Biomedical subjects

W W Barker

Publications and source records attributed to W W Barker.

At least 37 records · Page 2Linked to original sources

PubMed1998

Depressive symptomatology in first-degree family caregivers of Alzheimer disease patients: a cross-ethnic comparison.

This study investigated the prevalence of depressive symptoms among White Hispanic (WH) and White non-Hispanic (WNH) first-degree family caregivers. We screened 653 primary caregivers of family members with possible or probable Alzheimer disease who presented at our outpatient memory disorders clinic. Caregiver depression was assessed utilizing the Center for Epidemiologic Studies-Depression (CES-D) Scale. Overall, depression (CES-D scores > or = 16) was more common among WH (45%) than among WNH (36%) caregivers (p < 0.05). Elevated CES-D scores among the entire caregiving sample were also linked with being a female spouse (p=0.002), increased level of patient cognitive impairment (p=0.002), and patient psychosis (p=0.002). Risk factors for caregiver depression were identified and compared when the sample was stratified by ethnicity (WH and WNH) and generation (spouses and children). Patient cognitive impairment was a predictor of caregiver depression only among WH spouses and children, whereas patient psychosis was a predictor only among WNH spouses. Female caregiver gender was the most robust risk factor for caregiver depression, being a predictor in all groups except WH children. Implications of this study include the need for increased clinical sensitivity to depression in ethnic minority caregivers, treatment of psychiatric morbidity in dementia caregivers, and respite care for caregivers with high risk for depression.

Adult↗

PubMed1998

The factor structure of the Cornell Scale for Depression in Dementia among probable Alzheimer's disease patients.

The authors rated 137 outpatients with probable Alzheimer's disease (AD) on the Cornell Scale for Depression in Dementia (CSDD) as part of routine evaluation. Principal-factors analysis with varimax rotation resulted in a four-factor solution that accounted for 43.1% of the common variance. The four factors included general depression (lack of reactivity to pleasant events, poor self-esteem, pessimism, loss of interest, physical complaints, psychomotor retardation, sadness); rhythm disturbances (difficulty falling asleep, multiple night awakenings, early morning awakenings, weight loss, diurnal variation of mood); agitation/psychosis (agitation, mood-congruent delusions, suicide); and negative symptoms (appetite loss, weight loss, lack of energy, loss of interest, lack of reactivity to pleasant events). The observed factor structure showed moderate concordance with the five symptom clusters proposed in the original presentation of the CSDD.

Aged↗

PubMed1997

Interfamilial and intrafamilial phenotypic heterogeneity in familial Alzheimer's disease.

The features of Alzheimer's disease (AD) are very heterogenous, and some component of the variability of AD is likely to be related to genetic factors. To investigate this question, we evaluated 19 clinical neuropsychiatric and brain imaging features in 32 familial Alzheimer's disease (FAD) kindred, primarily of late onset. Within families, patients displayed a high degree of phenotypic heterogeneity (PH), which occurred irrespective of gender, ethnicity, or apolipoprotein E genotype. Overall, an equivalent amount of PH was observed in both the between- (37%) and within-family (31%) groups. However, for onset age and rate of decline between families, there was greater PH than within families (P = .002 and P = .01, respectively). A similar trend was found for severity of cortical atrophy (P = .05). These observations suggest a weak genetic influence, and possibly strong nongenetic influences, on the degree of phenotypic heterogeneity in late-onset FAD. In early-onset AD kindred, a much smaller degree of phenotypic heterogeneity may be expected within families, because genetic influences in phenotypic expression tend to be more prominent in early-onset cases.

Aged↗

PubMed1996

Alzheimer's disease: interaction of apolipoprotein E genotype, family history of dementia, gender, education, ethnicity, and age of onset.

