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Raj C Shah

Publications and source records attributed to Raj C Shah.

8 recordsLinked to original sources

Decision rules guiding the clinical diagnosis of Alzheimer's disease in two community-based cohort studies compared to standard practice in a clinic-based cohort study.

We developed prediction rules to guide the clinical diagnosis of Alzheimer's disease (AD) in two community-based cohort studies (the Religious Orders Study and the Rush Memory and Aging Project). The rules were implemented without informant interviews, neuroimaging, blood work or routine case conferencing. Autopsies were performed at death and the pathologic diagnosis of AD made with a modified version of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria. We compared the positive predictive value of the clinical diagnosis in the two community-based studies to the positive predictive value of the clinical diagnosis of AD made by standard clinical practice in a clinic-based cohort study using AD pathology as the gold standard. Of 306 clinic cases with probable AD, 286 (93.5%) met CERAD neuropathologic criteria for AD; the results were comparable for those with possible AD (51 of 54, 94.4%). Of 141 study subjects with probable AD, 130 (92.2%) met CERAD neuropathologic criteria for AD; the results were lower but acceptable for those with possible AD (26 of 37, 70.3%). The results were similar in secondary analyses using alternate neuropathologic criteria for AD. The clinical diagnosis of AD can be made in community-based studies without the use of informant interviews, neuroimaging, blood work or routine case conferencing. This approach holds promise for reducing the operational costs of epidemiologic studies of aging and AD.

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Hippocampal disconnection contributes to memory dysfunction in individuals at risk for Alzheimer's disease.

The concept of amnestic mild cognitive impairment (MCI) describes older people who show a decline predominantly in memory function, but who do not meet criteria for dementia. Because such individuals are at high risk for developing Alzheimer's disease, they are of great interest for understanding the prodromal stages of the disease process. The mechanism underlying memory dysfunction in people with MCI is not fully understood. The present study uses quantitative, high-resolution structural MRI techniques to investigate, in vivo, the anatomical substrate of memory dysfunction associated with MCI. Changes in brain structures were assessed with two imaging techniques: (i) whole-brain, voxel-based morphometry to determine regions of reduced white matter volume and (ii) sensitive volumetric segmentation of the entorhinal cortex and hippocampus, gray matter regions that are critically important for memory function. In participants with amnestic MCI, compared with age-matched controls, results showed a significant decrease in white matter volume in the region of the parahippocampal gyrus that includes the perforant path. There was also significant atrophy in both the entorhinal cortex and the hippocampus. Regression models demonstrated that both hippocampal volume and parahippocampal white matter volume were significant predictors of declarative memory performance. These results suggest that, in addition to hippocampal atrophy, disruption of parahippocampal white matter fibers contributes to memory decline in elderly individuals with MCI by partially disconnecting the hippocampus from incoming sensory information.

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The relation of cigarette smoking to incident Alzheimer's disease in a biracial urban community population.

The relationship between smoking status and incident Alzheimer's disease (AD) was investigated in a random stratified sample of a biracial community in Chicago. Analyses are based on 1,064 persons (of 1,134 evaluated) who had data on smoking status, disease incidence, and key covariates such as apolipoprotein allele status. During a mean of about 4 years of follow-up, 170 persons met criteria for incident AD. Current smoking was associated with increased risk of incident AD (OR = 3.4, 95% CI = 1.4-8.0) compared to persons who never smoked. There was no apparent increase in risk of AD for former smokers compared to persons who never smoked (OR = 0.9, 95% CI = 0.5-1.7). Apolipoprotein E allele status modified this association in that former smokers with a upsilon4 allele were less likely to develop AD (p = 0.04) than those who never smoked. Former smokers also appeared to have a reduced risk of developing AD as their pack-years of smoking increased (p = 0.02)such that the odds of developing AD increased by 50% for every 10 years of smoking cessation (OR = 1.3, CI = 0.9-1.7). The results suggest that older people who currently smoke are more likely to develop AD compared to those who never smoked; the relation between those who used to smoke but quit and the risk of AD is complex and requires further research.

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Personality and incident disability in older persons.

