Biomedical subjects

Y Stern

Publications and source records attributed to Y Stern.

At least 145 records · Page 8Linked to original sources

PubMed1996

Depressed mood and the incidence of Alzheimer's disease in the elderly living in the community.

BACKGROUND: It remains unclear whether depression increases the risk for dementia in the elderly. We evaluated the relationship between depressed mood at baseline and the incidence of dementia, particularly Alzheimer's disease, in the elderly living in the community. METHODS: A total of 1070 elderly individuals, aged 60 years or older, were identified as part of a registry for dementia in the Washington Heights community of North Manhattan, NY. In a prospective, longitudinal design with follow-up for 1 to 5 years, annual physician evaluation and neuropsychological testing were used to assess levels of cognitive impairment and to diagnose dementia. Depressive symptoms were evaluated with the 17-item Hamilton Rating Scale for Depression. Based on clinical considerations and a validity study, a positive score for the depressed mood item was used in statistical analyses. To confirm the results, the total Hamilton Rating Scale for Depression score was also evaluated as the "depression" variable. RESULTS: Of the 1070 subjects, 218 met criteria for dementia at baseline evaluation. In the 852 subjects without dementia, depressed mood was more common in individuals with greater cognitive impairment. In a follow-up study of 478 of these subjects without dementia (mean +/- SD, 2.54 +/- 1.12 years of follow-up), the effect of baseline depressed mood on the end-point diagnosis of dementia (93% had possible or probable Alzheimer's disease) was evaluated in a Cox proportional hazards model. Depressed mood at baseline was associated with an increased risk of incident dementia (relative risk, 2.94; 95% confidence interval, 1.76 to 4.91; P < .001). This effect remained after adjustment for age, gender, education, language of assessment, Blessed Memory Information and Concentration test scores, and Blessed Functional Activity Scale scores (relative risk, 2.05; 95% confidence interval, 1.16 to 3.62; P < .02). Similar results were obtained when the total Hamilton Rating Scale for Depression score was used as the depression variable, with the use of the same covariates (relative risk, 1.07 per point interval; 95% confidence interval, 1.02 to 1.11; P < .01). CONCLUSIONS: Depressed mood moderately increased the risk of developing dementia, primarily Alzheimer's disease. Whether depressed mood is a very early manifestation of Alzheimer's disease, or increases susceptibility through another mechanism, remains to be determined.

Age Factors↗

PubMed1996

Angiogenesis in follicular tumors of the thyroid.

BACKGROUND: Experimental evidence suggests that tumor growth beyond a certain size and tumor ability to metastasize depend on the degree to which the tumor can stimulate an angiogenic response. METHODS: Fifteen thyroid specimens of microinvasive follicular carcinoma were examined for vascularization by immunohistochemical stain with antifactor VIII antibodies and compared with an equal number of follicular adenomas. RESULTS: Pleomorphic areas in the histological specimens of follicular carcinomas had a higher rate of vascularization as did areas of tumor adjacent to or penetrating the capsule. These features were not noted in follicular adenomas. CONCLUSIONS: Our findings indicate that vascularity may play a role in extracapsular extension and tumor aggression in follicular thyroid carcinomas.

Adenocarcinoma, Follicular↗

PubMed1996

Inferior parietal perfusion, lateralization, and neuropsychological dysfunction in Alzheimer's disease.

The severity of inferior parietal perfusion deficits in Alzheimer's disease (AD) is strongly associated with global intellectual decline. The relationship to specific losses of neuropsychological functioning, however, is less clear, as is the relative importance of the side (left vs. right) of hemispheric deficit. In this study, 53 patients with probable AD and 35 elderly controls received both a resting 133Xe rCBF measurement and neuropsychological examination. AD patients demonstrated the expected bilateral deficits in inferior parietal perfusion, as well as impairment on measures of mental status, intelligence verbal and visual memory, attention, language, and construction abilities. The severity of this bilateral parietal deficit, in turn, was associated with virtually all of these AD-related neuropsychological impairments, most strongly with declining Performance IQ. Left-sided deficits correlated better with overall declines in IQ, as well as with declining attention and language fluency. Right-sided deficits, on the other hand, correlated best with declines in mental status and--paradoxically--verbal memory and contributed independently to declines in Full Scale and Performance IQ. In terms of the number and strength of their association to neuropsychological measures, left-sided deficits appear much more predicative of cognitive decline in AD. Right-sided deficits, however, may be most important in predicting aspects of performance skill that are only indirectly assessed in standard paper-and-pencil format. Overall, it appears that both sides make significant, but independent contributions to general functional decline in AD, but that left-sided deficits are more closely associated with cognitive decline in measured by most standard neuropsychological measures.

