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Biomedical subjects

Y Stern

Publications and source records attributed to Y Stern.

At least 19 recordsLinked to original sources

Familial aggregation of Alzheimer disease among whites, African Americans, and Caribbean Hispanics in northern Manhattan.

BACKGROUND: Alzheimer disease (AD) aggregates in families. OBJECTIVE: To compare the familial aggregation and lifetime risk of AD to the age of 90 years in the first-degree relatives of patients with AD and unrelated controls among Caribbean Hispanics, African Americans, and whites in Washington Heights, Manhattan, New York, NY. METHODS: Family history of AD and demographic information were obtained from informants of 435 patients with probable or possible AD concerning 1577 siblings and parents and from 1094 controls without dementia concerning 3952 siblings and parents. RESULTS: Lifetime risk of AD to the age of 90 years was 25.9% in relatives of patients and 19.1% in relatives of controls. Rate ratio (RR) for AD in relatives of patients compared with relatives of controls was 1.5 overall (95% confidence interval [CI], 1.2-1.9), and was greater for siblings (RR, 1.8; 95% CI, 1.2-2.5) than for parents (RR, 1.2; 95% CI, 0.9-1.8). Within ethnic groups, RR for AD among relatives was significantly elevated in whites (RR, 2.0; 95% CI, 1.2-3.3) and Hispanics (RR, 1.5; 95% CI, 1.1-2.1), but the difference did not reach statistical significance in African Americans (RR, 1.4; 95% CI, 0.7-2.7). Risk of AD was greater among relatives who were women compared with men (RR, 1.5; 95% CI, 1.2-1.9). CONCLUSIONS: Familial aggregation of AD was increased among families of patients compared with those of controls in all 3 ethnic groups. Risk of AD was highest among siblings and women relatives.

Aged

Spontaneous respiration anesthesia for respiratory papillomatosis.

Several anesthetic techniques for microlaryngeal laser surgery in children have been advocated. The objective of this study was to evaluate the operative conditions and safety of the spontaneous respiration anesthesia technique for carbon dioxide laser surgery in children with recurrent respiratory papillomatosis (RRP). The anesthetic and operative records of 60 pediatric patients with RRP who underwent microlaryngeal laser surgeries between 1991 and 1997 were reviewed. Papilloma location, severity of involvement, oxygen saturation, airway stability, need for intubation, duration of procedure, and complications were recorded. The patients underwent 744 surgical procedures. Two hundred two procedures were randomly studied (statistical power > or = 80%). The supraglottis and glottis were most commonly involved. Most of the papillomas were graded as moderate or severe disease. Complications occurred in 11 procedures. The surgical procedure was completed in all cases. No variable had predictive value regarding the outcome. Spontaneous respiration anesthesia is an efficient and relatively safe technique for microlaryngeal laser surgery in children with RRP.

Adolescent

Rate of memory decline in AD is related to education and occupation: cognitive reserve?

OBJECTIVE: To determine whether the rate of decline in performance on a memory test is more rapid in AD patients with higher versus lower educational and occupational attainment. BACKGROUND: Epidemiologic and imaging studies have suggested that, given comparable clinical severity of dementia, AD pathology is more advanced in patients with higher educational and occupational attainment. Because educational and occupational attainment should not influence the progression of AD pathology, and because severe AD pathology will eventually produce a mortality-causing condition, people with higher attainment might experience clinical AD for a shorter time and have a more rapid clinical progression. METHODS: A total of 177 AD patients were tested yearly for up to four study visits with the Selective Reminding Test (a memory test). Analysis of prospective change in the total recall score was performed by applying generalized estimating equations to regression analyses with repeated measures. RESULTS: At the initial visit, scores were comparable in the high- and low-education and the high- and low-occupation groups. Overall, memory scores declined by approximately 1 point yearly (p<0.01). There was a more rapid decline in memory scores in patients with higher educational (p<0.057) and higher occupational attainment (p<0.02). The authors then stratified patients based on their initial memory scores. The more rapid decline in memory scores associated with higher educational and occupational attainment was noted only in the group with low initial scores (p<0.05 for both). The full group and stratified group analyses were also repeated controlling for other potentially relevant variables including age, gender, race, ethnicity, and the presence of extrapyramidal signs, stroke, or at least one apolipoprotein E-epsilon4 allele. The results remained unchanged. CONCLUSIONS: Memory declined more rapidly in AD patients with higher educational and occupational attainment. This adds support to the idea that the discontinuity between the degree of AD pathology and the observed clinical severity of AD is mediated through some form of reserve.

