Background: Patients with Alzheimer's disease (AD) are more prone to seizures and myoclonus, but relative risk of these symptoms among other dementia types is unknown. Objective: To determine incidence of seizures and myoclonus in the three most common neurodegenerative dementias: AD, dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD). Methods: Our institution's medical records were reviewed for new-onset unprovoked seizures and myoclonus in patients meeting criteria for AD (n = 1,320), DLB (n = 178), and FTD (n = 348). Cumulative probabilities of developing seizures and myoclonus were compared between diagnostic groups, whereas age-stratified incidence rates were determined relative to control populations. Results: The cumulative probability of developing seizures after disease onset was 11.5% overall, highest in AD (13.4%) and DLB (14.7%) and lowest in FTD (3.0%). The cumulative probability of developing myoclonus was 42.1% overall, highest in DLB (58.1%). The seizure incidence rates, relative to control populations, were nearly 10-fold in AD and DLB, and 6-fold in FTD. Relative seizure rates increased with earlier age-at-onset in AD (age <50, 127-fold; 50-69, 21-fold; 70+, 2-fold) and FTD (age <50, 53-fold; 50-69, 9-fold), and relative myoclonus rates increased with earlier age-at-onset in all groups. Seizures began an average of 3.9 years after the onset of cognitive or motor decline, and myoclonus began 5.4 years after onset. Conclusions: Seizures and myoclonus occur with greater incidence in patients with AD, DLB, and FTD than in the general population, but rates vary with diagnosis, suggesting varied pathomechanisms of network hyperexcitability. Patients often experience these symptoms early in disease, suggesting hyperexcitability could be an important target for interventions.
Bibliographical noteFunding Information:
Antiseizure drug therapy improves cognitive and behavioral function in transgenic mouse models of AD, and clinical trials using antiseizure drugs for AD-associated network hyperexcitability are ongoing. The findings of this study raise the possibility that similar strategies might benefit patients with FTD and The authors would like to first and foremost acknowledge the patients and family members who were seen at the Memory and Aging Center. We would also like to thank the clinical and research staff of the Memory and Aging Center; Andreas Lazaris, William Jagust, and Gil Rabinovici for providing the amyloid imaging; and Anna Karydas for genetics support. This study was supported by the National Institutes of Health (NIH) grants K23 AG038357 (KAV) and F32 AG050434 (KGR), a grant from the Alzheimer’s Association, PCTRB-13-288476, made possible by Part the Cloud™ (KAV), the John Douglas French Alzheimer’s Foundation (KAV and EK), the Larry L. Hillblom Foundation, 2015-A-034-FEL (KGR), and the Robert Katz-man, MD, Clinical Research Training Fellowship in Alzheimer’s Research sponsored by the American Brain Foundation and Alzheimer’s Association (EK).
© 2017 - IOS Press and the authors.
- Alzheimer's disease
- dementia with Lewy bodies
- frontotemporal dementia