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. 2020 Oct;267(10):2941-2948.
doi: 10.1007/s00415-020-09937-7. Epub 2020 Jun 2.

Seizures in Alzheimer's disease are highly recurrent and associated with a poor disease course

Jonathan Vöglein  1   2 , Ingrid Ricard  3 , Soheyl Noachtar  2 , Walter A Kukull  4 , Marianne Dieterich  1   2   5   6 , Johannes Levin  7   8   9 , Adrian Danek  10   11
Affiliations

Seizures in Alzheimer's disease are highly recurrent and associated with a poor disease course

Jonathan Vöglein et al. J Neurol. 2020 Oct.

Abstract

Background: Seizures are an important comorbidity in Alzheimer's disease (AD). Conflicting results regarding clinical parameters associated with seizures in AD were previously reported. Data on seizure recurrence risk, a crucial parameter for treatment decisions, are lacking.

Methods: National Alzheimer's Coordinating Center data were analyzed. Seizure prevalence in AD and an association with disease duration were investigated. Associations of seizures with age of AD onset and with cognitive and functional performance, and seizure recurrence risk were studied.

Results: 20,745 individuals were investigated. In AD dementia, seizure recurrence risk was 70.4% within 7.5 months. Seizure history was associated with an earlier age of onset of cognitive symptoms (seizures vs. no seizures: 64.7 vs. 70.4 years; p < 0.0001) and worse cognitive and functional performance (mean MMSE score: 16.6 vs. 19.6; mean CDR-sum of boxes score: 9.3 vs. 6.8; p < 0.0001; adjusted for disease duration and age). Seizure prevalence increased with duration of AD dementia (standardized OR = 1.55, 95% CI = 1.39-1.73, p < 0.0001), rising from 1.51% at 4.8 years to 5.43% at 11 years disease duration. Seizures were more frequent in AD dementia compared to normal controls (active seizures: 1.51% vs. 0.35%, p < 0.0001, OR = 4.34, 95% CI = 3.01-6.27; seizure history: 3.14% vs. 1.57%, p < 0.0001, OR = 2.03, 95% CI = 1.67-2.46).

Conclusion: Seizures in AD dementia feature an exceptionally high recurrence risk and are associated with a poor course of cognitive symptoms. AD patients are at an increased risk for seizures, particularly in later disease stages. Our findings emphasize a need for seizure history assessment in AD, inform individual therapeutic decisions and underline the necessity of systematic treatment studies of AD-associated epilepsy.

Keywords: Alzheimer’s disease; Epilepsy; Seizure prevalence; Seizure recurrence risk; Seizures.

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Conflict of interest statement

Johannes Levin reports speaker fees from Bayer Vital, consulting fees from Axon Neuroscience and Ionis Pharmaceuticals, author fees from Thieme medical publishers and W. Kohlhammer GmbH medical publishers, non-financial support from Abbvie and compensation for duty as part-time CMO from MODAG, outside the submitted work. Adrian Danek receives funding from Advocacy for Neuroacanthocytosis Patients and received speaker honoraria from The International Parkinson and Movement Disorder Society, Clienia Schlössli AG, Blutspende Zürich, Kantonsspital Aarau AG, München Klinik, and Bayer. He serves as an editorial board member of Translational Neuroscience. All other authors report no conflict of interest.

Figures

Fig. 1
Fig. 1
Flow chart depicting the study population at baseline and separation into subgroups. For pre-symptomatic Alzheimer’s disease, a normal cognitive status at baseline and a diagnosis of Alzheimer’s disease dementia at follow-up was required. For impaired-not-MCI due to Alzheimer’s disease and MCI due to Alzheimer’s disease, both a presumptive etiologic diagnosis of Alzheimer’s disease at baseline and a diagnosis of Alzheimer’s disease dementia at follow-up were required. Groups that were included in analyses are shown in bold. MCI mild cognitive impairment
Fig. 2
Fig. 2
Grouped scatter plot depicting CDR-SB as a function of the presence of a history of seizures and disease duration. There was a highly significant effect of the presence of a history of seizures on CDR-SB towards abnormal over disease duration. Middle lines represent the linear fits of the data, upper and lower lines represent 95% confidence intervals. CDR-SB clinical dementia rating-sum of boxes
Fig. 3
Fig. 3
Association of prevalence of active seizures and disease duration in patients with Alzheimer’s disease dementia. Logistic regression with disease duration squared transformed and standardized as explanatory variable (Quadratic equation: logit{P(“having a seizure”|disease duration = d)} = − 3.56 + 0.44 × (d−md/sdd)2 with md = 72.7 and sdd = 35.0 being the mean and the standard deviation over all disease durations). The effect of disease duration on seizure prevalence was highly significant in patients with AD dementia (OR = 1.55, 95% CI = 1.39–1.73, p < 0.001)
Fig. 4
Fig. 4
Prevalence of seizures in the various stages of Alzheimer’s disease and in controls. Prevalence of active seizures and a history of seizures were higher in AD dementia patients compared to controls. No differences in seizure prevalence in pre-dementia stages of AD compared to controls were found. AD Alzheimer’s disease, MCI mild cognitive impairment. *p < 0.001
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