Aged

Influence of APOE genotype on familial aggregation of AD in an urban population.

OBJECTIVE: To examine the influence of the proband's APOE genotype on AD among first-degree relatives in a community-based study of African Americans, whites, and Caribbean Hispanics. METHODS: History of AD and demographic information were obtained on 1,073 siblings and parents of 312 patients with AD and 2,722 siblings and parents of 802 nondemented controls. APOE genotyping was performed on all 1,114 patients and controls. RESULTS: A higher proportion of patients with AD (35%) than controls (27%) had one or more APOE-epsilon4 alleles (p = 0.03). When compared with relatives of controls without an APOE-epsilon4 allele, the risk for AD was increased in first-degree relatives of both patients (rate ratio [RR] = 1.9, 95% confidence interval [CI] = 1.2 to 3.1) and controls (RR = 1.8, 95% CI = 1.2 to 2.6) with one or more APOE-epsilone alleles, regardless of ethnic group. There was a similar trend of increased risk in relatives of patients without an APOE-epsilon4 allele, but this was limited to Hispanics and African Americans. CONCLUSIONS: The presence of an APOE-epsilon4 allele increases risk for AD among first-degree relatives, regardless of the probands' disease status, among all ethnic groups. Relatives of patients without an APOE-epsilon4 allele were also at increased risk for AD among Hispanics and African Americans, suggesting that other genes or risk factors may influence risk.

Aged

Low-density lipoprotein cholesterol and the risk of dementia with stroke.

CONTEXT: Next to Alzheimer disease, vascular dementia is the second most common form of dementia in the elderly, yet few specific risk factors have been identified. OBJECTIVE: To investigate the relationship of plasma lipids and lipoproteins to dementia with stroke. DESIGN AND SETTING: Prospective longitudinal community-based study over a 7-year period (1991-1998). PARTICIPANTS: A total of 1111 nondemented participants (mean [SD] age, 75.0 [5.9] years) were followed up for an average of 2.1 years (range, 1-7.8 years). MAIN OUTCOME MEASURE: Incident dementia with stroke according to standardized criteria, by baseline levels of total plasma cholesterol and triglycerides, low-density lipoprotein (LDL) cholesterol, LDL levels corrected for lipoprotein(a), high-density lipoprotein cholesterol, lipoprotein(a), and apolipoprotein E genotype. RESULTS: Two hundred eighty-six (25.7%) of the 1111 subjects developed dementia during follow-up; 61 (21.3%) were classified as having dementia with stroke and 225 (78.7%) as having probable Alzheimer disease. Levels of LDL cholesterol were significantly associated with an increased risk of dementia with stroke. Compared with the lowest quartile, the highest quartile of LDL cholesterol was associated with an approximately 3-fold increase in risk of dementia with stroke, adjusting for vascular risk factors and demographic variables (relative risk [RR], 3.1; 95% confidence interval [CI], 1.5-6.1). Levels of LDL corrected for lipoprotein(a) were an even stronger predictor of dementia with stroke in the adjusted multivariate analysis. Compared with the lowest quartile, the RR of dementia with stroke for the highest quartile of lipoprotein(a)-corrected LDL cholesterol was 4.1 (95% CI, 1.8-9.6) after adjusting for vascular factors and demographic variables. Lipid or lipoprotein levels were not associated with the development of Alzheimer disease in our cohort. CONCLUSIONS: Elevated levels of LDL cholesterol were associated with the risk of dementia with stroke in elderly patients. Further study is needed to determine whether treatment of elevated LDL cholesterol levels will reduce the risk of dementia with stroke.

