Ten years preceding a diagnosis of neurodegenerative disease in Europe and Australia: medication use, health conditions, and biomarkers associated with Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis.

BACKGROUND: Many studies have investigated early predictors for Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). However, evidence is sparse regarding specific and common predictors for these diseases. We aimed to identify medication use, health conditions, and blood biomarkers that might be associated with the risk of AD, PD, and ALS ten years later. METHODS: We conducted population-based nested case-control studies of AD, PD, and ALS using electronic medical records in Europe (France, the UK, and Sweden) and Australia. We retrieved data on medication use, diagnosed health conditions, and measured blood biomarkers from electronic medical records or biomedical cohorts. Conditional logistic regression models and meta-analysis were applied to assess the associations between these factors and the risk of receiving a diagnosis of AD, PD, or ALS. FINDINGS: We included a total of 149,642 AD cases (mean age: 79.1-81.2 years), 252,696 PD cases (73.2-75.9 years), and 27,533 ALS cases (64.4-69.6 years). The prescription of psychoanaleptics and nasal preparations was consistently associated with an increased risk of AD, PD, and ALS 5-10 years later. Constipation and use of related medications were associated with an increased risk of AD and PD, while diabetes and use of antidiabetics were associated with a reduced risk of ALS. A higher level of triglycerides was associated with a lower risk of AD, whereas a higher level of Apolipoprotein B was associated with a lower risk of PD, 5-10 years later. INTERPRETATION: Psychoanaleptics and nasal preparations may serve as common predictors for diagnosis of AD, PD, and ALS 5-10 years later. Conversely, the increased prevalence of constipation is specific to AD and PD, while the decreased prevalence of diabetes and use of antidiabetics is specific to ALS. FUNDING: EU Joint Programme-Neurodegenerative Disease Research.