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Biomedical subjects

M S Albert

Publications and source records attributed to M S Albert.

At least 37 records · Page 2Linked to original sources
PubMed2000

Postmenopausal hormone therapy and cognitive function in healthy older women.

OBJECTIVE: Accumulating biologic evidence suggests that estrogen is related to cognitive function. Several epidemiologic investigations have reported that hormone therapy may reduce the risk of Alzheimer's disease. However, fewer studies have examined the relation of postmenopausal hormone use to general cognitive function in nondemented older women. Thus, we examined the association of hormone therapy to performance on four cognitive tests among healthy participants of the Nurses' Health Study. DESIGN: Cohort study. SETTING: The Nurses' Health Study, an ongoing prospective cohort study begun in 1976. PARTICIPANTS: From the Nurses' Health Study, 2138 women aged 70-78 years. MEASUREMENTS: From 1995-1999 we administered four cognitive tests (Telephone Interview for Cognitive Status (TICS), immediate and delayed recall of the East Boston Memory Test (EBMT), and verbal fluency) by telephone. Hormone use was ascertained from biennial questionnaires beginning in 1976. Linear and logistic regression models were used to calculate multivariate-adjusted differences in scores and relative risks of a low score for never users compared to current and past hormone users. RESULTS: After adjustment for confounders, neither current nor long-term hormone users demonstrated better performance on an overall measure of cognition (TICS), or on three tests of verbal memory (immediate and delayed recall of the EBMT, immediate recall of the TICS 10-word list) than never users. On the test of verbal fluency, current hormone users scored significantly better than never users (linear regression estimate of the difference in score = 0.78 points, 95% confidence interval (CI) 0.19-0.38, P = .01 for any current use; and 0.91 points, 95% CI 0.28-1.54, P = .005 for > or = 5 years current use). Current hormone users also had a 30% decrease (RR = 0.70, 95% CI 0.45-1.09) in their risk of a low score on the test of verbal fluency. These results were similar for women taking estrogen alone and estrogen combined with a progestin. CONCLUSIONS: Verbal fluency may be enhanced among women taking postmenopausal hormones, however, there is little support for better overall cognitive function in hormone users than nonusers.

Aged↗
PubMed2000

The effect of race and health-related factors on naming and memory. The MacArthur Studies of Successful Aging.

OBJECTIVES: The purpose of the analyses was to examine the impact of health-related variables on race differences in neuropsychological functioning (Boston Naming Task). METHODS: Using cross-sectional data from the MacArthur Successful Aging Study, the authors examined the relationship of demographic characteristics, health status, health habits, physical functioning, and speed of performance to naming and incidental recall of items from the Boston Naming Task. Participants were 1,175 healthy African American and European American older persons 70 to 79 years old. RESULTS: Regression analyses indicated that although race differences persisted for confrontational naming after controlling for demographic and health factors, there was no effect due to race for incidental recall scores or for savings scores for recall. DISCUSSION: The racial differences found in test performance may reflect differences in cultural appropriateness of the material rather than differences in ability.

Black or African American↗
PubMed2000

Use of structural magnetic resonance imaging to predict who will get Alzheimer's disease.

We used magnetic resonance imaging (MRI) measurements to determine whether persons in the prodromal phase of Alzheimer's disease (AD) could be accurately identified before they developed clinically diagnosed dementia. Normal subjects (n = 24) and those with mild memory difficulty (n = 79) received an MRI scan at baseline and were then followed annually for 3 years to determine which individuals subsequently met clinical criteria for AD. Patients with mild AD at baseline were also evaluated (n = 16). Nineteen of the 79 subjects with mild memory difficulty "converted" to a diagnosis of probable AD after 3 years of follow-up. Baseline MRI measures of the entorhinal cortex, the banks of the superior temporal sulcus, and the anterior cingulate were most useful in discriminating the status of the subjects on follow-up examination. The accuracy of discrimination was related to the clinical similarity between groups. One hundred percent (100%) of normal subjects and patients with mild AD could be discriminated from one another based on these MRI measures. When the normals were compared with the individuals with memory impairments who ultimately developed AD (the converters), the accuracy of discrimination was 93%, based on the MRI measures at baseline (sensitivity = 0.95; specificity = 0.90). The discrimination of the normal subjects and the individuals with mild memory problems who did not progress to the point where they met clinical criteria for probable AD over the 3 years of follow-up (the "questionables") was 85% and the discrimination of the questionables and converters was 75%. The apolipoprotein E genotype did not improve the accuracy of discrimination. The specific regions selected for each of these discriminations provides information concerning the hierarchical fashion in which the pathology of AD may affect the brain during its prodromal phase.

