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...

No abstract

No abstract

Structured psychiatric interviews were administered to 60 children with complex partial seizure disorder (CPS). 40 children with primary generalized epilepsy with absences (PGE), and 48 control children, aged 5 to 16 years. Significantly more patients with epilepsy had psychiatric diagnoses compared with the control children. There were no statistically significant differences, however, in the number of patients with CPS and PGE with psychiatric diagnoses. Other than a schizophrenia‐like psychosis found only in the patients with CPS, the two groups of patients had similar psychiatric diagnoses. The presence of psychopathology was related to significantly lower IQ scores and socioeconomic status, but not to seizure‐related factors. These findings suggest that the psychopathology of children with CPS and PGE reflects different subtle neuropsychological deficits.