Biomedical subjects

Y Stern

Publications and source records attributed to Y Stern.

At least 19 recordsLinked to original sources

PubMed2001

Influence of leisure activity on the incidence of Alzheimer's disease.

OBJECTIVE: To determine whether leisure activities modify the risk for incident dementia. BACKGROUND: Although high educational and occupational attainments have been associated with reduced risk of incident dementia, the relation between leisure activities and dementia risk has not been adequately investigated. METHODS: A total of 1,772 nondemented individuals aged 65 years or older, living in northern Manhattan, New York, were identified and followed longitudinally in a community-based cohort incidence study. Subjects' leisure activities at baseline were assessed, annual examinations with the same standardized neurologic and neuropsychological measures were performed for up to 7 years (mean 2.9 years), and incident dementia was assessed as the main outcome measure. Cox proportional hazards models, adjusting for age, ethnic group, education, and occupation, were used to estimate the relative risk (RR) of incident dementia associated with high leisure activities. RESULTS: Of the 1,772 subjects, 207 became demented. The risk of dementia was decreased in subjects with high leisure activities (RR, 0.62; 95% CI 0.46 to 0.83). The association of high leisure with decreased RR of incident dementia was present even when baseline cognitive performance, health limitations interfering with desired leisure activities, cerebrovascular disease, and depression were considered. CONCLUSIONS: The data suggest that engagement in leisure activities may reduce the risk of incident dementia, possibly by providing a reserve that delays the onset of clinical manifestations of the disease.

Age Factors↗

PubMed2001

Chromosome-12 mapping of late-onset Alzheimer disease among Caribbean Hispanics.

Linkage to chromosome 12p for familial Alzheimer disease (AD) has been inconsistent. Using 35 markers near the centromere of chromosome 12, we investigated 79 Caribbean Hispanic families with AD. Two-point linkage analysis using affected sib pairs yielded LOD scores of 3.15 at D12S1623 and 1.43 at D12S1042. The LOD score at D12S1623 decreased to 1.62 in families with late-onset (age >65 years) AD (LOAD), but the LOD score at D12S1042 was unchanged. Among families negative for the apolipoprotein E (APOE-epsilon 4) allele, the LOD score for D12S1623 was lower (1.01), whereas that for D12S1042 increased to 1.73. Among families positive for the APOE-epsilon 4 allele, none of the LOD scores reached 1. Multipoint affected-relative-pair analysis showed peaks at D12S1623 (nonparametric linkage [NPL] score 1.52; P=.028) and near D12S1042, at D12S1057 (NPL score 1.57; P=.027). NPL scores for both D12S1623 and D12S1057 increased in families affected with LOAD, but, in APOE-epsilon 4-negative families, only scores for the region flanking D12S1623 remained elevated (NPL score 1.74; P=.013). This study of Caribbean Hispanics with familial AD extends and provides modest evidence of linkage to loci on chromosome 12p. Linkage varied by age at onset of AD and by the presence or absence of the APOE-epsilon 4 allele.

Adult↗

PubMed2001

A founder mutation in presenilin 1 causing early-onset Alzheimer disease in unrelated Caribbean Hispanic families.