Aged↗
PubMed1999

Assessment of cognition in advanced AD: the test for severe impairment.

The Test for Severe Impairment (TSI) was compared with the Mini-Mental State Examination (MMSE) and a modified MMSE (mMMSE) in a multisite, longitudinal study of AD. The TSI correlated highly with the MMSE (r = 0.83) and the mMMSE (r = 0.82), but was not redundant. There was a wide range of scores on the TSI among those scoring in the severely impaired range on the MMSE and mMMSE. The slope of cognitive change over time detected by the TSI was greater than that revealed by the MMSE or the mMMSE. Performance on the TSI was a significant predictor of survival. The TSI is a valid measure that is sensitive to cognitive change over time in severely demented patients with AD.

Aged↗
PubMed1999

Change in cognitive function in older persons from a community population: relation to age and Alzheimer disease.

OBJECTIVE: To examine change in cognitive function in older persons sampled from a community population, and its relation to age and Alzheimer disease. DESIGN: Prospective cohort study with an average of 3.5 years of follow-up. SETTING: East Boston, Mass--a geographically defined, urban, working-class community. PARTICIPANTS: A stratified, random sample of persons 65 years and older underwent uniform, structured clinical evaluation for Alzheimer disease. The 388 persons (89.2% of those eligible) who completed at least 1 annual follow-up evaluation were studied: 97 had Alzheimer disease at baseline; 95 developed Alzheimer disease during the study; and 196 were unaffected. OUTCOME MEASURES: Eight cognitive performance tests were administered, then converted to population-weighted z scores and averaged to create a composite summary measure of cognitive function. Initial level of and change in this score were the outcome measures. RESULTS: In the population as a whole, many persons experienced a decline in cognitive performance, and age was related to both initial level and rate of decline. Analyses were conducted in 3 subgroups: persons with Alzheimer disease at baseline, those who developed Alzheimer disease during the study, and those who remained unaffected. In both Alzheimer disease subgroups, substantial cognitive decline was observed, but neither initial level nor rate of decline was related to age. In unaffected persons, little cognitive decline was evident, and there was a small, inverse association of age with initial level of cognitive function. CONCLUSION: In a general population sample, there was little evidence of cognitive decline during a 3.5-year period among persons who remained free of Alzheimer disease.

Aged↗
PubMed1999

T(1) of (129)Xe in blood and the role of oxygenation.

In previous experiments by the authors, in which hyperpolarized (129)Xe was dissolved in fresh blood samples, the T(1) was found to be strongly dependent on the oxygenation level, the values increasing with oxygenation: T(1) was about 4 s in deoxygenated samples and about 13 s in oxygenated samples. C. H. Tseng et al. (1997, J. Magn. Reson. 126, 79-86), on the other hand, recently reported extremely long T(1) values using hyperpolarized (129)Xe to create a "blood foam" and found that oxygenation decreased T(1). In their experiments, the continual and rapid exchange of hyperpolarized (129)Xe between the gas phase (within blood-foam bubbles) and the dissolved phase (in the skin of the bubbles) necessitated a complicated analysis to extract the effective blood T(1). In the present study, the complications of hyperpolarized (129)Xe exchange dynamics have been avoided by using thermally polarized (129)Xe dissolved in whole blood and in suspensions of lysed red blood cells (RBC). During T(1) measurements in whole blood, the samples were gently and continuously agitated, for the entire course of the experiment, to avert sedimentation. Oxygenation was found to markedly increase the T(1) of (129)Xe in blood, as originally measured, and it shifts the RBC resonance to a higher frequency. Carbon monoxide has a similar but somewhat stronger effect.

Humans↗
PubMed1999

Magnetic resonance imaging of the thorax. Past, present, and future.

Magnetic resonance is a valuable modality of extreme flexibility for specific problem-solving capability in the thorax. This article reviews MR applications in the imaging of great vessels, which are currently the most important applications in the thorax; other established applications in the thorax; and pulmonary functional MR imaging.

