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Yaakov Stern

Publications and source records attributed to Yaakov Stern.

At least 55 records · Page 3Linked to original sources
PubMed2004

Positive evidence against human hippocampal involvement in working memory maintenance of familiar stimuli.

Subjects (n = 40) performed a delayed item recognition task for visually presented letters with three set sizes (1, 3 or 6 letters). Accuracy was close to ceiling at all set sizes, so we took set size as a proxy for WM load (i.e. the amount of information being maintained in WM). Functional magnetic resonance imaging (fMRI) signal associated with the delay period increased in a nearly linear fashion with WM load in the left inferior frontal gyrus/anterior insula (possibly Broca's area, BA 44/45), right anterior insula, bilateral caudate, bilateral precentral gyrus (BA 6), bilateral middle frontal gyrus (BA 9/46), bilateral inferior parietal lobule (with foci in both BA 39 and 40), left superior parietal lobule (BA 7), medial frontal gyrus (BA 6), anterior cingulate gyrus (BA 32) and bilateral superior frontal gyrus (BA 8). These results lend support to the idea that at least some of the cortical mechanisms of WM maintenance, potentially rehearsal, exhibit a scaling with WM load. In contrast, the delay-related fMRI signal in hippocampus followed an inverted U-shape, being greatest during the intermediate level of WM load, with relatively lower values at the lowest and highest levels of WM load. This pattern of delay-related fMRI activity, orthogonal to WM load, is seemingly not consonant with a role for hippocampus in WM maintenance of phonologically codable stimuli. This finding could possibly be related more to the general familiarity of the letter stimuli than their phonological codability per se.

Adult↗
PubMed2004

Identification and differential vulnerability of a neural network in sleep deprivation.

The study aimed to identify task-related brain activation networks whose change in expression exhibits subject differences as a function of differential susceptibility to sleep deprivation. Brain activity during a non-verbal recognition memory task was investigated in an event-related functional MRI paradigm both prior to and after 48 h of sleep deprivation. Nineteen healthy subjects participated. Regional covariance analysis was applied to data. An activation network pattern was identified whose expression decreased from pre- to post-sleep deprivation in 15 out 19 subjects (P < 0.05). Differential decrease in expression correlated with worsening performance in recognition accuracy (P < 0.05). Sites of de-activation were found in the posterior cerebellum, right fusiform gyrus and precuneus, and left lingual and inferior temporal gyri; increased activation was found in the bilateral insula, claustrum and right putamen. A network whose expression decreased after sleep deprivation and correlated with memory performance was identified. We conclude that this activation network plays a role in cognitive function during sleep deprivation.

Adaptation, Physiological↗
PubMed2004

Cognitive reserve-mediated modulation of positron emission tomographic activations during memory tasks in Alzheimer disease.

BACKGROUND: Cognitive reserve (CR) is the ability of an individual to cope with advancing brain pathological abnormalities so that he or she remains free of symptoms. Epidemiological data and evidence from positron emission tomography suggest that it may be mediated through education or IQ. OBJECTIVE: To investigate CR-mediated differential brain activation in Alzheimer disease (AD) subjects compared with healthy elderly persons. PARTICIPANTS: Using radioactive water positron emission tomography, we scanned 12 AD patients and 17 healthy elderly persons while performing a serial recognition memory task for nonverbalizable shapes under 2 conditions: low demand, in which one shape was presented in each study trial, and titrated demand, in which the study list length was adjusted so that each subject recognized shapes at approximately 75% accuracy. Positron emission tomographic scan acquisition included the encoding and recognition phases. A CR factor score that summarized years of education, National Adult Reading Test estimated IQ, and Wechsler Adult Intelligence Scale-Revised vocabulary subtest score (explaining 71% of the total variance) was used as an index of CR. Voxel-wise, multiple regression analyses were performed with the "activation" difference (titrated demand-low demand) as the dependent variables and the CR factor score as the independent one. Brain regions where regression slopes differed between the 2 groups were identified. RESULTS: The slopes were significantly more positive for the AD patients in the left precentral gyrus and in the left hippocampus and significantly more negative in the right fusiform, right middle occipital, left superior occipital, and left middle temporal gyri. CONCLUSION: Brain regions where systematic relationships (slopes) between subjects' education-IQ and brain activation differ as a function of disease status may mediate the differential ability to cope with (ie, delay or modify) clinical manifestations of AD.

Aged↗
PubMed2004

Attenuated central nervous system infection in advanced HIV/AIDS with combination antiretroviral therapy.