CONTEXT: Genetic determinants of Alzheimer disease (AD) have not been comprehensively examined in Caribbean Hispanics, a population in the United States in whom the frequency of AD is higher compared with non-Hispanic whites. OBJECTIVE: To identify variant alleles in genes related to familial early-onset AD among Caribbean Hispanics. DESIGN AND SETTING: Family-based case series conducted in 1998-2001 at an AD research center in New York, NY, and clinics in the Dominican Republic. PATIENTS: Among 206 Caribbean Hispanic families with 2 or more living members with AD who were identified, 19 (9.2%) had at least 1 individual with onset of AD before the age of 55 years. MAIN OUTCOME MEASURE: The entire coding region of the presenilin 1 gene and exons 16 and 17 of the amyloid precursor protein gene were sequenced in probands from the 19 families and their living relatives. RESULTS: A G-to-C nucleotide change resulting in a glycine-alanine amino acid substitution at codon 206 (Gly206Ala) in exon 7 of presenilin 1 was observed in 23 individuals from 8 (42%) of the 19 families. A Caribbean Hispanic individual with the Gly206Ala mutation and early-onset familial disease was also found by sequencing the corresponding genes of 319 unrelated individuals in New York City. The Gly206Ala mutation was not found in public genetic databases but was reported in 5 individuals from 4 Hispanic families with AD referred for genetic testing. None of the members of these families were related to one another, yet all carriers of the Gly206Ala mutation tested shared a variant allele at 2 nearby microsatellite polymorphisms, indicating a common ancestor. No mutations were found in the amyloid precursor protein gene. CONCLUSIONS: The Gly206Ala mutation was found in 8 of 19 unrelated Caribbean Hispanic families with early-onset familial AD. This genetic change may be a prevalent cause of early-onset familial AD in the Caribbean Hispanic population.

Age of Onset↗

PubMed2001

Mortality and apolipoprotein E in Hispanic, African-American, and Caucasian elders.

To investigate whether mortality risk is influenced by apolipoprotein E (APOE) genotype and whether the risk differs by ethnicity, we compared the mortality risk in 2,112 individuals > or = 65 years of age residing in northern Manhattan in New York. Mortality risks associated with the APOE genotype, adjusted for sex, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides, differed significantly by ethnic group. Among Caucasian and Hispanics, the E2/E3 genotype was associated with the lowest mortality risk in the multivariate Cox proportional hazards modeling, adjusted for lipid levels, whereas mortality risk did not differ substantially between the E4/E3 and E3/E3 genotypes. Among African-Americans, the E2/E3 genotype was not associated with the lowest mortality risk, but the E4/E3 genotype was. Adjustment for heart disease, diabetes, and stroke reduced mortality risk associated with each genotype by about 50% for all ethnic groups, but the patterns remained the same. Although we cannot rule out the possibility of a healthy survival bias, our analyses designed to examine healthy survival by comparing risk of mortality in groups who were younger or older at entry do not support this possibility. Our findings suggest that the APOE genotype is associated with mortality and that the genotypic risks differ by ethnic group. Nearly 50% of the mortality risk associated with the APOE genotype appears to act through major chronic diseases, but those diseases only partially explain the mechanism by which the genotypic risk acts. To better understand the observed ethnic differences in mortality risk by genotype, a detailed prospective study is needed to examine the relationships among APOE, other candidate genes, health conditions, and eventual death.

Aged↗

PubMed2001

Diabetes mellitus and risk of Alzheimer's disease and dementia with stroke in a multiethnic cohort.

Research on the relation between diabetes mellitus and dementia has produced conflicting results, and the relation has not been investigated among Blacks and Hispanics. In this study, Cox proportional hazards models were used to analyze longitudinal data from 1,262 elderly subjects without dementia at baseline (1991-1996) who were followed for an average of 4.3 years between 1992 and 1997. Outcomes were incident Alzheimer's disease and dementia associated with stroke. The prevalence of diabetes was 20% at baseline. The adjusted relative risk of Alzheimer's disease among persons with diabetes as compared with those without diabetes was 1.3 (95% confidence interval (CI): 0.8, 1.9). The adjusted relative risk for the composite outcome of Alzheimer's disease and cognitive impairment without dementia (without stroke) in subjects with diabetes was 1.6 (95% CI: 1.2, 2.1). The adjusted relative risk of stroke-associated dementia in persons with diabetes was 3.4 (95% CI: 1.7, 6.9). Among Blacks and Hispanics, approximately one third of the risk of stroke-associated dementia was attributable to diabetes (33% (95% CI: 31, 36) and 36% (95% CI: 33, 37), respectively), as compared with 17% (95% CI: 13, 22) among Whites. The finding of an association between diabetes and the composite outcome of Alzheimer's disease and cognitive impairment without dementia (without stroke) is consistent with prior reports of a modest relation between diabetes and Alzheimer's disease.

