PubMed Health⌕ Search

Biomedical subjects

Yaakov Stern

Publications and source records attributed to Yaakov Stern.

At least 73 records · Page 4Linked to original sources

Stroke and the risk of Alzheimer disease.

BACKGROUND: Alzheimer disease (AD) and stroke are common in elderly individuals, but the relation between these 2 disorders remains uncertain. OBJECTIVE: To investigate the association between a clinical history of stroke and subsequent risk of AD. DESIGN: A cohort of 1766 Medicare recipients without dementia participated in a longitudinal follow-up study from 1992 through 1999 in upper Manhattan, New York, NY. History of stroke and presence of cardiovascular risk factors were ascertained at the onset of the study. Incidence rates for AD among those with and without stroke were calculated; proportional hazards ratios were computed using age at onset of the disease as the time-to-event variable. RESULTS: The annual incidence for AD was 5.2% among individuals with stroke vs 4% for those without stroke. The hazards ratio for AD among those with a history of stroke was 1.6 (95% confidence interval, 1.0-2.4) compared with those without stroke. Of the vascular risk factors, hypertension, diabetes, and heart disease, only diabetes related to risk of AD in the absence of stroke. Stroke remained weakly associated with AD in the absence of these factors, but risk significantly increased with the additional factors of hypertension (relative risk, 2.3; 95% confidence interval, 1.4-3.6), diabetes (relative risk, 4.6; 95% confidence interval, 2.2-9.5), or heart disease (relative risk, 2.0; 95% confidence interval, 1.2-3.2). CONCLUSIONS: Stroke is associated with AD among elderly individuals. The relation is strongest in the presence of known vascular risk factors. The observed association between stroke and AD might relate to an underlying systemic vascular disease process, or alternatively, to the additive effects of stroke and AD pathologic features, leading to an earlier age at onset of disease.

Aged↗

Association of life activities with cerebral blood flow in Alzheimer disease: implications for the cognitive reserve hypothesis.

BACKGROUND: Regional cerebral blood flow (CBF), a good indirect index of cerebral pathologic changes in Alzheimer disease (AD), is more severely reduced in patients with higher educational attainment and IQ when controlling for clinical severity. This has been interpreted as suggesting that cognitive reserve allows these patients to cope better with the pathologic changes in AD. OBJECTIVE: To evaluate whether premorbid engagement in various activities may also provide cognitive reserve. DESIGN: We evaluated intellectual, social, and physical activities in 9 patients with early AD and 16 healthy elderly controls who underwent brain H(2)(15)O positron emission tomography. In voxelwise multiple regression analyses that controlled for age and clinical severity, we investigated the association between education, estimated premorbid IQ, and activities, and CBF. RESULTS: In accordance with previous findings, we replicated an inverse association between education and CBF and IQ and CBF in patients with AD. In addition, there was a negative correlation between previous reported activity score and CBF in patients with AD. When both education and IQ were added as covariates in the same model, a higher activity score was still associated with more prominent CBF deficits. No significant associations were detected in the controls. CONCLUSIONS: At any given level of clinical disease severity, there is a greater degree of brain pathologic involvement in patients with AD who have more engagement in activities, even when education and IQ are taken into account. This may suggest that interindividual differences in lifestyle may affect cognitive reserve by partially mediating the relationship between brain damage and the clinical manifestation of AD.

Aged↗

The rate of cognitive decline and risk of reaching clinical milestones in Alzheimer disease.

BACKGROUND: Previous studies revealed that cognitive test scores were related to functional outcome in Alzheimer disease (AD). However, the relationship between the rate of cognitive decline at the initial disease phase and the risk of reaching clinical milestones in subsequent years has not yet been examined. OBJECTIVE: To examine whether the rate of cognitive decline predicts the risk of reaching functional milestones in patients with probable AD. DESIGN: A 5-year prospective study was conducted at 3 sites. SETTING: Outpatient research and treatment centers. PARTICIPANTS: Patients diagnosed with probable AD (N = 236; mean age, 73 years; 59% women; mean years of education, 13). MAIN OUTCOME MEASURES: Modified Mini-Mental State Examination (mMMSE) scores were used to assess the rate of cognitive decline over time. Total dependence score and 2 clinical milestones: (1) the need to be dressed, groomed, and washed and (2) receiving a level of care equivalent to a placement in a health-related facility, were derived from the Dependence Scale. RESULTS: General estimating equation analyses revealed that the rate of cognitive decline during the entire follow-up period was positively related to an increase in total dependence scores. Cox analyses showed that a fast rate of decline during the first year was related to an increase in the risk of reaching clinical milestones in subsequent years. Analyses controlled for age, sex, education, and baseline mMMSE scores. CONCLUSION: A fast rate of cognitive decline was associated with increasing risk of reaching clinical milestones in AD.

