognitively unimpaired older adults enrolled in theCHARIOT-PRO SubStudy.Methods: 502 cognitively unimpaired participants aged 60-85 years were assessed with RBANS in both screening and baseline clinicvisits using alternate versions (median time gap of 3.5 months). We tested PE based on differences between test and retest scoresin total scale and domain-specific indices. Multiple linear regressions were used to examine factors influencing PE, after adjustingfor age, sex, education level, APOE‐ε4 carriage and initial RBANS score. The latter and PE were also evaluated as predictors foramyloid positivity status based on defined thresholds, using logistic regression.Results: Participants’ total scale, immediate memory and delayed memory indices were significantly higher in the second test thanin the initial test (Cohen’s dz = 0.48, 0.70 and 0.35, P < 0.001). On the immediate memory index, the PE was significantly lower inthe amyloid positive group than the amyloid negative group (P = 0.022). Older participants (≥ 70 years), women, non‐APOE‐ε4carriers, and those with worse initial RBANS test performance had larger PE. No associations were found between brain MRIparameters and PE. In addition, attenuated practice effects in immediate or delayed memory index were independent predictorsfor amyloid positivity (P < 0.05).Conclusion: Significant practice effects on RBANS total scale and memory indices were identified in cognitively unimpaired olderadults. The association with amyloid sta
Lai H, Sharma A, Chang K, et al., 2022, Historical cardiometabolic trajectories in T2D patients by dementia status in England by sex, ethnicity, and deprivation, DUK, Publisher: ELSEVIER IRELAND LTD, ISSN: 0168-8227
Sharma A, Lai H, Chang K, et al., 2022, A 20-year follow-up of cardiometabolic trajectories amongst individuals with type 2 diabetes before dementia diagnosis by ethnic group, DUK, Publisher: WILEY, ISSN: 0742-3071
Abbott K, Posma JM, Garcia Perez I, et al., 2022, Evidence-Based Tools for Dietary Assessments in Nutrition Epidemiology Studies for Dementia Prevention, The journal of prevention of Alzheimer's disease, ISSN: 2274-5807
Increasing evidence proposes diet as a notable modifiable factor and viable target for the reduction of Alzheimer’s Disease risk and age-related cognitive decline. However, assessment of dietary exposures is challenged by dietary capture methods that are prone to misreporting and measurement errors. The utility of -omics technologies for the evaluation of dietary exposures has the potential to improve reliability and offer new insights to pre-disease indicators and preventive targets in cognitive aging and dementia. In this review, we present a focused overview of metabolomics as a validation tool and framework for investigating the immediate or cumulative effects of diet on cognitive health.
Price G, Udeh-Momoh C, Kivipelto M, et al., 2022, Dementia Prevention: A Global Challenge in Urgent Need of Solutions, JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE, Vol: 9, Pages: 1-2, ISSN: 2274-5807
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Zheng B, Su B, Udeh-Momoh C, et al., 2022, Associations of cardiovascular and non-cardiovascular comorbidities with dementia risk in patients with diabetes: results from a large UK cohort study, JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE, Vol: 9, Pages: 86-91, ISSN: 2274-5807
BackgroundType 2 diabetes (T2D) is an established risk factor for dementia. However, it remains unclear whether the presence of comorbidities could further increase dementia risk in diabetes patients.ObjectivesTo examine the associations between cardiovascular and non-cardiovascular comorbidities and dementia risk in T2D patients.DesignPopulation-based cohort study.SettingThe UK Clinical Practice Research Datalink (CPRD).Participants489,205 T2D patients aged over 50 years in the UK CPRD.MeasurementsMajor cardiovascular and non-cardiovascular comorbidities were extracted as time-varying exposure variables. The outcome event was dementia incidence based on dementia diagnosis or dementia-specific drug prescription.ResultsDuring a median of six years follow-up, 33,773 (6.9%) incident dementia cases were observed. Time-varying Cox regressions showed T2D patients with stroke, peripheral vascular disease, atrial fibrillation, heart failure or hypertension were at higher risk of dementia compared to those without such comorbidities (HR [95% CI] = 1.64 [1.59–1.68], 1.37 [1.34–1.41], 1.26 [1.22–1.30], 1.15 [1.11–1.20] or 1.10 [1.03–1.18], respectively). Presence of chronic obstructive pulmonary disease or chronic kidney disease was also associated with increased dementia risk (HR [95% CI] = 1.05 [1.01–1.10] or 1.11 [1.07–1.14]).ConclusionsA range of cardiovascular and non-cardiovascular comorbidities were associated with further increases of dementia risk in T2D patients. Prevention and effective management of these comorbidities may play a significant role in maintaining cognitive health in T2D patients.
