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Biomedical subjects

R Katzman

Publications and source records attributed to R Katzman.

At least 73 records · Page 4Linked to original sources

Reduced protein kinase C immunoreactivity and altered protein phosphorylation in Alzheimer's disease fibroblasts.

Abnormal protein kinase C levels and protein kinase C-dependent phosphorylation are biochemical alterations in brain tissue obtained from patients with Alzheimer's disease. Because many biochemical and biophysical abnormalities are found in peripheral tissues of patients with Alzheimer's disease, we studied protein kinase C levels and the in vitro phosphorylation of proteins under protein kinase C-activating conditions in fibroblasts derived from patients with Alzheimer's disease. The concentration of protein kinase C-like immunoreactivity was reduced in Alzheimer's disease samples, although the protein kinase C activity determined by the phosphorylation of exogenous histone was not. The degree of in vitro phosphorylation of an Mr 79,000 protein in the presence of protein kinase C activators was less in Alzheimer's disease than in control fibroblast cytosol, and a reduction was more prominent in cases of familial Alzheimer's disease than in sporadic Alzheimer's disease. Therefore, the aberrant phosphorylation mediated by protein kinase C is found not only in the brain but also in fibroblasts.

Alzheimer Disease↗

Decreased adhesiveness of Alzheimer's disease fibroblasts: is amyloid beta-protein precursor involved?

The adhesiveness of fibroblasts derived from Alzheimer's disease (AD) patients to a plastic substratum was assessed as the proportion of cells attached to a plastic dish bottom after a 30-minute incubation in culture medium of cells dissociated in ethylenediaminetetraacetic acid and was compared with the adhesiveness of normal fibroblasts from non-AD controls. It was found that the normal fibroblasts adhered better to plastic than did AD cells. This reduced adhesiveness was observed in fibroblasts derived from both sporadic and familial AD patients. Because of the possible involvement of amyloid beta-protein precursor (ABPP) in the process of cellular adhesion, the amount of ABPP messenger RNA was measured in these fibroblasts and was found to be decreased in the familial AD fibroblasts, although not in cells from sporadic AD patients. Furthermore, there were fewer molecules detected by an anti-ABPP antibody in conditioned media from familial AD fibroblasts as compared with media from control fibroblasts. Therefore, although it is possible that the reduced adhesiveness of familial AD fibroblasts may result from genetic deficits in ABPP gene expression, the reduced adhesiveness of sporadic AD fibroblasts most likely results from certain deficits in molecules other than the ABPP.

Alzheimer Disease↗

Development of dementing illnesses in an 80-year-old volunteer cohort.

We have prospectively followed over a 5-year period 434 volunteers who were at intake ambulatory, functional, presumably nondemented, and between 75 and 85 years of age. Fifty-six (an incidence of 3.53 per 100 person-years at risk) developed a progressive dementia: 32 met diagnostic criteria for Alzheimer's disease (AD) (an incidence of 2.0 per 100 person-years at risk), 15 had vascular or mixed dementia, and 9 had other disorders or remain undiagnosed. New cases of dementia were as common as myocardial infarction and twice as common as stroke. Risk factors for both dementia and AD were age (over 80) and gender (female); other reported risk factors such as family history, prior head injury, thyroid disease, maternal age, and smoking were not risk factors for AD in this elderly cohort. Prior stroke was the major risk factor for vascular or mixed dementia; diabetes and left ventricular hypertrophy but not a history of hypertension per se were also risk factors for vascular dementia. The major predictor of the development of AD was the mental status score on entry. The 58.5% of the cohort who made zero to two errors on a 33-item mental status test had a less than 0.6% per year chance of developing AD, whereas the 16% of the cohort with five to eight errors on this test developed AD at a rate of over 12% per year. Thus, it is possible to identify a large cohort of 80-year-olds who are at low risk for AD and a smaller cohort at very high risk.

Aged↗

Abnormal pattern electroretinogram in Alzheimer's disease: evidence for retinal ganglion cell degeneration?

We recorded pattern-reversal electroretinograms, flash electroretinograms, pattern-reversal visual evoked potentials, and flash visual evoked potentials in 6 patients with clinically diagnosed Alzheimer's disease and 6 age- and sex-matched control subjects. The mean amplitude of the pattern-reversal electroretinogram in the Alzheimer patients was significantly less than that of the control group (p = 0.004). This anomaly of the pattern-reversal electroretinogram may be a reflection of documented axonal depletion within the optic nerve and the degeneration of retinal ganglion cells seen in Alzheimer's disease. We found Alzheimer patients to have normal pattern-reversal visual evoked potentials and flash electroretinograms, but a delayed second positive component of the flash visual evoked potential. This combination of findings may be of diagnostic import in Alzheimer's disease.

Action Potentials↗

Single-stage cluster sampling with a telescopic respondent rule: a variation motivated by a survey of dementia in elderly residents of Shanghai.

