Biomedical subjects

Yaakov Stern

Publications and source records attributed to Yaakov Stern.

90 records · Page 5Linked to original sources

PubMed2002

Familial Alzheimer disease among Caribbean Hispanics: a reexamination of its association with APOE.

OBJECTIVES: To reexamine the association between the apolipoprotein E epsilon4 allele (APOE epsilon4) and familial Alzheimer disease (AD), and to search for novel genes that may be associated with susceptibility in Caribbean Hispanic families with a history of AD. METHODS: Families were identified in Caribbean Hispanic communities in the greater New York City area, the Dominican Republic, and Puerto Rico. Each family in the study cohort included at least 2 living relatives with a history of dementia. All family members underwent neuropsychological testing and medical and neurological examinations to establish the presence or absence of dementia and to specify the type of dementia. RESULTS: Over a 2(1/2)-year period, 203 families were identified. Of these, 19 families had at least 1 family member with onset of dementia before age 55 years, with 8 of the 19 families showing an association with a previously unreported presenilin mutation. Multiple cases of AD were identified in 29 families. Overall, there were 236 affected sibling pairs with AD available for analysis. The average age at onset was 74 years. The presence of APOE epsilon4 was strongly associated with AD. CONCLUSIONS: Both early-onset and late-onset familial AD occur in Caribbean Hispanics. In contrast to sporadic AD, late-onset familial AD among Caribbean Hispanics is strongly associated with APOE epsilon4. Future attempts to identify additional susceptibility genes should consider the effects of APOE epsilon4.

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PubMed2002

A controlled prospective study of neuropsychological dysfunction following carotid endarterectomy.

BACKGROUND: Although subtle cognitive injury as revealed by neuropsychological testing occurs in a substantial number of patients following carotid endarterectomy (CEA), there is controversy about whether this finding is a result of the surgery or the anesthesia. OBJECTIVES: To examine the changes in neuropsychological test performance in patients following CEA vs a control group of patients older than 60 years following spine surgery, so as to determine whether neuropsychological dysfunction after CEA is a result of surgery or anesthesia. METHODS: Patients undergoing CEA (n = 80) and lumbar spine surgery (n = 25) were assessed with a battery of neuropsychological tests preoperatively and on postoperative days 1 and 30. The neuropsychological performance of patients in the control group was used to normalize performance for patients in the CEA group, by calculating z scores using the mean and SD of the change scores in the control group. Significant cognitive dysfunction was defined as performance that exceeded 2 SDs above the mean performance of patients in the control group. RESULTS: Postoperative days 1 and 30 total deficit scores were significantly worse in the CEA group compared with the controls. When individual test results were examined, the CEA group performed significantly worse than the controls on the Rey Complex Figure test and Halstead-Reitan Trails B on day 1, and on the Rey Complex Figure on day 30. Overall, cognitive dysfunction was seen in 22 patients (28%) in the CEA group on day 1 and in 11 (23%) of 48 patients on day 30. CONCLUSIONS: Subtle cognitive decline following CEA occurs and persists for at least several weeks after surgery. This decline was absent in a control group.

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PubMed2002

Longitudinal assessment of patient dependence in Alzheimer disease.

BACKGROUND: The Dependence Scale measures the amount of assistance patients with dementia require in performing daily activities. Validity and reliability of this scale have been demonstrated, but the progression throughout long periods in patients with Alzheimer disease (AD) has not previously been examined. OBJECTIVE: To determine the longitudinal course of patient dependence in a cohort of prospectively followed AD patients. METHODS: Two hundred thirty AD patients enrolled in the Predictors Study were followed up prospectively at 6-month intervals for an average of 6.5 visits. The Dependence Scale was administered to a caregiver, and patients were assessed with the modified Mini-Mental State Examination (mMMSE) and the Blessed Dementia Rating Scale. Dependence level and the additive sum of the Dependence Scale items were considered for analysis. RESULTS: Generalized estimating equations to regression analyses were used to determine that both Dependence Scale scores and dependence level significantly decline with time. By covarying mMMSE scores and self-care deficits factor scores of the Blessed Dementia Rating Scale, generalized estimating equations analysis also demonstrated that change in patient dependence was independent of global cognitive decline and other measures of activities of daily living, respectively. CONCLUSIONS: This study shows the validity of the Dependence Scale and demonstrated that dependency in AD significantly declines with time independent of global cognition and other self-care deficits. The scale is a valuable instrument for outcomes research, efficacy trials, and behavioral research in AD.

Activities of Daily Living↗

PubMed2002

Imaging hippocampal function across the human life span: is memory decline normal or not?

