TNAs Linked to Major Vascular Disease, Dementia Risk

Caroline Cassels
January 3, 2008 — Nonfocal transient neurologic attacks (TNAs) significantly increase the risk of major vascular disease and dementia – findings that contest the long-held belief that they are benign.
A large, prospective, population-based study showed patients who experienced TNAs with nonfocal symptoms, had approximately a 1.6-fold increased risk for stroke and dementia vs those without TNAs.
Furthermore, investigators found individuals with a combination of focal and nonfocal TNAs (also known as mixed symptoms) had a particularly poor prognosis with a high risk for stroke, vascular dementia, ischemic heart disease, and vascular death vs the referent group.
"Our findings challenge the strong but unfounded conviction that nonfocal TNAs are harmless. On the contrary, our findings suggest that nonfocal TNAs are not only a risk factor for stroke, but also for dementia," write Monique Breteler, MD, PhD, from the Erasmus Medical Center in Rotterdam, the Netherlands, and colleagues.
The study is published in the December 26 issue of the Journal of the American Medical Association.
Although conventional diagnostic criteria for focal TNAs — otherwise known as transient ischemic attacks (TIAs) — are clear and well established, the classification and treatment of nonfocal TNAs remain uncertain.
The study authors note that symptoms of nonfocal TNA can include syncope, acute confusion, or transient global amnesia that have no known cause.
"Although the assumption that patients with TIA are at high risk of major vascular disease has repeatedly been confirmed since 1975, hardly any studies have challenged and verified the assumption that nonfocal TNAs have a benign clinical course," the investigators note.
Similar Incidence As TIAs
Part of the Rotterdam Study, a large, ongoing prospective cohort study investigating the prevalence and incidence of risk factors for chronic disease in elderly people, the aim of the current research was to determine the incidence and prognosis of focal, nonfocal, and mixed TNAs.
The study included 6062 participants 55 years or older who were free of stroke, myocardial infarction, and dementia at baseline (1990 - 1993).
All subjects were subsequently followed up for incident strokes, TIAs, ischemic heart disease, dementia, and death until January 1, 2005. Associations between incident TNAs and subsequent adverse events were then analyzed.
Of the total study group, a TNA occurred in 548 participants. Of these, 282 had a focal TNA, 228 had a nonfocal TNA, and 38 had a mixed TNA. The median age at the time of TNA was 79 years, and 69% of patients were women.
The study showed that nonfocal TNAs were almost as frequent as focal TNAs, with an incidence of 4.7 and 3.8 per 1000 person-years for focal and nonfocal TNAs, respectively. Furthermore, risk for both types of events strongly increased with advancing age.
With an incidence rate of 0.6 per 1000 person-years, mixed TNAs were less frequent and their relationship with age was less clear.
Rally Cry for More Evaluation, Research
In an accompanying editorial, S. Claiborne Johnston, MD, PhD, of the University of California, San Francisco, the prognosis of nonfocal TNA with its increased risk for stroke and vascular dementia may warrant more detailed assessment of such patients.
He notes a cholesterol panel, glucose level, hemoglobin A1c concentrations, and possible cardiac monitoring and echocardiography may help identify underlying risk factors for vascular disease in patients with nonfocal TNA.
With treatment, he adds, it may be that this patient group could also benefit from standard prevention practices recommended for patients with TIA including antiplatelet, statin, and antihypertensive therapy.
"Even though TNA is likely to be only of transient utility because clinicians must quickly move to more specific diagnoses to provide appropriate treatment for patients, this entity should be considered a rally cry for more extensive evaluation or consultation in those patients, as well as for further research," Dr. Johnston writes.
The Rotterdam Study is supported by Erasmus Medical Center Rotterdam; Erasmus University Rotterdam; the Netherlands Organization for Scientific Research; the Netherlands Organization for Health Research and Development; the Research Institute for Diseases in the Elderly; the Ministry of Education, Culture, and Science; and the Ministry of Health, Welfare, and Sports. The Netherlands Organization for Scientific Research supported this study. Three of the study authors have obtained funding. The remaining study authors have disclosed no relevant financial relationships.
Dr. Johnston has disclosed no relevant financial relationships.
JAMA. 2007;298:2877-2885, 2912-2913.