Aortic Diseases↗
PubMed1999

Emotion processing in the visual and auditory domains by patients with Alzheimer's disease.

The ability to process emotional information was assessed in 42 individuals: 23 patients with Alzheimer's disease (AD) and 19 healthy elderly controls. Four tasks assessed the ability to recognize emotion in audiotaped voices, in drawings of emotional situations, and in videotaped vignettes displaying emotions in facial expression, gestures, and body movements. Hemispheric dominance for processing facial expressions of emotions was also examined. There were no consistent group differences in the ability to process emotion presented via the auditory domain (i.e., nonverbal sounds, such as crying or shrieking, and speech prosody). Controls were, however, significantly better than the AD patients in identifying emotions depicted in drawings of emotional situations and in videotaped scenes displaying faces, gestures, and body movements. These differences were maintained after statistically adjusting for the visuospatial abilities of the participants. After a statistical adjustment for abstraction ability, some of the tasks continued to differentiate the groups (e.g., the emotional drawings task, the videotaped displays of faces), but others did not. These results confirm and extend previous results indicating that AD patients do not have a primary deficit in the processing of emotion. They suggest that the difficulties of the AD patients in perceiving emotion are secondary to the cognitive impairments associated with AD.

Aged↗
PubMed1998

Development of hyperpolarized noble gas MRI.

Magnetic resonance imaging using the MR signal from hyperpolarized noble gases 129Xe and 3He may become an important new diagnostic technique. Alex Pines (adapting the hyperpolarization technique pioneered by William Happer) presented MR spectroscopy studies using hyperpolarized 129Xe. The current authors recognized that the enormous enhancement in the delectability of 129Xe, promised by hyperpolarization, would solve the daunting SNR problems impeding their attempts to use 129Xe as an in vivo MR probe, especially in order to study the action of general anesthetics. It was hoped that hyperpolarized 129Xe MRI would yield resolutions equivalent to that achievable with conventional 1H2O MRI, and that xenon's solubility in lipids would facilitate investigations of lipid-rich tissues that had as yet been hard to image. The publication of hyperpolarized 129Xe images of excised mouse lungs heralded the emergence of hyperpolarized noble-gas MRI. Using hyperpolarized 3He, researchers have obtained images of the lung gas space of guinea pigs and of humans. Lung gas images from patients with pulmonary disease have recently been reported. 3He is easier to hyperpolarize than 129Xe, and it yields a stronger MR signal, but its extremely low solubility in blood precludes its use for the imaging of tissue. Xenon, however, readily dissolves in blood, and the T1, of dissolved 129Xe is long enough for sufficient polarization to be carried by the circulation to distal tissues. Hyperpolarized 129Xe dissolved-phase tissue spectra from the thorax and head of rodents and humans have been obtained, as have chemical shift 129 Xe images from the head of rats. Lung gas 129Xe images of rodents, and more recently of humans, have been reported. Hyperpolarized 129Xe MRI (HypX-MRI) may elucidate the link between the structure of the lung and its function. The technique may also be useful in identifying ventilation-perfusion mismatch in patients with pulmonary embolism, in staging and tracking the success of therapeutic approaches in patients with chronic obstructive airway diseases, and in identifying candidates for lung transplantation or reduction surgery. The high lipophilicity of xenon may allow MR investigations of the integrity and function of excitable lipid membranes. Eventually, HypX-MRI may permit better imaging of the lipid-rich structures of the brain. Cortical brain function is one perfusion-dependent phenomena that may be explored with hyperpolarized 129Xe MR. This leads to the exciting possibility of conducting hyperpolarized 129Xe functional MRI (HypX-fMRI) studies.

Administration, Inhalation↗
PubMed1998

Biomedical imaging using hyperpolarized noble gas MRI: pulse sequence considerations.

Hyperpolarized noble gas MRI is a new technique for imaging of gas spaces and tissues that have been hitherto difficult to image, making it a promising diagnostic tool. The unique properties of hyperpolarized species, particularly the non-renewability of the large non-equilibrium spin polarization, raises questions about the feasibility of hyperpolarized noble gas MRI methods. In this paper, the critical issue of T1 relaxation is discussed and it is shown that a substantial amount of polarization should reach the targets of interest for imaging. We analyse various pulse sequence designs, and point out that total scan times can be decreased so that they are comparable or shorter than tissue T1 values. Pulse sequences can be optimized to effectively utilize the non-renewable hyperpolarization, to enhance the SNR, and to eliminate image artifacts. Hyperpolarized noble gas MRI is concluded to be quite feasible.

