The ϵ4 allele of the cholesterol transport protein apolipoprotein E is associated with an elevated plasma total cholesterol (TC) level and an increased risk of developing Alzheimer disease (AD). The use of statins has been associated with a reduced risk of developing AD; however, there were no data directly relating lifetime plasma TC levels to the risk of developing AD. This study by Tan et al relates repeated measures of plasma TC in the Framingham original cohort to the risk of developing AD. Of 1026 stroke- and dementia-free subjects, 77 developed AD between 1992 and 2000. Baseline and lifetime (average) plasma TC levels were not related to the risk of AD. Further studies to evaluate the relation between statin use and the risk of AD appear warranted; if a benefit is confirmed, an explanation other than cholesterol lowering should be sought.
This analysis of a cohort of 290 patients presenting in the 1990s to a Belgian University hospital with a prolonged febrile illness of uncertain origin indicates that the cause of the fever remains elusive in many, especially in patients with episodic fevers. The increasing sophistication of medical technology has as yet failed to improve the diagnostic acumen. Noninfectious inflammatory diseases emerge as the prevailing diagnostic category. A limited number of disorders made up the majority of diagnoses. Hematological malignancies accounted for the most deaths. Patients discharged without diagnosis generally had a favorable prognosis. While the traditional definition of fever of unknown origin requires an investigational workup of 1 week's duration without reaching a diagnosis, shortening this interval to 3 days has no major impact on the case-mix.
There is substantial evidence that migraine is a risk factor for stroke. The aim of the study by Jousilahti et al was to assess whether chronic unspecified headache predicts the risk of stroke. Among 35 056 Finnish subjects, 16.7% of women and 8.9% of men reported having chronic headache at baseline. During the follow-up, self-reported headache was associated with the risk of stroke in men but not in women. During the first year of follow-up, men with chronic headache had a 4-times higher risk of stroke compared with men without headache. The association between headache and the risk of stroke attenuated markedly by the duration of follow-up but remained statistically significant in the 5- and 23-year follow-up. Since the association between headache and the risk of stroke was particularly strong during a short follow-up, chronic headache may be a marker of the underlying disease process leading to acute stroke. The sex difference observed in this association may be due to a higher prevalence and a more heterogeneous etiology of headache in women compared with men.
The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) Collaborative Group has previously reported that blood pressure lowering with the angiotensin-converting enzyme inhibitor, perindopril, and the diuretic, indapamide, reduced the risk of recurrent stroke by 28% in 6105 patients with previous stroke or transient ischemic attack. In this issue, the group reports that this treatment is associated with reduced risks of dementia and cognitive decline that are mediated through stroke avoidance. The composite outcomes of dementia with recurrent stroke and of cognitive decline with recurrent stroke are reduced by 34% and 45%, respectively. The authors recommend that blood pressure lowering with perindopril and indapamide be considered for all patients with cerebrovascular disease.
Effects of treatment on the risks of dementia.
In This Issue of Archives of Internal Medicine. Arch Intern Med. 2003;163(9):999. doi:10.1001/archinte.163.9.999