Biomedical subjects

Sujuan Gao

Publications and source records attributed to Sujuan Gao.

18 recordsLinked to original sources

PubMed2007

A mixed-effects model for cognitive decline with non-monotone non-response from a two-phase longitudinal study of dementia.

Most longitudinal studies of elderly are characterized by substantial drop-out due to death and many other factors beyond the control of the investigators. In a two-phase longitudinal study of dementia, subjects with cognitive impairment skip the first phase survey in the next follow-up, leading to intermittent missing variables measured in that phase. In the context of analysing pre-dementia cognitive decline in an elderly population, both of the two causes of non-response can potentially be informative in the sense that the missingness is dependent on the unobserved outcome. To take these factors into account, mixed-effects models are constructed to allow the outcome and the multiple causes of missing values to share the same 'random parameter' or random effect. The crucial assumption of our model is that the random effects of the model for the outcome and that of the model for the missing-data indicators are linked in a deterministic manner. It can be thought of as an approximation of a more general and realistic situation, in which the two models have distinct, yet dependent, random effects. We conduct a simulation study to investigate possible deviations of the estimates under such a scenario. A second simulation illustrates the magnitude of the bias in estimating the difference of decline rate between two groups when the random effects are linked in different manners for the two groups.

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PubMed2006

Association of apolipoprotein E genotype and Alzheimer disease in African Americans.

BACKGROUND: Alzheimer disease (AD) is the most frequent cause of dementia. Even though the incidence of AD in the African American population is similar to or higher than that in persons of European descent, AD in African Americans is understudied. Identification of genetic risk factors in African Americans is essential for understanding the etiology of AD. OBJECTIVE: To determine the effect of apolipoprotein E (APOE) genotype on the risk of AD in elderly African Americans. DESIGN: Population-based longitudinal study of AD. SETTING: Indianapolis, Ind. PARTICIPANTS: African Americans 65 years and older. MAIN OUTCOME MEASURES: APOE genotype and diagnosis of AD. RESULTS: The APOE genotype was determined in 1822 samples. Of these, 690 were clinically evaluated: 318 were normal, and 162 had a diagnosis of AD. The presence of APOE epsilon4 was significantly associated with increased risk of AD (epsilon3/epsilon4: OR, 2.32; 95% confidence interval [CI], 1.41-3.82; and epsilon4/epsilon4: OR, 7.19; 95% CI, 3.00-17.29, compared with the epsilon3/epsilon3 genotype). There was also a significant protective effect with APOE epsilon2 (epsilon2/epsilon2 and epsilon2/epsilon3: OR, 0.42; 95% CI, 0.20-0.89). CONCLUSIONS: These findings are in marked contrast to the lack of association between APOE and AD in the Ibadan, Nigeria, sample of this project. These results suggest that other genetic factors and different environmental influences may play a role in the risk for AD in individuals of African ancestry.

Black or African American↗

PubMed2006

APOE epsilon4 is not associated with Alzheimer's disease in elderly Nigerians.

Since 1992, research teams from Indiana University and the University of Ibadan have been collecting and comparing data from two diverse, elderly populations to identify risk factors for dementia and Alzheimer's disease. Apolipoprotein E (APOE) was genotyped in 2,245 Nigerian samples. Of these, 830 had a diagnosis: 459 were normal, and 140 had dementia including 123 diagnosed with Alzheimer's disease. In contrast with other populations, the APOE epsilon4 allele was not significantly associated with Alzheimer's disease or dementia. This lack of association in the Yoruba might reflect genetic variation, environmental factors, as well as genetic/environmental interactions.

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PubMed2006

Validation analysis of informant's ratings of cognitive function in African Americans and Nigerians.