Aged↗

PubMed1996

Polymorphisms in the human apolipoprotein-J/clusterin gene: ethnic variation and distribution in Alzheimer's disease.

Apolipoprotein-J/clusterin (APOJ/CLI) shares many biological properties with apolipoprotein-E (APOE) including, but not limited to, avid binding with beta-amyloid peptide. Thus, APOJ/CLI warrants scrutiny as a candidate Alzheimer's disease (AD) susceptibility gene. We identified seven nucleotide sequence polymorphisms in APOJ/ CLI, two of which, in exon 7, after the predicted amino acid sequence. The JVIIB variant is an asparagine-to-histidine substitution, which deletes a glycosylation signal at amino acid 317; the JVIIC variant is an aspartate-to-asparagine substitution, which forms a new glycosylation signal at position 328. Both of these coding variants, as well as two neutral polymorphisms in exon 2, were more frequent in African-Americans than Hispanics and were rare in Caucasians. However, no individual coding or noncoding variant was consistently associated with AD. At the population level, APOJ/CLI polymorphisms are frequent among persons of African descent, but probably do not alter susceptibility to AD.

Black or African American↗

PubMed1996

Comparative study of visual and verbal short-term memory in English and Spanish speakers: testing a linguistic hypothesis.

It has been proposed that differences in digit span performance between English and Spanish speakers are due to the greater number of syllables per digit in the Spanish language. To test this hypothesis, we studied the performance of 30 English- and 30 Spanish-speaking elders on the Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Span Subtest, a modified digit span test that was linguistically comparable for both languages, and the Corsi Block Test. Consistent with previous reports, we found that English speakers scored significantly higher than Spanish speakers on WAIS-R Digit Span Forward. Group differences were reduced on the modified Digit Span Forward, but remained significant. English and Spanish speakers scored comparably on Digit Span Backward (WAIS-R and modified) and Visual Span. We suggest that although differences in the number of syllables per digit string are in part responsible for the lower performance of Spanish speakers on Digit Span Forward, cultural and educational issues also contribute to the observed differences between English and Spanish speakers.

Adult↗

PubMed1996

Application of a growth curve approach to modeling the progression of Alzheimer's disease.

BACKGROUND: Studies using clinical measures to track AD progression often assume linear declines over the entire course of the disease, which may not be justified. The objective of this study was to model change in measures of the clinical severity of Alzheimer's disease (AD) over time. METHODS: We developed a method to apply growth curve models to prospective data and characterize AD patients' functional change over time. Data from the modified Mini-Mental State Examination (mMMSE) and measures of basic and instrumental ADL, administered semiannually for up to 5 years to 236 patients with probable AD, were modeled. RESULTS: The rate of decline in mMMS scores per 6-month interval gradually increased as scores dropped from the maximum of 57 to 20. The rate of decline then decreased as scores approached 0, resulting in an inverse "S" curve. The rate of increase in instrumental ADL scores per interval attenuated as the scores increased, while that for basic ADL scores across intervals was constant. CONCLUSIONS: Differences in the pattern of progression of the three measures is in part a function of their psychometric properties. The progression curves may also reflect content-specific features of the instruments. Superimposition of the modeled decline in these three content areas suggests a hypothetical model of the relative timing of cognitive and functional changes in AD.

Activities of Daily Living↗

PubMed1996

Quality of life in patients with Alzheimer's disease as reported by patient proxies.

