Search PubMed⌕ Search

Biomedical subjects

R Duara

Publications and source records attributed to R Duara.

At least 19 recordsLinked to original sources
PubMed1996

Risk of dementia among relatives of Alzheimer's disease patients in the MIRAGE study: What is in store for the oldest old?

Despite recent advances in the molecular genetics of Alzheimer's disease (AD), several fundamental questions concerning risk of illness are unresolved, namely, if Mendelian factors account for the incidence of the disease, and if AD is an inevitable consequence of the aging process. This study was designed to address these issues and other aspects of familial aggregation of the disorder. A consecutive sample of 1,694 patients who met criteria for a diagnosis of probable or definite AD were ascertained in 13 centers participating in the Multi-Institutional Research in Alzheimer Genetic Epidemiology (MIRAGE) project. Lifetime risk and age at onset of AD among various strata of 12,971 first-degree relatives was estimated using survival analysis procedures. The lifetime risk of AD in first-degree relatives was 39.0% +/- 2.1% by age 96 years. Age-specific risk of AD declined after age 90 and the data set included 61 apparently unaffected persons who survived to age 96 without becoming demented. Female relatives had a higher risk of AD than male relatives at all ages. By age 80, children of conjugal AD couples had a cumulative risk of 54%, 1.5 times greater than the sum of the risks to children having affected mothers or fathers, and nearly 5 times greater than the risk to children having normal parents. Children of affected fathers had a cumulative risk that was 1.4 times the corresponding risk to children of affected mothers. Risk assessment in early-onset and late-onset families, using various strategies for determining the age cut-off, yielded contradictory results. These data suggest the following: (1) the lifetime risk among relatives does not support a simple autosomal dominant inheritance pattern of disease; (2) women are innately more susceptible to AD than men; (3) the proportion of hereditary cases may be higher in men than women; (4) distinction between early- onset and late-onset forms of AD has little meaning in the absence of a biological marker; (5) the risk of AD decreases after age 90; and (6) AD therefore may not be an inevitable concomitant of the aging process, a conclusion that has profound implications for basic and applied AD research. The age- and sex-specific lifetime risks derived from this study are sufficiently robust to be a reliable source of information for counseling relatives of AD patients.

Age Factors↗
PubMed1996

Alzheimer's disease: interaction of apolipoprotein E genotype, family history of dementia, gender, education, ethnicity, and age of onset.

We evaluated 197 patients with predominantly late-onset Alzheimer's disease (AD) who belonged to several ethnic groups and analyzed the relationship of age of onset of AD to the presence or absence of several risk factors in this entire group of patients. The apolipoprotein E (apoE) epsilon 4 allele frequency, which was 29% in all patients (compared with the reported population mean of 13.7%, p < 0.001, did not vary significantly between ethnic groups but declined significantly with increasing age. The apoE epsilon 2 allele frequency was 3%, compared with the reported population mean of 7.4% (p = 0.001). The frequency of a positive family history of dementia in first-degree relatives (FH +) (overall 45%) did not vary significantly between ethnic groups. ApoE epsilon 4-positive (epsilon 4+) patients tended to have a higher FH + rate (58%) than apoE epsilon 4-negative (epsilon 4-) patients (40%) (p = 0.02). When the potential risk factors of gender, education, FH+ status, and epsilon 4+ status were examined together in a multiple linear-regression analysis, FH+ and epsilon 4+ status (but not gender or education) were significant (they were both associated with an earlier age of onset of AD). In a post-hoc analysis, we found a reduced age of onset in women, but not men, who were both FH + and epsilon 4+. Additionally, those probands who were epsilon 4+ were more likely to inherit the disease from their mothers than their fathers. The mechanism by which epsilon 4+ and FH+ status operate as risk factors may be by their effect on the age of onset of AD.

Black or African American↗
PubMed1996

Evidence for major gene inheritance of Alzheimer disease in families of patients with and without apolipoprotein E epsilon 4.

Apolipoprotein E (APOE) genotype is the single most important determinant to the common form of Alzheimer disease (AD) yet identified. Several studies show that family history of AD is not entirely accounted for by APOE genotype. Also, there is evidence for an interaction between APOE genotype and gender. We carried out a complex segregation analysis in 636 nuclear families of consecutively ascertained and rigorously diagnosed probands in the Multi-Institutional Research in Alzheimer Genetic Epidemiology study in order to derive models of disease transmission which account for the influences of APOE genotype of the proband and gender. In the total group of families, models postulating sporadic occurrence, no major gene effect, random environmental transmission, and Mendelian inheritance were rejected. Transmission of AD in families of probands with at least one epsilon 4 allele best fit a dominant model. Moreover, single gene inheritance best explained clustering of the disorder in families of probands lacking epsilon 4, but a more complex genetic model or multiple genetic models may ultimately account for risk in this group of families. Our results also suggest that susceptibility to AD differs between men and women regardless of the proband's APOE status. Assuming a dominant model, AD appears to be completely penetrant in women, whereas only 62%-65% of men with predisposing genotypes develop AD. However, parameter estimates from the arbitrary major gene model suggests that AD is expressed dominantly in women and additively in men. These observations, taken together with epidemiologic data, are consistent with the hypothesis of an interaction between genes and other biological factors affecting disease susceptibility.

