Nonfocal Transient Neurologic Attacks Originate More From Socioeconomic Determinants Than Cardiovascular Risk Factors

Mohammed Kamran Ikram, MD

Data from the Rotterdam study found that the risk of nonfocal transient neurologic attacks (TNAs), or episodes of neurologic symptoms, was higher among older and less educated individuals, but does not appear to be associated with cardiovascular risk factors. Overall, the data provides evidence that the origins of these attacks are more from socioeconomic determinants, which may aid in clinical decision making and provide greater context for patients experiencing nonfocal TNAs.¹

Published in Neurology, this specific analysis of the Rotterdam study investigated the incidence and potential risk factors of nonfocal TNAs in 14,096 participants (mean age, 65.5 years) who were followed for a long-term period. Across 204,474 person-years (PYs) of follow-up across 3 different study cohorts initiated in 1990, 2000, and 2006, 518 (3.7%) index nonfocal TNAs occurred.

The overall incidence rate (IR) of index nonfocal TNA was 253.3 (95% CI, 232.2-275.9) per 100,000 PYs of follow-up, with attacks occurring more frequently in patients of older age (HR per 5-year increase, 1.47; 95% CI, 1.40-1.55) and with lower education (HR, 1.62; 95% CI, 1.15-2.29). Nonfocal TNA occurred less often with antithrombotic use (HR, 0.59; 95% CI, 0.39-0.90) and carotid plaque (HR, 0.80; 95% CI, 0.65-1.00), but these associations lost statistical significance when excluding participants with prevalent vascular disease.

In the study, senior author Mohammed Kamran Ikram, MD, principal investigator of neuro-epidemiology at Erasmus MC, and colleagues found that 1 in every 9 individuals experienced any TNA, with a total of 1586 index TNAs (11.3%) occurring. Of these, 1121 (70.7%) were transient ischemic attacks (TIAs) and 465 (29.3%) were nonfocal in nature. As expected, cardiovascular risk factors were strongly linked with TIA risk, with higher rates observed in older participants (HR per 5-year increase, 1.30, 95% CI 1.26–1.35) and in those with hypertension (HR, 1.22, 95% CI 1.07–1.40), dyslipidemia (HR 1.13, 95% CI 1.00–1.27), increased carotid IMT (HR, 1.06, 95% CI 1.00–1.12), and a history of stroke (HR, 1.91, 95% CI 1.40–2.63).

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Ikram et al noted that the crude IR of TIA in the study was almost 5 times higher than that observed in the comparable Framingham Heart study, suggesting the population used may have experienced TNA more frequently. Despite this, study investigators wrote that this may be attributed to a higher sociodemographic status or ethnic differences between the study population used, which was of Dutch background, and that of the Framingham Heart study.

The final observation—that no classical cardiovascular risk factor independently predicted nonfocal TNA—contrasted prior studies. Previous work has implicated occluded internal carotid arteries, MRI markers of cerebral small vessel disease, and cerebral hypoperfusion as possible causes, while hypertension and diabetes have been suggested to underlie nonfocal TNAs mimicking vertebrobasilar dysfunction, including nonrotatory dizziness and bilateral weakness.

"Nevertheless, we did not find any evidence for any association with cardiovascular risk factors in this study, suggesting that nonfocal TNAs occur for a different reason than a cardiovascular disturbance on a population level," Ikram et al wrote.¹ "Possible reasons for our contrasting results may be attributed to differences in study design and underlying study population. Previous studies are predominantly cross-sectional in nature, which are less suitable for establishing temporal relationships when compared with this study with extensive follow-up. Furthermore, these studies were performed in hospital settings, which restrict analyses to patient samples only, possibly leading to overestimations of effects."

REFERENCE
1. Berghout BP, Bos D, Kavousi M, et al. Incidence and Determinants of Nonfocal Transient Neurologic Attacks: The Rotterdam Study. Neurology. 2025;105(3). doi:10.1212/WNL.0000000000213854