Brain trauma is accompanied by regional alterations of brain metabolism, reduction in metabolic rates and possible energy crisis. We hypothesize that microdialysis markers of energy crisis are present during the critical period of intensive care despite the absence of brain ischemia. In all, 19 brain injury patients (mean GCS 6) underwent combined positron emission tomography (PET) for metabolism of glucose (CMRglu) and oxygen (CMRO 2 ) and cerebral microdialysis (MD) at a mean time of 36 h after injury. Microdialysis values were compared with the regional mean PET values adjacent to the probe. Longitudinal MD data revealed a 25% incidence rate of metabolic crisis (elevated lactate/pyruvate ratio (LPR)440) but only a 2.4% incidence rate of ischemia. Positron emission tomography imaging revealed a 1% incidence of ischemia across all voxels as measured by oxygen extraction fraction (OEF) and cerebral venous oxygen content (CvO 2 ). In the region of the MD probe, PET imaging revealed ischemia in a single patient despite increased LPR in other patients. Lactate/pyruvate ratio correlated negatively with CMRO 2 (Po0.001), but not with OEF or CvO 2 . Traumatic brain injury leads to a state of persistent metabolic crisis as reflected by abnormal cerebral microdialysis LPR that is not related to ischemia.

The major known genetic risk for Alzheimer's disease (AD), apolipoprotein E-4 (APOE-4), is associated with lowered parietal, temporal, and posterior cingulate cerebral glucose metabolism in patients with a clinical diagnosis of AD. To determine cognitive and metabolic decline patterns according to genetic risk, we investigated cerebral metabolic rates by using positron emission tomography in middle-aged and older nondemented persons with normal memory performance. A single copy of the APOE-4 allele was associated with lowered inferior parietal, lateral temporal, and posterior cingulate metabolism, which predicted cognitive decline after 2 years of longitudinal follow-up. For the 20 nondemented subjects followed longitudinally, memory performance scores did not decline significantly, but cortical metabolic rates did. In APOE-4 carriers, a 4% left posterior cingulate metabolic decline was observed, and inferior parietal and lateral temporal regions demonstrated the greatest magnitude (5%) of metabolic decline after 2 years. These results indicate that the combination of cerebral metabolic rates and genetic risk factors provides a means for preclinical AD detection that will assist in response monitoring during experimental treatments.apolipoprotein E ͉ positron emission tomography ͉ cerebral glucose metabolism ͉ age-associated memory impairment A lzheimer's disease (AD) accounts for approximately twothirds of late-life dementias, afflicting an estimated 8% of people age 65 years and older (1). In the United States alone, AD victims total nearly four million, and annual cost estimates, including caregiver productivity losses and costs of medical, long-term, and home care, approach $90 billion (2, 3). The disease's gradual decline in memory, other cognitive functions, behaviors, and daily functions progress until patients eventually require total care from others (4).Mild memory complaints build gradually years before patients develop dementia, and neurofibrillary tangles (5) and neuritic plaques (6), the neuropathological hallmarks of AD, are present in older persons with memory complaints too mild to warrant a diagnosis of dementia. Amyloid deposits have been observed in middle-aged nondemented persons decades before they reach the age at risk for late-onset AD (7). Moreover, diffuse plaques in nondemented elderly persons are associated with an accelerated age-related cortical cholinergic deficit, which could represent a clinical stage preceding dementia (8). Such observations have stimulated interest in ''preclinical'' AD markers aimed at identifying candidates who may benefit from novel antidementia treatments. Randomized, placebo-controlled trials of cholinesterase inhibitors, anti-oxidants, and anti-inflammatory agents are already in progress for such conditions as mild cognitive impairment (9) or age-associated memory impairment (AAMI) (10). These experimental drug trials use standard clinical examination methods to identify subjects and follow cognitive decline (4, 11). Because many people with mild memory c...

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