Black or African American↗

PubMed2001

Clinical trials in HIV-associated cognitive impairment: cognitive and functional outcomes.

Cognitive and functional outcomes are of primary interest in the design of efficacy trials in HIV-associated cognitive impairment. In a longitudinal cohort study, weak associations were found between measures of cognitive performance and commonly used measures of daily functioning (mostly self-report measures) in HIV-infected individuals. Modifications of current functional scales or new functional instruments are needed to assess the clinical relevance of cognitive changes in clinical trials of HIV-associated cognitive impairment.

AIDS Dementia Complex↗

PubMed2001

Incidence of AD in African-Americans, Caribbean Hispanics, and Caucasians in northern Manhattan.

OBJECTIVE: To compare the incidence rates for AD among elderly African-American, Caribbean Hispanic, and white individuals and to determine whether coincident cerebrovascular disease contributes to the inconsistency in reported differences among ethnic groups. METHODS: This was a population-based, longitudinal study over a 7-year period in the Washington Heights and Inwood communities of New York City. Annual incidence rates for AD were calculated and compared by ethnic group, and cumulative incidence adjusted for differences in education, diabetes, cardiovascular risk factors, and stroke was calculated. RESULTS: The age-specific incidence rate for probable and possible AD was 1.3% (95% CI, 0.8 to 1.7) per person-year between the ages of 65 and 74 years, 4.0% (95% CI, 3.2 to 4.8) per person-year between ages 75 and 84 years, and 7.9% (95% CI, 5.5 to 10.5) per person-year for ages 85 and older. Compared to white individuals, the cumulative incidence of AD to age 90 years was increased twofold among African-American and Caribbean Hispanic individuals. Adjustment for differences in number of years of education, illiteracy, or a history of stroke, hypertension, heart disease, or diabetes did not change the disproportionate risks among the three ethnic groups. CONCLUSION: The incidence rate for AD was significantly higher among African-American and Caribbean Hispanic elderly individuals compared white individuals. The presence of clinically apparent cardiovascular or cerebrovascular disease did not contribute to the increased risk of disease. Because the proportion of African-American and Caribbean Hispanic individuals reaching ages 65 and older in the United States is increasing more rapidly than the proportion of white individuals, it is imperative that this disparity in health among the elderly be understood.

Aged↗

PubMed2001

An investigation of clinical correlates of Lewy bodies in autopsy-proven Alzheimer disease.

BACKGROUND: Studies of patients meeting clinical and pathologic criteria for Alzheimer disease (AD) have not consistently found associations between the presence of Lewy bodies (LBs) at postmortem examination and a higher frequency during life of the clinical features of dementia with LBs. OBJECTIVE: To evaluate the clinical correlates of LBs in patients with AD. DESIGN AND METHODS: Fifty-one patients were diagnosed as having probable AD during life and met pathologic criteria for AD. Semiquantitative ratings for LBs were obtained in 4 brain regions: substantia nigra, cingulate, insular cortex, and hippocampus. The patients had been followed up semiannually for up to 9.9 years before death, and clinical features associated with dementia with LBs, including extrapyramidal signs and visual hallucinations, were assessed at each study visit. Logistic regression analyses determined whether patients who had LBs were more likely than those without LBs to express specific clinical signs during follow-up. Cox analyses determined whether patients with LBs developed clinical signs or died earlier. Generalized estimating equations were used to compare rates of cognitive or functional change. RESULTS: Nineteen of the 51 patients had at least 1 LB in one of the studied regions. In no case was a significant relation noted between LBs and the presence of a measured clinical sign. No LB measure was associated with an increased risk of developing any of the evaluated clinical signs earlier in the disease. There was no association between the presence of LBs and more rapid mortality or more rapid disease progression. CONCLUSIONS: In patients diagnosed as having AD during life, we did not observe a relation of LBs noted during postmortem examination with the presence of any clinical feature that we assessed or with the rapidity of disease progression. The relation between LBs and specific clinical manifestations may be tenuous in these patients.