We evaluated 197 patients with predominantly late-onset Alzheimer's disease (AD) who belonged to several ethnic groups and analyzed the relationship of age of onset of AD to the presence or absence of several risk factors in this entire group of patients. The apolipoprotein E (apoE) epsilon 4 allele frequency, which was 29% in all patients (compared with the reported population mean of 13.7%, p < 0.001, did not vary significantly between ethnic groups but declined significantly with increasing age. The apoE epsilon 2 allele frequency was 3%, compared with the reported population mean of 7.4% (p = 0.001). The frequency of a positive family history of dementia in first-degree relatives (FH +) (overall 45%) did not vary significantly between ethnic groups. ApoE epsilon 4-positive (epsilon 4+) patients tended to have a higher FH + rate (58%) than apoE epsilon 4-negative (epsilon 4-) patients (40%) (p = 0.02). When the potential risk factors of gender, education, FH+ status, and epsilon 4+ status were examined together in a multiple linear-regression analysis, FH+ and epsilon 4+ status (but not gender or education) were significant (they were both associated with an earlier age of onset of AD). In a post-hoc analysis, we found a reduced age of onset in women, but not men, who were both FH + and epsilon 4+. Additionally, those probands who were epsilon 4+ were more likely to inherit the disease from their mothers than their fathers. The mechanism by which epsilon 4+ and FH+ status operate as risk factors may be by their effect on the age of onset of AD.

Black or African American↗

PubMed1995

Clinicopathologic study of probable Alzheimer disease: assessment of criteria for excluding cerebrovascular disease.

The National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer Disease and Related Disorders Association criteria for probable Alzheimer disease (AD) require exclusion of non-AD dementia-producing conditions but do not specify how the non-AD conditions are to be identified. We addressed this issue for the case of cerebrovascular disease (CVD) by defining exclusion rules based on commonly described clinical features: (a) history of strokelike episodes; (b) history of stepwise cognitive decline; (c) focal deficits on neurological examination; and (d) evidence of significant CVD on neuroimaging. We applied these rules retrospectively to clinical records for 92 cognitively impaired patients who otherwise met criteria for probable AD and whose brains were subsequently available for postmortem examination. We used Fisher's exact test to assess the effectiveness of the exclusion rules in predicting the presence of CVD on autopsy. Prediction was better than chance when all four clinical features were used together (p = 0.0008) and when the stepwise decline or neuroimaging criteria were used alone (p = 0.03 and p = 0.05, respectively). Overall, the CVD exclusion rules were deficient because of low accuracy (50.0%) and low sensitivity (52.6%). These results support provisional use of the CVD criteria chosen for this study but suggest that modifications are needed for acceptable diagnostic accuracy and sensitivity to be achieved.

Alzheimer Disease↗

PubMed1994

Neural-network classification of normal and Alzheimer's disease subjects using high-resolution and low-resolution PET cameras.

UNLABELLED: Neural-network classification methods were applied to studies of FDG-PET images of the brain acquired from a total of 77 "probable" Alzheimer's disease and 124 normal subjects at two different centers. METHODS: Classification performances, as determined by relative-operating-characteristic (ROC) analyses of cross-validation experiments, were measured for FDG PET images obtained with either a 15-mm FWHM PETT V or a 6-mm FWHM Scanditronix PC-1024-7B camera for various methods of data representation. Neural networks were trained to distinguish between normal and abnormal subjects on the basis of regional metabolic patterns. For both databases, classification performance could be improved by increasing the "resolution" of the representation (decreasing the region size) and by normalizing the regional metabolic values to the value of a reference region (occipital region). RESULTS: The optimal classification performance for Scanditronix data (ROC area = 0.95) was higher than that for PETT V data (ROC area = 0.87). Under Bayesian theory, the classification performance with Scanditronix data corresponded to an ability to change a pre-test probability of disease of 50% to a post-test probability of either 90% for a positive classification or 10% for a negative classification. CONCLUSION: This classification can be used to either strongly confirm or rule out the presence of abnormalities.

Aged↗

PubMed1993

A comparative analysis of neuropsychological test performance of Spanish-speaking and English-speaking patients with Alzheimer's disease.

Because the diagnosis of dementia is highly dependent on the identification of neuropsychological deficits, there have been increasing concerns regarding cultural bias in tests designed to measure cognitive and intellectual function in English-speaking and Spanish-speaking adults. Despite their widespread clinical use, the effects of potential cultural bias on these measures among these two groups are largely unknown. We assembled a group of 76 females who received an NINCDS-ADRDA clinical diagnosis of Alzheimer's disease (AD). Half of these subjects were primary Spanish speakers, and the other half reported English as their primary language. All subjects were matched on chronological age and severity of memory impairment. Factors such as educational attainment and depression were entered into the analyses as covariates. The two groups were compared with respect to their performance on a battery of neuropsychological tests that are representative of what is typically used to diagnose the presence and severity of dementia. The finding that Spanish-speaking AD patients scored lower on specific neuropsychological measures is discussed in terms of inherent language biases and the possible lack of saliency of a number of these tests. The results obtained further suggest the need to modify certain neuropsychological indices so that they will better serve diverse ethnic and cultural groups.