BACKGROUND: Before the introduction of combination antiretroviral therapy (CART), neurological disease correlated with cerebrospinal fluid (CSF) levels of human immunodeficiency virus (HIV) RNA. OBJECTIVE: To investigate the relationships among HIV RNA levels, immune activation markers, and neurological status in patients receiving CART. DESIGN: Multicenter cohort study. SETTING: Academic neurology departments. PATIENTS: A total of 371 patients unselected for neurological complaints and with CD4 cell counts less than 200/microL or with cognitive symptoms and CD4 cell counts less than 300/microL were enrolled into the Northeastern AIDS Dementia cohort in 1998-2002. Diagnoses of HIV-associated dementia (HIV-D) and minor cognitive-motor disorder (MCMD) were obtained with a computerized algorithm. Plasma and CSF levels of HIV RNA, monocyte chemotactic protein 1, macrophage colony-stimulating factor, and tumor necrosis factor alpha were quantified. RESULTS: The mean +/- SD age was 41.5 +/- 7.2 years, and the mean +/- SD educational level was 12.3 +/- 2.2 years. Seventy percent of the cohort was black, and 30% were women. The mean +/- SD CD4 cell count was 136.8 +/- 87.9/microL, and CART was used in 71%. Twenty-nine percent of the patients were unimpaired (n = 106), 36% had MCMD (n = 133), and 35% had HIV-D (n = 128). Mean log(10) CSF HIV RNA copies per milliliter was 2.6 +/- 0.8, with no differences among the neurological groups, even after adjustments for baseline CD4 cell counts and antiretroviral therapy. Cerebrospinal fluid HIV RNA was undetectable in 47% of unimpaired, 46% of MCMD, and 43% of HIV-D patients (P = .91). Plasma levels of monocyte chemotactic protein type 1 and tumor necrosis factor alpha correlated weakly with HIV RNA levels but did not distinguish those with neurological deficits. CONCLUSIONS: In contrast to observations in individuals not treated with CART, we found no relationship between CSF markers and neurological status in this CART-using cohort with advanced HIV/AIDS. This was not explicable by demographic differences or plasma virological control. CART may substantially attenuate the degree of central nervous system HIV infection and immune activation, and in CART users, CSF HIV RNA and immune activation markers may fail to discriminate milder degrees of HIV-D and MCMD.

Acquired Immunodeficiency Syndrome↗
PubMed2004

APOE and APOC1 promoter polymorphisms and the risk of Alzheimer disease in African American and Caribbean Hispanic individuals.

BACKGROUND: The APOE epsilon4 allele is a genetic risk factor for Alzheimer disease (AD), though the strength of the association varies by ethnic group. Polymorphisms in regulatory sequences of APOE have also been related to AD, but the effects are inconsistent across studies. METHODS: We examined the association between AD and variants in 3 APOE promoters and in the promoter of the adjacent APOC1 gene in African American and Caribbean Hispanic individuals. Polymorphisms tested were the -491A/T, -427T/C, and -219G/T (Th1/E47cs) in the APOE promoter and the HpaI variant in the APOC1 promoter. Using standard research criteria for AD, overall odds ratios were computed and repeated stratified by presence or absence of APOE epsilon4. RESULTS: The APOC1 HpaI+ variant was associated with AD in Caribbean Hispanic individuals, but strong linkage disequilibrium with the APOE epsilon4 allele indicated that this was not an independent effect. No promoter variant in APOE or APOC1 was associated with AD before or after adjusting for age, education, sex, and multiple comparisons. Estimated haplotypes including -219G/T, APOE, and APOC1 differed significantly in Caribbean Hispanic patients and controls but not in African American participants. This effect was primarily owing to the -219G/T-APOE haplotype, but we did not detect significant allele-specific differences in promoter activity comparing reporter constructs containing the APOE -219G and -219 T alleles. CONCLUSION: These findings exclude a strong or independent influence of APOE or APOC1 promoter polymorphisms on the variation in APOE-related risk of AD in African American and Caribbean Hispanic individuals.

Black or African American↗
PubMed2004

Comparison of dementia with Lewy bodies to Alzheimer's disease and Parkinson's disease with dementia.

