235 results found
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., Eur J Epidemiol
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.
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
- Author Web Link
- Citations: 1
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
- Author Web Link
- Citations: 6
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
- Author Web Link
- Citations: 25
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
Nalder L, Zheng B, Chiandet G, et al., 2021, Vitamin B12 and folate status in cognitively healthy older adults and associations with cognitive performance, Journal of Nutrition, Health and Aging, Vol: 25, Pages: 287-294, ISSN: 1279-7707
Objectives: To determine prevalence of vitamin B12 and folate deficiency and associations with cognitive performance in participants recruited for the Cognitive Health in Ageing Register: Investigational, Observational, and Trial Studies in Dementia Research: Prospective Readiness cOhort Study (CHARIOTPRO) SubStudy (CPRO-SS). Design: Cross-sectional analysis of data collected in the screening phase for the CPRO-SS. Setting: Participants were recruited from the Chariot Register at Imperial College London comprising approximately 39,000 community dwelling volunteers. Participants: Community dwelling individuals aged 60-85 years with B vitamin biomarker measures available were included (n=1946). After medical history and other exclusions, 1347 cognitively healthy participants were included for analysis of cognitive data. Measurements: Cognitive status was assessed with the Repeatable Battery for Neuropsychological Status (RBANS). Assays included vitamin B12 and folate, followed by serum methylmalonic acid and homocysteine levels for those with low vitamin B12. Gender-specific linear regression analysis was performed for associations between cognition and biomarkers. Non-gender specific regression for groups graded by B vitamin deficiency severity were also performed. Results: Vitamin B12 deficiency (<148pmol/L) was found in 17.2% of individuals and folate deficiency (<10nmol/L) in 1% of our participants. Low vitamin B12 was associated with poorer memory (p<0.03) in men. A high BMI predicted poorer attention and visuospatial indices (p<0.05). A regression analysis by B12 level revealed associations with poorer attention (β -6.46; p=0.004) for the deficient group and with immediate memory (β -2.99; p=0.019) for those categorised as severely deficient. Conclusion: Older men and women are pro
Wilson H, Politis M, Rabiner E, et al., 2020, Novel PET biomarkers to disentangle molecular pathways across age-related neurodegenerative diseases, Cells, Vol: 9, ISSN: 2073-4409
There is a need to disentangle the etiological puzzle of age-related neurodegenerative diseases, whose clinical phenotypes arise from known, and as yet unknown, pathways that can act distinctly or in concert. Enhanced sub-phenotyping and the identification of in vivo biomarker-driven signature profiles could improve the stratification of patients into clinical trials and, potentially, help to drive the treatment landscape towards the precision medicine paradigm. The rapidly growing field of neuroimaging offers valuable tools to investigate disease pathophysiology and molecular pathways in humans, with the potential to capture the whole disease course starting from preclinical stages. Positron emission tomography (PET) combines the advantages of a versatile imaging technique with the ability to quantify, to nanomolar sensitivity, molecular targets in vivo. This review will discuss current research and available imaging biomarkers evaluating dysregulation of the main molecular pathways across age-related neurodegenerative diseases. The molecular pathways focused on in this review involve mitochondrial dysfunction and energy dysregulation; neuroinflammation; protein misfolding; aggregation and the concepts of pathobiology, synaptic dysfunction, neurotransmitter dysregulation and dysfunction of the glymphatic system. The use of PET imaging to dissect these molecular pathways and the potential to aid sub-phenotyping will be discussed, with a focus on novel PET biomarkers.