Activities of Daily Living↗

Onset of dementia is associated with age at menopause in women with Down's syndrome.

Women with Down's syndrome experience early onset of both menopause and Alzheimer's disease. This timing provides an opportunity to examine the influence of endogenous estrogen deficiency, indicated by age at menopause, on risk of Alzheimer's disease. A community-based sample of 163 postmenopausal women with Down's syndrome, 40 to 60 years of age, was ascertained through the New York State Developmental Disability service system. Information from cognitive assessments, medical record review, neurological evaluation, and caregiver interviews was used to establish ages for onset of menopause and dementia. We used survival and multivariate regression analyses to determine the relation of age at menopause to age at onset of Alzheimer's disease, adjusting for age, level of mental retardation, body mass index, and history of hypothyroidism or depression. Women with early onset of menopause (46 years or younger) had earlier onset and increased risk of Alzheimer's disease (AD) compared with women with onset of menopause after 46 years (rate ratio, 2.7; 95% confidence interval [CI], 1.2-5.9). Demented women had higher mean serum sex hormone binding globulin levels than nondemented women (86.4 vs 56.6 nmol/L, p = 0.02), but similar levels of total estradiol, suggesting that bioavailable estradiol, rather than total estradiol, is associated with dementia. Our findings support the hypothesis that reductions in estrogens after menopause contribute to the cascade of pathological processes leading to AD.

Adult↗

Sertraline treatment of elderly patients with depression and cognitive impairment.

BACKGROUND: There is little information on the efficacy and side effects of antidepressant treatment in elderly patients with combined depression and cognitive impairment without dementia (DEP-MCI), and it is unclear if cognitive performance improves with antidepressant response in these patients. METHODS: In 39 elderly DEP-MCI patients, changes in depression and cognitive impairment were evaluated with open sertraline treatment up to 200 mg/day for 12 weeks. RESULTS: Of the 26 completers, 17 were responders and nine were non-responders. Diagnostic subtype of depression was unrelated to response. ANCOVA on WAIS-R digit symbol percent change scores revealed a significant effect for responder status (F = 5.59, p < 0.03), and age (F = 0.24, p < 0.64) and education (F = 1.64, p < 0.22) were not significant covariates. From pre-trial to post-trial, responders improved in WAIS-R digit symbol percent change scores (Mean -10% SD 24) while non-responders declined (Mean 14% SD 18; t = 2.60, p < 0.02). Other neuropsychological measures were unrelated to response. Percent change in HRSD scores showed significant inverse correlations with percent change in several cognitive measures. CONCLUSIONS: DEP-MCI patients showed moderate clinical response to sertraline treatment. When responders were compared to non-responders, cognitive improvement was limited to one measure of attention and executive function. Overall, there was little cognitive improvement with antidepressant treatment. The findings indirectly suggest that lack of improvement in cognition following treatment of depression in DEP-MCI patients may be associated with increased risk of meeting diagnostic criteria for dementia during follow-up.

Aged↗

Relation of cognitive reserve and task performance to expression of regional covariance networks in an event-related fMRI study of nonverbal memory.

Cognitive reserve (CR) has been established as a mechanism that can explain individual differences in the clinical manifestation of neural changes associated with aging or neurodegenerative diseases. CR may represent individual differences in how tasks are processed (i.e., differences in the component processes), or in the underlying neural circuitry (of the component processes). CR may be a function of innate differences or differential life experiences. To investigate to what extent CR can account for individual differences in brain activation and task performance, we used fMRI to image healthy young individuals while performing a nonverbal memory task. We used IQ estimates as a proxy for CR. During both study and test phase of the task, we identified regional covariance patterns whose change in subject expression across two task conditions correlated with performance and CR. Common brain regions in both activation patterns were suggestive of a brain network previously found to underlie overt and covert shifts of spatial attention. After partialing out the influence of task performance variables, this network still showed an association with the CR, i.e., there were reserve-related physiological differences that presumably would persist were there no subject differences in task performance. This suggests that this network may represent a neural correlate of CR.

Adult↗

Dementia in community-dwelling elderly patients: A comparison of survey data, medicare claims, cognitive screening, reported symptoms, and activity limitations.

