medwireNews: A first-time transient ischemic attack (TIA) may be a risk factor for long-term cognitive decline similar in degree to that following a first-time stroke, although the mechanisms for this risk remain unclear, suggest findings from an analysis of the REGARDS study.
“TIA-associated cognitive decline suggests a need to reevaluate post-TIA management and to screen regularly for cognitive change,” say Victor Del Bene (The University of Alabama at Birmingham Heersink School of Medicine, USA) and colleagues.
The REGARDS study was carried out between 2003 and 2007 in 48 US states, and followed up through to 2022, with the purpose of exploring regional and racial differences in the risk for first-time stroke. From 2006, the participants completed a brief neuropsychological test battery by phone every other year, which included Consortium to Establish a Registry for Alzheimer Disease (CERAD) Word List Learning, CERAD Word List Delayed Recall, letter F verbal fluency, and animal naming verbal fluency.
In the current analysis, the investigators used the mean of the four cognitive tests to create a standardized composite cognitive outcome score. This was used to compare pre- and post-event cognitive trajectories over a median 14.1 years of follow-up in 356 participants who had a single, diffusion-weighted image-negative, adjudicated TIA (mean age 66.6 years; 53% women; 71% White) and 965 who had a stroke (mean age 66.8 years; 51% men; 63% White).
A community control group of 14,882 individuals who were adjudicated asymptomatic (mean age 63.2 years; 57% women; 64% White) and were assigned an arbitrary index date were also included for comparison.
Mean composite cognitive performance scores were significantly lower, indicating worse cognitive performance, prior to the baseline event in the stroke group than both the TIA group and the control group, at respective scores of –0.25 versus –0.05 and 0.00, with scores not significantly different between the latter two groups.
At the time of the index event, the researchers observed a significantly larger decline in composite cognitive performance in the stroke participants compared with the TIA and control groups, with corresponding scores of –0.14 versus 0.01 and –0.03. Again, the TIA group did not differ significantly from the control group.
However, the annual rate of cognitive decline among patients with TIA after the index event was more rapid compared with that for the control group, at –0.05 versus –0.02, despite not being significantly different prior to the event (–0.03 and –0.02, respectively).
Moreover, the annual rate of cognitive decline after a TIA did not differ significantly from that after a stroke (–0.04).
They report that the decline in post-event cognitive function in patients with TIA was primarily due to reductions in immediate and delayed auditory verbal recall rather than verbal fluency.
“These findings suggest that despite the quick resolution of symptoms and no radiological evidence of injury, TIA appears to be sufficient either directly or indirectly to initiate a pathological process leading to long-term changes in cognition,” say the study authors in JAMA Neurology.
They found that taking into account low-density lipoprotein cholesterol, obesity, low exercise, use of statins or anticoagulants, and depression had little effect on the cognitive change they observed across any of the three groups.
The researchers therefore suggest that other possible mechanisms may be concurrent underlying pathology, such as cerebral amyloid angiopathy, or disruption of the gamma-aminobutyric acid system or blood–brain barrier.
In a related editorial, Eric Smith (University of Calgary, Alberta, Canada) and Babak Navi (Weill Cornell Medicine, New York, USA) point out the study’s strengths, including the “population-based cohort, long follow-up period, restriction to TIAs without acute infarctions on imaging, validation of cerebrovascular events by a vascular neurologist, and the rigorous statistical analyses and adjustments to control for confounding.”
They say the results diverge from the conventional view that “TIAs are supposed to resolve without permanent injury to the brain.”
The editorialists suggest that “[s]troke-prevention specialists and primary care practitioners should question patients with TIAs, and ideally an informant such as a spouse, about the presence of cognitive symptoms and be prepared to do a cognitive screen.”
And they point out that “[t]his screening is even more important now that disease-modifying therapies for Alzheimer disease, which could cause subtle decline unmasked by a TIA, are available.”
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JAMA Neurol 2025; doi:10.1001/jamaneurol.2024.5082
JAMA Neurol 2025; doi:10.1001/jamaneurol.2024.5090