Memory function commonly declines in later life. Whether memory decline represents a disease process or whether it is part of normal aging remains unknown. Here we answer this question by assessing the function of multiple subregions that make up the hippocampal circuit across the human life span. A newly developed MRI approach--designed to detect functional changes in individual hippocampal subregions--was used to assess the hippocampal circuit in 70 subjects between 20 and 88 years of age. Using strict parametric criteria, analysis revealed that function in two hippocampal subregions--the subiculum and the dentate gyrus--decline normally with age. In contrast, function in the entorhinal cortex declines pathologically. Single-subject analysis revealed that hippocampal dysfunction, found in 60% of elders was selectively correlated with memory decline. These results show that memory decline is caused by different mechanisms and suggests how memory decline should be approached clinically.

Adult↗

PubMed2002

Combined effect of age and severity on the risk of dementia in Parkinson's disease.

Age and severity of extrapyramidal signs have been consistently associated with incident dementia in Parkinson's disease. We evaluated the separate and combined effects of age and severity of extrapyramidal signs on the risk of incident dementia in Parkinson's disease in the setting of a population-based prospective cohort study. Age and the total Unified Parkinson's Disease Rating Scale motor score at baseline evaluation were dichotomized at the median. Four groups of Parkinson's disease patients were defined: younger age/low severity (reference), younger age/high severity, older age/low severity, and older age/high severity. Risk ratios for incident dementia were calculated with Cox proportional hazards models controlling for gender, education, ethnicity, and duration of Parkinson's disease. Of 180 patients, 52 (28.9%) became demented during a mean follow-up period of 3.6 +/- 2.2 years. The median age at baseline of the Parkinson's disease patients was 71.8 years (range, 38.5-95.9 years), and the median total Unified Parkinson's Disease Rating Scale motor score was 24 (range, 2-65). The group with older age/high severity had a significantly increased risk of incident dementia (relative risk, 9.7; 95% confidence interval, 3.9-24.4) compared with the group with younger age/low severity (reference), whereas the groups with older age/low severity (relative risk, 1.6; 95% confidence interval, 0.5-4.8) and younger age/high severity (relative risk, 1.2; 95% confidence interval, 0.5-3.2) did not. These findings suggest that the increased risk of incident dementia in Parkinson's disease associated with age and severity of extrapyramidal signs is related primarily to their combined effect rather than separate effects.

Adult↗

PubMed2002

Do risk factors for Alzheimer's disease predict dementia in Parkinson's disease? An exploratory study.

The extent to which concomitant Alzheimer's disease (AD) is etiologically related to the development of dementia in Parkinson's disease (PD) remains controversial. We explored the association of four risk factors associated with AD, including head injury, smoking, hypertension, and diabetes mellitus, with incident dementia in PD. A cohort of 180 nondemented PD patients from the Washington Heights community in northern Manhattan, New York, completed a risk factor questionnaire at baseline and was followed annually with neurological and neuropsychological evaluations. The association of baseline variables with incident dementia was analyzed by using Cox proportional hazards models. All analyses controlled for age at baseline, gender, years of education, duration of PD, and total Unified Parkinson's Disease Rating Scale (UPDRS) motor score at baseline. Of 180 patients (mean age, 71.0 +/- 10.3 years), 52 (29%) became demented during a mean follow-up period of 3.6 +/- 2.2 years. Head injury risk ratio ([RR] 0.9; 95% confidence interval [CI], 0.4-2.2; P = 0.9), hypertension (RR, 0.7; 95% CI, 0.4-1.4, P = 0.3), and diabetes mellitus (RR, 0.8; 95% CI, 0.3-2.3; P = 0.7) were not significantly associated with incident dementia in the Cox models. Patients who reported having ever smoked were at increased risk for the development of dementia compared with nonsmokers (RR, 2.0; 95% CI, 1.0-3.9; P = 0.05). Current smoking was significantly associated with incident dementia (RR, 4.5; 95% CI, 1.2-16.4; P = 0.02), whereas past smoking approached significance (RR, 1.9; 95% CI, 0.9-3.7; P = 0.07). Although an inverse association between smoking and PD has been reported in several studies, our study showed a positive association between smoking and dementia in the setting of PD. The association of smoking with incident dementia in PD deserves further study.

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PubMed2002

Memory and executive function impairment predict dementia in Parkinson's disease.

