Transient episodes of neurological symptoms—muscle weakness, double vision, or other signs that last less than 24 hours—reveal underlying circulatory problems in the brain. When these “ministrokes” show themselves with focal symptoms that affect one part of the body, they are diagnosed as transient ischemic attacks (TIAs) and are associated with an elevated risk of stroke going forward. But attacks that present with more diffuse, non-localized signs like amnesia or acute confusion are harder to diagnose and are often not treated, and have generally been considered less harmful.
That thinking may change with a new report that people who experience nonfocal transient neurological symptoms also have a higher risk for subsequent stroke and dementia as well. The work, from Monique Breteler and colleagues at the Erasmus Medical Center, Rotterdam, the Netherlands, suggests a new classification of transient neurological attack (TNA) that encompasses nonfocal symptoms as potential indicators of serious underlying problems. The study was published in the December 26 issue of JAMA.
In the study, lead author Michiel Bos and coworkers analyzed TNAs among 6,062 residents of Rotterdam aged 55 or older who were followed up for 12-15 years. In 60,535 person-years of follow-up, they found nonfocal TNAs almost as frequently as focal TNAs. The incidence of mixed episodes was much lower. Participants who suffered a focal TNA had about double the risk of stroke, an elevation slightly lower than that seen in previous studies. Those with nonfocal TNA also had a higher risk of stroke, but also dementia, especially vascular dementia. Mixed TNAs carried the worst prognosis, with increased risk of stroke, ischemic heart disease, vascular death, and dementia compared to subjects without TNA.
The study’s strengths come from the large population studied, with nearly complete follow-up in collaboration with primary care doctors. However, diagnoses were made from medical records and patient recall, which may not be entirely reliable. Nonetheless, the authors write, “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.”
In an accompanying editorial, S. Claiborne Johnston of the University of California, San Francisco, writes, “Most physicians already are appropriately concerned about patients with TIA, but the study by Bos et al. extends that concern to those often diagnosed as possible TIA or left without a diagnosis. 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 these patients, as well as for further research.”
After a diagnosis of TIA, statins are often prescribed to reduce the risk of subsequent stroke. This action of statins has been cited as one mechanism by which they could slow the development of dementia, but the relationship between statins, cognitive decline, and AD is still unclear. In a study published online January 16 in Neurology, investigators at Rush University Medical Center, Chicago, Illinois, report that statin use is not associated with changes in cognitive function or Alzheimer neuropathology measured at autopsy.
In the study, lead author Zoe Arvanitakis and colleagues assessed changes in cognitive function or Alzheimer neuropathology in 929 participants of the Religious Orders Study of older Catholic clergy, of which 119 were statin users. The participants, free of dementia at baseline, were evaluated for up to 12 years. The group included 262 who were followed through to brain autopsy. The results are nearly all negative, indicating that statin use was not related to incident AD, or to any changes in either global or domain-specific cognition. Statin use had no effect on global AD pathology (extent of plaques and tangles upon autopsy). People taking statins were less likely to have amyloid pathology, but among those users with amyloid, there was no relation between statin use and amyloid load.
Within the limitation of the small study, the authors conclude that “overall, these studies do not support a relation between statins and AD or cognitive decline among older persons.” The results conflict with another study examining statin use and AD pathology, which showed a reduction in neurofibrillary tangle pathology in statin users (Li et al., 2007). It is also at odds with several epidemiological studies, including a large one that indicated simvastatin, at least, protected against AD and Parkinson disease (see ARF related news story and comment).—Pat McCaffrey
- Li G, Larson EB, Sonnen JA, Shofer JB, Petrie EC, Schantz A, Peskind ER, Raskind MA, Breitner JC, Montine TJ. Statin therapy is associated with reduced neuropathologic changes of Alzheimer disease. Neurology. 2007 Aug 28;69(9):878-85. PubMed.
- Bos MJ, van Rijn MJ, Witteman JC, Hofman A, Koudstaal PJ, Breteler MM. Incidence and prognosis of transient neurological attacks. JAMA. 2007 Dec 26;298(24):2877-85. PubMed.
- Johnston SC. Transient neurological attack: a useful concept?. JAMA. 2007 Dec 26;298(24):2912-3. PubMed.
- Arvanitakis Z, Schneider JA, Wilson RS, Bienias JL, Kelly JF, Evans DA, Bennett DA. Statins, incident Alzheimer disease, change in cognitive function, and neuropathology. Neurology. 2008 May 6;70(19 Pt 2):1795-802. PubMed.