A comparison between early presentation of dementia with Lewy Bodies, Alzheimer's disease and Parkinson's disease: evidence from routine primary care and UK Biobank data

OBJECTIVE: To simultaneously contrast prediagnostic clinical characteristics of individuals with a final diagnosis of dementia with Lewy Bodies, Parkinson's disease, Alzheimer's disease compared to controls without neurodegenerative disorders. METHODS: Using the longitudinal THIN database in the UK, we tested the association of each neurodegenerative disorder with a selected list of symptoms and broad families of treatments, and compared the associations between disorders to detect disease-specific effects. We replicated the main findings in the UK Biobank. RESULTS: We used data of 28,222 patients with PD, 20,214 with AD, 4,682 with DLB and 20,214 controls. All neurodegenerative disorders were significantly associated with the presence of multiple clinical characteristics before their diagnosis including sleep disorders, falls, psychiatric symptoms and autonomic dysfunctions. When comparing DLB patients with patients with PD and AD patients, falls, psychiatric symptoms and autonomic dysfunction were all more strongly associated with DLB in the five years preceding the first neurodegenerative diagnosis. The use of statins was lower in patients who developed PD and higher in patients who developed DLB compared to AD. In PD patients, the use of statins was associated with the development of dementia in the five years following PD diagnosis. INTERPRETATION: Prediagnostic presentations of falls, psychiatric symptoms and autonomic dysfunctions were more strongly associated with DLB than PD and AD. This study also suggests that whilst several associations with medications are similar in neurodegenerative disorders, statin usage is negatively associated with Parkinson's Disease but positively with DLB and AD as well as development of dementia in PD

Association Between Diseases and Symptoms Diagnosed in Primary Care and the Subsequent Specific Risk of Multiple Sclerosis

International audienceObjective: Previous studies have reported a possible prodrome in multiple sclerosis (MS) defined by non-specific symptoms including mood disorder or genito-urinary symptoms and increased health care use detected several years before diagnosis. This study aimed to evaluate agnostically the associations between diseases and symptoms diagnosed in primary care and the risk of multiple sclerosis (MS) relative to controls and two other autoimmune inflammatory diseases with similar population characteristics, namely lupus and Crohn’s disease.Methods: A case-control study was conducted using electronic health records from the Health Improvement Network database in the UK and France. We agnostically assessed the associations between 113 diseases and symptoms in the five years before and after diagnosis in patients with subsequent diagnosis of MS. Individuals with a diagnosis of MS were compared to individuals without MS, and individuals with two other auto-immune diseases, Crohn’s disease and lupus.Results: The study population consisted of patients with MS (n= 20,174), patients without MS (n=54,790), patients with Crohn’s disease (n=30,477) or patients with lupus (n=7,337). Twelve ICD-10 codes were significantly positively associated with the risk of MS compared to controls without MS. After considering ICD-10 codes suggestive of neurological symptoms as the first diagnosis of MS, five ICD-10 codes remained significantly associated with MS: depression (UK OR 1.22 [95%CI 1.11-1.34]), sexual dysfunction (1.47 [1.11-1.95]), constipation (1.5 [1.27-1.78]), cystitis (1.21 [1.05-1.39]), and urinary tract infections of unspecified site (1.38 [1.18-1.61]). However, none of these conditions was selectively associated with MS in comparisons with both lupus and Crohn’s disease. All five ICD-10 codes identified were still associated with MS during the five years after diagnosis.Conclusion: We identified 5 health conditions associated with subsequent MS diagnosis, which may be considered not only prodromal but also early-stage symptoms. However, these health conditions overlap with prodrome of two other autoimmune diseases, hence lacking specificity to MS

Changes in the use of psychotropic drugs during the course of Alzheimer's disease: A large‐scale longitudinal study of French medical records

International audienceIntroduction: We aim to understand how patients with Alzheimer's disease (AD) are treated by identifying in a longitudinal fashion the late-life changes in patients' medical history that precede and follow AD diagnosis. Methods: We use prescription history of 34,782 patients followed between 1996 and 2019 by French general practitioners. We compare patients with an AD diagnosis, patients with mild cognitive impairment (MCI), and patients free of mental disorders. We use a generalized mixed-effects model to study the longitudinal changes in the prescription of eight drug types for a period 15 years before diagnosis and 10 years after. Results: In the decades preceding diagnosis, we find that future AD patients are treated significantly more than MCI patients with most psychotropic drugs and that most studied drugs are increasingly prescribed with age. At the time of diagnosis, all psychotropic drugs except benzodiazepines show a significant increase in prescription, while other drugs are significantly less prescribed. In the 10 years after diagnosis, nearly all categories of drugs are less and less prescribed including antidementia drugs. Discussion: Pre-diagnosis differences between future AD patients and MCI patients may indicate that subtle cognitive changes are recognized and treated as psychiatric symptoms. The disclosure of AD diagnosis drastically changes patients' care, priority being given to the management of psychiatric symptoms. The decrease of all prescriptions in the late stages may reflect treatment discontinuation and simplification of therapeutic procedures. This study therefore provides new insights into the medical practices for management of AD