OBJECTIVE: To measure behaviors indicative of quality of life (QOL) in patients with Alzheimer's disease and to examine correlates of patient QOL. DESIGN: Cross-sectional investigation. SETTING: Multi-center study. PARTICIPANTS: Sample of 130 diagnosed patients. PRINCIPAL OUTCOME MEASURES: Proxy ratings of (1) the frequency, opportunity, and enjoyment of 15 non-ADL activities potentially within the capacity of a demented person, and (2) the frequency of a series of positive and negative affects, evident in clearly demarcated facial and bodily expressions. RESULTS: QOL ratings were reliably elicited. Family and institutional caregivers differed only in reports of opportunity for patient activity. Frequency of activities declined with increasing severity of dementia. The frequency of negative affects increased and positive affects declined with increasing severity of dementia, but correlations were weak. High QOL, defined by frequent activity and positive affect, was evident in a quarter of the sample. In multivariate models, functional and cognitive status independently predicted QOL among community-resident older adults; only absence of antipsychotics was related to QOL among older people in nursing homes. Patient education, a marker of premorbid state, independently predicted some activity patterns. CONCLUSIONS: Although the subjective world of the demented patient is not directly accessible, readily observable behaviors offer a basis for assessing QOL.

Affect↗

PubMed1996

Recovery of cognitive function after stroke.

BACKGROUND AND PURPOSE: Previous studies have suggested that recovery of cognitive function after stroke is maximal within the first 3 months after onset. We performed the present study to investigate the long-term course and clinical correlates of improvement in generalized cognitive function after ischemic stroke. METHODS: We administered a battery of neuropsychological tests to 151 patients (age, 70.4 +/- 7.7 years; education, 10.4 +/- 4.6 years) at 3 months and then annually after stroke. We transformed their test results into z scores based on the performance of a stroke-free normative group, averaged those scores to create a summary score, and defined improvement in annual examinations as an increase in that summary score greater than two standard deviations above the mean first annual change of the normative group. We then used logistic regression to determine whether stroke location, syndrome, or recurrence; vascular risk factors; dementia status; depression; or demographic variables were associated with improvement. RESULTS: We found that 19 of the 151 patients exhibited improvement, which was evident only at the first annual examination in most cases. Logistic regression determined that improvement was significantly related to left hemisphere infarction relative to brain stem/cerebellar infarction (odds ratio [OR], 5.57), while the presence of a major hemispheral stroke syndrome showed a trend toward significance (OR, 3.32). Diabetes mellitus was significantly associated with a failure to exhibit improvement (OR, 0.12). Based on the logistic model, the probability of long-term improvement would be 54.0% for a patient with a left hemisphere infarct and a major hemispheral syndrome but only 11.9% if diabetes was also present. CONCLUSIONS: Long-term improvement in generalized cognitive function may be evident after stroke in association with left hemisphere infarction and severe hemispheral syndromes, while it may be compromised by diabetes, possibly because of an increased burden of cerebrovascular disease.

Aged↗

PubMed1996

Risk factors for incident dementia after stroke. Role of hypoxic and ischemic disorders.

BACKGROUND AND PURPOSE: Stroke significantly increases the risk of dementia in the elderly, yet the risk factors for incident dementia after ischemic stroke are not well understood. We attempted to determine whether hypoxic-ischemic (HI) disorders, which may result from comorbid medical conditions (eg. seizures, cardiac arrhythmias, pneumonia), would be an independent risk factor for the development of new dementia after stroke. METHODS: We prospectively followed 185 initially nondemented patients with ischemic stroke (age, 70.3 +/- 7.7 years) for a maximum of 52.8 months. We diagnosed the presence of dementia at annual examinations based on neuropsychological testing and modified DSM-III-R criteria. HI disorders were identified by record review or examination during hospitalization. We used Kaplan-Meier analysis to determine the cumulative proportion of patients with and without HI disorders who survived free of dementia and used Cox models to estimate the relative risk of dementia associated with HI disorders. RESULTS: The cumulative proportion (+/- SE) surviving without dementia was 51.7 +/- 10.9% in the HI group versus 78.2 +/- 4.3% in the non-HI group after 52.8 months of observation. The relative risk of incident dementia associated with HI events was 4.3 (95% confidence interval = 1.9 to 9.6) after we adjusted for demographic factors, recurrent stroke, and baseline cognitive function. CONCLUSIONS: We conclude that HI disorders may be a significant independent risk factor for incident dementia after stroke, even after adjustment for other recognized predictors of cognitive decline. Recognition of HI cerebral damage as a possible pathogenic mechanism for dementia after stroke may allow targeted therapeutic interventions to prevent subsequent cognitive deterioration.

Aged↗

PubMed1996

Nuclear DNA content of the tall cell variant of papillary carcinoma of the thyroid gland.

