Associations between primary care electrocardiography and non-Alzheimer dementia

Isaksen, Jonas L. and Ghouse, Jonas and Skov, Morten W. and Olsen, Morten S. and Holst, Anders G. and Pietersen, Adrian and Nielsen, Jonas B. and Maier, Anja and Graff, Claus and Frikke-Schmidt, Ruth and Kanters, Jørgen (2022) Associations between primary care electrocardiography and non-Alzheimer dementia. Journal of Stroke and Cerebrovascular Diseases, 31 (9). 106640. ISSN 1052-3057 (

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Objectives: To determine whether electrocardiogram (ECG) markers are associated with incident non-Alzheimer's dementia (non-AD) and whether these markers also improve risk prediction for non-AD. Materials and methods: We retrospectively included 170,605 primary care patients aged 60 years or older referred for an ECG by their general practitioner and followed them for a median of 7.6 years. Using Cox regression, we reported hazard ratios (HRs) for electrocardiogram markers. Subsequently, we evaluated if addition of these electrocardiogram markers to a clinical model improved risk prediction for non-AD using change in area under the receiver-operator characteristics curve (AUC). Results: The 5-year cumulative incidence of non-AD was 3.4 %. Increased heart rate (HR=1.06 pr. 10 bpm [95% confidence interval: 1.04–1.08], p<0.001), shorter QRS duration (HR=1.07 pr. 10 ms [1.05–1.09], p<0.001), elevated J-amplitude (HR=1.16 pr. mm [1.08–1.24], p<0.001), decreased T-peak amplitude (HR=1.02 pr. mm [1.01–1.04], p=0.002), and increased QTc (HR=1.08 pr. 20 ms [1.05–1.10], p<0.001) were associated with an increased rate of non-AD. Atrial fibrillation on the ECG (HR=1.18 [1.08–1.28], p<0.001) Sokolow-Lyon index > 35 mm (HR=1.31 [1.18–1.46], p<0.001) and borderline (HR=1.18 [1.11–1.26], p<0.001) or abnormal (HR=1.40 [1.27–1.55], p<0.001) QRS-T angle were also associated with an increased rate of non-AD. Upon addition of ECG markers to the Cox model, 5-year and 10-year C-statistic (AUC) improved significantly (delta-AUC, 0.36 [0.18–0.50] and 0.20 [0.03–0.35] %-points, respectively). Conclusions: ECG markers typical of an elevated cardiovascular risk profile were associated with non-AD and improved both 5-year and 10-year risk predictions for non-AD.


Isaksen, Jonas L., Ghouse, Jonas, Skov, Morten W., Olsen, Morten S., Holst, Anders G., Pietersen, Adrian, Nielsen, Jonas B., Maier, Anja ORCID logoORCID:, Graff, Claus, Frikke-Schmidt, Ruth and Kanters, Jørgen;