Traumatic Brain Injury Associates with an Earlier Onset in Sporadic Frontotemporal Dementia

Article type: Research Article

Authors: Soppela, Helmi^a | Krüger, Johanna^{b; c; d} | Hartikainen, Päivi^e | Koivisto, Anne^{a; f; g} | Haapasalo, Annakaisa^e | Borroni, Barbara^{h; i} | Remes, Anne M.^{b; c; j} | Katisko, Kasper^a | Solje, Eino^{a; f; *}

Affiliations: [a] Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland | [b] Research Unit of Clinical Neuroscience, Neurology, University of Oulu, Oulu, Finland | [c] MRC, Oulu University Hospital, Oulu, Finland | [d] Neurocenter, Neurology, Oulu University Hospital, Oulu, Finland | [e] A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland | [f] Neuro Center, Neurology, Kuopio University Hospital, Kuopio, Finland | [g] Neuro Center, Neurology, Helsinki University Hospital, Helsinki, Finland | [h] Department of Clinical and Experimental Sciences, Centre for Neurodegenerative Disorders, University of Brescia, Brescia, Italy | [i] Neurology Unit, ASST Spedali Civili Brescia, Brescia, Italy | [j] Clinical Neurosciences, University of Helsinki, Helsinki, Finland

Correspondence: [*] Correspondence to: Eino Solje, MD, PhD, Adjunct Professor, Research Director, University of Eastern Finland – Institute of clinical medicine, Neurology, P.O. Box 1627 (Yliopistonranta 1C) FI-70211 Kuopio, Finland. Tel.: +358 408425553; E-mail: [email protected].

Abstract: Background:Currently, there are few studies considering possible modifiable risk factors of frontotemporal dementia (FTD). Objective:In this retrospective case-control study, we evaluated whether a history of traumatic brain injury (TBI) associates with a diagnosis of FTD or modulates the clinical phenotype or onset age in FTD patients. Methods:We compared the prevalence of prior TBI between individuals with FTD (N = 218) and age and sex-matched AD patients (N = 214) or healthy controls (HC; N = 100). Based on the patient records, an individual was categorized to the TBI+ group if they were reported to have suffered from TBI during lifetime. The possible associations of TBI with age of onset and disease duration were also evaluated in the whole FTD patient group or separately in the sporadic and genetic FTD groups. Results:The prevalence of previous TBI was the highest in the FTD group (19.3%) when compared to the AD group (13.1%, p = 0.050) or HC group (12%, p = 0.108, not significant). Preceding TBI was more often associated with the sporadic FTD cases than the C9orf72 repeat expansion-carrying FTD cases (p = 0.003). Furthermore, comparison of the TBI+ and TBI- FTD groups indicated that previous TBI was associated with an earlier onset age in the FTD patients (B = 3.066, p = 0.010). Conclusion:A preceding TBI associates especially with sporadic FTD and with earlier onset of symptoms. The results of this study suggest that TBI may be a triggering factor for the neurodegenerative processes in FTD. However, understanding the precise underlying mechanisms still needs further studies.

Keywords: Comorbidity, dementia, frontotemporal dementia, head trauma, risk factors, traumatic brain injury

DOI: 10.3233/JAD-220545

Journal: Journal of Alzheimer's Disease, vol. 91, no. 1, pp. 225-232, 2023