Thrombolysis in elderly stroke patients in Italy (TESPI) trial and updated meta-analysis of randomized controlled trials.

BACKGROUND: Since its approval, the use of alteplase had been limited to patients aged ≤80 years. AIMS: TESPI trial had been designed to evaluate whether alteplase treatment within 3 h in patients with acute ischemic stroke aged >80 years resulted in favorable benefit/risk ratio compared with standard care. The meta-analysis of randomized controlled trials was updated to put findings in the context of all available evidence. METHODS: TESPI was a multicenter, open-label with blinded outcome evaluation, randomized, controlled trial. Main clinical endpoints were 90-day favorable functional outcome (mRS score 0-2) and mortality and symptomatic intracerebral hemorrhage. The trial was prematurely terminated for ethical reasons after publication of IST-3 trial which provided evidence of treatment benefit in elderly. RESULTS: Of the planned 600 patients, 191 (88 assigned to alteplase) were enrolled. Overall, 24/83 (28.9%) alteplase patients had a favorable outcome compared to 22/95 (23.2%) controls (non-significant absolute difference of 5.7% for alteplase; OR 1.35, 95% CI 0.69-2.64, P = 0.381). Rates of death were non-significantly lower in the alteplase patients (18.1% vs. 26.5%); rates of symptomatic intracerebral hemorrhage were similar between the two groups (5.9% vs. 5.1%). The updated meta-analysis showed consistent results with prior estimates and add weights. CONCLUSIONS: The effects of alteplase observed in this interrupted trial did not reach statistical significance, probably for the small numbers, but are consistent with and add weight to the sum total of the randomized evidence demonstrating that alteplase is beneficial in patients with acute ischemic stroke aged over 80 years, particularly if given within 3 h.

Is MCI really just early dementia? A systematic review of conversion studies.

OBJECTIVES: Older people commonly present with memory loss although on assessment are not found to have a full dementia complex. Previous studies have suggested however that people with subjective and objective cognitive loss are at higher risk of dementia. We aimed to determine from the literature the rate of conversion from mild cognitive impairment to dementia. METHODS: Systematic review of MedLine, PsychLit and EmBase. RESULTS: We identified 19 longitudinal studies published between 1991 and 2001 that addressed conversion of mild cognitive impairment to dementia. Overall the rate of conversion was 10% but with large differences between studies. The single biggest variable accounting for between study heterogeneity was source of subjects, with self-selected clinic attenders having the highest conversion rate. The most important factor accounting for heterogeneity within studies was cognitive testing, with poor performance predicting conversion with a high degree of accuracy. CONCLUSIONS: These data strongly support the notion that subjective and objective evidence of cognitive decline is not normal and predicts conversion to dementia. The more stringent the measures of both variables the better the prediction of conversion. Mild cognitive impairment, appropriately diagnosed, is a good measure with which to select subjects for disease modification studies.