Beta-amyloid associated differential effects of APOE ε4 on brain metabolism in cognitively normal elderly.

OBJECTIVE: Although apolipoprotein (APOE) ε4 allele is a well-established risk factor for late-onset Alzheimer disease (AD), the mechanism of its effects on AD pathogenesis is not fully understood. We aimed to investigate the effects of APOE genotype on regional cerebral glucose metabolism in cognitively normal (CN) elderly. We further tried to elucidate whether or not such effects are associated with beta-amyloid protein (Aß) deposition. METHODS: 31 CN elderly participants underwent clinical examination, a range of neuropsychological tests, APOE genotyping, and Pittsburgh compound-B- and fluorodeoxyglucose-PET scans. RESULTS: 17 APOE ε4 carriers and 15 non-carriers were included. Both hypometabolic and hypermetabolic regions were observed in ε4 carriers compared with noncarriers when age, education, and sex were controlled. When the degree of global cerebral Aß deposition was adjusted, the hypometabolic regions in the temporo-parietal area (i.e., BA 22 and 39) largely disappeared, whereas the hypermetabolic regions persisted in medial frontal and anterior temporal areas (i.e., BA 38, 11, and 39). Behaviorally, verbal episodic memory scores of APOE ε4 carriers were slightly lower than those of noncarriers, though still within normal range. CONCLUSIONS: Our findings indicate that decreased cerebral glucose metabolism in the temporoparietal junction associated with APOE ε4 in CN elderly appears to be mediated by Aß deposition, and the effect of APOE ε4 on hypermetabolism in the frontal and anterior temporal regions is independent of Aß and may be associated with presence of compensatory mechanism in CN elderly with the ε4 allele.

Development of the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet (CERAD-K): clinical and neuropsychological assessment batteries.

A Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet (CERAD-K) was created. The English-American version of CERAD clinical and neuropsychological assessment batteries was translated into Korean, and the psychometrical properties of the cognitive tests in the CERAD-K were established. In the translation, including back-translation, the basic structures of all measures in the original CERAD batteries were maintained. The CERAD-K was administered in a standardized manner to 106 dementia patients (aged 70.4 +/- 8.1 years), including 78 Alzheimer's disease (AD) patients, and 186 controls (aged 68.4 +/- 4.6 years) who were recruited from 3 university hospitals and 2 elderly welfare centers. The cognitive tests in the CERAD-K successfully differentiated controls from the dementia patients and from the AD patients. They also showed substantial interrater reliability and 1-month test-retest reliability. The CERAD-K is an equally reliable and valid equivalent for the English version of the CERAD clinical and neuropsychological assessment batteries.

Influence of the apolipoprotein E type 4 allele on cerebral glucose metabolism in Alzheimer's disease patients.

It is still unclear whether apolipoprotein E epsilon 4 (APOE E4) influences the cerebral glucose metabolism abnormalities found in Alzheimer's disease (AD), although APOE E4 is a well-known risk factor for AD. [(18)F]Fluorodeoxyglucose PET was conducted in patients with very mild (n=17), mild (n=27), and moderate-to-severe (n=19) AD. The presence of APOE E4 was associated with greater reduction of glucose metabolism in the left inferior temporal region in very mild AD but neither in mild nor in moderate-to-severe AD. These findings favor the hypothesis that APOE E4 is related mainly to the development of AD, not to its progression.

A normative study of the CERAD neuropsychological assessment battery in the Korean elderly.

This study aimed to explore the effects of age, education and gender on the performance of eight tests in the Korean version of the CERAD neuropsychological assessment battery and to provide normative information on the tests in the Korean elderly. The battery was administered to 618 healthy volunteers aged from 60 to 90. People with serious neurological, medical and psychiatric disorders, including dementia, were excluded. Multiple linear regression analyses were performed to assess the relative contribution of the demographic factors on the score of each cognitive test. Age, education, and gender were found to have significant effects on the performance of many tests in the battery. Based on these results, 4 overlapping age normative tables (60 to 74, 65 to 79, 70 to 84, and 75 to 90 years of age) with 3 educational strata (0 to 3 years, 4 to 6 years, and 7 years and more) for both genders are presented. The normative information will be useful for a clinical interpretation of the CERAD neuropsychological battery in Korean elderly as well as for comparing the performance of the battery across countries.