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. ### Competing Interest Statement FM, LG and BE are full time employees of Cegedim. J.C.C. has served in advisory boards for Biogen, Denali, Idorsia, Prevail Therapeutic, Servier, Theranexus, UCB; and received grants from Sanofi and the Michael J Fox Foundation outside of this work. Other authors declare no competing interests. ### Funding Statement The research leading to these results has received funding from the joint program in neurodegenerative diseases (JPND) ANR-21-JPW2-0002-01 (LeMeReND) and the program "Investissements d'avenir" ANR-10-IAIHU-06. This work was funded in part by the French government under management of Agence Nationale de la Recherche as part of the "Investissements d' avenir" program, reference ANR-19-P3IA-0001 (PRAIRIE 3IA Institute). BCD is supported by a CJ Martin Fellowship (NHMRC, APP1161356) and the CNRS. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Approval was sorted before carrying out this study (and for the use of datasets). The study was a retrospective analysis of secondary anonymised patient data only. For the UK THIN database, data is only available to researchers carrying out approved medical research. Ethical approval was granted by the NHS South-East Multicentre Research Ethics Committee in 2003 (ref: 03/01/073) for establishment of the THIN database, and it was updated in 2011. A further update and approval was granted in 2020 by the NHS South Central, Oxford C Research Ethics Committee (Ref: 20/SC/0011). The study was approved by the THIN Scientific Research Committee (SRC) (SRC reference 20-002). Researchers willing to replicate the results should address a request to the Cegedim company (info@the-health-improvement-network.co.uk). Informed consent was obtained from all UKB participants. Procedures are controlled by a dedicated Ethics and Guidance Council (http://www.UK Biobank.ac.uk/ethics), with the Ethics and Governance Framework available at http://www.UK Biobank.ac.uk/wp-content/uploads/2011/05/EGF20082.pdf. IRB approval was also obtained from the North West Multi-centre Research Ethics Committee. This research has been conducted using the UK Biobank Resource under Application Number 53185. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The data used in the preparation of the article are available from the Cegedim company upon reasonable request (info@the-health-improvement-network.co.uk).