Aged↗

PubMed2001

Factors associated with incident human immunodeficiency virus-dementia.

BACKGROUND: Antecedents to human immunodeficiency virus-dementia (HIV-D) are poorly understood. OBJECTIVE: To identify risk factors for HIV-D. METHODS: Subjects who are positive for HIV who have CD4+ counts either below 200/microL or below 300/microL with evidence of cognitive impairment were enrolled in this study. Neurologic, cognitive, functional, and laboratory assessments were done semiannually for up to 30 months. Human immunodeficiency virus-dementia was diagnosed using American Academy of Neurology criteria for probable HIV-1-associated dementia complex. RESULTS: One hundred forty-six nondemented patients were enrolled, 45 of whom subsequently met criteria for incident HIV-D. In univariate analyses using the Cox proportional hazards regression model, the following variables were significantly associated with time to develop dementia: cognitive: abnormal scores on Timed Gait, Verbal Fluency, Grooved Pegboard, and Digit Symbol tests; attention-memory, psychomotor, and executive function domain scores; and the diagnosis of minor cognitive/motor disorder; neurologic and medical: increased abnormalities on the neurologic examination, extrapyramidal signs, history of HIV-related medical symptoms; functional: higher reported role or physical function difficulties. Depression was also a strong risk factor, along with sex, hematocrit, hemoglobin, and beta2-microglobulin levels. In a multivariate model that used cognitive domain scores, covariates with significant hazard ratios included depression, executive dysfunction, and the presence of minor cognitive/motor disorder. CONCLUSION: Cognitive deficits, minor cognitive/motor disorder, and depression may be early manifestations of HIV-D.

AIDS Dementia Complex↗

PubMed2001

Selective deficits in verbal working memory associated with a known genetic etiology: the neuropsychological profile of duchenne muscular dystrophy.

Forty-one boys diagnosed with Duchenne muscular dystrophy (DMD) were each compared to an unaffected sibling on a battery of neuropsychological tests. Verbal. visuospatial, attention/memory, abstract thinking, and academic achievement skills were tested. Results indicated the boys with DMD performed similarly to their siblings on the majority of measures, indicating intact verbal, visuospatial, long-term memory, and abstract skills. However, the DMD group did significantly more poorly than their siblings on specific measures of story recall, digit span, and auditory comprehension, as well as in all areas of academic achievement (reading, writing, and math). This profile indicates that verbal working memory skills are selectively impaired in DMD, and that that likely contributes to limited academic achievement. The association between the known impact of the genetic mutation on the development of the central nervous system and boys' cognitive profile is discussed.

Adolescent↗

PubMed2001

Circuit mechanisms underlying memory encoding and retrieval in the long axis of the hippocampal formation.

Circuits within the hippocampal formation are active during memory processing. Here we used functional magnetic resonance imaging (fMRI) to examine multiple sites across the long axis of the hippocampal formation while subjects performed different phases of an associative memory task, learning to associate faces with names. Viewing faces and hearing names in isolation resulted in separate hippocampal activation patterns. Pairing faces with names resulted a spatially redistributed activation pattern, rather than a simple summation of the activation patterns resulting from viewing faces and hearing names in isolation. Recalling names when cued with faces reactivated a pattern similar to that found during paired training. Finally, the activation patterns representing faces and names were found to be experience dependent, emerging with repeated exposure. Interpreted in the context of hippocampal anatomy and physiology, these findings reveal hippocampal circuit mechanisms that underlie memory encoding and retrieval.

Adult↗

PubMed2001

Neuropsychological test performance: a study of non-Hispanic White elderly.

This study examined within-group differences in neuropsychological test performance between US versus foreign-born English-speaking White elders. Participants included 193 randomly selected English-speaking elderly community residents who self-identified as non-Hispanic White. Participants were classified as US (n = 106) or foreign-born (n = 87). All participants were independently diagnosed by a physician as nondemented. After controlling for years of education, participants born in the United States obtained significantly higher scores on measures of verbal abstract reasoning, naming, and fluency than foreign-born elders. These results suggest that although non-Hispanics White are often treated as a homogeneous group, performance differences exist even within this group. Effects of acculturation level and language use on cognitive styles may help explain these findings.