Pneumococcal vaccination coverage in France by general practitioners in adults with a high risk of pneumococcal disease

Streptococcus pneumoniae, the main cause of community-acquired pneumonia (CAP), also leads to exacerbations, hospitalizations, and mortality in chronic obstructive pulmonary disease (COPD) and congestive heart failure (CHF). The risk of CAP is increased in patients with diabetes mellitus (DM), and the risk of invasive pneumococcal disease is increased in HIV-infected patients. Pneumococcal vaccination is recommended for these patients in France. The objective was a large survey of pneumococcal vaccination coverage (PVC) by general practitioners (GPs) in these patients in France. Diagnosis and treatment forms were extracted from the database of 2000 GPs. The GPs and population panels were representative of the metropolitan populations. The primary endpoint was the comparison of PVC in the adult patients diagnosed with COPD, CHF, DM, or HIV infection during the study (April 2013–April 2017) and the control (March 2012–March 2013) periods. Of the 17,865 and 4,690 patients identified, 756 (4%) and 267 (6%) were vaccinated, respectively. During the study period, the PVC was significantly higher (35/282, 12%) in HIV-infected patients and lower in patients with DM (95/5994, 2%) than in other patients. Even though French pneumococcal vaccine recommendations in adults were updated in 2013, the PVC did not increase according to the years of the study period and slightly increased according to time after diagnosis. S. pneumoniae is responsible only for some CAP and meningitis, and incomplete protection by vaccine, hesitancy from practitioners and patients, and the moving schedule of vaccination could explain the results. New tools and/or strategies must be implemented to increase PVC in France. Abbreviations: CAP: community-acquired pneumonia; COPD: chronic obstructive pulmonary diseases; CHF: congestive heart failure; DM: diabetes mellitus; IPD: invasive pneumococcal disease; HIV: human immunodeficiency virus; PVC: pneumococcal vaccination coverage; PCV7: 7-valent pneumococcal conjugate vaccine; PCV13: 13-valent pneumococcal conjugate vaccine; PPSV23: 23-valent pneumococcal polysaccharide vaccine; GPs: general practitioners; CLM: Cegedim Logiciels Médicaux; MLM: monLogicielMedical; ICD-10: International Classification of Diseases; CNIL: Commission nationale de l’informatique et des libertés; HPV: human papillomavirus; HBV: hepatitis B viru

Pneumococcal vaccination coverage in France by general practitioners in adults with a high risk of pneumococcal disease

Streptococcus pneumoniae, the main cause of community-acquired pneumonia (CAP), also leads to exacerbations, hospitalizations, and mortality in chronic obstructive pulmonary disease (COPD) and congestive heart failure (CHF). The risk of CAP is increased in patients with diabetes mellitus (DM), and the risk of invasive pneumococcal disease is increased in HIV-infected patients. Pneumococcal vaccination is recommended for these patients in France. The objective was a large survey of pneumococcal vaccination coverage (PVC) by general practitioners (GPs) in these patients in France. Diagnosis and treatment forms were extracted from the database of 2000 GPs. The GPs and population panels were representative of the metropolitan populations. The primary endpoint was the comparison of PVC in the adult patients diagnosed with COPD, CHF, DM, or HIV infection during the study (April 2013–April 2017) and the control (March 2012–March 2013) periods. Of the 17,865 and 4,690 patients identified, 756 (4%) and 267 (6%) were vaccinated, respectively. During the study period, the PVC was significantly higher (35/282, 12%) in HIV-infected patients and lower in patients with DM (95/5994, 2%) than in other patients. Even though French pneumococcal vaccine recommendations in adults were updated in 2013, the PVC did not increase according to the years of the study period and slightly increased according to time after diagnosis. S. pneumoniae is responsible only for some CAP and meningitis, and incomplete protection by vaccine, hesitancy from practitioners and patients, and the moving schedule of vaccination could explain the results. New tools and/or strategies must be implemented to increase PVC in France. Abbreviations: CAP: community-acquired pneumonia; COPD: chronic obstructive pulmonary diseases; CHF: congestive heart failure; DM: diabetes mellitus; IPD: invasive pneumococcal disease; HIV: human immunodeficiency virus; PVC: pneumococcal vaccination coverage; PCV7: 7-valent pneumococcal conjugate vaccine; PCV13: 13-valent pneumococcal conjugate vaccine; PPSV23: 23-valent pneumococcal polysaccharide vaccine; GPs: general practitioners; CLM: Cegedim Logiciels Médicaux; MLM: monLogicielMedical; ICD-10: International Classification of Diseases; CNIL: Commission nationale de l’informatique et des libertés; HPV: human papillomavirus; HBV: hepatitis B viru