Aged

Assessment of cognition in advanced AD: the test for severe impairment.

The Test for Severe Impairment (TSI) was compared with the Mini-Mental State Examination (MMSE) and a modified MMSE (mMMSE) in a multisite, longitudinal study of AD. The TSI correlated highly with the MMSE (r = 0.83) and the mMMSE (r = 0.82), but was not redundant. There was a wide range of scores on the TSI among those scoring in the severely impaired range on the MMSE and mMMSE. The slope of cognitive change over time detected by the TSI was greater than that revealed by the MMSE or the mMMSE. Performance on the TSI was a significant predictor of survival. The TSI is a valid measure that is sensitive to cognitive change over time in severely demented patients with AD.

Aged

Selective decline in memory function among healthy elderly.

OBJECTIVE: To use longitudinally acquired data to establish whether aging is associated with memory decline. BACKGROUND: Memory loss is one of the most frequent complaints among the elderly. Nevertheless, age-related memory decline remains controversial in large part because it has been established with cross-sectional studies. METHODS: A total of 212 community-based healthy people were followed prospectively and evaluated annually with a neuropsychological battery testing memory and other cognitive domains. To control for the learning effect-the improvement in test performance associated with repeated exposure-longitudinal performance was compared between two age groups. RESULTS: The older age group displayed a relative decline in memory performance with time. In contrast to memory, a relative age-related decline was not observed in tests of language, visuospatial ability, and abstract reasoning. Furthermore, within the memory domain, age-related decline was restricted to a specific aspect of memory, manifesting only in a measure sensitive to the acquisition and early retrieval of new information, and not in a measure of memory retention. This profile of age-related cognitive decline anatomically localizes to the hippocampal formation. CONCLUSION: This study establishes age-related memory decline using longitudinal data, and shows that this decline does not occur diffusely across multiple cognitive domains. Both early AD as well as non-AD processes likely contribute to age-related memory decline, and continued follow-up may reveal distinguishing features between these two.

Aged

The influence of smoking on the risk of Alzheimer's disease.

OBJECTIVE: To investigate the relationship between cigarette smoking and Alzheimer's disease (AD) in a prospective community-based study in northern Manhattan. BACKGROUND: Results from previous case-control studies suggest that there is a protective effect of smoking on AD. However, the recent prospective Rotterdam Study found that there was an increased risk of AD for smokers, particularly those without an apolipoprotein E (APOE)-epsilon4 allele. METHODS: The authors examined data from a community-based longitudinal study of local elders residing in northern Manhattan to determine whether tobacco use increases or decreases the risk of AD. Information regarding the frequency of tobacco use was obtained in structured interviews at the baseline assessment. Standardized clinical assessments were subsequently completed on each subject at annual visits during which incident cases of AD were identified. RESULTS: The relative risk (RR) of AD among former smokers was 0.7 (95% CI, 0.5 to 1.1). The RR among current smokers was 1.9 (95% CI, 1.2 to 3.0). Smokers without an APOE-epsilon 4 allele had the highest risk of AD (RR = 2.1; 95% CI, 2.1 to 3.7) compared with those with an APOE-epsilon 4 allele (RR = 1.4; 95% CI, 0.6 to 3.3). CONCLUSIONS: Our results are consistent with the observation that smoking increases the risk of AD. However, we found that among previous smokers who quit smoking, there may be a slight reduction in the risk of AD.

Aged

Risk of Alzheimer's disease in relatives of Parkinson's disease patients with and without dementia.