We compared the clinical and neuropsychological pattern of dementia with Lewy bodies (DLB) to Alzheimer's disease (AD) and Parkinson's disease with dementia (PD-d). Sixteen patients clinically diagnosed with DLB were compared with two groups of patients with PD-d (n = 15) and AD (n = 16) matched for level of dementia. Isolated cognitive impairment was the most common form of presentation in AD (93.8%) and DLB (31.3%) groups, while parkinsonism was in 100% of PD-d subjects. Psychoses associated with cognitive impairment at the beginning of the disease were more frequent in DLB patients (31.3%) than in AD (6.3%) and PD-d (0%) groups. There were no significant differences in Unified Parkinson Disease Rating Scale motor-subscale scores between DLB and PD-d patients. DLB and PD-d patients performed significantly worse on attentional functions and better on memory tests than AD. DLB patients also showed lower scores than AD subjects on visual memory, visuoperceptive, and visuoconstructive tests. No significant differences were found between PD-d group and DLB subjects on any neuropsychological test. We were unable to find any differences in cognitive tasks between PD-d and DLB subjects. Clinical features and neuropsychological deficiencies of DLB (attentional, visuoperceptive, and visuoconstructive deficits) and PD (attentional deficits) compared to AD (amnesic syndrome) can contribute to accurate identification of these entities and to the understanding of the neuropathological and neurochemical substrate underlying these diseases.

Aged↗
PubMed2004

Cognitive reserve: implications for diagnosis and prevention of Alzheimer's disease.

Epidemiologic evidence suggests that higher occupational attainment and education, as well as increased participation in intellectual, social, and physical aspects of daily life, are associated with slower cognitive decline in healthy elderly and may reduce the risk of incident Alzheimer's disease (AD). There is also evidence from structural and functional imaging studies that patients with such life experiences can tolerate more AD pathology before showing signs of clinical dementia. It has been hypothesized that such aspects of life experience may result in functionally more efficient cognitive networks and, therefore, provide a cognitive reserve that delays the onset of clinical manifestations of dementia. In this article, we review some of the relevant literature of the noted associations between markers of cognitive reserve and AD and discuss the possible mechanisms that may explain these associations.

Activities of Daily Living↗
PubMed2004

An event-related fMRI study of the neurobehavioral impact of sleep deprivation on performance of a delayed-match-to-sample task.

Eighteen subjects (ages 18-35) underwent event-related functional magnetic resonance imaging (efMRI) while performing a delayed-match-to-sample (DMS) task before and immediately after 48 h of sustained wakefulness. The DMS trial events were: a 3-s study period of either a one-, three-, or six-letter visual array; a 7-s retention interval; and a 3-s probe period, where a button press indicated whether the probe letter was in the study array. Ordinal Trend Canonical Variates Analysis (OrT CVA) was applied to the data from the probe period for trials with six-letter study lists prior to and immediately following sleep deprivation to find an activation pattern whose expression decreased with sleep deprivation in as many subjects as possible, while being present in both conditions. The first principal component of the OrT analysis identified a covariance pattern whose expression decreased as a function of sleep deprivation in 17 of 18 subjects (p<0.001). While overall expression of the pattern showed a systematic decrease with sleep deprivation, the brain regions that make up the pattern show covarying increases and decreases in activation. Regions that decreased their activation were noted in the parietal (BA 7 and 40), temporal (BA 37, 38 and 39) and occipital (BA 18 and 19) lobes; regions that increased their activation were noted in the cerebellum, basal ganglia, thalamus and the anterior cingulate gyrus (BA 32). The reduction in pattern expression with sleep deprivation for each subject was related to the change in performance on the DMS task. Subject decreases in pattern expression were correlated with reductions in recognition accuracy (p<0.05), increased intra-individual variability in reaction time (p<0.005) and increased lapsing (p<0.005).

Adult↗
PubMed2004

Covariance PET patterns in early Alzheimer's disease and subjects with cognitive impairment but no dementia: utility in group discrimination and correlations with functional performance.

Although multivariate analytic techniques might identify diagnostic patterns that are not captured by univariate methods, they have rarely been used to study the neural correlates of Alzheimer's disease (AD) or cognitive impairment. Nonquantitative H2(15)O PET scans were acquired during rest in 17 probable AD subjects selected for mild severity [mean-modified Mini Mental Status Examination (mMMS) 46/57; SD 5.1], 16 control subjects (mMMS 54; SD 2.5) and 23 subjects with minimal to mild cognitive impairment but no dementia (mMMS 53; SD 2.8). Expert clinical reading had low success in discriminating AD and controls. There were no significant mean flow differences among groups in traditional univariate SPM Noxel-wise analyses or region of interest (ROI) analyses. A covariance pattern was identified whose mean expression was significantly higher in the AD as compared to controls (P = 0.03; sensitivity 76-94%; specificity 63-81%). Sites of increased concomitant flow included insula, cuneus, pulvinar, lingual, fusiform, superior occipital and parahippocampal gyri, whereas decreased concomitant flow was found in cingulate, inferior parietal lobule, middle and inferior frontal, supramarginal and precentral gyri. The covariance analysis-derived pattern was then prospectively applied to the cognitively impaired subjects: as compared to subjects with Clinical Dementia Rating (CDR) = 0, subjects with CDR = 0.5 had significantly higher mean covariance pattern expression (P = 0.009). Expression of this pattern correlated inversely with Selective Reminding Test total recall (r = -0.401, P = 0.002), delayed recall (r = -0.351, P = 0.008) and mMMS scores (r = -0.401, P = 0.002) in all three groups combined. We conclude that patients with AD may differentially express resting cerebral blood flow covariance patterns even at very early disease stages. Significant alterations in expression of resting flow covariance patterns occur even for subjects with cognitive impairment. Expression of covariance patterns correlates with cognitive and functional performance measures, holding promise for meaningful associations with underlying biopathological processes.