BACKGROUND AND OBJECTIVE: Population-based estimates of dementia can vary widely depending on the data source and methodology used to assess cognitive impairment. The aim of this study was to assess individual and composite measures of dementia constructed using survey and administratively collected medical data for the purpose of improving insight into inherent and avoidable biases and the interpretation of these measures. METHODS: A national survey of 5089 community-dwelling elderly persons was linked to 5 years of Medicare claims. Kappa coefficients were used to assess dementia agreement between survey, cognitive screen, and claims. Odds ratios (ORs), adjusted for age, gender, and education, were computed to assess the relation of single- and multi-source dementia variables to cognitive symptoms and activity limitations. RESULTS: Dementia prevalence among persons aged 65 and over ranged from 4.5% to 16.8% across sources. Agreement in case identification between data sources was low, ranging from 0.15 to 0.41. Despite low agreement, ORs were consistently increased for limitations in cognitively related activities/symptoms and non-overlapping dementia sources. CONCLUSION: The finding that non-overlapping dementia data sources are associated with significantly increased limitations in cognitive activities suggests that forecasts of national dementia-related resource use based on single-source data could produce serious underestimates of future need.

Activities of Daily Living↗

Cognitive reserve modulates functional brain responses during memory tasks: a PET study in healthy young and elderly subjects.

Cognitive reserve (CR) is the ability of an individual to cope with advancing brain pathology so that he remains free of symptomatology. Epidemiological evidence and in vivo neurometabolic data suggest that CR may be mediated through education or IQ. The goal of this study was to investigate CR-mediated differential brain activation in 17 healthy young adults and 19 healthy elders. Using nonquantitative H(2)(15)O PET scanning, we assessed relative regional cerebral blood flow while subjects performed a serial recognition memory task under two conditions: nonmemory control (NMC), 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 shapes at approximately 75% accuracy. A factor score that summarized years of education and scores on two IQ indices was used as an index of CR. Voxel-wise, multiple regression analyses were performed with TD minus NMC difference PET counts as the dependent variable and the CR variable as the independent variable of interest. We identified brain regions where regression slopes were different from zero in each separate group, and also those where regression slopes differed between the two age groups. The slopes were significantly more positive in the young in the right inferior temporal gyrus, right postcentral gyrus, and cingulate, while the elderly had a significantly more positive slope in left cuneus. Brain regions where systematic relationships between CR and brain activation differ as a function of aging are loci where compensation for aging has occurred. They may mediate differential ability to cope with brain changes in aging.

Adult↗

Ischemic stroke and depression.

Previous studies of depression after stroke have reported widely variable findings, possibly due to differences between studies in patient characteristics and methods for the assessment of depression, small sample sizes, and the failure to examine stroke-free reference groups to determine the base rate of depression in the general population. In an effort to address certain of those methodologic issues and further investigate the frequency and clinical determinants of depression after stroke, we administered the Structured Interview Guide for the Hamilton Depression Rating Scale (SIGH-D) and neurological, neuropsychological, and functional assessments to 421 patients (age = 71.5 +/- 8.0 years) 3 months after ischemic stroke and 249 stroke-free control subjects (age = 70.8 +/- 6.7 years). We required a SIGH-D total score > 11 for the identification of depression. We found that depression was less frequent (47/421 patients, or 11.2%, and 13/249 control subjects, or 5.2%), less severe, and less persistent in our stroke cohort than previously reported, possibly due to the underrepresentation of patients with a premorbid history of affective illness. Depression was associated with more severe stroke, particularly in vascular territories that supply limbic structures; dementia; and female sex. SIGH-D item analyses suggested that a reliance on nonsomatic rather than somatic symptoms would result in the most accurate diagnoses of depression after ischemic stroke.

Aged↗

The neuropsychological profiles of mild Alzheimer's disease and questionable dementia as compared to age-related cognitive decline.

Test scores from a comprehensive neuropsychological battery administered to 1602 subjects consisting of 1347 subjects with probable Alzheimer's disease (AD), 100 subjects with questionable dementia (QD) and 155 non-demented elderly control subjects were cross-sectionally analyzed. Subjects with probable AD were categorized as mild (n = 244), moderate (n = 480), severe (n = 376), and very severe (n = 247) according to modified mini mental status exam (mMMSE) scores. Mean scores on individual neuropsychological tests are provided for each group of subjects. Stratified random sampling was performed to select a sample of mild AD subjects who were matched in age and education to non-demented elderly controls, and analyses focused on the performance of QD subjects and mild AD subjects, whose scores were compared to those of the elderly control subjects. Selected scores were organized by cognitive domain and logistic regressions were used to determine the domains and individual tests within each that were most predictive of group status. Results suggested a profile of scores associated with QD and mild AD including impaired recall of verbal information for both groups. Areas of lower functioning in QD subjects as compared to elderly controls included category fluency and visuospatial ability.