De Natale ER, Wilson H, Udeh-Momoh C, et al., 2022, How molecular imaging studies can disentangle disease mechanisms in age-related neurodegenerative disorders, Aging: From Fundamental Biology to Societal Impact, Pages: 455-492, ISBN: 9780128241318
The population aged over 65 is growing fast worldwide, and is predicted to reach 1.5 billion by the year 2050. In parallel, relentlessly progressive neurodegenerative diseases, including Alzheimer’s disease and other late-onset dementias, Parkinson’s disease and other movement disorders affect elderly individuals and are emerging as a major socioeconomic and healthcare challenge. Neurodegeneration is a long process preceding clinical symptomatology by decades, where aging is the most important risk factor. In search for solutions and new therapies, the attention towards neurodegenerative diseases is shifting from the description of clinical symptoms and signs to the characterization of biological alterations spanning across the disease continuum, including the preclinical stages. In vivo neuroimaging with positron emission tomography and magnetic resonance imaging have contributed remarkably to elucidating the pathogenic and pathophysiological mechanisms underpinning neurodegenerative conditions, characterizing biomarkers of neurodegeneration and facilitating the individuation of therapeutic targets and early drug development. As such, these in vivo imaging technologies carry the promise of significantly contributing to the advancement of the precision medicine model in this group of late-onset diseases. This chapter reviews the advances of in vivo molecular imaging in investigating the biological mechanisms of aging and age-related neurodegeneration, with a perspective towards the translation of state-of-the-art neuroimaging technologies to a more precise phenotypic characterization of patients, assisting in the discovery and development of novel and efficacious medicines, based on innovative clinical trials with clinically meaningful outcome measures. This ultimately improves clinical management, quality of life and a better prognosis to future sufferers of these debilitating diseases of old age.
Ford J, Kafetsouli D, wilson H, et al., 2022, At a Glance: An Update on Neuroimaging and Retinal Imaging in Alzheimer’s Disease and Related Research, The journal of prevention of Alzheimer's disease, ISSN: 2274-5807
Udeh-Momoh C, Zheng B, Sandebring-Matton A, et al., 2021, Blood Derived Amyloid Biomarkers for Alzheimer's Disease Prevention, JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE, Vol: 9, Pages: 12-21, ISSN: 2274-5807
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Udeh-Momoh C, Watermeyer T, Sindi S, et al., 2021, Health, lifestyle and psycho-social determinants of poor sleep quality during the Early Phase of the COVID-19 pandemic: a focus on UK older adults deemed clinically extremely vulnerable, Frontiers in Public Health, Vol: 9, Pages: 1-11, ISSN: 2296-2565
Background: Several studies have assessed the impact of COVID-19-relatedlockdownson sleep quality across global populations. However, no study to date has specifically assessed at-riskpopulations, particularly those at highest risk of complications from coronavirus infection deemed “clinically-extremely-vulnerable-(COVID-19CEV)” [as defined by Public Health England, 2020].Methods: In this cross-sectional study, we surveyed 5,558 adults aged ≥50 years (of whom 523 met criteria for COVID-19CEV) during the first pandemic wave that resulted in a nationwide-lockdown (April-June 2020) with assessments of sleep quality (an adapted sleep scale that captured multiple sleep indices before and during the lockdown), health/medical, lifestyle, psychosocial and socio demographic factors. We examined associations between these variablesand sleep quality;and explored interactions of COVID-19CEV status with significant predictors of poor sleep,to identify potential moderating factors. Results: 37% of participants reported poor sleep quality which was associated with younger age, female sex and multimorbidity. Significant associations with poor sleep included health/medical factors: COVID-19 