In this report, we consider the situation in which one wishes to identify a cohort of a specified number of individuals within each of several domains for future follow-up studies based on a single-stage cluster sampling design. We develop sample size formulae relevant to this situation and introduce a variation of single-stage cluster sampling that seems more suitable in this situation than is ordinary single-stage cluster sampling. The basis for this variation is the concept that the definition of eligible respondents is not the same for all clusters. The use of this modified respondent rule (which we call telescopic) enables one to meet specified sample sizes in all domains of interest without the need to sample extra individuals in some domains. We used a version of this sampling design successfully in the field with a survey of elderly persons conducted in Shanghai, People's Republic of China.

Age Factors↗

Cross-cultural studies of dementia: use of a Chinese version of the Blessed-Roth Information-Memory-Concentration test in a Shanghai dementia survey.

A culturally adapted Chinese version of the Blessed-Roth Information-Memory-Concentration test (CIMC) was used in a dementia screening survey of a probability sample of 5,055 elderly Shanghai residents. The individual items on the CIMC that best predicted the overall score were similar to the best predictor of an American version of the IMC. Performance on the CIMC was markedly affected by the level of education or lack thereof. In a subsample for whom clinical diagnoses were obtained, it was possible to establish cutoff values on the CIMC by stratifying the sample according to education.

Aged↗

Cognitive impairment among elderly adults in Shanghai, China.

This study reports the methods and initial findings of the first longitudinal study of Alzheimer's disease and dementia in China. A probability sample of 5,055 noninstitutionalized elderly persons in Shanghai was tested directly during the first phase of the study using a Chinese version of the Mini-Mental State Examination (MMSE). Details of sampling design and data collection procedures are described. Overall, some 4.1 percent of adults 55 years or older may be classified as having severe cognitive impairment, and 14.4 percent are mild cases. The rates for females are higher than for males by a ratio of 3.75 in the severe category, and 2.6 in the mild group. Within each age group, cognitive impairment rates vary by education. Multiple logistic regression was used to examine, within each age group, the nature of the association between the presence of a cognitive impairment and educational level controlling for sex. The results showed that educational attainment has a highly significant inverse relationship with prevalence of cognitive impairments (severe vs others). On the other hand, when educational attainment was controlled for in the logistic regression model, sex was significantly associated with prevalence of cognitive disorders for the age groups 65-74 and 75 years or older, but not for the group 55-64 years. These findings suggest the impact that basic educational deficits have on human cognitive functioning as measured through tests like the MMSE. Cross-tabulations of impairment rates according to marital status, economic status, and health-related problems are also presented.

Activities of Daily Living↗

Optic nerve head drusen and pseudotumor cerebri.

A 42-year-old woman presented with a history of headache. Results of funduscopic examination revealed elevated disc margins and bilateral optic nerve head drusen. Lumbar puncture, head computed tomography, and fluorescein fundus angiography results were consistent with the diagnosis of pseudotumor cerebri and coexistent disc drusen. Visual loss was demonstrated by formal perimetry. Headaches were unresponsive to a medical regimen that included prednisone, glycerol, acetazolamide, furosemide, and repeated lumbar punctures. A lumbar peritoneal shunt was performed, with immediate resolution of headache. Optic disc drusen can be associated with pseudotumor cerebri and can lead to diagnostic confusion.

Adult↗

Alzheimer's disease as an age-dependent disorder.

Alzheimer's disease is the most significant of the age-related diseases of the brain. The incidence of Alzheimer's at age 80 is twenty-fold that at age 60 years. In one study the incidence at age 80 surpassed that of stroke. Three major advances have occurred in regard to Alzheimer's disease: (1) clinical diagnosis has markedly improved and now approaches 90% accuracy; (2) understanding of the biology of Alzheimer's has increased with delineation of specific fibrous protein abnormalities and identification of the amyloid precursor gene and the gene linked to familial Alzheimer's, both genes being located on chromosome 21; and (3) there have been advances in the correlation of specific nerve cell involvement and neurotransmitter changes with physiological (position emission tomography), behavioural and neuropsychological manifestations.

Aged↗

Clinical, pathological, and neurochemical changes in dementia: a subgroup with preserved mental status and numerous neocortical plaques.

Postmortem examination was performed on 137 residents (average age 85.5 years) of a skilled nursing facility whose mental status, memory, and functional status had been evaluated during life. Seventy-eight percent were demented using conservative criteria; 55% had characteristic Alzheimer's disease. Choline acetyltransferase and somatostatin were significantly reduced in the brains of patients with Alzheimer's disease as compared with age-matched nursing home control subjects, although the degree of the reduction was less severe than found in subjects less than 80 years of age. Ten subjects whose functional and cognitive performance was in the upper quintile of the nursing home residents, as good as or better than the performance of the upper quintile of residents without brain pathology (control subjects), showed the pathological features of mild Alzheimer's disease, with many neocortical plaques. Plaque counts were 80% of those of demented patients with Alzheimer's disease. Choline acetyltransferase and somatostatin levels were intermediate between controls and demented patients with Alzheimer's disease. The unexpected findings in these subjects were higher brain weights and greater number of neurons (greater than 90 micron 2 in a cross-sectional area in cerebral cortex) as compared to age-matched nursing home control subjects. These people may have had incipient Alzheimer's disease but escaped loss of large neurons, or alternatively, started with larger brains and more large neurons and thus might be said to have had a greater reserve.