Tall cell carcinoma of the thyroid gland is an aggressive variant of papillary carcinoma. A high nuclear DNA content has been associated with aggressive clinical behavior and an unfavorable prognosis in several malignant human tumors. It was also described in differentiated thyroid carcinoma. Therefore, analysis of the nuclear DNA content may yield information predictive of aggressive behavior. Accordingly, the DNA content of the tall cell variant was measured and compared with that of the usual form of papillary carcinoma by flow cytometry. Although all the aneuploid tumors were in the tall cell variant group, the difference in nuclear content was not statistically significant. We conclude that differences in the clinical behavior of these neoplasms are not related to alterations in DNA ploidy.

Aneuploidy↗

PubMed1996

Neurologic consequences of HTLV-II infection in injection-drug users.

Several case reports have suggested an association between human T-cell lymphotropic virus type II (HTLV-II) infection and chronic neurologic disease. We performed serial neurologic examinations in injection-drug users (IDU), a group known to be at increased risk for HTLV-II infection. At baseline, those infected with HTLV-II alone, human immunodeficiency virus (HIV) alone, or both were significantly more likely to have neurologic disability than uninfected subjects. Longitudinally, HTLV-II infection was independently associated with the development of global neurologic disability and neuropathy, suggesting that HTLV-II causes neurologic disease.

AIDS Dementia Complex↗

PubMed1996

The Clinical Dementia Rating scale: community-based validation of "profound' and "terminal' stages.

The original version of the Clinical Dementia Rating (CDR) scale correlates with other dementia rating scales, and predicts nursing home (NH) admission and death. To validate the extended components of the scale, we analyzed data from subjects participating in a community-based study of dementia. The extended CDR scale also correlated with measures of dementia severity and NH residence. "Profound" and "terminal" stages predicted shortened survival. The extended CDR scale should be useful in studies of the later stages of dementia.

Activities of Daily Living↗

PubMed1996

A preliminary study of apolipoprotein E genotype and psychiatric manifestations of Alzheimer's disease.

We evaluated the frequency of depression and psychosis in 46 patients with AD and 135 control subjects with the apolipoprotein (APO) E3/3 or E3/4 genotype. Patients with AD and the APOE3/4 genotype had a more than threefold increase in the signs of depression and psychosis when compared with either patients with the APOE3/3 genotype or to control subjects. Our preliminary study suggests that the phenotype of AD associated with the epsilon 4 allele is more likely to include psychiatric manifestations.

Aged↗

PubMed1996

Gender Differences in HIV-Related Neurological Progression in a Cohort of Injecting Drug Users Followed for 3.5 Years.

We evaluated potential gender differences in the development of HIV related neurologic impairment, by matching 38 pairs of HIV positive male and female injecting drug users on their baseline age, education, disease stage and CD4 counts, and following them for 3.5 years. Adjusting for age, education, drug use, history of head injury and baseline CD4 count, more women had sensory abnormalities and symptoms than men at baseline, but the odds of having neurological impairment, particularly extrapyramidal signs and sensory abnormalities were increased over time in men but not in women. Men with ARC or AIDS had more neurological impairment than women in similar stages of illness. This study suggests further investigations of gender differences in HIV disease progression.

CD4 Lymphocyte Count↗

PubMed1996

Serial MRI in HIV Infection With and Without Neurologic Impairment.

To assess the relationship of longitudinal brain magnetic resonance imaging (MRI) and infection with human immunodeficiency virus (HIV), a cohort of HIV+ and HIV− gay men and injection drug users (IDU) were evaluated prospectively. Subjects underwent two evaluations including MRI scans, neurologic examinations, neuropsychological assessments and lymphocyte subset determinations one year apart. MRI changes over a one year period were analyzed with respect to serostatus, risk group, CD4 counts, neurological findings and neuropsychological performance. The frequency of MRI changes was no different in subjects with or without HIV infection and no new opportunistic infections or neoplasms were seen. However, among HIV+ subjects with CD4 count < 200 at the time of the initial scan, an increase in white matter hyperintensities was significantly more common. Also among HIV+ subjects, atrophy increased in association with declining CD4 count. Finally, subjects who developed significant neurologic deterioration in one year were much more likely to have increased atrophy. These results suggest that while there are morphological brain changes associated with HIV infection, they are most often seen in association with immunologic or neurologic deterioration.