CEV status, higher BMI, arthritis, pulmonary disease, and mental health disorders; and the following lifestyle and psychosocial factors: living alone, higher alcohol consumption, an unhealthy diet and higher depressive and anxiety symptoms. Moderators of the negative relationship between COVID-19 CEV status and good sleep quality were marital status, loneliness, anxiety and diet. Within this subgroup, less anxious and less lonely males, as well as females with healthier diets, reported better sleep. Conclusions: Sleep quality in older adults was compromised during the sudden unprecedented nation-wide lockdown due to distinct modifiable factors. An important contribution of our study is the assessment of a &ldquo
Ahmadi Abhari S, Bandosz P, Kivimaki M, et al., 2021, Impact of COVID19 on years of life lost with and without disability across 18 European-countries, World Congress of Epidemiology (WCE)
Lai H, Chang K, Sharabiani M, et al., 2021, 19-YEAR TRAJECTORIES OF CARDIO-METABOLIC FACTORS AMONG PATIENTS WITH TYPE 2 DIABETES BY DEMENTIA STATUS IN ENGLAND, EDC, Publisher: BMJ PUBLISHING GROUP, Pages: A12-A12, ISSN: 0143-005X
Salman D, Beaney T, Robb C, et al., 2021, The impact of social restrictions during the COVID-19 pandemic on the physical activity levels of adults aged 50-92 years: a baseline survey of the CHARIOT COVID-19 Rapid Response prospective cohort study, BMJ Open, Vol: 11, Pages: 1-12, ISSN: 2044-6055
Objectives: Physical inactivity is more common in older adults, is associated with social isolation and loneliness, and contributes to increased morbidity and mortality. We examined the effect of social restrictions to reduce COVID-19 transmission in the UK (lockdown), on physical activity (PA) levels of older adults, and the social predictors of any change.Design: Baseline analysis of a survey-based prospective cohort study Setting: Adults enrolled in the Cognitive Health in Ageing Register for Investigational and Observational Trials (CHARIOT) cohort from General Practitioner (GP) practices in North West London were invited to participate from April to July 2020.Participants: 6,219 cognitively healthy adults aged 50 to 92 years completed the survey.Main outcome measures: Self-reported PA before and after the introduction of lockdown, as measured by Metabolic Equivalent of Task (MET) minutes. Associations of PA with demographic, lifestyle and social factors, mood and frailty.Results: Mean PA was significantly lower following the introduction of lockdown, from 3,519 MET minutes/week to 3,185 MET minutes/week (p<0.001). After adjustment for confounders and pre-lockdown PA, lower levels of PA after the introduction of lockdown were found in those who were over 85 years old (640 [95% CI: 246 to 1034] MET minutes/week less); were divorced or single (240 [95% CI: 120 to 360] MET minutes/week less); living alone (277 [95% CI: 152 to 402] MET minutes/week less); reported feeling lonely often (306 [95% CI: 60 to 552] MET minutes/week less); and showed symptoms of depression (1007 [95% CI: 1401 to 612] MET minutes/week less) compared to those aged 50-64 years, married, co-habiting, and not reporting loneliness or depression, respectively. Conclusions and Implications: Markers of social isolation, loneliness and depression were associated with lower PA following the introduction of lockdown in the UK. Targeted interventions to increase PA in these groups should be consid
Zheng B, Su B, Price G, et al., 2021, Glycemic control, diabetic complications, and risk of dementia in patients with diabetes: results from a large UK cohort study, Diabetes Care, Vol: 44, Pages: 1556-1563, ISSN: 0149-5992