Identifying health conditions associated with Alzheimer's disease up to 15 years before diagnosis: an agnostic study of French and British health records

International audienceBackground The identification of modifiable risk factors for Alzheimer’s disease is paramount for early prevention and the targeting of new interventions. We aimed to assess the associations between health conditions diagnosed in primary care and the risk of incident Alzheimer’s disease over time, up to 15 years before a first Alzheimer’s disease diagnosis.Methods In this agnostic study of French and British health records, data from 20 214 patients with Alzheimer’s disease in the UK and 19 458 patients with Alzheimer’s disease in France were extracted from The Health Improvement Network database. We considered data recorded from Jan 1, 1996, to March 31, 2020 in the UK and from Jan 4, 1998, to Feb 20, 2019, in France. For each Alzheimer’s disease case, a control was randomly assigned after matching for sex and age at last visit. We agnostically tested the associations between 123 different diagnoses of the International Classification of Diseases, 10th revision, extracted from health records, and Alzheimer’s disease, by running a conditional logistic regression to account for matching of cases and controls. We focused on three time periods before diagnosis of Alzheimer’s disease, to separate risk factors from early symptoms and comorbidities.Findings Unadjusted odds ratios (ORs) and 95% CIs for the association between Alzheimer’s disease and various health conditions were estimated, and p values were corrected for multiple comparisons. In both the British and French studies, ten health conditions were significantly positively associated with increased Alzheimer’s disease risk, in a window of exposure from 2–10 years before Alzheimer’s disease diagnosis, comprising major depressive disorder (UK OR 1·34, 95% CI 1·23–1·46; France OR 1·73, 1·57–1·91), anxiety (UK OR 1·36, 1·25–1·47; France OR 1·50, 1·36–1·65), reaction to severe stress and adjustment disorders (UK OR 1·40, 1·24–1·59; France OR 1·83, 1·55–2·15), hearing loss (UK OR 1·19, 1·11–1·28; France OR 1·51, 1·21–1·89), constipation (UK OR 1·31, 1·22–1·41; France OR 1·59, 1·44–1·75), spondylosis (UK OR 1·26, 1·14–1·39; France OR 1·62, 1·44–1·81), abnormal weight loss (UK OR 1·47, 1·33–1·63; France OR 1·88, 1·56–2·26), malaise and fatigue (UK OR 1·23, 1·14–1·32; France OR 1·59, 1·46–1·73), memory loss (UK OR 7·63, 6·65–8·76; France OR 4·41, 3·07–6·34), and syncope and collapse (UK OR 1·23, 1·10–1·37; France OR 1·57, 1·26–1·96). Depression was the first comorbid condition associated with Alzheimer’s disease, appearing at least 9 years before the first clinical diagnosis, followed by anxiety, constipation, and abnormal weight loss.Interpretation These results from two independent primary care databases provide new evidence on the temporality of risk factors and early signs of Alzheimer’s disease that are observable at the general practitioner level. These results could guide the implementation of new primary and secondary prevention policies

Identifying health conditions associated with Alzheimer's disease up to 15 years before diagnosis: an agnostic study of French and British health records