We analyzed the association of neuropsychological test impairment at baseline with the development of dementia in idiopathic Parkinson's disease (PD) patients. A cohort of nondemented PD patients from northern Manhattan, NY was followed annually with neurological and neuropsychological evaluations. The neuropsychological battery included tests of verbal and nonverbal memory, orientation, visuospatial ability, language, and abstract reasoning. The association of baseline neuropsychological tests scores with incident dementia was analyzed using Cox proportional hazards models. The analysis controlled for age, gender, education, duration of PD, and the total Unified Parkinson's Disease Rating Scale motor score at baseline. Forty-five out of 164 patients (27%) became demented during a mean follow-up of 3.7 +/- 2.3 years. Four neuropsychological test scores were significantly associated with incident dementia in the Cox model: total immediate recall (RR: 0.92, 95% CI: 0.87-0.97, P = 0.001) and delayed recall (RR: 0.73, 95% CI: 0.59-0.91, P = 0.005) of the Selective Reminding Test (SRT), letter fluency (RR: 0.87, 95% CI: 0.77-0.99, P = 0.03), and Identities and Oddities of the Mattis Dementia Rating Scale (RR: 0.85, 95% CI: 0.73-0.98, P = 0.03). When the analysis was performed excluding patients with a clinical dementia rating of 0.5 (questionable dementia) at baseline evaluation, total immediate recall and delayed recall were still predictive of dementia in PD. Our results indicate that impairment in verbal memory and executive function are associated with the development of dementia in patients with PD.

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PubMed2002

Functional magnetic resonance imaging study of word recognition in normal elders.

Four healthy, cognitively intact elders participated. Subjects underwent fMRI scanning while performing a word recognition task with an easy condition (low demand) and a difficult condition titrated to each subject's ability (titrated demand). Relative to low, titrated demand was associated with increased activation of the left medial frontal (cluster level P <.002), right superior temporal (P <.007) and right superior parietal cortices (P<.001). Increased activation of bilateral cortical areas by elders during the more challenging titrated demand compared with low demand may indicate recruitment of additional brain regions, enabling subjects to maintain performance despite increasing difficulty. Alternatively, the bilateral activation on this word recognition task may reflect compensatory use of right hemisphere networks.

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PubMed2002

Age-related changes in source memory retrieval: an ERP replication and extension.

Event-related potentials (ERPs) were recorded (62 scalp sites) from young (M=22) and older (M=66) adults during tests of item recognition and source memory, in a replication and extension of a previous study [Psychol. Aging 14 (1999) 390-413]. Participants studied two temporally distinct lists of sentences (each with two unassociated nouns). At test, in response to studied and unstudied nouns, participants made old/new, followed by source (i.e., list) judgments. Several measures were employed to enhance the source memory performance of the older adults. These were successful, as the old adults showed source memory performance comparable to that of the young subjects from the previous study (67%). Nonetheless, the younger adults significantly outperformed the older adults on measures of item and source memory performance. The ERPs revealed that both age groups showed a robust early, posterior-maximal episodic memory (EM) effect. However, despite their enhanced source memory performance, the ERPs of the old failed to show a robust late, right-prefrontal EM effect, which was again present in the ERPs of the young. By contrast, the older adults showed a central negative component not seen in the ERPs of the young. These results are consistent with the frontal lobe deficit hypothesis of aging and provide some evidence that old and young may use distinct cortical networks during source memory retrieval.

Adult↗

PubMed2002

Reading level attenuates differences in neuropsychological test performance between African American and White elders.

The current study sought to determine if discrepancies in quality of education could explain differences in cognitive test scores between African American and White elders matched on years of education. A comprehensive neuropsychological battery was administered to a sample of African American and non-Hispanic White 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 had no history of Parkinson's disease, stroke, mental illness, or head injury. The Reading Recognition subtest from the Wide Range Achievement Test-Version 3 was used as an estimate of quality of education. A MANOVA revealed that African American elders obtained significantly lower scores than Whites on measures of word list learning and memory, figure memory, abstract reasoning, fluency, and visuospatial skill even though the groups were matched on years of education. However, after adjusting the scores for WRAT-3 reading score, the overall effect of race was greatly reduced and racial differences on all tests (except category fluency and a drawing measure) became nonsignificant. These findings suggest that years of education is an inadequate measure of the educational experience among multicultural elders, and that adjusting for quality of education may improve the specificity of certain neuropsychological measures.

Black or African American↗

PubMed2002

HIV-associated cognitive impairment before and after the advent of combination therapy.