Echo-Planar Imaging↗
PubMed1998

Alpha-2 macroglobulin is genetically associated with Alzheimer disease.

Alpha-2-macroglobulin (alpha-2M; encoded by the gene A2M) is a serum pan-protease inhibitor that has been implicated in Alzheimer disease (AD) based on its ability to mediate the clearance and degradation of A beta, the major component of beta-amyloid deposits. Analysis of a deletion in the A2M gene at the 5' splice site of 'exon II' of the bait region (exon 18) revealed that inheritance of the deletion (A2M-2) confers increased risk for AD (Mantel-Haenzel odds ratio=3.56, P=0.001). The sibship disequilibrium test (SDT) also revealed a significant association between A2M and AD (P=0.00009). These values were comparable to those obtained for the APOE-epsilon4 allele in the same sample, but in contrast to APOE-epsilon4, A2M-2 did not affect age of onset. The observed association of A2M with AD did not appear to account for the previously published linkage of AD to chromosome 12, which we were unable to confirm in this sample. A2M, LRP1 (encoding the alpha-2M receptor) and the genes for two other LRP ligands, APOE and APP (encoding the amyloid beta-protein precursor), have now all been genetically linked to AD, suggesting that these proteins may participate in a common neuropathogenic pathway leading to AD.

Age of Onset↗
PubMed1998

White matter changes with normal aging.

We evaluated brain tissue compartments in 72 healthy volunteers between the ages of 18 and 81 years with quantitative MRI. The intracranial fraction of white matter was significantly lower in the age categories above 59 years. The CSF fraction increased significantly with age, consistent with previous reports. The intracranial percentage of gray matter decreased somewhat with age, but there was no significant difference between the youngest subjects and the subjects above 59. A covariance adjustment for the volume of hyperintensities did not alter the foregoing results. The intracranial percentage of white matter volume was strongly correlated with the percentage volume of CSF. The finding of a highly significant decrease with age in white matter, in the absence of a substantial decrease in gray matter, is consistent with recent neuropathologic reports in humans and nonhuman primates.

Adolescent↗
PubMed1998

Preclinical prediction of Alzheimer's disease using SPECT.

BACKGROUND: Regional cerebral perfusion measured by single photon emission computed tomography (SPECT) was examined as a preclinical predictor of the development of Alzheimer's disease (AD). METHODS: Singular value decomposition was used to produce 20 SPECT factors (known as vectors) (n=152). Vector scores were then computed for four groups (n=136), differing in cognitive status: Group 1--normal controls at both baseline and follow-up; Group 2--subjects with "questionable" AD at both baseline and follow-up; Group 3--subjects with questionable AD at baseline who converted to AD on follow-up (Converters); Group 4--subjects with AD at baseline. All SPECT data in the analyses were gathered at baseline. RESULTS: The four groups could be distinguished on the basis of their baseline SPECT data (p < or = 0.00005; hit rate=83%). Regional decreases in perfusion were most prominent among Converters in the hippocampal-amygdaloid complex, the posterior cingulate, the anterior thalamus, and the anterior cingulate. Inclusion of apolipoprotein E status did not significantly improve the discrimination. CONCLUSIONS: SPECT data gathered and analyzed in this manner may be useful as one aspect of the preclinical prediction of AD. Three of the four brain regions important for discriminating Converters from normal controls involve a distributed brain network pertaining to memory, suggesting that this network may be selectively affected in the earliest stages of AD.

Aged↗
PubMed1998

Use of singular value decomposition to characterize age and gender differences in SPECT cerebral perfusion.