OBJECTIVE: To determine whether first-degree relatives of PD patients with dementia were at increased risk for the development of AD compared with first-degree relatives of nondemented PD patients and nondemented normal subjects from the community. METHODS: A structured family history interview was administered to 146 nondemented PD patients, 120 patients with PD and dementia, and 903 normal subjects from the community to ascertain the presence of AD among parents and siblings of these subjects. Cox proportional hazards models with double censoring techniques for missing information were used to model the risk of AD among relatives. RESULTS: No increase in risk of AD was found among parents of patients with PD and dementia or parents of nondemented PD patients compared with parents of normal subjects. However, siblings of demented PD patients were three times as likely (relative risk [RR] = 3.2, 95% confidence interval [CI] = 1.1 to 9.4, p < 0.04) as siblings of normal subjects to develop AD. When only siblings >65 years of age were considered, there was a fivefold increase in risk of AD among siblings of demented PD patients compared with siblings of normal subjects (RR = 4.9, 95% CI = 1.1 to 21.4, p < 0.03). The risk of AD was also increased for female relatives, regardless of whether the woman was a relative of a demented PD patient, a nondemented PD patient, or a normal subject. Ethnicity and APOE genotype did not affect dementia status among relatives. CONCLUSIONS: The increased risk of AD in siblings of demented PD patients compared with siblings of normal subjects supports the possibility of familial aggregation of AD and PD with dementia.

Aged

A clinicopathological comparison of community-based and clinic-based cohorts of patients with dementia.

OBJECTIVES: To compare the sensitivity and specificity of the clinical diagnosis of Alzheimer disease, the distribution of pathological causes, and the demographic and clinical characteristics of 2 different groups of patients with dementia. DESIGN: Retrospective clinicopathological study. SETTING: A memory disorder clinic in a university hospital and a multiethnic community. PATIENTS: Sixty-three patients from a memory disorder clinic and 26 patients from a large community-based study who underwent autopsy after clinical evaluation. MAIN OUTCOME MEASURES: Differential distribution of clinical and pathological findings, with clinicopathological correlations. RESULTS: Clinic patients were younger at diagnosis, more educated, and more likely to be white. Of the 63 clinic patients we evaluated, 29 (46%) had a pathological diagnosis of definite AD, 15 (24%) had a diagnosis of mixed AD, and 19 (30%) had a diagnosis of another type of dementia. The pathological diagnoses in the community patients were distributed as follows: 6 (23%) had definite AD, 6 (23%) had mixed AD, 6 (23%) had cerebrovascular disease, and 8 (31%) had another type of dementia. The difference in distribution of pathological diagnoses between these 2 groups was only significant for cerebrovascular diseases. For patients seen at the clinic, the sensitivity of the clinical diagnosis of AD was 98% and the specificity was 84%; for the community group, the sensitivity was 92% and the specificity was 79%. CONCLUSIONS: The difference in sensitivity and specificity of clinical diagnosis was not statistically significant between the groups of clinic patients and community patients. Dementia associated with cerebrovascular disease was more prevalent in the community sample. This difference may be attributable to clinical and demographic differences between the 2 groups.

Age Factors

Does the presence of a tracheoesophageal fistula predict the outcome of laryngeal cleft repair?

OBJECTIVE: To determine if the presence of a tracheo-esophageal fistula (TEF) alters outcome following laryngeal cleft repair. DESIGN: A retrospective review of patients diagnosed and treated for laryngeal clefts, with a minimum follow-up period of 1 year. SETTING: An academic tertiary care children's hospital. PATIENTS: Twenty-five pediatric patients diagnosed and surgically treated for laryngeal cleft. MAIN OUTCOME MEASURES: Each chart was reviewed to determine if patients with a laryngeal cleft had been diagnosed with TEF and had undergone a surgical TEF repair procedure. The success of the surgery was evaluated based on the resolution of symptoms and the endoscopic evaluation of the repair site. RESULTS: Twenty-five patients were reviewed for study purposes. Fourteen had a history of TEF repair and 11, no history of TEF. All 25 patients underwent surgical repair of the laryngeal cleft. Twelve of the 14 patients with a history of TEF repair experienced a breakdown of the laryngeal cleft repair. Only 1 of the 11 patients with no history of TEF experienced such a breakdown. In 8 of 9 patients with a laryngotracheoesophageal type I cleft, surgical repair was not successful. CONCLUSIONS: In our series, patients with laryngeal clefts who also had a history of TEF had a much higher incidence of breakdown of cleft repair compared with patients with no history of TEF. This finding is not conclusive and requires further investigation. The failure of cleft repair correlated with the severity of the cleft. The importance of these associations may lead to enhanced surgical planning and realistic preoperative family expectations.