Aged↗

PubMed1993

A comparison of familial and sporadic Alzheimer's disease.

Using a liberal criterion, a conservative probability-based criterion, and a criterion for autosomal dominant inheritance, we classified 36%, 13.5%, and 6.4% of 311 patients, respectively, as having familial Alzheimer's disease (FAD). The mean age of onset was over 70 years for all three categories of FAD. FAD and sporadic Alzheimer's disease (SAD) cases did not differ in clinical features, incidence of risk factors for dementia, or MRI or PET features. We observed earlier age of onset of AD to be related positively to longer duration of disease. Except for the autosomal dominant AD group, there was an earlier age of onset in FAD probands. The inheritance of AD from mothers was from 1.7 to 3.6 times more frequent than from fathers. Among SAD patients only, we found a preponderance of women, who were more frequently affected than would be expected from the male/female ratio in the general population of the same average age. Language performance tended to be less affected in FAD than in SAD patients, contrary to some previous reports.

Aged↗

PubMed1992

Viability of neocortical function shown in behavioral activation state PET studies in Alzheimer disease.

Twenty subjects with mildly to moderately severe Alzheimer disease (AD) and 14 normal elderly control subjects were studied using [18F]fluorodeoxyglucose and positron emission tomography (PET) to investigate regional cerebral glucose metabolism during both a resting state and a behavioral activation state, utilizing a reading memory task (RMT). The RMT produced significant global metabolic activation of 15 +/- 15% in normal subjects and 11 +/- 13% in AD subjects. The occipital regions were preferentially activated, but all regions in both groups were also significantly activated. The RMT did not allow a better discrimination of AD patients from normal controls on the basis of regional metabolic deficits. Regions in the AD group that were individually classified as hypometabolic during rest also exhibited metabolic activation. The apparent viability of hypometabolic regions in AD patients challenges current hypotheses regarding the cause of abnormal metabolism in AD.

Alzheimer Disease↗

PubMed1992

Evaluation of a neural-network classifier for PET scans of normal and Alzheimer's disease subjects.

The value of PET as an objective diagnostic tool for dementia may depend on the degree to which abnormal metabolic patterns can be detected by quantitative classification methods. In these studies, a neural-network classifier based on coarse region of interest analyses was used to classify normal and abnormal FDG-PET scans. The performance of neural networks and of an expert reader were evaluated by cross-validation testing. When the "abnormal" class was represented by subjects with clinical diagnoses of "Probable Alzheimer's," the areas under the relative-operating-characteristic (ROC) curves were 0.85 and 0.89 for the neural network and the expert reader, respectively. When testing with abnormal subjects represented by "Possible AD" cases, ROC areas for both the network and the expert were 0.81. The neural network out-performed discriminant analysis. It is concluded that PET has potential for the detection of abnormal brain function in dementing diseases, and that the combination of neural networks and PET is a useful diagnostic tool. Despite the low-resolution "view" afforded the neural network, its performance was nearly equivalent to that of an expert reader.

Adult↗

PubMed1991

Neuroanatomic differences between dyslexic and normal readers on magnetic resonance imaging scans.

The areas of six bilateral brain segments in the right and left hemispheres, on a horizontal brain section, and the area of subdivisions of the corpus callosum, on a midsagittal brain section, were measured on magnetic resonance images obtained from 21 dyslexic and 29 control subjects. In the entire group, the frontal half of the horizontal brain section showed asymmetry, with the right side being larger, whereas posteriorly only the occipital polar segment was asymmetrical, with the left side being larger. Dyslexic subjects exhibited asymmetry, with the right side greater than the left side, in contrast to the relatively symmetrical pattern that is normally observed in the midposterior segment that corresponds to the angular gyrus. In the corpus callosum, dyslexic subjects were found to have a larger splenium than nondyslexic subjects, and dyslexic female subjects were found to have a larger splenium than dyslexic male subjects. Because transcallosal pathways connecting the left and right angular gyrus regions traverse through the splenium of the corpus callosum, the above findings in dyslexic subjects suggest an anatomic abnormality in the angular gyrus region.