Adult↗
PubMed1995

Evidence that the APOE locus influences rate of disease progression in late onset familial Alzheimer's Disease but is not causative.

An association has been observed in several independent data sets between late onset Alzheimer's Disease (AD) and the APOE locus on chromosome 19. We have examined the genotype in family history positive (FHP) and family history negative (FHN) cases and find a distortion of the APOE allele frequencies in accord with previous studies. However, when we examined the allele distribution of the at-risk siblings of the FHP group we found an excess of the epsilon 4 allele which also differs significantly from historic controls but not from the affected siblings. The age distribution of the affected and unaffected siblings was similar, suggesting that the allelic frequency distortion in the unaffected siblings was not due to their being below the mean age of onset. Lod score linkage analysis, with age dependent onset and non-stringent specification of the genetic parameters, did not suggest linkage to the APOE locus. Furthermore, an analysis of variance of the age of disease free survival suggested that APOE genotype contributes a small fraction of the total variance indicating that the APOE locus is a poor predictor of disease free survival age within late onset families. One explanation for the age dependent association reported by other groups, and our results, is that the APOE locus enhances the rate of progression of the disease process in otherwise predisposed individuals and that variation at this locus is not able in and of itself to cause the disease. We suggest this hypothesis is compatible with the current literature regarding APOE and AD.

Age Factors↗
PubMed1995

Deterioration of functional capacities in Alzheimer's disease after a 1-year period.

There is a paucity of data regarding Alzheimer's disease (AD) patients' longitudinal deterioration in the ability to conduct numerous activities required for daily living. In this study, 52 patients with AD were assessed at baseline and at a 1-year follow-up using the Direct Assessment of Functional Status (DAFS) scale, an objective, well-validated measure of a broad spectrum of functional capacities that is administered within the clinical setting. An important finding was that the level of initial performance on each of the 11 functional tasks measured did not relate to the degree of functional decline in that particular area. Communication skills, such as using the telephone (deterioration among 35.4% of the patients) and preparing a letter for mailing (deterioration among 32.7%), showed the most frequent deterioration among patients upon follow-up. More than half of the AD patients studied demonstrated impairment on one or both of these measures. The pattern of findings indicates that many subtests of the DAFS were sensitive to functional decline after a 1-year period and that the scale has utility in objectively establishing longitudinal patterns of deterioration.

Aged↗
PubMed1995

South Florida Program on Aging and Health. Assessing the prevalence of Alzheimer's disease in three ethnic groups.

The South Florida Program on Aging and Health was initiated in 1992 with the aim to assess physical and mental health of the elderly in Dade County and provide a basis for public health policy. This report describes the methodology applied in the study and preliminary screening results in a probability sample of 2,400 African American, Cuban American and white non-Hispanic American elderly men and women. Of 2,013 participants screened by May 1995, 11.5% had cognitive impairment. An increase in prevalence from 4-7% to 25-36% with advancing age was found among men and women of each group, from the youngest (65-74) to the oldest (85+ years). Male and female prevalences were similar but vary by ethnic group and age.

Black or African American↗
PubMed1994

Apperceptive visual agnosia: a case study.

A man with an infarction of his inferior temporal and occipital association cortex bilaterally, which spared primary visual cortex, had impaired visual recognition of objects, faces, colors, words, and gestures. Analysis of visual function indicated that the recognition failures resulted from an agnosia, rather than elemental visual impairment. Whereas his impairment of gesture recognition appeared to be related to an associative agnosia, his inability to recognize objects was related to an apperceptive agnosia. There may be four subtypes of apperceptive agnosia: one where the internal object representations or structural descriptions are impaired, another where an adequate percept cannot be derived, a third where the internal referent and percept are dissociated, and a fourth where both levels are impaired. Our patient demonstrated a failure to relate individual elements to the whole, a failure to integrate multiple elements, and a reliance on global perception. He had normal object imagery. These results suggest that, whereas internal representations were intact, he was unable to form adequate perceptual representations.

Aged↗
PubMed1994

Neural-network classification of normal and Alzheimer's disease subjects using high-resolution and low-resolution PET cameras.