OBJECTIVES: To examine informant validity using the Community Screening Interview for Dementia (CSI 'D') both cross-sectionally and longitudinally in two very different cultures and to explore the effects of informants and study participants' characteristics on the validity of informants' reports. METHODS: Elderly African Americans age 65 years and older residing in Indianapolis, USA and elderly Yoruba Nigerians age 65 years and older residing in Ibadan, Nigeria were assessed on cognitive functioning using the CSI 'D' at baseline (1992-1993) and five-year follow-up (1997-1998). At baseline, the informant validity in both samples was evaluated against participants' cognitive tests using Pearson correlation and regular regression models. At follow-up, informants ratings on cognitive decline were assessed against participants' cognitive decline scores from baseline to follow-up using biserial correlation and logistic regressions. RESULTS: At baseline, informants' reports on cognitive functioning significantly correlated with cognitive scores in both samples (Indianapolis:r = -0.43, p < 0.001; Ibadan:r = -0.47, p < 0.001). The participant-informant relationships significantly affected the informants' reports in the two samples with different patterns (p = 0.005 for Indianapolis and p < 0.001 for Ibadan) at a given level of cognitive functioning. African Americans spouses reported more cognitive problems, while siblings reported more problems for the Yoruba Nigerians. At follow-up, informants' ratings on cognitive decline significantly correlated with the cognitive decline scores (Indianapolis r = 0.38, p < 0.001; Ibadan r = 0.32, p < 0.001). The characteristics of study participants and informants had little impact on the informants' ratings on cognitive decline. CONCLUSIONS: Informant reports are valid in assessing the cognitive functioning of study participants both cross-sectionally and longitudinally in two very different cultures, languages and environments.

Black or African American↗

PubMed2005

Activity and connectivity of brain mood regulating circuit in depression: a functional magnetic resonance study.

BACKGROUND: Functional imaging studies indicate that imbalances in cortico-limbic activity and connectivity may underlie the pathophysiology of MDD. In this study, using functional Magnetic Resonance Imaging (fMRI), we investigated differences in cortico-limbic activity and connectivity between depressed patients and healthy controls. METHODS: Fifteen unmedicated unipolar depressed patients and 15 matched healthy subjects underwent fMRI during which they first completed a conventional block-design activation experiment in which they were exposed to negative and neutral pictures. Next, low frequency blood oxygenation dependent (BOLD) related fluctuations (LFBF) data were acquired at rest and during steady-state exposure to neutral, positive and negative pictures. LFBF correlations were calculated between anterior cingulate cortex (ACC) and limbic regions--amygdala (AMYG), pallidostriatum (PST) and medial thalamus (MTHAL) and used as a measure of cortico-limbic connectivity. RESULTS: Depressed patients had increased activation of cortical and limbic regions. At rest and during exposure to neutral, positive, and negative pictures cortico-limbic LFBF correlations were decreased in depressed patients compared to healthy subjects. CONCLUSIONS: The finding of increased activation of limbic regions and decreased LFBF correlations between ACC and limbic regions is consistent with the hypothesis that decreased cortical regulation of limbic activation in response to negative stimuli may be present in depression.

Adult↗

PubMed2005

The Stick Design test: a new measure of visuoconstructional ability.

Visuoconstructional ability is an important domain for assessment in dementia. Use of graphomotor measures dominate this area; however, participants with low education produce results that cannot be easily interpreted. Our objective was to develop and validate a nongraphomotor assessment of visuoconstructional ability for use in dementia evaluations in persons with low or no education. In a longitudinal, population-based study of dementia among Yoruba residents of Ibadan, Nigeria aged 65 years and older, participants underwent clinical assessment with a battery of cognitive tests and consensus diagnosis. Performance on two visuoconstructional tests, Constructional Praxis and Stick Design, were compared. Gender, age, and education affected performance on both tests. The Stick Design test was more acceptable than Constructional Praxis as measured by the number of participants with total test failure (3.9% vs. 15.1%). The Stick Design test was significantly more sensitive to cognitive impairment and dementia than the Constructional Praxis test. We conclude that Stick Design is a reasonable test of visuoconstructional ability in older cohorts with very limited educational exposure and literacy.

Aged↗

PubMed2005

Antidepressant effect on connectivity of the mood-regulating circuit: an FMRI study.

The mechanisms by which antidepressant-induced neurochemical changes lead to physiological changes in brain circuitry and ultimately an antidepressant response remain unclear. This study investigated the effects of sertraline, a selective serotonin reuptake inhibitor antidepressant, on corticolimbic connectivity, using functional magnetic resonance imaging (fMRI). In all, 12 unmedicated unipolar depressed patients and 11 closely matched healthy control subjects completed two fMRI scanning sessions at baseline and after 6 weeks. Depressed patients received treatment with sertraline between the two sessions. During each fMRI session, subjects first completed a conventional block-design experiment. Next, connectivity between cortical and limbic regions was measured using correlations of low-frequency blood oxygen level-dependent (BOLD) fluctuations (LFBF) during continuous exposure to neutral, positive, and negative pictures. At baseline, depressed patients had decreased corticolimbic LFBF correlations compared to healthy subjects during the resting state and on exposure to emotionally valenced pictures. At rest and on exposure to neutral and positive pictures, LFBF correlation between the anterior cingulate cortex and limbic regions was significantly increased in patients after treatment. However, on exposure to negative pictures, corticolimbic LFBF correlations remained decreased in depressed patients. The results of this study are consistent with the hypothesis that antidepressant treatment may increase corticolimbic connectivity, thereby possibly increasing the regulatory influence of cortical mood-regulating regions over limbic regions.