The objective of this study was to describe the occurrence of HIV dementia and neuropsychological testing abnormalities in a new cohort of HIV-seropositive individuals at high risk for HIV dementia and to compare these results to a cohort before the advent of highly active antiretroviral therapy (HAART). HAART has been associated with improvements in cognitive performance in some HIV-infected patients. However, it is uncertain whether HAART has changed the frequency of specific neurocognitive abnormalities. Baseline data from 272 HIV-seropositive subjects in the Dana cohort recruited from January, 1994, to December, 1995, and 251 HIV-seropositive subjects in the Northeastern AIDS Dementia Consortium (NEAD) cohort recruited from April, 1998, to August, 1999, were compared. Participants in both cohorts received nearly identical assessments. After adjusting for differences in age, education, gender, race, and CD4 count between the two cohorts, there were no differences in the occurrence of HIV dementia or abnormalities either 1 SD or 2 SDs below established norms for any of the neuropsychological tests. Even though HAART has reduced the incidence of HIV dementia, HIV-associated cognitive impairment continues to be a major clinical problem among individuals with advanced infection.

AIDS Dementia Complex↗

PubMed2002

Incidence of dementia after ischemic stroke: results of a longitudinal study.

BACKGROUND AND PURPOSE: A number of cross-sectional epidemiological studies have reported that one fourth of elderly patients meet criteria for dementia 3 months after ischemic stroke, but few longitudinal studies of the incidence of dementia after stroke have been performed. We conducted the present study to investigate the incidence and clinical predictors of dementia after ischemic stroke. METHODS: We administered neurological, neuropsychological, and functional assessments annually to 334 ischemic stroke patients (age, 70.4+/-7.5 years) and 241 stroke-free control subjects (age, 70.6+/-6.5 years), all of whom were nondemented in baseline examinations. We diagnosed incident dementia using modified Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition criteria requiring deficits in memory and > or =2 additional cognitive domains, as well as functional impairment. RESULTS: The crude incidence rate of dementia was 8.49 cases per 100 person-years in the stroke cohort and 1.37 cases per 100 person-years in the control cohort. A Cox proportional-hazards analysis found that the relative risk (RR) of incident dementia associated with stroke was 3.83 (95% CI, 2.14 to 6.84), adjusting for demographic variables and baseline Mini-Mental State Examination score. Within the stroke cohort, intercurrent medical illnesses associated with cerebral hypoxia or ischemia were independently related to incident dementia (RR, 4.40; 95% CI, 2.20 to 8.85), adjusting for recurrent stroke, demographic variables, and baseline Mini-Mental State Examination score. CONCLUSIONS: The risk of incident dementia is high among patients with ischemic stroke, particularly in association with intercurrent medical illnesses that might cause cerebral hypoxia or ischemia, suggesting that cerebral hypoperfusion may serve as a basis for some cases of dementia after stroke.

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PubMed2002

Predictors of cognitive dysfunction after subarachnoid hemorrhage.

BACKGROUND: Cognitive dysfunction is a common and disabling sequela of subarachnoid hemorrhage (SAH). Although several clinical and radiographic findings have been implicated in the pathogenesis of cognitive dysfunction after SAH, few prospective studies have comprehensively and simultaneously evaluated these risk factors. METHODS: Between July 1996 and March 2000, we prospectively evaluated 113 of 248 consecutively admitted nontraumatic SAH patients alive at 3 months with a comprehensive neuropsychological evaluation. Summary scores for 8 cognitive domains were calculated to express test performance relative to the entire study population. Clinical and radiographic variables associated with domain-specific cognitive dysfunction were identified with forward stepwise multiple regression, with control for the influence of demographic factors. RESULTS: The study participants were younger (P=0.005), less often white (P=0.006), and had better 3-month modified Rankin scores (P=0.001) than those who did not undergo neuropsychological testing. The proportion of subjects who scored in the impaired range (>2 SD below the normative mean) on each neuropsychological test ranged from 10% to 50%. Predictors of cognitive dysfunction in 2 or more domains in the multivariate analysis included global cerebral edema (4 domains), left-sided infarction (3 domains), and lack of a posterior circulation aneurysm (2 domains). Other variables consistently associated with cognitive dysfunction in the univariate analysis included admission Hunt-Hess grade >2 and thick SAH in the anterior interhemispheric and sylvian fissures. CONCLUSIONS: Global cerebral edema and left-sided infarction are important risk factors for cognitive dysfunction after SAH. Treatment strategies aimed at reducing neurological injury related to generalized brain swelling, infarction, and clot-related hemotoxicity hold the best promise for improving cognitive outcomes after SAH.

Acute Disease↗

PubMed2002

What is cognitive reserve? Theory and research application of the reserve concept.