UNLABELLED: Neural-network classification methods were applied to studies of FDG-PET images of the brain acquired from a total of 77 "probable" Alzheimer's disease and 124 normal subjects at two different centers. METHODS: Classification performances, as determined by relative-operating-characteristic (ROC) analyses of cross-validation experiments, were measured for FDG PET images obtained with either a 15-mm FWHM PETT V or a 6-mm FWHM Scanditronix PC-1024-7B camera for various methods of data representation. Neural networks were trained to distinguish between normal and abnormal subjects on the basis of regional metabolic patterns. For both databases, classification performance could be improved by increasing the "resolution" of the representation (decreasing the region size) and by normalizing the regional metabolic values to the value of a reference region (occipital region). RESULTS: The optimal classification performance for Scanditronix data (ROC area = 0.95) was higher than that for PETT V data (ROC area = 0.87). Under Bayesian theory, the classification performance with Scanditronix data corresponded to an ability to change a pre-test probability of disease of 50% to a post-test probability of either 90% for a positive classification or 10% for a negative classification. CONCLUSION: This classification can be used to either strongly confirm or rule out the presence of abnormalities.

Aged↗
PubMed1993

Temporal lobe surface area measurements on MRI in normal and dyslexic readers.

In a neuroanatomical study of dyslexia, measurements were made of the superior surface of the temporal lobe (SSTL) on MRI scans in a sample of 17 dyslexics and 21 non-dyslexic subjects. Both anterior and posterior halves of the SSTL area showed significant leftward asymmetry in non-dyslexics, but showed symmetry in dyslexics. The total SSTL area showed greater leftward asymmetry in non-dyslexics than in dyslexics. The dyslexics also revealed a significant correlation (r = 0.69, P = 0.005) between Woodcock-Johnson Passage Comprehension scores and posterior SSTL asymmetry, such that those with higher scores had more leftward asymmetry. This suggests that among dyslexics the direction of SSTL asymmetry may serve as a risk factor and/or a marker for the severity of reading comprehension problems.

Adolescent↗
PubMed1993

A comparative analysis of neuropsychological test performance of Spanish-speaking and English-speaking patients with Alzheimer's disease.

Because the diagnosis of dementia is highly dependent on the identification of neuropsychological deficits, there have been increasing concerns regarding cultural bias in tests designed to measure cognitive and intellectual function in English-speaking and Spanish-speaking adults. Despite their widespread clinical use, the effects of potential cultural bias on these measures among these two groups are largely unknown. We assembled a group of 76 females who received an NINCDS-ADRDA clinical diagnosis of Alzheimer's disease (AD). Half of these subjects were primary Spanish speakers, and the other half reported English as their primary language. All subjects were matched on chronological age and severity of memory impairment. Factors such as educational attainment and depression were entered into the analyses as covariates. The two groups were compared with respect to their performance on a battery of neuropsychological tests that are representative of what is typically used to diagnose the presence and severity of dementia. The finding that Spanish-speaking AD patients scored lower on specific neuropsychological measures is discussed in terms of inherent language biases and the possible lack of saliency of a number of these tests. The results obtained further suggest the need to modify certain neuropsychological indices so that they will better serve diverse ethnic and cultural groups.

Aged↗
PubMed1993

Analysis of the c-FOS gene on chromosome 14 and the promoter of the amyloid precursor protein gene in familial Alzheimer's disease.

The c-FOS gene product, a putative transacting transcriptional regulator of the amyloid precursor protein (APP) gene, is a candidate locus for the familial Alzheimer's disease (FAD) mutation on chromosome 14 (FAD14). In light of this functional relationship, we investigated the nucleotide sequence and segregation of c-FOS and the nucleotide sequence of the 5' APP promoter. Single-stranded conformational polymorphisms (SSCPs) in the c-FOS gene revealed that c-FOS closely cosegregates with the FAD14 gene but does not show allelic association with FAD. A conservative third-position T-->C mutation was demonstrated in exon 2 (codon 84) of c-FOS, and a C-->G substitution was detected at -209 bp in the 5' promoter of APP. Neither were unique to FAD and are unlikely to be pathogenic or secondary modifiers of the FAD phenotype. We conclude that the c-FOS open reading frame is probably not the site of the FAD14 locus, but we cannot exclude the existence of modifier loci on chromosome 21.

Adult↗
PubMed1993

A comparison of familial and sporadic Alzheimer's disease.

Using a liberal criterion, a conservative probability-based criterion, and a criterion for autosomal dominant inheritance, we classified 36%, 13.5%, and 6.4% of 311 patients, respectively, as having familial Alzheimer's disease (FAD). The mean age of onset was over 70 years for all three categories of FAD. FAD and sporadic Alzheimer's disease (SAD) cases did not differ in clinical features, incidence of risk factors for dementia, or MRI or PET features. We observed earlier age of onset of AD to be related positively to longer duration of disease. Except for the autosomal dominant AD group, there was an earlier age of onset in FAD probands. The inheritance of AD from mothers was from 1.7 to 3.6 times more frequent than from fathers. Among SAD patients only, we found a preponderance of women, who were more frequently affected than would be expected from the male/female ratio in the general population of the same average age. Language performance tended to be less affected in FAD than in SAD patients, contrary to some previous reports.