Aged↗
PubMed2004

Obesity enhances verbal memory in postmenopausal women with Down syndrome.

Several lines of evidence suggest that the loss of estrogen after menopause may play a role in cognitive declines associated with Alzheimer's disease (AD). In postmenopausal women, the principal source of estrogen is estrone, which is influenced by body mass index (BMI). Increased BMI in postmenopausal women is associated with higher levels of serum estradiol and estrone. We hypothesized that obesity could have a beneficial effect on cognition with advancing age. We compared the performance of healthy nondemented obese and non-obese women with Down syndrome (DS) on a broad spectrum of cognitive tests. Estrone levels were 66.9% higher in obese than in non-obese postmenopausal women, and 136% higher in obese than in non-obese premenopausal women. Obese postmenopausal women performed significantly better than non-obese women on measures of verbal memory and on an omnibus test of neuropsychological function, but did not differ significantly in verbal fluency, language, praxis or visuospatial functioning. Among premenopausal women, there was no difference in cognitive function between obese and non-obese women. Our results support the hypothesis that higher endogenous estrogen levels after menopause are associated with better performance on verbal memory.

Adult↗
PubMed2004

Inter- and intraindividual variability in recognition memory: effects of aging and estrogen use.

Traditionally, studies of cognitive aging have focused on comparing the average performance of younger and older adults, whereas variability around the mean has been attributed to task-irrelevant noise. The present study examined the hypothesis that variability in memory performance increases with age and that estrogen helps temper age-related increases in variability. Postmenopausal estrogen users, estrogen and progestin (est + prog) users, and nonusers, as well as younger women, completed 16 blocks of an item-source memory task. Older women showed greater variability than younger women on measures of dispersion and consistency. Estrogen users, but not est + prog users, performed more consistently than nonusers. Overall, age-related increases in variability differed with the type of variability measured, and estrogen use, but not est + prog use, appeared to reduce age-related increases in at least 1 form of variability.

Adolescent↗
PubMed2004

Explicit contamination contributes to aging effects in episodic priming: behavioral and ERP evidence.

We examined the impact of explicit contamination on age-related changes in episodic priming. We recorded event-related brain potentials (ERPs) from older and younger adults to primed and unprimed nouns tested in a recognition memory task. Results revealed that the magnitude of priming was greater in the younger adults. ERPs revealed a priming effect in the younger adults that was absent in older adults. Findings suggest that explicit contamination may account for the reported aging effect: Item memory was correlated with episodic priming and ERP priming in younger adults, but not older adults; item memory was associated with episodic priming after aging effects were controlled for; and the topographies of the young's priming and item memory effects were indistinguishable. Given the apparent vulnerability to contamination by explicit memory, we suggest caution when researchers use an episodic priming paradigm to assess aging effects in implicit memory.

Adolescent↗
PubMed2004

Older adults' reports of formal care hours and administrative records.

PURPOSE: Personal assistance care is a Medicaid benefit in New York, but few data are available on its prevalence and contribution to home care. We examined these issues in a New York City sample by assessing older adults' reports of weekly home care hours and Medicaid billing records. DESIGN AND METHODS: With help from New York City's Human Resources Administration, we identified all respondents in an ongoing population-based survey of Medicare enrollees who were receiving Medicaid-reimbursed personal assistance care in 1996. RESULTS: Of respondents in the sample, 10.3% (185 of 1,902 alive through 1996) had Medicaid claims for personal assistance care. The mean was 46.1 hr/week for reported hours and 40.1 hr/week for administrative claims. Accuracy of reported hours was evident in a high correlation (r =.91; p <.001) between respondent reports and authorized claims, and a consistently high and mostly constant ratio of billed to reported hours across all categories of activities of daily living disability. IMPLICATIONS: In this urban, low income, and mostly minority sample, older adults' reports of weekly formal care hours were valid when matched against administrative records. Respondent reports of formal care hours were valid even in complex care situations.