Abnormalities, Multiple

Differential regional dysfunction of the hippocampal formation among elderly with memory decline and Alzheimer's disease.

The hippocampal formation is composed of separate anatomical regions interconnected to form a circuit, and investigating abnormal hippocampal function is most revealing at the level of these regions. Until recently, regional analysis of the hippocampal formation could be performed only in animals or in human postmortem tissue. Here, we report a method using functional magnetic resonance imaging that evaluates the hippocampal regions in vivo, and we use this method to study elderly with normal memory, with isolated memory decline, and with probable Alzheimer's disease (AD). Although age-related memory decline occurs commonly, the cause of this decline remains unknown, with disagreement as to whether this decline represents one or more etiologies. Analysis revealed two distinct patterns of regional dysfunction among elderly with isolated memory decline--one pattern similar to that found in elders with AD, involving all hippocampal regions, and a second pattern with dysfunction restricted to only one hippocampal region, the subiculum. These results offer direct evidence of hippocampal dysfunction associated with memory decline in the elderly, and implicate both predementia AD and non-AD processes as possible underlying causes.

Aged

Plasma amyloid beta-peptide 1-42 and incipient Alzheimer's disease.

Mutations in the amyloid precursor protein and presenilin 1 and 2 genes result in elevated plasma levels of the amyloid beta-peptide species terminating at amino acid residue 42 (A beta1-42). In a longitudinal study of unrelated elderly individuals, those who subsequently developed Alzheimer's disease had higher plasma levels of A beta1-42 at entry than did those who remained free of dementia. The results indicate that elevated plasma levels of the released A beta peptide A beta1-42 may be detected several years before the onset of symptoms, supporting that extracellular A beta1-42 plays an important role in the pathogenesis of late-onset Alzheimer's disease.

Age of Onset

Cerebral blood flow patterns underlying the differential impairment in category vs letter fluency in Alzheimer's disease.

Verbal fluency tasks are used to assess language functioning in Alzheimer's disease (AD), and performance typically declines as the disease progresses. However, several studies have shown that Category Fluency performance (produce words from a category) declines faster than Letter Fluency performance (produce words beginning with a certain letter), which is not the case for other dementias. The purpose of this study was to determine if each of these two types of fluency tasks was associated with different patterns of cerebral blood flow abnormality in AD. A resting, Xenon-inhalation regional cerebral blood flow measurement (133Xe rCBF) and neuropsychological evaluation was administered to 25 patients with probable AD and 24 healthy elderly controls. Stepwise regression using rCBF measures as predictor variables was used to predict Category and Letter Fluency performance, in both a combined group of patients and controls, and in the patient group alone. Correlations were also computed between rCBF variables and the difference between normatively corrected scores on each task for each subject, which characterized the extent of the discrepancy between them. In full sample regressions, both Category and Letter Fluency were predicted by education and the decline in left inferior parietal flow, a focal AD-related deficit. Additional variance in Category fluency, however, was predicted by global mean flow, while additional variance in Letter Fluency was predicted by frontal flow. Within the patient sample, in turn, the primary predictor of Category Fluency was mean flow; the primary predictor of Letter Fluency was left-sided frontal flow. Analysis of the fluency difference score revealed that relatively greater impairment of Category Fluency was associated with more typical, AD-related deficits in posterior temporal and parietal perfusion. When the two were equivalently impaired, typical AD-related deficits were accompanied by marked deficits in frontal perfusion. These findings are consistent with the underlying neuropsychology of these tasks, and suggest that Category Fluency's stronger association to the most typical CBF deficits of AD account for its greater sensitivity to this disease. Letter Fluency deficits, on the other hand, carry significant information about the degree to which perfusion deficits have spread to frontal cortex.

Aged

Effect of literacy on neuropsychological test performance in nondemented, education-matched elders.