Aged↗
PubMed1992

Viability of neocortical function shown in behavioral activation state PET studies in Alzheimer disease.

Twenty subjects with mildly to moderately severe Alzheimer disease (AD) and 14 normal elderly control subjects were studied using [18F]fluorodeoxyglucose and positron emission tomography (PET) to investigate regional cerebral glucose metabolism during both a resting state and a behavioral activation state, utilizing a reading memory task (RMT). The RMT produced significant global metabolic activation of 15 +/- 15% in normal subjects and 11 +/- 13% in AD subjects. The occipital regions were preferentially activated, but all regions in both groups were also significantly activated. The RMT did not allow a better discrimination of AD patients from normal controls on the basis of regional metabolic deficits. Regions in the AD group that were individually classified as hypometabolic during rest also exhibited metabolic activation. The apparent viability of hypometabolic regions in AD patients challenges current hypotheses regarding the cause of abnormal metabolism in AD.

Alzheimer Disease↗
PubMed1992

Genetic evidence for a novel familial Alzheimer's disease locus on chromosome 14.

Familial Alzheimer's disease (FAD) has been shown to be genetically heterogeneous, with a very small proportion of early onset pedigrees being associated with mutations in the amyloid precursor protein (APP) gene on chromosome 21, and some late onset pedigrees showing associations with markers on chromosome 19. We now provide evidence for a major early onset FAD locus on the long arm of chromosome 14 near the markers D14S43 and D14S53 (multipoint lod score z = 23.4) and suggest that the inheritance of FAD may be more complex than had initially been suspected.

Aged↗
PubMed1992

A comparative analysis of functional status among Spanish- and English-speaking patients with dementia.

The assessment of functional capacity is regarded as an important part of a comprehensive diagnostic work-up for dementia. However, there is a paucity of data regarding comparative functional performance among different ethnic/cultural groups. In this study, we compared Spanish- and English-speaking dementia patients and normal controls on a comprehensive functional assessment battery administered within the clinical setting. Despite equivalent levels of cognitive impairment, Spanish-speaking dementia patients evidenced more difficulties on certain functional tasks relative to their English-speaking counterparts. On the other hand, Spanish- and English-speaking controls did not differ with regards to their functional performance. Results suggest that the extent of deterioration in specific functional subskills may be related to the degree to which they have been overlearned and practiced. Further, they indicate the potential utility of direct functional assessment in both Spanish- and English-speaking populations.

Activities of Daily Living↗
PubMed1992

Evaluation of a neural-network classifier for PET scans of normal and Alzheimer's disease subjects.

The value of PET as an objective diagnostic tool for dementia may depend on the degree to which abnormal metabolic patterns can be detected by quantitative classification methods. In these studies, a neural-network classifier based on coarse region of interest analyses was used to classify normal and abnormal FDG-PET scans. The performance of neural networks and of an expert reader were evaluated by cross-validation testing. When the "abnormal" class was represented by subjects with clinical diagnoses of "Probable Alzheimer's," the areas under the relative-operating-characteristic (ROC) curves were 0.85 and 0.89 for the neural network and the expert reader, respectively. When testing with abnormal subjects represented by "Possible AD" cases, ROC areas for both the network and the expert were 0.81. The neural network out-performed discriminant analysis. It is concluded that PET has potential for the detection of abnormal brain function in dementing diseases, and that the combination of neural networks and PET is a useful diagnostic tool. Despite the low-resolution "view" afforded the neural network, its performance was nearly equivalent to that of an expert reader.

Adult↗
PubMed1991

Neuroanatomic differences between dyslexic and normal readers on magnetic resonance imaging scans.

The areas of six bilateral brain segments in the right and left hemispheres, on a horizontal brain section, and the area of subdivisions of the corpus callosum, on a midsagittal brain section, were measured on magnetic resonance images obtained from 21 dyslexic and 29 control subjects. In the entire group, the frontal half of the horizontal brain section showed asymmetry, with the right side being larger, whereas posteriorly only the occipital polar segment was asymmetrical, with the left side being larger. Dyslexic subjects exhibited asymmetry, with the right side greater than the left side, in contrast to the relatively symmetrical pattern that is normally observed in the midposterior segment that corresponds to the angular gyrus. In the corpus callosum, dyslexic subjects were found to have a larger splenium than nondyslexic subjects, and dyslexic female subjects were found to have a larger splenium than dyslexic male subjects. Because transcallosal pathways connecting the left and right angular gyrus regions traverse through the splenium of the corpus callosum, the above findings in dyslexic subjects suggest an anatomic abnormality in the angular gyrus region.

Adult↗