Activities of Daily Living↗
PubMed2004

Phonological dyslexia: a test case for reading models.

Following brain damage, skilled readers may encounter more severe problems in reading nonwords than familiar words, a type of deficit referred to as phonological dyslexia. We report on 2 individuals with Alzheimer's disease who show phonological dyslexia. Although highly accurate in reading familiar words aloud (even those with irregular spelling, such as sew), they were quite impaired in nonword reading. Both patients performed well in phonological tasks involving the repetition, identification, and manipulation of phonemes of orally presented words and nonwords. These results challenge the idea, proposed in the context of connectionist and evolutionary theories, that phonological dyslexia originates from a phonological deficit. However, the results are consistent with reading models, such as the dual-route model, that attribute phonological dyslexia to a deficit that selectively affects the reading mechanisms responsible for deriving the sounds of nonwords. According to these models, such a deficit is not necessarily accompanied by a more general phonological impairment.

Aged↗
PubMed2004

A comparison of family history of psychiatric disorders among patients with early- and late-onset Alzheimer's disease.

OBJECTIVE: Both early-onset Alzheimer's Disease (EOAD) and late-onset Alzheimer's Disease (LOAD) present with cognitive and psychiatric features. Some studies suggest that EOAD patients are more likely than LOAD patients to have psychiatric symptoms. If this is true, relatives of EOAD patients with a similar clinical presentation may be more likely to be misclassified as having a primary noncognitive psychiatric disorder rather than a dementing disorder. Family history studies may underestimate familial aggregation of EOAD. METHODS: The authors compared the presence of psychiatric symptoms in parents and siblings of 131 EOAD patients (diagnosed at or before age 60), with the parents and siblings of 131 LOAD patients (diagnosed at or after age 65). Early onset Alzheimer's Disease and LOAD patients were matched for diagnosis (probable versus possible AD), gender, and ethnic group. Logistic regression analysis was performed on the outcome variable of patient group (EOAD, LOAD) with family history of psychiatric symptoms as the risk factor, adjusting for family size and patient's education. RESULTS: There was a nearly two and one-half-fold increase in family history of psychiatric symptoms among EOAD patients when compared with LOAD patients (RR = 2.4; 95% C.I. 1.2-4.7). CONCLUSIONS: The authors found preliminary evidence of a higher prevalence of a history of psychiatric symptoms among relatives of EOAD patients when compared to LOAD patients. This may be due to differential misclassification of AD, a syndromic disorder with both noncognitive psychiatric and cognitive deficits in relatives of EOAD patients. Alternatively, shared genetic or other familial etiologies may underlie subtypes of EOAD and some psychiatric disorders.

Age of Onset↗
PubMed2004

Acculturation, reading level, and neuropsychological test performance among African American elders.

The independent effects of cultural and educational experience on neuropsychological test performance were examined among 503 nondemented African Americans ages 65 and older. Measures of cultural experience (acculturation) and quality of education (reading level) were administered. Reading level was the most influential predictor of cognitive test performance, even after accounting for age, sex, years of education, and acculturation level. Age had small but significant unique effects on most measures, especially word list learning. Years of education had independent effects on measures of verbal abstraction, fluency, and figure matching. More acculturated African Americans obtained higher scores on most measures; however, after accounting for age, years of education, sex, and reading level, the effect of acculturation was diminished. The results suggest that quality of education and cultural experience influence how older African Americans approach neuropsychological tasks; therefore, adjustment for these variables may improve specificity of neuropsychological measures.

Acculturation↗
PubMed2004

Age-related differences in executive control of working memory.

In two experiments, we used dual-task methodology to assess the effect of aging on executive control of working memory. We hypothesized that (1) age-related dual-task costs would be observed even when individual tasks represent different perceptual modalities; (2) age would modulate the effect of increased temporal overlap on dual-task performance; and (3) the vulnerability of specific memory mechanisms to interference would be age related. We found that aging was associated with disproportionate dual-task costs that increased when extending the overlap between individual tasks. The effect of interference with encoding, and arguably output, was disproportionately larger in old than in young individuals. Ensuring that individual tasks represent different perceptual modalities is important but insufficient when using dual-task methodology to assess the effect of aging on executive function. The degree of temporal overlap between individual tasks and the sensitivity of specific memory operations to interference should be considered, as well.

Adult↗