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T Gomez-Isla

Publications and source records attributed to T Gomez-Isla.

25 records · Page 2Linked to original sources
PubMed1996

Apolipoprotein E and cognitive change in an elderly population.

The apolipoprotein E (apoE) epsilon 4 allele is overrepresented, and the apoE epsilon 2 allele underrepresented, in Alzheimer's disease. To assess the risk of cognitive impairment in individuals with these genotypes in the general population, we studied a population-based sample of 1,899 individuals 65 years and older as a follow-up to the Iowa 65+ Rural Health Study. Multiple regression and logistic regression analyses demonstrated significant effects of apoE epsilon 4 and apoE epsilon 2 in predicting performance on a delayed recall task over a 4- to 7-year period. The magnitude of this effect was, however, fairly modest, with odds ratios for developing impairment of approximately 1.37 (95% confidence interval: 1.007, 1.850; p = 0.045) for apoE epsilon 4 and 0.53 (95% confidence interval: 0.368, 0.777; p = 0.001) for apoE epsilon 2. These effects were more pronounced in women than men. Importantly, 85% of elderly apoE E4/4 individuals (average age, 81) scored in the unimpaired range on a screening mental status test. Thus, many individuals reach old age without cognitive impair- ment despite inheritance of one or two apoE epsilon 4 alleles. This suggests that apoE genotyping will have limited utility as a diagnostic or prognostic indicator of cognitive decline in individuals.

Aged↗
PubMed1996

A newly identified polymorphism in the apolipoprotein E enhancer gene region is associated with Alzheimer's disease and strongly with the epsilon 4 allele.

Apolipoprotein E allele 4 (apoE epsilon 4) is a major risk factor for late-onset AD. Inheritance of this allele is associated with an earlier age of onset of dementia in individuals with AD. It is unknown whether other polymorphisms in the apoE gene may influence the effect of apoE epsilon 4 on AD. We screened portions of the promoter enhancer element and of the apoE receptor binding domain for other polymorphisms that could affect risk of AD. In particular, a C/G polymorphism at position +113 of the apoE mRNA in the apoE intron 1 enhancer element (IE1) has been recently identified. We found no other polymorphisms. We studied the relationship of the two alleles of the IE1 polymorphism with AD and found an apparent association between IE1 G and AD (n = 94; p = 0.0515). However, the IE1 G allele is also closely associated with apoE epsilon 4 (p < 0.0001). When the presence of apoE epsilon 4 is covaried, the association between the IE1 G allele and AD is no longer statistically significant (odds ratio = 1.29, 95% confidence interval: 0.44, 3.78). In contrast, epsilon 4 is still highly associated with AD when IE1 G is controlled for (odds ratio = 5.91, 95% confidence interval: 3.29, 10.63). Furthermore, there is no significant association between the age of onset of dementia and the inheritance of the G allele. We believe that the apparent association between IE1 G and AD is a consequence of the association between the epsilon 4 and IE1 G alleles.

Adult↗
PubMed1996

Apolipoprotein E genotype does not influence rates of cognitive decline in Alzheimer's disease.

BACKGROUND: Inheritance of the apolipoprotein E (apoE) epsilon 4 allele is a risk factor for developing Alzheimer's disease (AD) and is associated with a lower age of dementia onset. The purpose of this study was to determine whether apoE genotypes differentially influence the course of cognitive decline in AD dementia. METHODS: We administered nine cognitive tests that assessed explicit memory, attention, language, visuospatial function, frontal-lobe function, and logical reasoning abilities to 66 probable AD patients every 6 to 24 months over a span of up to 5.5 years. We identified apoE genotype by a PCR-based method; there were 16 patients with epsilon 3/3, 34 with epsilon 3/4, and 16 with epsilon 4/4. Using regression statistical methods, we computed the change in performance for each test for each patient over time. We then analyzed the mean change in each test in patients grouped according to apoE genotype. RESULTS: For the AD patients as a group, performance on all cognitive tests declined significantly over time, but the rate of decline did not vary significantly across apoE genotypes on any cognitive test. Specifically, the rate of cognitive decline was not faster in patients with an epsilon 4 allele than in those with epsilon 3/3. CONCLUSIONS: These results indicate that the mechanism placing individuals with an epsilon 4 allele at risk for developing AD does not influence the rate of cognitive decline. These observations imply that the influence of apoE epsilon 4 either precedes or occurs at an early point in the AD disease process.

Aged↗
PubMed1995

Apolipoprotein E epsilon 4 and cerebral hemorrhage associated with amyloid angiopathy.

Cerebral amyloid angiopathy (CAA) is characterized by cerebrovascular deposition of the amyloid beta-peptide, leading to intracerebral hemorrhage in severe cases. Other than rare familial cases, the only identified risks for CAA are advancing age and accompanying Alzheimer's disease. We tested whether the apolipoprotein E epsilon 4 (apoE epsilon 4) allele was associated with CAA and hemorrhage and whether this association was independent of Alzheimer's disease. The apoE epsilon 4 genotype was determined without knowledge of the pathology for 93 postmortem cases systematically graded for severity of CAA and for 15 patients with CAA-associated intracerebral hemorrhage. We found a significant and independent effect of the apoE genotype in both cohorts. Among the postmortem cases, the presence of apoE epsilon 4 increased the odds ratio for moderate or severe CAA by 2.9-fold, relative to cases without epsilon 4; two copies of epsilon 4 increased the odds ratio 13.1-fold. In the cohort of CAA-associated cerebral hemorrhages, the apoE epsilon 4 allele frequency was 0.40, significantly greater than the control frequency of 0.14. The increase in CAA remained even after controlling for the presence of Alzheimer's disease, suggesting that apoE epsilon 4 is a risk factor for CAA and CAA-related hemorrhage, independent of its association with Alzheimer's disease.

Alleles↗