Adult↗

PubMed1991

Cerebrocerebellar relationship during behavioral activation: a PET study.

The effect of behavioral activation on cerebral and cerebellar glucose metabolism was studied in normal subjects when performing either a verbal memory task or a tactile somatosensory task. Each subject was also studied in a resting state control condition, either 1 h earlier or later than the activation task. Compared to the resting state, both tasks produced asymmetrical metabolic activation, which was opposite in direction within the cerebral and cerebellar hemispheres. In both tasks, the difference of activation of CMRglc in the right and left hemispheres in the cerebellum was negatively correlated with that in the sensory-motor region. This apparently coupled metabolic activation of one cerebellum and areas within the opposite cerebral hemisphere represents the inverse of the crossed cerebellar diaschisis phenomenon commonly observed when a vascular lesion affects one cerebral hemisphere and hypometabolism occurs in the opposite cerebellum. Because these correlations were selective and concordant with known anatomical connections, and were found in two different tasks, they suggest strong functional connections between these specific brain regions.

Aged↗

PubMed1991

Positron emission tomographic studies during serial word-reading by normal and dyslexic adults.

Positron-emission tomography (PET) was used to study regional cerebral metabolic activity during oral reading in right-handed adult males with, and without a childhood and family history of developmental dyslexia. Significant group differences in normalized regional metabolic values were revealed in prefrontal cortex and in the lingual (inferior) region of the occipital lobe. Lingual values were bilaterally higher for dyslexic than normal readers. In contrast to the asymmetry observed in prefrontal and lingual regions in nondyslexic subjects during reading, the dyslexic pattern was more symmetric. These results demonstrate that individuals who suffered from familial developmental dyslexia as children, activate different brain regions during reading as adults, as compared to individuals without such childhood history.

Adult↗

PubMed1991

Metabolic asymmetries in asymptomatic HIV-1 seropositive subjects: relationship to disease onset and MRI findings.

Fifteen male homosexual subjects (mean age 31.6 +/- 7.2 yr) who were asymptomatic, but HIV-1 seropositive (HIV+) were compared to 15 male age-matched HIV-1 seronegative (HIV-) subjects using resting PET/FDG studies and MR scans. Mean cerebral metabolic rates for glucose (mg/100 g/min) in the HIV+ and HIV- subjects were 7.7 +/- 1.7 and 7.0 +/- 2.1, (p = 0.44), respectively. An index of regional metabolic asymmetry for the whole brain was 5.8% +/- 3.2% in the HIV+ and 2.7% +/- 2.3% in the HIV- (p = 0.002), and the difference was most prominent in the prefrontal area. Significant asymmetries were found in 10/15 HIV+ subjects, primarily in prefrontal (7/15) and premotor (4/15) regions. MRI scans showed no abnormalities on clinical or quantitative evaluation in HIV+ subjects. Upon follow-up of HIV+ subjects over 18-40 mo, seven became symptomatic, of which two died. There was no relationship between the presence of PET scan abnormalities and earlier onset of symptomatic disease.

Adult↗

PubMed1990

MR signal abnormalities in memory disorder and dementia.