Aged↗

PubMed2001

Predictor index of mortality in dementia patients upon entry into long-term care.

BACKGROUND: The purpose of this study was to develop an algorithm that predicts survival in patients with dementia upon entry into long-term care. There are, as yet, no predictive equations developed for those in the late stages of Alzheimer's disease (AD). METHODS: This was a prospective, observational study of 132 patients with dementia (61% with AD) followed for up to 5.0 years (median of 41.0 months) after admission to a long-term care facility for dementia patients. Information on demographic characteristics, physical health, and cognitive, emotional, and behavioral characteristics was collected shortly after admission and entered as predictors of time until death in Cox regressions. Findings were used to derive an index predicting mortality. RESULTS: There were 60 deaths among the 132 patients (45.4% mortality), with an average survival of 22.4 months in those who died. Better physical health and the presence of delusions were associated with longer survival. These two variables were aggregated into the Copper Ridge Index (CRI). Each one-point increase on the CRI was associated with a four-fold greater likelihood of death over 5 years. CONCLUSIONS: A predictive equation incorporating measures of general physical health and delusions accurately predicted time to death in dementia patients in long-term care.

Aged↗

PubMed2001

Serum S100B protein levels are correlated with subclinical neurocognitive declines after carotid endarterectomy.

OBJECTIVE: Carotid endarterectomy (CEA) is an effective means of stroke prevention among appropriately selected patients; however, neuropsychometric testing has revealed subtle cognitive injuries in the early postoperative period. The purpose of this study was to establish whether serum levels of two biochemical markers of cerebral injury were correlated with postoperative declines in neuropsychometric test performance after CEA. METHODS: Fifty-five consecutive patients underwent a battery of neuropsychometric tests 24 hours before and 24 hours after elective CEA. Two patients were excluded because of postoperative strokes. The pre- and postoperative serum levels of S100B protein and neuron-specific enolase for injured patients, defined as those who exhibited significant declines in neuropsychometric test performance (n = 12), were compared with the levels for uninjured patients (n = 41). RESULTS: There were no significant differences in the baseline S100B levels for the two groups. Injured patients exhibited significantly higher S100B levels, compared with uninjured patients, at 24, 48, and 72 hours after surgery (P < 0.05). There were no significant differences in neuron-specific enolase levels for injured and uninjured patients at any time point. CONCLUSION: These data suggest that subtle cerebral injuries after CEA, even in the absence of overt strokes, are associated with significant increases in serum S100B but not neuron-specific enolase levels. Analyses of earlier time points in future studies of subtle cognitive injuries and biochemical markers of cerebral injury after CEA may be revealing.

Aged↗

PubMed2001

Overcoming the language barrier in visual field testing.

PURPOSE: To evaluate the effect of using recorded instructions in patients' native language compared with interpreter-assisted instructions on the reliability and duration of the visual field test. PATIENTS AND METHODS: Sixty patients referred for visual field testing were included in the study. Thirty-five had limited or no knowledge of the Hebrew language, and 25 control patients were fluent in Hebrew, the native language. None had previous experience with automated perimetry. Patients were randomized to receive recorded instructions on the visual field test in their native language or translator-assisted instructions by the technician before performing the test. For each patient, the time required for instructions and test performance and the reliability indices were documented. RESULTS: The method of instruction (recorded or interpreter-assisted) did not affect the time required for patient instructions (66 +/- 24 seconds and 57 +/- 30 seconds, respectively), the time for test performance (7.2 +/- 1.5 minutes and 7.8 +/- 1.8 minutes, respectively), and test reliability as measured by the rate of fixation losses. Regardless of the method of explanation, the time required for instructions and for performing the test were significantly shorter for Hebrew speakers than for non-Hebrew speakers. CONCLUSION: The use of a recorded explanation in the patient's native language before visual field testing is an applicable method for patient instruction. Clinics in areas with multilingual populations may use this method to save technicians time, without adversely affecting the time required for performing the test and its reliability.