Aged↗

Medication management skill in HIV: I. Evidence for adaptation of medication management strategies in people with cognitive impairment. II. Evidence for a pervasive lay model of medication efficacy.

People with HIV-related cognitive impairment may change the way they manage medication regimens, relying on a fixed medication schedule each day to avoid missed doses. Using a medication recall diary, we identified people who took medication on exactly the same schedule over 3 days and those with more variable medication schedules. Patients with low scores on executive and psychomotor tests were more likely to report fixed medication schedules; memory performance, by contrast, was not associated with reported medication regimen. Patients with low scores on executive and psychomotor tests were also less accurate in pouring medicines in the Medication Management Test. More than three fourths of these HIV+ patients assumed that medicines with higher milligram dosages were stronger than medicines with smaller milligram dosages, even across different classes of medicines. In a non-HIV sample, 28% endorsed the belief, suggesting it is a widespread way of thinking about medication strength. A performance test of medication management sheds light on the ways patients take medicines and how beliefs about medicines affect medication regimens.

Adult↗

Psychopathological features in Alzheimer's disease: course and relationship with cognitive status.

OBJECTIVES: To examine the course, clinical correlates, and relationship between cognitive status and psychopathological features in patients with probable Alzheimer's disease (AD) followed over a 5-year period. DESIGN: Cohort study with follow-up of 5 years. SETTING: Patients were recruited at three sites: 91 patients at Columbia Medical Center, 84 at Johns Hopkins School of Medicine, and 61 at Massachusetts General Hospital. PARTICIPANTS: Patients diagnosed with probable AD (n = 236) enrolled in a longitudinal study (Predictors study). MEASUREMENTS: Wandering/agitation, physical aggression, hallucinations, and delusions were evaluated at 6-month intervals using the Columbia Scale for Psychopathology in Alzheimer's Disease. Descriptive analyses were used to provide estimates of prevalence and course of psychopathological features. General estimating equations determined the odds of having any of the four psychopathological behaviors as a function of cognitive status. Markov analyses provided 6-month transition probabilities for psychopathological behaviors given patients' cognitive status and the presence or absence of such behaviors in the previous evaluation. RESULTS: For wandering/agitation, prevalence (39-57%) and persistence increased as a function of time and decrement in cognitive status. Physical aggression was less prevalent (6-22%) and increased as a function of cognitive decline but tended to persist only in the more severely impaired patients. Delusions (34-49%) reached a peak at the second year and then declined. The odds of delusions were maximal with intermediate decline but remained persistent regardless of cognitive status. Hallucinations, despite some fluctuations, were relatively stable during the follow-up period (8-17%) and moderately persistent. CONCLUSION: Psychopathological features, particularly wandering/agitation and delusions, in AD were common throughout the disease course. The natural history and persistence of the four psychopathological features varied. These findings provide important information to clinicians and caregivers regarding the course, predictability, and possible treatment of psychopathological behaviors in patients with probable AD.

Aged↗

Cognitive reserve and lifestyle.

The concept of cognitive reserve (CR) suggests that innate intelligence or aspects of life experience like educational or occupational attainments may supply reserve, in the form of a set of skills or repertoires that allows some people to cope with progressing Alzheimer's disease (AD) pathology better than others. There is epidemiological evidence that lifestyle characterized by engagement in leisure activities of intellectual and social nature is associated with slower cognitive decline in healthy elderly and may reduce the risk of incident dementia. There is also evidence from functional imaging studies that subjects engaging in such leisure activities can clinically tolerate more AD pathology. It is possible that aspects of life experience like engagement in leisure activities may result in functionally more efficient cognitive networks and therefore provide a CR that delays the onset of clinical manifestations of dementia.

Adaptation, Physiological↗

Literacy and memory decline among ethnically diverse elders.