Adult↗

PubMed2004

A shared random effect parameter approach for longitudinal dementia data with non-ignorable missing data.

A significant source of missing data in longitudinal epidemiologic studies on elderly individuals is death. It is generally believed that these missing data by death are non-ignorable to likelihood based inference. Inference based on data only from surviving participants in the study may lead to biased results. In this paper we model both the probability of disease and the probability of death using shared random effect parameters. We also propose to use the Laplace approximation for obtaining an approximate likelihood function so that high dimensional integration over the distributions of the random effect parameters is not necessary. Parameter estimates can be obtained by maximizing the approximate log-likelihood function. Data from a longitudinal dementia study will be used to illustrate the approach. A small simulation is conducted to compare parameter estimates from the proposed method to the 'naive' method where missing data is considered at random.

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PubMed2004

Selecting pre-screening items for early intervention trials of dementia--a case study.

Our goal was to review and extend statistical methods for discriminating between normal subjects and those with dementia or cognitive impairment. We compared six different methods to one constructed by expert opinion, in their brevity and predictive power. The methods include logistic regression and neural networks, with standard and least absolute shrinkage and selection operator (LASSO) variable selection, as well as decision trees with and without boosting. These methods were applied to the baseline data of a subgroup of subjects in a dementia study, using their screening interview items to predict their clinical diagnosis of normal or non-normal (cognitively impaired or demented). The derived models were then validated on a different subgroup of subjects in the same study who had the screening and clinical diagnosis two to five years later. Performance of different models was compared based on their sensitivity and specificity in the validation sample. Generally, the six statistical methods performed slightly to moderately better than the expert-opinion model. Neural networks generally performed better than the logistic and decision tree models. LASSO improved the performance of logistic and neural network models, but it eliminated few input variables in the neural network. The single decision tree performed at least as well as the standard logistic model, and with fewer items, making it an attractive pre-screening tool. Using the boosting option for decision trees did not substantially improve the performance. We recommend that for each situation, different methods of classification should be attempted to obtain optimal results for a given purpose.

Black or African American↗

PubMed2004

Alzheimer's disease, genes, and environment: the value of international studies.

OBJECTIVE: To describe the construction of a disease model incorporating both genetic an environmental factors in the etiology of Alzheimer's disease (AD), using data generated from the Indianapolis-Ibadan dementia project (I-IDP). METHOD: The I-IDP is a longitudinal comparative study of the prevalence and incidence o dementia in 2 communities: elderly African Americans living in Indianapolis, Indiana, an Yoruba living in Ibadan, Nigeria. RESULTS: African Americans are more than twice as likely as Yoruba to develop AD. Possible explanations for this finding include genetic factors: the possession of the apolipoprotein E epsilon4 allele does not increase risk for AD among Yoruba but confers a sligh increase in AD risk for African Americans. As well, environmental factors may play a role: African Americans have a higher risk of vascular risk factors than do Yoruba. CONCLUSIONS: International comparative studies, particularly those involving population from developing and developed countries, offer a unique opportunity for applying new in formation regarding population genetics to traditional AD risk factor research.

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PubMed2003

An illness-death stochastic model in the analysis of longitudinal dementia data.

A significant source of missing data in longitudinal epidemiological studies on elderly individuals is death. Subjects in large scale community-based longitudinal dementia studies are usually evaluated for disease status in study waves, not under continuous surveillance as in traditional cohort studies. Therefore, for the deceased subjects, disease status prior to death cannot be ascertained. Statistical methods assuming deceased subjects to be missing at random may not be realistic in dementia studies and may lead to biased results. We propose a stochastic model approach to simultaneously estimate disease incidence and mortality rates. We set up a Markov chain model consisting of three states, non-diseased, diseased and dead, and estimate the transition hazard parameters using the maximum likelihood approach. Simulation results are presented indicating adequate performance of the proposed approach.

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PubMed2003

Connected speech intelligibility of children with cochlear implants and children with normal hearing.