Peters S, Broberg K, Gallo V, et al., 2020, Blood metal levels and amyotrophic lateral sclerosis risk: a prospective cohort, Annals of Neurology, Vol: 89, Pages: 125-133, ISSN: 0364-5134
ObjectiveMetals have been suggested as a risk factor for amyotrophic lateral sclerosis (ALS), but only retrospective studies are available to date. We compared metal levels in prospectively collected blood samples from ALS patients and controls, to explore whether metals are associated with ALS mortality.MethodsA nested ALS case–control study was conducted within the prospective EPIC (European Prospective Investigation into Cancer and Nutrition) cohort. Cases were identified through death certificates. We analyzed metal levels in erythrocyte samples obtained at recruitment, as a biomarker for metal exposure from any source. Arsenic, cadmium, copper, lead, manganese, mercury, selenium, and zinc concentrations were measured by inductively coupled plasma–mass spectrometry. To estimate ALS risk, we applied conditional logistic regression models.ResultsThe study population comprised 107 cases (65% female) and 319 controls matched for age, sex, and study center. Median time between blood collection and ALS death was 8 years (range = 1–15). Comparing the highest with the lowest tertile, cadmium (odds ratio [OR] = 2.04, 95% confidence interval [CI] = 1.08–3.87) and lead (OR = 1.89, 95% CI = 0.97–3.67) concentrations suggest associations with increased ALS risk. Zinc was associated with a decreased risk (OR = 0.50, 95% CI = 0.27–0.94). Associations for cadmium and lead remained when limiting analyses to noncurrent smokers.InterpretationThis is the first study to compare metal levels before disease onset, minimizing reverse causation. The observed associations suggest that cadmium, lead, and zinc may play a role in ALS etiology. Cadmium and lead possibly act as intermediates on the pathway from smoking to ALS. ANN NEUROL 20209999:n/a–n/a
Zheng B, Su B, Tzoulaki I, et al., 2020, Glycaemic control, diabetic complications, and risk of dementia among 0.5 million diabetes patients: a cohort study using the UK clinical practice research datalink, Annals of Neurology, Vol: 88, Pages: S97-S98, ISSN: 0364-5134
Ford J, Zheng B, Hurtado B, et al., 2020, Strategy or symptom: semantic clustering and risk of Alzheimer's disease-related impairment, Journal of Clinical and Experimental Neuropsychology, Vol: 42, Pages: 849-856, ISSN: 1380-3395
Alzheimer's disease (AD) is the most common form of dementia, impacting global cognitive performance, including episodic memory. Semantic clustering is a learning strategy involving grouping words of similar meaning and can improve episodic memory performance, e.g., list learning. As the APOE ε4 allele is the most validated genetic risk factor for AD, we predicted that its presence would be associated with poorer list learning performance, and we hypothesized that semantic clustering moderates or mediates this association. The sample comprised 699 healthy older adults participating in the CHARIOT PRO Main Study, 169 of whom were APOE ε4 carriers. Participants' ability to form groups of related stimuli (assessed via a categorization task, CAT), and their use of semantic clustering during list learning, were investigated using the Neuropsychological Assessment Battery (NAB). CAT scores predicted the use of semantic clustering in, and performance on, the list learning task. CAT scores were not significantly lower in APOE ε4 carriers, suggesting that the ability to categorize was preserved. However, APOE ε4 carriers made less use of semantic clustering in list learning. Semantic clustering use partially mediated the relationship between CAT scores and list learning performance, and, in women only, moderated the impact of APOE ε4 on list learning performance. The results suggest that better categorization ability is associated with greater use of mnemonic strategies and better performance on memory tasks regardless of genetic risk, but that APOE ε4 carriers make less use of such strategies. Furthermore, female APOE ε4 carriers may benefit more than their non-carriers from using semantic clustering to aid list learning. Thus, semantic clustering may be a contributing factor of their "cognitive reserve", compensating for potential deficits in episodic memory.
Zheng B, Tal R, Yang Z, et al., 2020, Cortisol hypersecretion and the risk of Alzheimer’s disease: A systematic review and meta-analysis, Ageing Research Reviews, Vol: 64, Pages: 1-11, ISSN: 1568-1637
BackgroundMorning cortisol levels have been reported to be elevated among patients with Alzheimer’s disease (AD); yet no meta-analysis has been conducted to confirm the existence and magnitude of this association. It also remains unclear whether hypercortisolism is a risk factor for AD.MethodsPubMed, EMBASE, and PsycINFO were systematically searched for eligible studies. Cross-sectional data were pooled using random-effects meta-analyses; the differences in morning cortisol levels between patients and cognitively normal controls were quantified. Longitudinal studies were qualitatively synthesised due to methodological heterogeneity.Results17,245 participants from 57 cross-sectional studies and 19 prospective cohort studies were included. Compared with cognitively normal controls, AD patients had moderately increased morning cortisol in blood (g = 0.422, P < 0.001; I2 = 48.5 %), saliva (g = 0.540, P < 0.001; I2 = 13.6 %), and cerebrospinal fluids (g = 0.565, P = 0.003; I2 = 75.3 %). A moderate elevation of morning cortisol was also detected in cerebrospinal fluids from patients with mild cognitive impairment (MCI) versus controls (g = 0.309, P = 0.001; I2 = 0.0 %). Cohort studies suggested that higher morning cortisol may accelerate cognitive decline in MCI or mild AD patients, but the results in cognitively healthy adults were inconsistent.ConclusionsMorning cortisol was confirmed to be moderately elevated in AD patients and may have diagnostic and prognostic values for AD.