OBJECTIVE: to examine the relation of personality to the development of disability in old age. METHODS: participants are 813 older Catholic nuns, priests and brothers without dementia or disability at study onset. As part of a uniform baseline evaluation, they completed standard measures of the five principal dimensions of personality. Disability was assessed at baseline and annually thereafter with the Katz scale. The relation of each trait to incident disability was assessed in proportional hazard models controlled for age, sex, education and selected clinical variables. RESULTS: during a mean of about 6 years of observation, 255 persons (31%) became dependent on at least one activity of daily living. Risk of becoming disabled was 85% [95% confidence interval (CI) = 80.5-89.6%] lower in persons with high (90th percentile) compared to low (10th percentile) extraversion and 50% (95% CI = 46.6-54.2%) lower in those with high compared to low conscientiousness, and controlling for chronic medical conditions, depressive symptoms or social and cognitive activity did not substantially affect these associations. By contrast, neuroticism had a marginal association with disability risk that was eliminated after controlling for depressive symptomatology, and openness and agreeableness were unrelated to disability risk. CONCLUSIONS: The results suggest that higher levels of extraversion and conscientiousness may be associated with a reduced risk of incident disability in old age.

Activities of Daily Living↗

Blood pressure and lower limb function in older persons.

BACKGROUND: Factors contributing to gait difficulties in elderly persons are considered to be multifactorial and are not well understood. The purpose of this study was to examine the association of blood pressure (BP) with change in lower limb function in older persons. METHODS: Eight hundred eighty-eight older Catholic clergy members without baseline dementia or Parkinson's disease were recruited from about 40 groups across the United States. At baseline, BP was measured, the presence of vascular diseases and diabetes was recorded, cognitive function was assessed, and medications were inspected. At baseline and subsequent annual visits, gait and balance were assessed using performance-based tasks from which a previously established composite measure of lower limb function was derived. RESULTS: In a general estimating equation analysis controlling for age, education, and gender, a 10 mmHg increment in systolic blood pressure (SBP) was associated with greater decline in lower limb function (estimate of interaction = -6.35 x 10(-3), standard error = 2.49 x 10(-3), p =.011). Thus, on average, lower limb function declined 28.7% faster in persons with an SBP of 160 mmHg than in persons with an SBP of 120 mmHg. This effect was unchanged after controlling for baseline vascular diseases, diabetes, or cognition. However, censoring individuals who developed stroke during the study made the relationship between SBP and change in lower limb function nonsignificant. CONCLUSIONS: SBP may be associated with decline in lower limb function in older persons.

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Relation of blood pressure to risk of incident Alzheimer's disease and change in global cognitive function in older persons.

PURPOSE: To examine the relation of systolic and diastolic blood pressure to incident Alzheimer's disease (AD) and rate of cognitive change. METHODS: Longitudinal cohort study with annual clinical evaluations. At baseline, blood pressure was measured, apolipoprotein E (APOE) genotyping was performed, and medications were reviewed. RESULTS: 824 older Catholic clergy members without baseline dementia were recruited from across the United States. During a mean of about 6 years of observation, 151 persons developed AD. In a proportional hazards model adjusted for age, sex and education, neither systolic (relative risk = 0.995; 95% CI: 0.986, 1.004, p = 0.249) nor diastolic (relative risk = 1.000; 95% CI: 0.985, 1.015, p = 0.975) blood pressure was related to AD incidence. In mixed effects models, neither systolic nor diastolic blood pressure was related to level or to annual rate of change on a global measure of cognition. These results did not change in subsequent models that accounted for the use of medications with antihypertensive properties or for the possession of an APOE epsilon4 allele. CONCLUSIONS: In a cohort of older persons with a majority taking medications with antihypertensive properties, we did not find a relationship between blood pressure and risk of AD or cognitive decline.

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Harm avoidance and disability in old age.

The relation of personality to disability in old age is not well understood. The authors examined the relation of harm avoidance, a trait indicating a tendency to worry, fear uncertainty, be shy, and tire easily, to disability in a group of 474 older persons without dementia. Participants completed the 35-item Harm Avoidance scale. Disability was assessed with the Rosow-Breslau scale, a self-report measure of physical mobility. Performance-based tests of lower limb functions were also administered from which composite measures of gait, balance, and strength were derived. In a logistic regression model controlled for age, sex, education, and lower limb function, persons with high levels of harm avoidance were nearly three times as likely to report mobility limitations as persons with low levels, and these effects largely reflected fatigability and fear of uncertainty. The association of harm avoidance with disability was not explained or modified by frailty, physical activity, depressive symptoms, neuroticism, extraversion, or cognition. The results suggest that harm avoidance is associated with disability in old age.

Activities of Daily Living↗