OBJECTIVE Type 2 diabetes is an established risk factor for dementia. However, the roles of glycemic control and diabetic complications in the development of dementia have been less well substantiated. This large-scale cohort study aims to examine associations of longitudinal HbA1c levels and diabetic complications with the risk of dementia incidence among patients with type 2 diabetes.RESEARCH DESIGN AND METHODS Data of eligible patients with diabetes, aged ≥50 years in the U.K. Clinical Practice Research Datalink from 1987 to 2018, were analyzed. Time-varying Cox regressions were used to estimate adjusted hazard ratios (HRs) and 95% CIs for dementia risk.RESULTS Among 457,902 patients with diabetes, 28,627 (6.3%) incident dementia cases were observed during a median of 6 years’ follow-up. Patients with recorded hypoglycemic events or microvascular complications were at higher risk of dementia incidence compared with those without such complications (HR 1.30 [95% CI 1.22–1.39] and 1.10 [1.06–1.14], respectively). The HbA1c level, modeled as a time-varying exposure, was associated with increased dementia risk (HR 1.08 [95% CI 1.07–1.09] per 1% HbA1c increment) among 372,287 patients with diabetes with postdiagnosis HbA1c records. Similarly, a higher coefficient of variation of HbA1c during the initial 3 years of follow-up was associated with higher subsequent dementia risk (HR 1.03 [95% CI 1.01–1.04] per 1-SD increment).CONCLUSIONS Higher or unstable HbA1c levels and the presence of diabetic complications in patients with type 2 diabetes are associated with increased dementia risk. Effective management of glycemia might have a significant role in maintaining cognitive health among older adults with diabetes.
Burns DK, Alexander RC, Welsh-Bohmer KA, et al., 2021, Safety and efficacy of pioglitazone for the delay of cognitive impairment in people at risk of Alzheimer's disease (TOMMORROW): a prognostic biomarker study and a phase 3, randomised, double-blind, placebo-controlled trial, LANCET NEUROLOGY, Vol: 20, Pages: 537-547, ISSN: 1474-4422
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Udeh-Momoh CT, Watermeyer T, Price G, et al., 2021, Protocol of the cognitive health in ageing register: investigational, observational and trial studies in dementia research (CHARIOT): prospective readiness cOhort (PRO) SubStudy., BMJ Open, Vol: 11, Pages: 1-12, ISSN: 2044-6055
INTRODUCTION: The Cognitive Health in Ageing Register: Investigational, Observational and Trial Studies in Dementia Research (CHARIOT): Prospective Readiness cOhort (PRO) SubStudy (CPSS), sponsored by Janssen Pharmaceutical Research & Development LLC, is an Alzheimer's disease (AD) biomarker enriched observational study that began 3 July 2015 CPSS aims to identify and validate determinants of AD, alongside cognitive, functional and biological changes in older adults with or without detectable evidence of AD pathology at baseline. METHODS AND ANALYSIS: CPSS is a dual-site longitudinal cohort (3.5 years) assessed quarterly. Cognitively normal participants (60-85 years) were recruited across Greater London and Edinburgh. Participants are classified as high, medium (amnestic or non-amnestic) or low risk for developing mild cognitive impairment-Alzheimer's disease based on their Repeatable Battery for the Assessment of Neuropsychological Status performance at screening. Additional AD-related assessments include: a novel cognitive composite, the Global Preclinical Alzheimer's Cognitive Composite, brain MRI and positron emission tomography and cerebrospinal fluid analysis. Lifestyle, other cognitive and functional data, as well as biosamples (blood, urine, and saliva) are collected. Primarily, study analyses will evaluate longitudinal change in cognitive and functional outcomes. Annual interim analyses for descriptive data occur throughout the course of the study, although inferential statistics are conducted as required. ETHICS AND DISSEMINATION: CPSS received ethical approvals from the London-Central Research Ethics Committee (15/LO/0711) and the Administration of Radioactive Substances Advisory Committee (RPC 630/3764/33110) The study is at the forefront of global AD prevention efforts, with frequent and robust sampling of the well-characterised cohort, allowing for detection of incipient pathophysiological, cognitive and functional changes that could inform therape
Vamos EP, Lai H, Sharabiani M, et al., 2021, 20-year trajectories of cardiometabolic factors among patients with type 2 diabetes before diagnosis of dementia in England, DUK, Publisher: WILEY, ISSN: 0742-3071
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