The objective of this study was to compare the connected speech intelligibility of children who use cochlear implants with that of children who have normal hearing. Previous research has shown that speech intelligibility improves from before cochlear implantation to after implantation and that the speech intelligibility of children who use cochlear implants compares favorably with that of children who use conventional hearing aids. However, no research has yet addressed the question of how the speech intelligibility of children who use cochlear implants compares to that of children with normal hearing. In the current study, archival data on connected speech intelligibility from 51 children with cochlear implants were compared with newly collected data from 47 children with normal hearing. Results showed that for children with cochlear implants, greater intelligibility was associated with both increased chronological age and increased duration of cochlear implant use. Consistent with previous studies, children with normal hearing achieved adult-like or near-adult-like intelligibility around the age of 4 years, but a similar peak in intelligibility was not observed for the children who used cochlear implants. On the whole, children with cochlear implants were significantly less intelligible than children with normal hearing, when controlling both for chronological age and for length of auditory experience. These results have implications for the socialization and education of children with cochlear implants, particularly with respect to on-time placement in mainstream educational environments with age peers.

Child↗

PubMed2003

The effect of short-term auditory deprivation on the control of intraoral pressure in pediatric cochlear implant users.

The purpose of this study was to determine whether 2 speech measures (peak intraoral air pressure [IOP] and IOP duration) obtained during the production of intervocalic stops would be altered as a function of the presence or absence of auditory stimulation provided by a cochlear implant (CI). Five pediatric CI users were required to produce repetitions of the words puppy and baby with their CIs turned on. The CIs were then turned off for 1 hr, at which time the speech sample was repeated with the CI still turned off. Seven children with normal hearing formed a comparison group. They were also tested twice, with a 1-hr intermediate interval. IOP and IOP duration were measured for the medial consonant in both auditory conditions. The results show that auditory condition affected peak IOP more so than IOP duration. Peak IOP was greater for /p/ than /b/ with the CI off, but some participants reduced or reversed this contrast when the CI was on. The findings suggest that different speakers with CIs may use different speech production strategies as they learn to use the auditory signal for speech.

Air Pressure↗

PubMed2003

Apolipoprotein E and mortality in African-Americans and Yoruba.

The literature on the association between apolipoprotein E (ApoE) and mortality across ethnic and age groups has been inconsistent. No studies have looked at this association in developing countries. We used data from the Indianapolis-Ibadan Dementia study to examine this association between APOE and mortality in 354 African-Americans from Indianapolis and 968 Yoruba from Ibadan, Nigeria. Participants were followed up to 9.5 years for Indianapolis and 8.7 years for Ibadan. Subjects from both sites were divided into 2 groups based upon age at baseline. A Cox proportional hazards regression model adjusting for age at baseline, education, hypertension, smoking history and gender in addition to time-dependent covariates of cancer, diabetes, heart disease, stroke, and dementia was fit for each cohort and age group. Having ApoE epsilon4 alleles significantly increased mortality risk in Indianapolis subjects under age 75 (hazard ratio: 2.00; 95% CI: 1.19-3.35; p = 0.0089). No association was found in Indianapolis subjects 75 and older (hazard ratio: 0.71; 95% CI: 0.45-1.10; p = 0.1238), Ibadan subjects under 75 (hazard ratio: 1.04; 95% CI: 0.78 to 1.40; p = 0.7782), or Ibadan subjects over 75 (hazard ratio: 1.21; 95% CI: 0.83 to 1.75; p = 0.3274).

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PubMed2003

A latent variable model approach for assembling and scoring screening tests for dementia.

In dementia studies, the diagnosis of dementia often relies on results of screening tests aimed at measuring various dimensions of cognitive functions. The current practice of scoring a screening test involves simply summing the correct responses from each item. However, this method may be imprecise and inefficient in the predictive power of the score for dementia. We propose a latent variable model approach for the scoring and item selection of such tests. We model the item responses to be random variables based on latent variables. We also model the disease outcomes to be a function of the latent variables. Maximum likelihood estimates are obtained by maximizing the joint likelihood functions of disease and the item responses over a specified distribution function for the latent variables. Variances of model parameters are estimated using a nonparametric bootstrap method. We illustrate the approach using a screening test for dementia from a community-based study.

Aged↗

PubMed2002

Preservation of cognitive function with antihypertensive medications: a longitudinal analysis of a community-based sample of African Americans.

