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R Katzman

Publications and source records attributed to R Katzman.

At least 19 recordsLinked to original sources

Comparisons of verbal fluency tasks in the detection of dementia of the Alzheimer type.

The performances of 89 patients with dementia of the Alzheimer type (DAT) and 53 demographically matched elderly normal control subjects were compared on four verbal fluency measures (category, letter, first names, and supermarket fluency). Receiver operating characteristic curves were plotted to determine each fluency tasks' sensitivity (ie, true-positive rate) and specificity (ie, true-negative rate). Category fluency demonstrated the greatest degree of discrimination between patients with DAT and normal control subjects (sensitivity, 100%; specificity, 92.5%); letter fluency was the least accurate (sensitivity, 89%; specificity, 85%). Separation of patients with DAT by gender revealed similar findings. In further analyses with a subgroup of 21 mildly impaired patients with DAT, category fluency lost none of its discriminative capabilities, whereas all other fluency measures showed marked reductions in discriminability. We conclude that this superiority of category fluency is due to its dependence on the structure of semantic knowledge, which deteriorates in the early stages of DAT.

Aged

Serological alpha 1-antichymotrypsin in Down's syndrome and Alzheimer's disease.

alpha 1-Antichymotrypsin (ACT) is a serine protease inhibitor that is markedly elevated in the serum and cerebrospinal fluid of patients with Alzheimer's disease (AD). Patients with Down's syndrome are known to develop neuropathological changes of AD by age 40 years and many become demented. Therefore, in the present study, we obtained serum ACT levels from patients with Down's syndrome and AD, diagnosed by autopsy or clinically, and healthy control subjects. Newman-Keuls' multiple range test revealed a significantly greater (p less than 0.01) mean ACT level in the Autopsy AD (906.4 +/- 94.64 mg/L) and Clinical AD (745.00 +/- 59.95 mg/L) groups in contrast to the Old Control group (531.00 +/- 23.05 mg/L). The mean ACT level of the Down's Syndrome group (513.33 +/- 14.73 mg/L) was not significantly different from that of the Young Control subjects. Furthermore, we did not observe a positive correlation of ACT levels with age in the Down's Syndrome group, in spite of the age-dependent premature increase in neuropathological changes of AD that are known to occur in patients with Down's syndrome. A positive correlation between serum ACT levels and the density of plaques or tangles, neuropathological hallmarks of AD, in brains of patients with AD also did not exist. Thus, our results suggest that ACT levels may not parallel the development of the classical neuropathological hallmarks of AD.

Adult

Criteria for the diagnosis of ischemic vascular dementia proposed by the State of California Alzheimer's Disease Diagnostic and Treatment Centers.

Accurate diagnosis of vascular dementia is important for the recognition of underlying pathophysiology and the institution of appropriate therapy. It is also important for the determination of the incidence and prevalence of not only vascular dementia but also Alzheimer's disease (AD), since differentiating between these two entities is often problematic. The State of California Alzheimer's Disease Diagnostic and Treatment Centers (ADDTC) herein propose criteria for the diagnosis of ischemic vascular dementia (IVD). These criteria broaden the conceptualization of vascular dementia, include the results of neuroimaging studies, emphasize the importance of neuropathologic confirmation, refine nosology, and identify areas that require further research. Parallel use of the proposed definitions of "possible" and "mixed" categories in the diagnosis of both AD and IVD would ensure compatibility between the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) criteria for AD and the ADDTC criteria for IVD. Uniform classification of subtypes of IVD will improve the generalizability of individual studies and aid in multicenter collaborations.

Brain Ischemia

Advances in Alzheimer's disease.

The problem of the etiology of Alzheimer's disease has not been solved. But in the past several years there have been significant extensions of our knowledge of the disease and advances in determining the molecular changes underlying the disorder. There is now convincing evidence that the dementia per se is caused by loss of neurons and synapses, particularly in neocortex and hippocampus. The molecular aspects of amyloid and its precursor protein have been defined. The nature of intracellular changes leading to accumulation of the paired helical filament is beginning to be understood. For the first time, putative risk factors can be described in terms of pathogenetic mechanisms. Thus, it may become possible in the not-too-distant future to discover interventions that will slow the progress of this devastating disease.

Alzheimer Disease

Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment.

We present here both linear regressions and multivariate analyses correlating three global neuropsychological tests with a number of structural and neurochemical measurements performed on a prospective series of 15 patients with Alzheimer's disease and 9 neuropathologically normal subjects. The statistical data show only weak correlations between psychometric indices and plaques and tangles, but the density of neocortical synapses measured by a new immunocytochemical/densitometric technique reveals very powerful correlations with all three psychological assays. Multivariate analysis by stepwise regression produced a model including midfrontal and inferior parietal synapse density, plus inferior parietal plaque counts with a correlation coefficient of 0.96 for Mattis's Dementia Rating Scale. Plaque density contributed only 26% of that strength.

Aged

Rapidly progressive dementia in a patient with the Lewy body variant of Alzheimer's disease.

A 65-year-old woman presented with a mild memory impairment, spatial disorientation, and poor task initiation. Progression was rapid over 3 months. She developed severe apathy, delusions, extrapyramidal features, and psychometrically quantified cognitive deterioration. Her brain showed many neocortical neuritic plaques and neurofibrillary tangles along with neocortical and brainstem Lewy bodies and temporal lobe spongiform vacuolization. This case is the most rapid deterioration documented of a patient with Alzheimer's disease and Lewy bodies.