MR imaging of the brain, performed in 86 normal subjects and 113 patients with objective memory disorder or dementia, demonstrated white- and gray-matter areas of high signal intensity on long TR images (short and long TE). Hyperintensities were analyzed with respect to size (on a scale of 0-3) and location: lesions were periventricular, subcortical, or cortical. The patients with memory disorder and dementia were categorized as having probable/possible Alzheimer disease, a combination of Alzheimer disease and multiinfarct cognitive disorder, or multiinfarct cognitive disorder alone on the basis of clinically determined Hachinski ischemic scores. Significant correlations were found between age and scores for periventricular lesions (r = .40, p less than .0005) and subcortical lesions (r = .39, p less than .0005) in normal subjects. Correlations were also found between the Hachinski ischemic score and scores for periventricular lesions (r = .21, p less than .01), subcortical lesions (r = .27, p less than .0002), and cortical lesions (r = .32, p less than .0005) in subjects with memory disorder/dementia. Comparing multiinfarct cognitive disorder, Alzheimer disease, and normal groups, the mean scores for periventricular lesions were 12.0 +/- 4.6, 7.6 +/- 4.8, and 3.4 +/- 2.6, while mean scores for subcortical lesions were 10.8 +/- 12.2, 4.1 +/- 6.4, and 0.8 +/- 1.2, respectively. Periventricular lesions were present in 99-100% of patients with Alzheimer disease and multiinfarct cognitive disorder. On the other hand, subcortical lesions, which were identified in 100% of patients with multiinfarct cognitive disorder, were present in only about half of the patients with Alzheimer disease. Thus, scores for both periventricular and subcortical lesions are positively correlated with age and risk factors for cerebrovascular disease and also are significantly increased in the presence of objective memory disorder or dementia. These results imply that in the subject groups considered here, elderly patients with vascular dementia are most likely to have severe white-matter abnormalities on MR scans. The score for subcortical lesions appears to be more helpful than the score for periventricular lesions in distinguishing vascular dementia from Alzheimer disease and normal aging, so that a patient with prominent subcortical white-matter abnormalities is more likely to have a diagnosis of vascular than degenerative dementia.

Adult↗

PubMed1989

Asymmetric somatosensory activation with right- vs left-hand stimulation: a positron emission tomographic study.

Metabolic activation of the right and left somatosensory cortices (SSC) in response to an active sensorimotor task (palpation and sorting of mah jongg tiles) was studied in 16 right-handed normal volunteers using positron emission tomography (PET) and a double-injection [18F]fluorodeoxyglucose strategy. In 8 subjects with right-hand stimulation, cerebral metabolic rate for glucose (CMRglc) in the contralateral SSC increased by 16.7 +/- 5.1% (mean +/- S.D.); the increase in the ipsilateral SSC was 4.8 +/- 3.2%. In contrast, in the 8 subjects with left-hand stimulation, the contralateral increase was 12.0 +/- 2.9% and the ipsilateral increase was 5.9 +/- 1.5%. Thus, contralateral SSC activation was significantly higher with stimulation of the right hand, while the ipsilateral/contralateral symmetry of activation was greater when the left hand was stimulated.

Adult↗

PubMed1989

Predominant left hemisphere metabolic dysfunction in dementia.

Thirty-one patients with probable Alzheimer's disease and 11 patients with memory disorders, attributable to multiple cerebral infarctions, were studied using 18-F-fluorodeoxyglucose-positron emission tomography scans. Asymmetry in cerebral glucose metabolism within these diagnostic groups was assessed by comparison with the metabolic rates obtained in age-equivalent healthy control subjects. A significantly greater number of individuals in both patient groups exhibited predominant left rather than right hemisphere hypometabolism. In addition, for patients with Alzheimer's disease, the degree of asymmetry was not related to either the severity or duration of dementia. These findings could be explained by greater susceptibility of the left hemisphere to degenerative or ischemic brain disease, by a specific sampling effect, or most likely, by greater metabolic deficits resulting from left rather than right hemisphere impairment.

Brain↗

PubMed1988

Increases in both cerebral glucose utilization and blood flow during execution of a somatosensory task.

To investigate local metabolic and hemodynamic interrelationships during functional activation of the brain, paired studies of local cerebral glucose utilization (lCMRGlc) and blood flow (lCBF) were carried out in 10 normal subjects (9 right-handed, 1 ambidextrous) at rest and during a unilateral discriminative somatosensory/motor task--palpation and sorting of mah-jongg tiles by engraved design. The extent of activation was assessed on the basis of percentage difference images following normalization to compensate for global shifts. The somatosensory stimulus elevated lCMRGlc by 16.9 +/- 3.5% (mean +/- standard deviation) and lCBF by 26.5 +/- 5.1% in the contralateral sensorimotor cortical focus; smaller increments were noted in the homologous ipsilateral site. The increments of lCMRGlc and lCBF correlated poorly with one another in individual subjects. Stimulation of the right hand resulted in significantly higher contralateral lCMRGlc activation (19.6%) than did stimulation of the left hand (14.1%) (p less than 0.005), whereas the lCBF response was independent of the hand stimulated. Our results indicate that both glycolytic metabolism and blood flow increase locally with the execution of an active sensorimotor task and suggest that both measures may serve as reliable markers of functional activation of the normal brain.

Adult↗