Literacy may be a more powerful indicator of brain reserve than years of education. Literacy level may be a proxy for native intellectual capacity or life experience that can compensate for brain damage or provide brain reserve. Alternately, the experience of acquiring literacy skills may in itself change the organization of the brain and increase protection against cognitive decline. However, because people with low levels of literacy obtain poor scores on most cognitive measures, only longitudinal studies can elucidate the role of reading ability in reserve. We determined whether literacy skills could predict cognitive change in a sample of 136 English-speaking African American, Caucasian, and Hispanic elders selected from a longitudinal aging study in New York City. According to a physician's independent examination, all participants were nondemented throughout the four longitudinal assessments. Literacy level was assessed using the WRAT-3 reading subtest. After accounting for age at baseline and years of education, GEE analyses showed that elders with low levels of literacy had a steeper decline in both immediate and delayed recall of a word list over time as compared to high literacy elders. Our findings suggest that literacy skills are protective against memory decline among nondemented elders.

Black or African American↗

Exploring the neural basis of cognitive reserve.

There is epidemiologic and imaging evidence for the presence of cognitive reserve, but the neurophysiologic substrate of CR has not been established. In order to test the hypothesis that CR is related to aspects of neural processing, we used fMRI to image 19 healthy young adults while they performed a nonverbal recognition test. There were two task conditions. A low demand condition required encoding and recognition of single items and a titrated demand condition required the subject to encode and then recognize a larger list of items, with the study list size for each subject adjusted prior to scanning such that recognition accuracy was 75%. We hypothesized that individual differences in cognitive reserve are related to changes in neural activity as subjects moved from the low to the titrated demand task. To test this, we examined the correlation between subjects' fMRI activation and NART scores. This analysis was implemented voxel-wise in a whole brain fMRI dataset. During both the study and test phases of the recognition memory task we noted areas where, across subjects, there were significant positive and negative correlations between change in activation from low to titrated demand and the NART score. These correlations support our hypothesis that neural processing differs across individuals as a function of CR. This differential processing may help explain individual differences in capacity, and may underlie reserve against age-related or other pathologic changes.

Adaptation, Physiological↗

Where do perseverations come from?

RB, a patient with probable Alzheimer's disease, makes continuous perseverations of single letters when writing (e.g. fruit-->fruuit), particularly on high frequency letters. An analysis of her errors reveals that her perseverations do not reflect letter substitutions or transpositions, nor do they suggest difficulty with geminates. No continuous perseverations were found in oral production, in graphic and simple motor tasks, and in oral spelling. RB's data do not support an attention deficit as the basis of her continuous perseverations. It is proposed that a deficit at the level of abstract letter representations is the source of RB's perseverations. The implications of this conclusion for accounts of perseveration and of spelling models are discussed.

Aged↗

Mortality in patients with dementia after ischemic stroke.

OBJECTIVE: Although dementia is typically considered to be a consequence of a variety of neurologic diseases, it can also serve as a risk factor for other adverse outcomes. The authors investigated dementia as a predictor of long-term survival among patients with ischemic stroke. METHODS: Neurologic, neuropsychological, and functional assessments were administered to 453 patients (mean age +/- SD, 72.0 +/- 8.3 years) 3 months after ischemic stroke. The authors diagnosed dementia in 119 (26.3%) of the patients using modified Diagnostic and Statistical Manual of Mental Disorders, Revised 3rd Edition, criteria requiring deficits in memory and two or more additional cognitive domains as well as functional impairment. Dementia as a predictor of long-term survival during up to 10 years of follow-up was then investigated. RESULTS: The mortality rate was 15.90 deaths per 100 person-years among patients with dementia and 5.37 deaths per 100 person-years among nondemented patients. A Cox proportional hazards analysis found that the relative risk (RR) of death was increased in association with dementia (RR = 2.4; 95% CI = 1.6 to 3.4), adjusting for the following: a major hemispheral stroke syndrome (RR = 1.4); a middle cerebral artery territory index stroke (RR = 1.7); a Stroke Severity Scale score of > or = 4, representing more severe stroke (RR = 1.8); atrial fibrillation (RR = 1.8); congestive heart failure (RR = 2.2); recurrent stroke occurring during follow-up (RR = 3.9); and demographic variables. The risk of death increased in association with the severity of dementia, but it did not differ by dementia subtype. CONCLUSIONS: Dementia is a significant independent risk factor for reduced survival after ischemic stroke, adjusting for other recognized predictors of mortality. The authors hypothesize that patients with dementia are at an elevated risk of mortality because of their increased burden of cerebrovascular disease, a tendency toward undertreatment for stroke prophylaxis among clinicians, or patient noncompliance with treatment regimens.

Aged↗