Publications
250 results found
Korologou-Linden R, Kalsi J, Kafetsouli D, et al., 2024, Novel Blood-Based Biomarkers and Disease Modifying Therapies for Alzheimer's Disease. Are we Ready for the New Era?, The Journal of prevention of Alzheimer's disease, ISSN: 2426-0266
Barbera M, Lehtisalo J, Perera D, et al., 2024, A multimodal precision-prevention approach combining lifestyle intervention with metformin repurposing to prevent cognitive impairment and disability: the MET-FINGER randomised controlled trial protocol., Alzheimers Res Ther, Vol: 16
BACKGROUND: Combining multimodal lifestyle interventions and disease-modifying drugs (novel or repurposed) could provide novel precision approaches to prevent cognitive impairment. Metformin is a promising candidate in view of the well-established link between type 2 diabetes (T2D) and Alzheimer's Disease and emerging evidence of its potential neuro-protective effects (e.g. vascular, metabolic, anti-senescence). MET-FINGER aims to test a FINGER 2.0 multimodal intervention, combining an updated FINGER multidomain lifestyle intervention with metformin, where appropriate, in an APOE ε4-enriched population of older adults (60-79 years) at increased risk of dementia. METHODS: MET-FINGER is an international randomised, controlled, parallel-group, phase-IIb proof-of-concept clinical trial, where metformin is included through a trial-within-trial design. 600 participants will be recruited at three sites (UK, Finland, Sweden). Participants at increased risk of dementia based on vascular risk factors and cognitive screening, will be first randomised to the FINGER 2.0 intervention (lifestyle + metformin if eligible; active arm) or to receive regular health advice (control arm). Participants allocated to the FINGER 2.0 intervention group at risk indicators of T2D will be additionally randomised to receive metformin (2000 mg/day or 1000 mg/day) or placebo. The study duration is 2 years. The changes in global cognition (primary outcome, using a Neuropsychological Test Battery), memory, executive function, and processing speed cognitive domains; functional status; lifestyle, vascular, metabolic, and other dementia-related risk factors (secondary outcomes), will be compared between the FINGER 2.0 intervention and the control arm. The feasibility, potential interaction (between-groups differences in healthy lifestyle changes), and disease-modifying effects of the lifestyle-metformin combination will be exploratory outcomes. The lifestyle int
Barbera M, Perera D, Matton A, et al., 2023, Multimodal Precision Prevention - A New Direction in Alzheimer's Disease, JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE, Vol: 10, Pages: 718-728, ISSN: 2274-5807
Green C, Beaney T, Salman D, et al., 2023, The impacts of social restrictions during the COVID-19 pandemic on the physical activity levels of over 50-year olds: The CHARIOT COVID-19 Rapid Response (CCRR) cohort study., PLoS One, Vol: 18, ISSN: 1932-6203
OBJECTIVES: To quantify the associations between shielding status and loneliness at the start of the COVID-19 pandemic, and physical activity (PA) levels throughout the pandemic. METHODS: Demographic, health and lifestyle characteristics of 7748 cognitively healthy adults aged >50, and living in London, were surveyed from April 2020 to March 2021. The International Physical Activity Questionnaire (IPAQ) short-form assessed PA before COVID-19 restrictions, and up to 6 times over 11 months. Linear mixed models investigated associations between shielding status and loneliness at the onset of the pandemic, with PA over time. RESULTS: Participants who felt 'often lonely' at the outset of the pandemic completed an average of 522 and 547 fewer Metabolic Equivalent of Task (MET) minutes/week during the pandemic (95% CI: -809, -236, p<0.001) (95% CI: -818, -275, p<0.001) than those who felt 'never lonely' in univariable and multivariable models adjusted for demographic factors respectively. Those who felt 'sometimes lonely' completed 112 fewer MET minutes/week (95% CI: -219, -5, p = 0.041) than those who felt 'never lonely' following adjustment for demographic factors. Participants who were shielding at the outset of the pandemic completed an average of 352 fewer MET minutes/week during the pandemic than those who were not (95% CI: -432, -273; p<0.001) in univariable models and 228 fewer MET minutes/week (95% CI: -307, -150, p<0.001) following adjustment for demographic factors. No significant associations were found after further adjustment for health and lifestyle factors. CONCLUSIONS: Those shielding or lonely at pandemic onset were likely to have completed low levels of PA during the pandemic. These associations are influenced by co-morbidities and health status.
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, MOVEMENT DISORDERS, ISSN: 0885-3185
Sadlon A, Takousis P, Evangelou E, et al., 2023, Association of Blood MicroRNA Expression and Polymorphisms with Cognitive and Biomarker Changes in Older Adults, JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE, ISSN: 2274-5807
Middleton LT, Touchon J, Vellas B, 2023, What Is Reasonable and Necessary for Alzheimer Patients from Randomized Clinical Trials to Clinical Practice?, JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE, Vol: 10, Pages: 331-332, ISSN: 2274-5807
Rolland Y, Sierra F, Ferrucci L, et al., 2023, Challenges in developing Geroscience trials, NATURE COMMUNICATIONS, Vol: 14
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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 & DEMENTIA, ISSN: 1552-5260
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.
Middleton LT, Riboli E, 2023, Dietary Cholesterol and Dementia Risk, JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE, ISSN: 2274-5807
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
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, NATURE COMMUNICATIONS, Vol: 13
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- Citations: 9
Novak G, Baker S, Karcher K, et al., 2022, P160 - Clinical trajectory of preclinical AD over 36 months in the chariot study, 15th Clinical Trials on Alzheimer’s Disease Conference, Publisher: Springer, ISSN: 2274-5807
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
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- Citations: 2
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.
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.
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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Udeh-Momoh C, Zheng B, Sandebring-Matton A, et al., 2022, 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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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, 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
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