BACKGROUND: Results of previous studies of white older adults suggest that antihypertensive medications preserve cognition. We assessed the long-term effect of antihypertensive medications on cognitive function in a community sample of African American older adults. METHODS: We conducted longitudinal surveys and clinical assessment of cognitive function in a random sample of 2212 community-dwelling African Americans 65 years and older. We identified 1900 participants without evidence of cognitive impairment at baseline, 1617 of whom had subsequent follow-up information, and 946 of whom had blood pressure measurements. Cognitive function was measured at baseline and at 2 and 5 years by means of scores on the Community Screening Instrument for Dementia and neuropsychological and clinical assessment for dementia and cognitive impairment. Prescription and nonprescription medication use was derived from in-home inspection of medications and participant and informant reports. RESULTS: Of 1900 participants, 288 (15.2%) developed incident cognitive impairment. Using logistic regression to control for the effects of age, sex, education, baseline cognitive scores, and hypertension and angina or myocardial infarction, we found that antihypertensive medications reduced the odds of incident cognitive impairment by 38% (odds ratio, 0.62; 95% confidence interval, 0.45-0.84). Corresponding analysis using blood pressure measurements on the subset of participants was inconclusive. CONCLUSION: Antihypertensive medication use is associated with preservation of cognitive function in older African American adults.

Black or African American↗

PubMed2002

Risk of mortality for dementia in a developing country: the Yoruba in Nigeria.

BACKGROUND: Limited data exist on the impact of dementia in developing nations, including its association with mortality. OBJECTIVE: The purpose of this paper is to assess the relationship between dementia and five-year mortality on a community dwelling elderly Yoruba population in the developing country of Nigeria and to compare those results with those from an elderly African-American community in Indianapolis. METHODS: A two-phase design was used to ascertain dementia status in two sites. In the first phase, the Community Screening Instrument for Dementia (CSI-D) was administered. In the second phase, subjects were sampled for the clinical assessment according to their CSI-D performance category. Proportional hazards regression was used to assess the relationship between mortality and cognitive status at both sites after adjusting for demographics and chronic disease conditions. RESULTS: For the entire screened population, poor and intermediate performance on the CSI-D is associated with increased mortality at both sites; however the effect of CSI-D performance did not significantly differ between the two sites. For the clinically assessed sample, dementia was significantly associated with increased mortality at both sites (Ibadan RR = 2.83, Indianapolis RR = 2.05), but the effect was not significantly different across the two sites. CONCLUSION: Dementia resulted in an increased risk of mortality for Yoruba of a magnitude similar to African-Americans suggesting that the impact of dementia on mortality risk may be similar for developing and developed countries.

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PubMedDate not supplied

International studies in dementia with particular emphasis on populations of African origin.

Epidemiologic studies on dementia generally have 2 major interacting objectives: descriptive, where rates of dementia and Alzheimer Disease (AD) are calculated for communities and selected populations, and analytic, which attempt to explain the observed phenotypic variations in communities and populations by identifying disease risk factors. The public health benefits derived from descriptive studies are exemplified by the recent published review of the global prevalence of dementia under the auspices of Alzheimer Disease International. This review emphasized the enormous and growing burden associated with dementia particularly for countries in the developing world and outlined strategies to influence policy making, planning, and healthcare allocation. One interesting feature of descriptive studies on dementia is that although the few epidemiologic studies conducted in Africa suggest that rates of dementia and AD are relatively low, rates of AD and dementia have been reported to be relatively high for African Americans. The Indianapolis-Ibadan Dementia Project has reported that the incidence rates for AD and dementia in Yoruba are less than half the incidence rates for AD and dementia in African Americans. Analytic studies are now underway to identify risk factors that may account for these rate differences. The risk factor model being applied, attempts to identify not only putative genetic and environmental factors but also their interactions. So far the major findings have included: apolipoprotein E e4, a major risk factor for AD in most populations, is also a risk factor for AD in African Americans but not for Yoruba; African Americans are at higher risk not only for AD, but also for diseases associated with increased cardiovascular risk such as hypertension, diabetes, and metabolic syndrome; African Americans have higher rates of hypercholesterolemia than Yoruba: there is an interaction between apolipoprotein E e4, cholesterol, and AD risk in both Yoruba and African Americans. We eventually hope to create a risk factor model that will not only account for the dementia rate differences between Yoruba and African Americans, but also help explain dementia rates in other developing and developed countries.

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