Mood Alterations in the Prodromal Phase of Sporadic Creutzfeldt-Jakob Disease

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare, rapidly progressive and fatal neurodegenerative disease. Definite sCJD diagnosis can only be made post mortem, and little is known about the prodromal phase of the disease.

To compare drug prescription patterns before the clinical onset of sCJD between patients and matched controls for exploration of potential risk factors and to assess correlations between drug exposure and sCJD survival.

This retrospective analysis was designed as a case-control study, with data collected from January 2013 to December 2020 and analyzed in 2023. Follow-up was available until December 2020. Cases were collected from the Austrian Reference Centre for Human Prion Diseases, which receives all suspected cases at a national level in Austria. The analyses were conducted at a single center. Patients with autopsy-confirmed sCJD were linked with insurance claims data, and a minimum of 10 control individuals were matched by sex, age at onset, and area of residence for each patient with sCJD.

Medication prescribed to 10% or more of the cohort with sCJD up to 5 years before symptom onset or the matching date in the control cohort.

Drug prescription before symptom onset or the matching date was compared between patients with sCJD and controls using conditional regression, and prescriptions in the cohort with sCJD were assessed for correlation with survival using Cox proportional hazard models.

A total of 129 patients with sCJD (median [IQR] age, 68.9 [62.4-75.5] years; 67 female [51.9%]) and 1350 controls (median [IQR] age, 69.0 [62.2-75.3] years; 700 female [51.9%]) were included. As compared with controls, patients with sCJD were found to have significantly higher odds of being prescribed selective serotonin reuptake inhibitors (SSRIs) in the year preceding disease onset (odds ratio, 2.86; 95% CI, 1.63-4.95; P < .001). SSRI prescription rates started to increase 3 years before symptom onset in the cohort with sCJD.

Results of this case-control study provide evidence for prodromal mood alterations as early as 3 years before symptom onset in patients with sCJD. Although sCJD remains an extremely rare cause of mood alterations, increased vigilance for neurodegenerative diseases in this setting could eventually help to extend the diagnostic window.