The current investigation compared neuropsychological test performance among nondemented literate and illiterate elders. The sample included participants in an epidemiological study of normal aging and dementia in the Northern Manhattan community. All participants were diagnosed as nondemented by a neurologist, and did not have history of Parkinson's disease, stroke, or head injury. Literacy level was determined by self-report. MANOVAs revealed a significant overall effect for literacy status (literate vs. illiterate) on neuropsychological test performance when groups were matched on years of education. The overall effect of literacy status remained significant after restricting the analyses to elders with no formal education, and after controlling for the effects of language of test administration. Specifically, illiterates obtained lower scores on measures of naming, comprehension, verbal abstraction, orientation, and figure matching and recognition. However tests of verbal list delayed recall, nonverbal abstraction, and category fluency were unaffected by literacy status, suggesting that these measures can be used to accurately detect cognitive decline among illiterate elders in this sample. Differences in organization of visuospatial information, lack of previous exposure to stimuli, and difficulties with interpretation of the logical functions of language are possible factors that contribute to our findings.

Aged

Longitudinal changes in sexual risk behavior among HIV+ and HIV- male injecting drug users.

UNLABELLED: Injecting drug users (IDUs) play a prominent role in the transmission of human immunodeficiency virus (HIV), particularly in urban areas such as New York City, where they comprise nearly half of all adult acquired immunodeficiency syndrome (AIDS) cases. Intervention studies have demonstrated that IDUs are responsive to safer sex messages, but sexual behavior appears to be more resistant to change than drug use behavior. This multidisciplinary study (without an intervention component) assesses changes in sexual risk behavior as a function of time, HIV status, and disease progression in a cohort of HIV+ and HIV- male IDUs (N = 144) for 4 years. RESULTS: For HIV+ and HIV- men, there were increases in abstinence and monogamy, with decreases in the frequency of unprotected vaginal/anal sex and sexual risk index scores. With the exception of monogamy, HIV+ men reported lower levels of risk. Although there was also a decline in substance use, this accounted for only some of the decline in sexual risk behavior. Among the HIV+ men, a CD4 level below 200 was associated with more abstinence and monogamy. HIV-related medical symptoms were associated with increased abstinence, less unprotected sex, and lower sexual risk index scores. Lower neuropsychological memory test scores were associated with increased abstinence and lower sexual risk index scores. Neurological impairment and depression were not associated with sexual risk behavior. CONCLUSION: IDU men in New York City have modified their sexual behavior toward safer practices. Lower levels of risk are found among HIV+ men, particularly those with more progressed HIV illness. Nevertheless, a substantial amount of sexual risk behavior remained in this cohort, indicating the continued need for education and intervention.

Adult

Hospitalization and Alzheimer's disease: results from a community-based study.

BACKGROUND: Prior studies offer conflicting findings on whether Alzheimer's disease (AD) is associated with an increased risk of hospitalization. METHODS: We investigated AD and hospitalization in the Washington Heights-Inwood Columbia Aging Project (WHICAP), a community-based study of 2,334 elders in New York City. In 1996, an electronic medical records system was established that allows an e-mail alert to be sent to the research team whenever WHICAP subjects are admitted to Columbia-Presbyterian Medical Center (CPMC), the site of hospital care for the majority of subjects. RESULTS: Of the WHICAP cohort, 13.1% was admitted to CPMC in 21 months of follow-up; 17.5% of AD patients and 11.9% of unaffected subjects were admitted (p<.01). Multivariate logistic regression models showed that more advanced AD (Clinical Dementia Rating scale 3+) was a significant risk factor for hospitalization independently of age, gender, education, comorbid medical conditions, and death in the follow-up period (OR 2.3; 95% CI: 1.1, 4.6); subjects with mild or moderate AD did not show a significantly elevated risk. The prevalence of psychiatric symptoms did not differ between AD subjects who were hospitalized in the reporting period and AD subjects who were not hospitalized. Infectious disease was a more common discharge diagnosis for subjects with AD (p<.05). CONCLUSIONS: In this community-based cohort, subjects with severe AD were more likely to be hospitalized than unaffected subjects. The increased use of hospital care by these AD patients appears to be specific to AD but is not a result of psychiatric morbidity or end-of-life care. Rather, a greater risk of medical complications that require hospital care, especially infections, appears to be characteristic of severe AD.

Age Factors