International audienceBackground The identification of modifiable risk factors for Alzheimer’s disease is paramount for early prevention and the targeting of new interventions. We aimed to assess the associations between health conditions diagnosed in primary care and the risk of incident Alzheimer’s disease over time, up to 15 years before a first Alzheimer’s disease diagnosis.Methods In this agnostic study of French and British health records, data from 20 214 patients with Alzheimer’s disease in the UK and 19 458 patients with Alzheimer’s disease in France were extracted from The Health Improvement Network database. We considered data recorded from Jan 1, 1996, to March 31, 2020 in the UK and from Jan 4, 1998, to Feb 20, 2019, in France. For each Alzheimer’s disease case, a control was randomly assigned after matching for sex and age at last visit. We agnostically tested the associations between 123 different diagnoses of the International Classification of Diseases, 10th revision, extracted from health records, and Alzheimer’s disease, by running a conditional logistic regression to account for matching of cases and controls. We focused on three time periods before diagnosis of Alzheimer’s disease, to separate risk factors from early symptoms and comorbidities.Findings Unadjusted odds ratios (ORs) and 95% CIs for the association between Alzheimer’s disease and various health conditions were estimated, and p values were corrected for multiple comparisons. In both the British and French studies, ten health conditions were significantly positively associated with increased Alzheimer’s disease risk, in a window of exposure from 2–10 years before Alzheimer’s disease diagnosis, comprising major depressive disorder (UK OR 1·34, 95% CI 1·23–1·46; France OR 1·73, 1·57–1·91), anxiety (UK OR 1·36, 1·25–1·47; France OR 1·50, 1·36–1·65), reaction to severe stress and adjustment disorders (UK OR 1·40, 1·24–1·59; France OR 1·83, 1·55–2·15), hearing loss (UK OR 1·19, 1·11–1·28; France OR 1·51, 1·21–1·89), constipation (UK OR 1·31, 1·22–1·41; France OR 1·59, 1·44–1·75), spondylosis (UK OR 1·26, 1·14–1·39; France OR 1·62, 1·44–1·81), abnormal weight loss (UK OR 1·47, 1·33–1·63; France OR 1·88, 1·56–2·26), malaise and fatigue (UK OR 1·23, 1·14–1·32; France OR 1·59, 1·46–1·73), memory loss (UK OR 7·63, 6·65–8·76; France OR 4·41, 3·07–6·34), and syncope and collapse (UK OR 1·23, 1·10–1·37; France OR 1·57, 1·26–1·96). Depression was the first comorbid condition associated with Alzheimer’s disease, appearing at least 9 years before the first clinical diagnosis, followed by anxiety, constipation, and abnormal weight loss.Interpretation These results from two independent primary care databases provide new evidence on the temporality of risk factors and early signs of Alzheimer’s disease that are observable at the general practitioner level. These results could guide the implementation of new primary and secondary prevention policies

A Comparison Between Early Presentation of Dementia with Lewy Bodies, Alzheimer's Disease, and Parkinson's Disease: Evidence from Routine Primary Care and UK Biobank Data

International audienceObjective The purpose of this study was to simultaneously contrast prediagnostic clinical characteristics of individuals with a final diagnosis of dementia with Lewy Bodies (DLB), Parkinson's disease (PD), and Alzheimer's disease (AD) compared with controls without neurodegenerative disorders. Methods Using the longitudinal THIN database in the United Kingdom, we tested the association of each neurodegenerative disorder with a selected list of symptoms and broad families of treatments, and compared the associations between disorders to detect disease‐specific effects. We replicated the main findings in the UK Biobank. Results We used data of 28,222 patients with PD, 20,214 with AD, 4,682 with DLB, and 20,214 healthy controls. All neurodegenerative disorders were significantly associated with the presence of multiple clinical characteristics before their diagnosis, including sleep disorders, falls, psychiatric symptoms, and autonomic dysfunctions. When comparing patients with DLB with patients with PD and patients with AD patients, falls, psychiatric symptoms, and autonomic dysfunction were all more strongly associated with DLB in the 5 years preceding the first neurodegenerative diagnosis. The use of statins was lower in patients who developed PD and higher in patients who developed DLB compared to patients with AD. In patients with PD, the use of statins was associated with the development of dementia in the 5 years following PD diagnosis. Interpretation Prediagnostic presentations of falls, psychiatric symptoms, and autonomic dysfunctions were more strongly associated with DLB than PD and AD. This study also suggests that although several associations with medications are similar in neurodegenerative disorders, statin usage is negatively associated with PD but positively with DLB and AD as well as development of dementia in PD

Data_Sheet_1_Time trends in the incidence of essential tremor: Evidences from UK and France primary care data.docx

IntroductionAlthough essential tremor (ET) is considered a common adult movement disorder, evidence on its incidence is still scant. This study aims at estimating ET incidence in two European countries, namely, the UK and France.MethodsIncident cases of ET were identified within the Health Improvement Network (THIN®) database between 1st January 2014 and 31 December 2019. Yearly crude and standardized incidence rates (IR) were estimated across the study period for both countries. Poisson regression models were built to assess temporal trends in IRs and differences between sexes and age classes.ResultsIn total, 4,970 and 4,905 incident cases of ET were identified in the UK and France, respectively. The yearly average crude IR (per 100,000 person-years) was 18.20 (95%CI: 15.09–21.32) in UK and 21.42 (17.83–25.00) in France, whereas standardized ones were 19.51 (18.97–20.01) and 19.50 (18.97-20.05). Regression analyses showed slightly increasing trends in both countries, higher incidence among males, and a significant increase with age. Yearly average IR increased from 3.96 (0.95–6.97) and 5.28 (1.12–9.44) in subjects aged 80 year in UK and France.ConclusionsStandardized ET incidence was comparable in the UK and France, showing a slight increase in both countries, reporting a higher value among people aged 60 years and older. This study outlines the need to conduct future studies to estimate the burden of ET in terms of disease control and healthcare resource utilization.</p