Robb C, Loots C, Ahmadi-Abhari S, et al., 2020, Associations of social isolation with anxiety and depression during the early COVID-19 Pandemic: a survey of older adults in London, UK, Frontiers in Psychiatry, Vol: 11, Pages: 1-12, ISSN: 1664-0640
The COVID-19 pandemic is imposing a profound negative impact on the health and wellbeing of societies and individuals, worldwide. One concern is the effect of social isolation as a result of social distancing on the mental health of vulnerable populations, including older people.Within six weeks of lockdown, we initiated the CHARIOT COVID-19 Rapid Response Study, a bespoke survey of cognitively healthy older people living in London,to investigate the impact of COVID-19 and associated social isolation on mental and physical wellbeing. The sample was drawn from CHARIOT, a register of people over 50 who have consented to be contacted for ageing related research. A total of 327,127 men and women (mean age=70.7 [SD=7.4]) participated in the baseline survey, May-July 2020. Participants were asked about changes to the 14 components of the Hospital Anxiety Depression scale (HADS) after lockdown was introduced in the UK,on 23rd March. A total of 12.8% of participants reported feeling worse on the depression components of HADS (7.8% men and 17.3% women) and 3612.3% reported feeling worse on the anxiety components (7.8% men and 16.5% women). Fewer participants reported feeling improved (1.5% for depression and 4.9% for anxiety). Women, younger participants, those single/widowed/divorced, reporting poor sleep, feelings of loneliness and who reported living alone were more likely to indicate feeling worse on both the depression and/or anxiety components of the HADS. There was a significant negative association between subjective loneliness and worsened components of both depression (OR 17.24, 95% CI 13.20, 22.50) and anxiety (OR 10.85, 95% CI 8.39, 14.03). Results may inform targeted interventions and help guide policy recommendations in reducing the effects of social isolation related to the pandemic, and beyond, on the mental health of older people.
Wilson H, Pagano G, de Natale ER, et al., 2020, Mitochondrial complex 1, sigma 1, and synaptic vesicle 2A in early drug-naive Parkinson's Disease, Movement Disorders, Vol: 35, Pages: 1416-1427, ISSN: 0885-3185
BackgroundDysfunction of mitochondrial energy generation may contribute to neurodegeneration, leading to synaptic loss in Parkinson's disease (PD). The objective of this study was to find cross‐sectional and longitudinal changes in PET markers of synaptic vesicle protein 2A, sigma 1 receptor, and mitochondrial complex 1 in drug‐naive PD patients.MethodsTwelve early drug‐naive PD patients and 16 healthy controls underwent a 3‐Tesla MRI and PET imaging to quantify volume of distribution of [11C]UCB‐J, [11C]SA‐4503, and [18F]BCPP‐EF for synaptic vesicle protein 2A, sigma 1 receptor, and mitochondrial complex 1, respectively. Nine PD patients completed approximately 1‐year follow‐up assessments.ResultsReduced [11C]UCB‐J volume of distribution in the caudate, putamen, thalamus, brain stem, and dorsal raphe and across cortical regions was observed in drug‐naive PD patients compared with healthy controls. [11C]UCB‐J volume of distribution was reduced in the locus coeruleus and substantia nigra but did not reach statistical significance. No significant differences were found in [11C]SA‐4503 and [18F]BCPP‐EF volume of distribution in PD compared with healthy controls. Lower brain stem [11C]UCB‐J volume of distribution correlated with Movement Disorder Society Unified Parkinson's Disease Rating Scale part III and total scores. No significant longitudinal changes were identified in PD patients at follow‐up compared with baseline.ConclusionsOur findings represent the first in vivo evidence of mitochondrial, endoplasmic reticulum, and synaptic dysfunction in drug‐naive PD patients. Synaptic dysfunction likely occurs early in disease pathophysiology and has relevance to symptomatology. Mitochondrial complex 1 and sigma 1 receptor pathology warrants further investigations in PD. Studies in larger cohorts with longer follow‐up will determine the validity of these PET markers to track disease progression. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, In
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