Timing of risk factors, prodromal features, and comorbidities of dementia from a large health claims case-control study

Abstract

Background: Many risk factors for dementia have been identified, but the timing of risk is less well understood. Here, we analyzed risk factors in a case-control study covering 10 years before an incident dementia diagnosis.

Methods: We designed a case-control study using insurance claims of outpatient consultations of patients with German statutory health insurance between January 1, 2012, and December 31, 2022. We included patients with an incident diagnosis of dementia and controls without a diagnosis of dementia matched 1:2 for age, sex, region, and earliest year of outpatient encounter. We selected exposures based on previous systematic reviews, case-control and cohort studies reporting on risk factors, comorbidities, and prodromal features of dementia. We calculated the prevalence of risk factors in cases and controls and odds ratios for each year before the index date, along with Bonferroni-corrected confidence intervals, using conditional logistic regression.

Results: We identified a total of 1,686,759 patients with incident dementia (mean (SD) age, 82.15 (6.90) years; 61.70% female) and 3,373,518 matched controls (mean (SD) age, 82.15 (6.90) years; 61.70% female). Study participants were followed up for a mean (SD) of 6.6 (2.3) years. Of the 63 risk factors and prodromal features examined, 56 were associated with an increased risk of dementia in all years during the 10th and the 1st year before the index date. These included established risk factors, such as depression, hypertension, hearing impairment, nicotine and alcohol abuse, obesity, hypercholesterolaemia, traumatic brain injury, and diabetes. The greatest risk, with odds ratios greater than 2.5, was conferred by delirium, memory impairment, mental retardation, personality and behavioral disorders, sensory disorders, schizophrenia, and psychosis. Cancer was associated with a reduced risk of dementia.

Conclusions: This large case-control study confirmed established risk factors of dementia. In addition, the study identified non-specific diagnoses that showed a steep increase in risk close to the index date, such as psychosis, conduct disorder, and other sensory disorders. Consideration of these diagnoses, which may represent prodromal features rather than risk factors for dementia, may help to identify people with dementia in routine care.

Keywords: Behavioral disorders; Cancer; Dementia incidence; Health claims data; Hypertension; Odds ratio; Risk trajectory.

Fig. 1

Prevalence in controls regressed on odds ratios. The graph plots the prevalence of each condition in the controls against the odds ratio for dementia risk. Annotated are the risk factors for dementia identified by the Lancet Commission and the World Health Organization (see Table 1). In addition, conditions with an OR > 2. were annotated. The interactive Supplementary Fig. 1 (online in Supplementary Material 2) allows identification of each individual condition in the graph. t2d – type 2 diabetes

Fig. 2

Prevalence of risk factors by year before the index date in cases and controls. a Prevalence of 2020 Lancet Commission and WHO risk factors. b Prevalence of psychiatric conditions. c Prevalence of cancer, migraine, impairments of sensory organs and sleep disorders. Prevalence of each condition (and 95% confidence intervals) by year before the index date in the cases and controls

Fig. 3

Odds ratios of all conditions in three time periods. The figure shows the odds ratios and their 95% confidence intervals for all conditions within the time periods 5 to 10 years, 2 to 4 years, and 1 year before the index date. The conditions are sorted in descending order by the size of the odds ratios in year 1 before the index date