Aged↗

PubMed2001

Cognitive correlates of obsessive and compulsive symptoms in Huntington's disease.

OBJECTIVE: The authors' goal was to examine the frequency and type of obsessive and compulsive symptoms in Huntington's disease. METHOD: The Yale-Brown Obsessive Compulsive Scale was used to assess obsessive and compulsive symptoms in 27 patients with Huntington's disease. The neuropsychological test performance of the 14 patients with at least one obsessive symptom and the seven patients with at least one compulsive symptom was compared with the performance of the patients without such symptoms. RESULTS: More than half of the patients with Huntington's disease endorsed obsessive or compulsive symptoms on the Yale-Brown scale. Patients with obsessive or compulsive symptoms showed significantly greater impairment on neuropsychological tests measuring executive function than those without such symptoms. CONCLUSIONS: Basal ganglia pathology in Huntington's disease may contribute to production of obsessive and compulsive symptoms and to executive performance deficits in these patients.

Analysis of Variance↗

PubMed2001

Role of laryngoscopy, dual pH probe monitoring, and laryngeal mucosal biopsy in the diagnosis of pharyngoesophageal reflux.

There is no standard for determining significant pharyngoesophageal reflux. This prospective blind comparison study compared dual pH probe studies, direct laryngoscopy, and mucosal biopsy in children without symptoms of gastroesophageal reflux who underwent airway evaluation. Significant reflux to the lower esophageal probe did not correlate with statistical significance with reflux to the upper probe. In this group of asymptomatic patients, a positive lower pH probe finding did not correlate with upper or lower esophageal mucosal inflammation. Eosinophilia in the esophageal mucosa is diagnostic of gastroesophageal reflux disease, and was seen in 5 of the laryngeal biopsies. A weak correlation was seen between positive findings at laryngoscopy and positive posterior cricoid biopsy in this group. There may be no consistent way to predict significant pharyngoesophageal reflux in asymptomatic patients. Single-probe pH testing will not predict significant pharyngoesophageal reflux with mucosal changes. Laryngoscopy and upper pH probe findings only weakly correlate with significant histologic findings. Laryngeal and posterior cricoid biopsy may be the only sensitive test for mucosal injury. Clinical trials of empiric antireflux therapy should be used to determine whether the laryngeal changes seen in these patients are reversible.

Biopsy↗

PubMed2001

Cognitive correlates of mnemonics usage and verbal recall memory in old age.

OBJECTIVES: The objectives of this study were to determine whether minimizing requisite processing resources to learn a word list would differentially improve recall of older adults and to examine the associations between memory and nonmemory cognitive abilities. BACKGROUND: It has been hypothesized that a reduction in general processing resources contributes to age-related declines in memory and other cognitive abilities. METHODS: Twenty-four young adults and 47 older adults were administered two semantically related word lists, one list with words blocked into their categories and the other with categories intermixed. Tests of attention and working memory, language, and abstract reasoning were interspersed with the memory tasks. Participants were classified as young (age range: 17-30 years), young-old (age range: 65-73 years), and old-old (age range: 74-87 years) to compare the effects of list condition (i.e., blocked vs. unblocked) on recall performance. Correlation and regression analyses were used to examine the cognitive correlates of recall performance. RESULTS: Expected age differences in recall performance were observed. Based on the resource-reduction hypothesis of cognitive aging, we hypothesized that the blocked presentation of the to-be-remembered list would minimize processing demands and therefore differentially benefit recall in older elderly participants. Contrary to our prediction, however, the relative benefits of blocked list presentation on recall measures were comparable for young and older participants. Correlations and regression analyses revealed that recall performance was more strongly associated with word finding ability than with working memory or abstract reasoning skills. CONCLUSIONS: Results suggest that level of recall of a semantically related word list and use of semantic clustering as an encoding strategy are associated more strongly with general word finding skills than with processing capacity.

Adolescent↗