Aged↗

Comparison of rate of annual change of mental status score in four independent studies of patients with Alzheimer's disease.

Longitudinal studies of subjects with autopsy-proven Alzheimer's disease in one skilled nursing home and of clinically diagnosed cases (NINCDS/ADRDA criteria) in three community cohorts are compared with regard to the annual rate of change in the error score of the Blessed information-memory-concentration test (IMC) in which the maximum number of errors possible is 33. The four cohorts differed significantly from each other in regard to age, education, sex, and the degree of dementia as measured by the initial IMC score. Subjects spanned the age range of 52 to 96 years and had 2 to 20 years of education. The rate of change in error score per year was similar whether the initial error score was 0 to 7, 8 to 15, or 16 to 23; however, the rate was reduced when the initial error score was 24 or above, due to a ceiling effect of the test. Among subjects with initial IMC scores less than 24, the annual rate of change varied considerably. However, the mean annual rate of change, 4.4 errors (SD +/- 3.6, SEM +/- 0.3) per year, was independent of residence in a nursing home, location of the study site, and of the patient's sex or education. Of particular importance was the finding that the rate of change in mental test score was independent of age. It can be concluded that the rate of cognitive deterioration in patients with Alzheimer's disease is quite variable among individuals and is independent of the patient's age and whether the patient resides in the community or in a nursing home.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

A Chinese version of the Mini-Mental State Examination; impact of illiteracy in a Shanghai dementia survey.

A dementia screening survey was carried out in Shanghai using a culturally adapted Chinese version of the Mini-Mental State Examination. A probability sample of 5055 community-dwelling elderly in Shanghai was surveyed, 1497 aged 55-64, 2187 aged 65-74, and 1371 aged 75 and over. In the 73.3% of the subjects who had gone to school, using the age and education adjustments suggested by Kittner et al. (1986), [Kittner et al. J Chron Dis 39: 163-170; 1986] suitable cutoff scores could readily be selected to identify the subjects who should be examined intensively for the presence of dementia. However, in the 26.7% who had not gone to school, there was a significant increase in low scores on the mental status test as well as a different error pattern, reflecting the lack of formal education. Methods for following cognitive changes in illiterate individuals need further development.

Aged↗

Cross-cultural and multi-ethnic dementia evaluation by mental status and memory testing.

Two studies investigated aspects of cross-cultural dementia evaluation. The first explored consequences of using different mental status tests; the second compared mental status and memory assessments for normal individuals aged 70-79 and 80-89 in Japan and in America. In a dementia screening clinic, scores from the Hasegawa mental status test could be converted to the Blessed scale without influencing patient classification (impaired vs. unimpaired). Younger subjects were slightly superior to older subjects in mental status in both comparison groups. Both Japanese groups performed better on the memory test than even the younger American group.

Aged↗

Senile dementia of the Alzheimer type without neocortical neurofibrillary tangles.

Senile dementia of the Alzheimer type (SDAT) is typified pathologically by neuritic plaques (NP) and neurofibrillary tangles (NFT) in the neocortex and hippocampus. However, in a large series of cases (60) over age 74 a significant minority (30%) lacked neocortical tangles. In order to determine if these latter cases (Group B) otherwise differ from the majority which have both neocortical plaques and tangles (Group A), various clinical and neuropathological parameters were measured for both groups and the results compared. The following indices were examined: degree of dementia, rate of progression of dementia, age at death, brain weight, cerebral hemispheric weight, cortical cell counts from the frontal, temporal, and parietal lobes, the number of neocortical NP, the number of hippocampal NP and NFT, and the levels of neocortical choline acetyltransferase and somatostatin. The two groups showed no statistically significant differences in any of these categories except for increased numbers of neocortical NP in Group A in midfrontal and superior temporal regions. However, cases in Group A showed greater pathologic abnormality in nearly every parameter, albeit without attaining statistical significance. We conclude that SDAT with neocortical NFT is the same disease as SDAT without them, although the presence of such tangles is associated with a tendency towards greater severity.

Aged↗

Hippocampal neurotrophic factor: characterization and response to denervation.

The rat hippocampus contains an acidic macromolecular neurotrophic factor (NTF) which supports the survival of cultured chick ciliary ganglion cells. Hippocampal NTF increases approximately 2-fold from birth to adulthood with no further change with aging. Disruption of extrinsic inputs to the hippocampus from the entorhinal cortex, locus coeruleus or contralateral hippocampus, but not from the septum, results in an increase in the concentration of NTF in the hippocampus. Destruction of intrinsic hippocampal neurons by kainic acid treatment is accompanied by a large increase in hippocampal NTF, a result consistent with a glial origin for the factor. This conclusion is supported by the finding that a lesion-induced rise in NTF can be suppressed by administration of methotrexate, an inhibitor of gliosis.

Adrenergic Fibers↗