Many functional imaging studies have demonstrated age-related alterations in cerebral blood flow during the resting state. However, few studies have addressed possible differences in functional response to cerebral activation. We assessed the response of visual cortex to photic stimulation in 9 normal elderly subjects and 17 normal younger subjects with blood oxygenation level dependent functional magnetic resonance imaging. We found that the amplitude of response in elderly subjects was significantly decreased compared to younger subjects (2.5 +/- 1.0% versus 4.0 +/- 1.6%, p = 0.01), suggesting a reduction in functional activation or an age-related alteration in the coupling of blood oxygenation to focal activation.

Context.-Clinical observations and case reports suggest that there are important cerebrovascular complications of cocaine use, but no studies have documented a direct link. Objective.-To determine whether low-dose cocaine administration induces cerebral vasoconstriction in healthy cocaine users. Design.-Randomized controlled trial. Subjects.-Twenty-four healthy and neurologically normal men (mean age, 29 years) reporting median cocaine use of 8 lifetime exposures (range, 3 to Ͼ40). Intervention.-Double-blind intravenous administration of cocaine (0.4 or 0.2 mg/kg) or placebo, with cerebral magnetic resonance angiography performed at baseline and 20 minutes following infusion. Main Outcome Measure.-Cocaine-induced angiographic change indicative of vasoconstriction, as independently and concordantly rated by 2 reviewers blind to treatment condition. Results.-Cocaine-induced cerebral vasoconstriction in a dose-related fashion (P=.03), with angiograms indicative of vasoconstriction found in 5 of 8 and 3 of 9 subjects receiving 0.4-and 0.2-mg/kg cocaine, respectively, compared with 1 of 7 subjects administered placebo. Outcome stratification by frequency of self-reported lifetime cocaine use (3-10 times, 11-40 times, or Ͼ40 times) revealed a statistically stronger dose-related effect (PϽ.001), suggesting that greater lifetime cocaine use was associated with a greater likelihood of vasoconstriction. Conclusions.-Cocaine administration induced dose-related cerebral vasoconstriction on magnetic resonance angiograms. These changes occurred at low cocaine doses and in the absence of other risk factors, including polydrug abuse, hypertension, or cerebrovascular disease. Outcome stratification by prior cocaine use statistically strengthened the relationship between cocaine administration and vasoconstriction, suggesting that cocaine may have a cumulative residual effect in promoting cerebrovascular dysfunction.

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