Atrophy↗

PubMed1996

Relative risk of Alzheimer disease and age-at-onset distributions, based on APOE genotypes among elderly African Americans, Caucasians, and Hispanics in New York City.

Apolipoprotein-E epsilon 4 (APOE-epsilon 4) has been consistently associated with Alzheimer disease (AD) and may be responsible for an earlier age at onset. We have previously reported a diminished association between APOE-epsilon 4 and AD in African Americans. Using a new method, which allows inclusion of censored information, we compared relative risks by APOE genotypes in an expanded collection of cases and controls from three ethnic groups in a New York community. The relative risk for AD associated with APOE-epsilon 4 homozygosity was increased in all ethnic groups (African American relative risk [RR]=3.0; 95% confidence interval [CI]=1.5-5.9; Caucasian RR=7.3, 95% CI=2.5-21.6; and Hispanic RR=2.5, 95% CI=1.1-5.7), compared with those with APOE-epsilon 3/epsilon 3 genotypes. The risk was also increased for APOE-epsilon 4 heterozygous Caucasians (RR=2.9, 95% CI=1.7-5.1) and Hispanics (RR=1.6, 95% CI=1.1-2.3), but not for African Americans (RR=0.6, 95% Ci=0.4-0.9). The age distribution of the proportion of Caucasians and Hispanics without AD was consistently lower for APOE-epsilon 4 homozygous and APOE-epsilon 4 heterozygous individuals than for those with other APOE genotypes. In African Americans this relationship was observed only in APOE-epsilon 4 homozygotes. These results confirm that APOE genotypes influence the RR of AD in Caucasians and Hispanics. Differences in risk among APOE-epsilon 4 heterozygote African Americans suggest that other genetic or environmental factors may modify the effect of APOE-epsilon 4 in some populations.

Age of Onset↗

PubMed1995

APOE genotype influences functional status among elderly without dementia.

The presence of apolipoprotein-epsilon 4 (APOE-epsilon 4) significantly increases the risk of Alzheimer's disease (AD). The association between APOE-epsilon 4 status and functional abilities was explored further in a multicultural sample of community-dwelling, non-demented elders. The sample was limited to cognitively-intact, community-dwelling elders, who were free of stroke or other neurologic disability. In 218 elders who met research criteria, the presence of APO-epsilon 4 was associated with poorer functional status, apart from the effects of neuropsychological performance, gender, age, and education (OR = 2.5, 95% CI: 1.3, 4.9). In 158 subjects without an APOE-epsilon 4 allele, 50% reported no functional limitation; in the 60 subjects with an epsilon 4 allele, only 28% reported no functional limitation (P < .01). The relationship was not explained by the distribution of co-morbidities. The association between poorer function and the presence of an APOE-epsilon 4 allele was evident in each ethnic group. In path analyses, the presence of an APOE-epsilon 4 allele was associated with decreased functional ability in non-demented elders not simply through an association with poorer cognitive status, but also independently. These results suggest that the APOE-epsilon 4 genotype is associated with functional deficit in people with normal neuropsychological profiles.

Aged↗

PubMed1995

The age at onset of Alzheimer's disease and an intracranial area measurement. A relationship.

OBJECTIVE: To examine the possibility that premorbid brain size may influence the age at onset of symptoms of Alzheimer's disease (AD). DESIGN: Retrospective case series. SETTING: Outpatients attending a memory disorders clinic in a tertiary referral center. PATIENTS: Twenty-eight female patients with the diagnosis of probable AD, selected for the availability of informant derived estimates of age at onset of symptoms and computed tomographic scans of the head satisfying angulation criteria. MAIN OUTCOME MEASURE: An average intracranial area of two adjacent computed tomographic scan sections appropriately angled was used as a correlate of premorbid brain size. Strict intracranial volume measurement was not performed. RESULTS: Age at onset of symptoms of AD correlated positively (r = .48, P = .009) with our measure of premorbid brain size. There was no confounding by education, height, or ethnicity. CONCLUSION: Premorbid brain size may be an important determinant of the age at onset of symptoms of AD. Epidemiologic studies of AD may need to assess the relationship between brain size and putative risk factors, eg, low educational attainment, since there is evidence that brain size is not distributed uniformly across populations.

Age of Onset↗