The idea of reserve against brain damage stems from the repeated observation that there does not appear to be a direct relationship between the degree of brain pathology or brain damage and the clinical manifestation of that damage. This paper attempts to develop a coherent theoretical account of reserve. One convenient subdivision of reserve models revolves around whether they envision reserve as a passive process, such as in brain reserve or threshold, or see the brain as actively attempting to cope with or compensate for pathology, as in cognitive reserve. Cognitive reserve may be based on more efficient utilization of brain networks or of enhanced ability to recruit alternate brain networks as needed. A distinction is suggested between reserve, the ability to optimize or maximize normal performance, and compensation, an attempt to maximize performance in the face of brain damage by using brain structures or networks not engaged when the brain is not damaged. Epidemiologic and imaging data that help to develop and support the concept of reserve are presented.

Aged↗

PubMedDate not supplied

Acquisition, recall, and forgetting of verbal information in long-term memory by young, middle-aged, and elderly individuals.

Memory performance by four age groups (30-45 years, 46-60 years, 61-75 years, and 76-90 years) was compared on a multi-trial verbal recall task with 20-minute and 1-day delay free recall and recognition trials. The rate of acquisition across 5 learning trials was similar for all ages except the youngest group whose performance was constrained by a ceiling effect. The level of acquisition achieved was less in the two oldest groups. Words gained across trials and words lost across trials made similar contributions to the shape of the learning curve for the acquisition trials. Subjective organization decreased with age, but remained strongly related to the number of words recalled during acquisition for all age groups. The two oldest age groups demonstrated significant declines in words recalled on the 20-minute and 1-day delay trials. A subset of the oldest group demonstrated more rapid forgetting at the 1-day delay when participants from all age conditions were matched on acquisition. Thus, many aspects of free recall were impaired with age, and variance measurement of recall showed greater inter-individual differences with increasing age. This increase in individual differences could reflect a single form of age-related memory impairment, or it could indicate that memory impairment in the elderly is due to multiple processes. The importance of testing across the life span and using tests that examine a variety of memory components and processes for establishing norms and clarifying age-related deficits are discussed.

Adult↗

PubMedDate not supplied

Cognitive reserve and Alzheimer disease.

Epidemiologic evidence suggests that individuals with higher IQ, education, occupational attainment, or participation in leisure activities have a reduced risk of developing Alzheimer disease (AD). The concept of cognitive reserve (CR) posits that individual differences in how tasks are processed provide differential reserve against brain pathology or age-related changes. This may take 2 forms. In neural reserve, preexisting brain networks that are more efficient or have greater capacity may be less susceptible to disruption. In neural compensation, alternate networks may compensate for pathology's disruption of preexisting networks. Imaging studies have begun to identify the neural substrate of CR. Because CR may modulate the clinical expression of AD pathology, it is an important consideration in studies of "preclinical" AD and treatment studies. There is also the possibility that directly enhancing CR may help forestall the diagnosis of AD.

Alzheimer Disease↗

PubMedDate not supplied

Cognitive reserve and Alzheimer disease.

Achievement↗

PubMedDate not supplied

Altered PET functional brain responses in cognitively intact elderly persons at risk for Alzheimer disease (carriers of the epsilon4 allele).

OBJECTIVE: Few previous studies have investigated the association between APOE genotype and brain activation during performance of cognitive tasks in healthy middle-aged and elderly subjects, and the results have been mixed. The authors investigated APOE-mediated differential brain activation in a group of healthy elderly subjects. METHODS: Using H215O positron emission tomography (PET), they imaged 32 healthy subjects (26 non-epsilon4 carriers and 6 epsilon4 carriers) performing a serial shape-recognition memory task under two conditions: Simple Demand (SD), in which one shape was presented in each study trial, and Titrated Demand (TD), in which study list length was adjusted so that each subject recognized words at approximately 75% accuracy. Multiple-regression analyses were performed, with the "activation" difference (TD-SD PET counts) as the dependent variable and the APOE genotype (presence versus absence of the epsilon4 allele) as the independent variable. RESULTS: Compared with non-carriers, epsilon4 carriers exhibited significantly decreased TD-SD activation differences in the left superior temporal, right superior frontal, left postcental, left precuneus, and posterior cingulate gyrus because epsilon4 carriers (versus non-carriers) showed increased activation during the SD and decreased activation during the TD condition. CONCLUSION: Patterns of brain activation during a nonverbal memory task differed as a function of APOE genotype and, therefore, of genetic risk for Alzheimer disease (AD). Differences in activation were not a reflection of task difficulty, but indicate memory-related altered cognitive processing. Brain regions with decreased activation in the epsilon4 subjects may result from subclinical incipient AD pathology and/or APOE-related neurophysiologic heterogeneity.

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