Aged

The prevalence of dementia and Alzheimer's disease in Shanghai, China: impact of age, gender, and education.

We report the prevalence rates for dementia and Alzheimer's disease (AD) obtained from a probability sample survey of 5,055 noninstitutionalized older persons in Shanghai, China. A two-stage procedure was used for case finding and case identification. A Chinese version of the Mini-Mental State Examination was used to determine cases of possible dementia. Three different cutoff points on this mental status test were used depending on the respondent's level of education. Clinical evaluations, based on functional assessments and psychiatric interview, medical and neurological examinations, three standardized mental status tests, and a selected group of psychometric tests, were made in the second stage of the study to ascertain the clinical diagnosis of dementia and AD utilizing the Diagnostic and Statistical Manual for Mental Disorders, edition 3 and National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria, respectively. The prevalence rate of dementia in persons 65 years and older was 4.6%. Clinically diagnosed AD accounted for 65% of the subjects with dementia. These findings indicate that the prevalence of dementia in Shanghai is very much higher than figures published earlier for China and Japan, and at the lower part of the range of values reported for community residents in the United States and other Western countries, but less than half of that reported in the recently published survey of the elderly in East Boston. Increasing age, gender (female), and low education are each highly significant and independent risk factors for dementia. One hypothesis to explain the increased prevalence in elderly women who had received no formal education invokes the possibility of an effect of early deprivation, perhaps lowering brain "reserve," allowing the symptoms of dementia to appear at an earlier date during disease progression.

Age Factors

Teaching the multidisciplinary team approach in a geriatrics miniresidency.

The miniresidency program in geriatrics begun in 1985 at the University of California, San Diego, School of Medicine acquaints practicing health professionals with a multidisciplinary team approach to the care of geriatric patients. The two-week program features participation in a multidisciplinary outpatient clinic, home visits, social work and nutrition consultations, and conferences with patients and families. Miniresidency members also participate in neurologic and neuropsychological evaluations and attend day care for demented adults. The 71 health professionals who completed the program during its first 20 months showed significant improvement on their scores between the pre- and posttests: the mean of all scores in the pretest was 51 out of a possible 80 (SD 15); the mean of all scores in the posttest was 75 out of a possible 80 (SD 4); p less than .001. The 77% who returned post-program evaluation questionnaires found the program "useful" or "very useful."

Geriatrics

The Lewy body variant of Alzheimer's disease: a clinical and pathologic entity.

Thirty-six clinically diagnosed and pathologically confirmed Alzheimer's disease (AD) patients included 13 with cortical and subcortical Lewy bodies (LBs). The patients with LBs appeared to constitute a distinct neuropathologic and clinical subset of AD, the Lewy body variant (LBV). The LBV group showed gross pallor of the substantia nigra, greater neuron loss in the locus ceruleus, substantia nigra, and substantia innominata, lower neocortical ChAT levels, and fewer midfrontal tangles than did the pure AD group, along with a high incidence of medial temporal lobe spongiform vacuolization. Analysis of neuropsychological tests from 9 LBV subjects and 9 AD patients matched for age and degree of dementia revealed greater deficits in attention, fluency, and visuospatial processing in the LBV group. Similar comparisons of neurologic examinations showed a significant increase in masked facies; in addition there was an increase in essential tremor, bradykinesia, mild neck rigidity, and slowing of rapid alternating movements in the LBV group. Extremity rigidity, flexed posture, resting tremor, or other classic parkinsonian features were not characteristic of the LBV patient. In some cases, it may be possible to diagnose LBV premortem on the basis of the clinical and neuropsychological features.

Aged

Women, myocardial infarction, and dementia in the very old.

Dementia is a major public health problem among the very old. Available information on incidence and prevalence is sparse and variable; however, there appears to be a higher prevalence among very old women. We present data from a prospective study of initially nondemented community-residing elderly. There were 75 incident dementia cases (up to 7 years of follow-up) of which at least 47% were probable Alzheimer's disease. Based on a proportional hazards analysis, women were over 3 times more likely to develop dementia than men despite controlling for baseline demographic, psychosocial, and medical history variables. Poor word fluency and a high normal Blessed test score at baseline were also strong predictors of dementia. We did not find age, head trauma, thyroid disease, or family history of dementia to be risk factors. A new finding is that history of myocardial infarction (MI) is associated with dementia, such that women with a history of MI were 5 times more prone to dementia than those without a history. This observation was not true for men.

Aged

Cross-cultural studies of dementia. A comparison of mini-mental state examination performance in Finland and China.

The Mini-Mental State Examination of Folstein et al was translated into and culturally adapted to Chinese and Finnish and used in dementia surveys involving probability samples of 2187 Shanghai elderly, aged 65 to 74 years, and 525 Finns of the same age group. The mean scores of these two groups were statistically different owing to the lower scores of Shanghai subjects who had no formal education. When this subset of 579 subjects was eliminated from the analysis, the distribution of total scores was almost identical in the two populations, suggesting that the Mini-Mental State Examination can be used in disease populations, provided education is taken into account. However, there remained cultural differences in regard to individual test items; the Chinese had better recall but did not do as well as Finnish or US subjects when asked to copy a figure.

Aged

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.

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