UNLABELLED: The main objective of this study was to characterize changes in brain perfusion associated with normal aging and gender. METHODS: Perfusion SPECT images using 99mTc-hexamethyl propyleneamine oxime (HMPAO) were obtained from 152 healthy subjects (67 men, 85 women) aged 50-92 yr. An automated method was developed to objectively assess image data from a large number of brain regions. Image data were reduced with singular value decomposition (SVD), which produced 20 eigenvectors capturing 97.05% of the total information content of 4320 regions from each subject. Subjects were scored individually on each vector. RESULTS: Multivariate analyses demonstrated that there were no significant differences in whole-brain HMPAO uptake with age, but age-related regional declines were seen in lateral ventricular regions. Women had higher HMPAO uptake than men in estimates of global perfusion and regional perfusion in the midcingulate/corpus callosum, inferior temporal and inferior parietal areas. CONCLUSION: These discriminations demonstrate that singular value deomposition of SPECT data may be used to assess differences in perfusion patterns between groups of subjects. They replicate several previous findings, both with respect to age-related changes in perfusion and with respect to gender differences. In addition, they identify a previously unreported gender difference in biparietal regions.

Aged↗
PubMed1997

The ageing brain: normal and abnormal memory.

With advancing age, the majority of individuals experience declines in their ability to learn and remember. An examination of brain structure and function in healthy older persons across the age range indicates that there are substantial changes in the brain that appear to be related to alterations in memory. The nature of the cognitive and neurobiological alterations associated with age-related change is substantially different from that seen in the early stages of a dementing illness, such as Alzheimer's disease. These differences have implications for potential intervention strategies.

Aging↗
PubMed1997

Predicting time to nursing home care and death in individuals with Alzheimer disease.

OBJECTIVE: To develop and validate an approach that uses clinical features that can be determined in a standard patient visit to estimate the length of time before an individual patient with Alzheimer disease (AD) requires care equivalent to nursing home placement or dies. DESIGN: Prospective cohort study of 236 patients, followed up semiannually for up to 7 years. A second validation cohort of 105 patients was also followed. SETTING: Three AD research centers. PATIENTS: All patients met National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable AD and had mild dementia at the initial visit. INTERVENTION: Predictive features, ascertained at the initial visit, were sex, duration of illness, age at onset, modified Mini-Mental State Examination (mMMS) score, and the presence or absence of extrapyramidal signs or psychotic features. MAIN OUTCOME MEASURES: (1) Requiring the equivalent of nursing home placement and (2) death. RESULTS: Prediction algorithms were constructed for the 2 outcomes based on Cox proportional hazard models. For each algorithm, a predictor index is calculated based on the status of each predictive feature at the initial visit. A table that specifies the number of months in which 25%, 50%, and 75% of patients with any specific predictor index value are likely to reach the end point is then consulted. Survival curves for time to need for care equivalent to nursing home placement and for time to death derived from the algorithms for selected predictor indexes fell within the 95% confidence bands of actual survival curves for patients. When the predictor variables from the initial visit for the validation cohort patients were entered into the algorithm, the predicted survival curves for time to death fell within the 95% confidence bands of actual survival curves for the patients. CONCLUSIONS: The prediction algorithms are a first but promising step toward providing specific prognoses to patients, families, and practitioners. This approach also has clear implications for the design and interpretation of clinical trials in patients with AD.

Age of Onset↗
PubMed1997

Apolipoprotein E epsilon4 and incidence of Alzheimer disease in a community population of older persons.

OBJECTIVE: To examine the relation between apolipoprotein E status and risk of Alzheimer disease (AD) in a defined population and estimate the fraction of incident AD attributable to the epsilon4 allele. DESIGN: Community-based cohort study. SETTING: East Boston, Mass. PARTICIPANTS: A random sample of 578 community residents aged 65 years and older free of AD. MAIN OUTCOME MEASURE: Clinical diagnosis of AD by uniform, structured evaluation. RESULTS: The increased risk of AD associated with the presence of the epsilon4 allele was less than that found in most family and case-control studies. Persons with the epsilon4/epsilon4 or epsilon3/epsilon4 genotypes had 2.27 (95% confidence interval, 1.06-4.89) times the risk of incident disease compared with those with the epsilon3/epsilon3 genotype. The epsilon4 allele accounted for a fairly small fraction of the incidence of AD; if the allele did not exist or had no effect on disease risk, the incidence would be reduced by only 13.7%. The effect of the epsilon4 allele on risk of AD did not appear to vary with age. CONCLUSIONS: The apolipoprotein E epsilon4 allele is an important genetic risk factor for AD but accounts for a fairly small fraction of disease occurrence in this population-based study. Continued efforts to identify other environmental and genetic risk factors are warranted.

Aged↗