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H Crystal

Publications and source records attributed to H Crystal.

18 recordsLinked to original sources
PubMed2000

Memory impairment on free and cued selective reminding predicts dementia.

OBJECTIVE: To estimate the relative rates of dementia in initially nondemented subjects with and without memory impairment defined by baseline free recall from the Free and Cued Selective Reminding (FCSR) test. BACKGROUND: Our approach to identifying persons at high risk for future dementia is to show the presence of memory impairment not caused by other cognitive deficits by using a memory test that controls attention and cognitive processing. When the conditions of testing are not adequately controlled, prediction is reduced because age-associated memory deficits due to other cognitive deficits are confused with dementia-associated memory deficits. METHODS: Longitudinal evaluation of 264 initially nondemented, elderly community volunteers from the Einstein Aging Study with clinical and psychometric examinations every 12 to 18 months for up to 10 years. MAIN OUTCOME MEASURES: Dementia was defined by an algorithmic definition that required a Blessed Information Memory and Concentration score >8 and clinical evidence of functional decline. RESULTS: Thirty-two incident cases of dementia developed during follow-up. Survival analyses indicated that subjects with impaired free recall at baseline had dementia develop (relative risk = 75.2, 95% CI = 9.9 to 567) over 5 years of follow-up at dramatically higher rates than subjects with intact free recall after adjusting for age, gender, and education. CONCLUSION: Poor performance on free recall from FCSR predicts future dementia. These findings support the existence of a preclinical phase of dementia characterized by memory impairment, which is present for at least 5 years before diagnosis.

Aged↗
PubMed1991

Hippocampal degeneration differentiates diffuse Lewy body disease (DLBD) from Alzheimer's disease: light and electron microscopic immunocytochemistry of CA2-3 neurites specific to DLBD.

Immunocytochemistry with antibodies to ubiquitin is currently the most sensitive method for detecting cortical Lewy bodies, which are a sine qua non for the diagnosis of diffuse Lewy body disease (DLBD), an increasingly recognized form of primary degenerative dementia. In the systematic application of ubiquitin immunocytochemistry to sections of hippocampus from control subjects and patients with a wide spectrum of neurodegenerative diseases, we noted the frequent occurrence of ubiquitin-immunoreactive neurites in the CA2-3 region in DLBD. The nature of these neurites was investigated with immunocytochemistry in DLBD, Alzheimer's disease (AD), normal elderly subjects, and Parkinson's disease (PD). Although the number of neurites varied from case to case, they were virtually always detected in DLBD but not in normal, AD, or PD brains. Double immunolabeling studies with anti-ubiquitin demonstrated a small fraction of double-stained neurites with antibodies to neurofilament or Alz-50, but no double staining with an antibody to Alzheimer neurofibrillary tangles. These results are different from those for neurites in AD, which are rarely seen in CA2-3 and which are immunoreactive with all these antibodies. Neuritic degeneration in the CA2-3 region of the hippocampus appears to be a specific histopathologic feature of DLBD.

Adolescent↗
PubMed1990

Object-memory evaluation for prospective detection of dementia in normal functioning elderly: predictive and normative data.

In a prospective study of dementia in initially normal functioning elderly, a brief form of the Fuld Object-Memory Evaluation (OM) was administered to 474 cognitively normal community-residing volunteers aged 75-85 at baseline and annually thereafter. Seventy-two subjects later became demented. Memory test data from the last annual evaluation before cognitive change was noted were available for 56. Although the entire population recalled 7.28 (SD = 1.33) of the 10 objects on Trial 1 of the test at baseline, these 56 subjects recalled only 5.96 (SD = 1.85). When recall of 6 or fewer objects was used as a predictor, the OM test identified 32 of the 56 who subsequently became demented. Compared to an estimated base rate of 15% for dementia, the predictive value of a positive test (PV+) was 39%, and that of a negative test (PV-) was 89%. With a cutoff of 5 or fewer items recalled, the PV+ rose to 59% and the PV- was 94%. Although the OM test was only moderately sensitive to incipient dementia (.57), it was fairly specific (.84), and lowering the cutoff to 5 increased the specificity to .96. Memory testing would therefore seem to hold promise as a predictor of dementia in cognitively normal elderly.

Aged↗
PubMed1990

Predicting development of dementia in the elderly with the Selective Reminding Test.

The ability to predict the development of dementia through the detection of memory impairment in nondemented individuals was assessed with the Selective Reminding Test (SR), a popular test of verbal memory functioning in the elderly. The SR was administered to 385 nondemented volunteer subjects (mean age = 80.4 years) enrolled in a longitudinal study of risk factors in the development of dementia. Of these, 36 subjects ultimately became demented. SR scores obtained from 1 to 2 years prior to the diagnosis of dementia were compared with a set of previously established cutoff scores derived from a cognitively normal elderly sample. The results demonstrated that sum of recall and delayed recall were the SR measures best able to predict dementia with sensitivities of 47% and 44%, respectively. The predictive values were 37% and 40%, respectively, or better than two-and-one-half times the base rate. The contributions of both the SR Test and the Fuld Object-Memory Test (OM) were discussed in terms of the further understanding of the characteristics of the preclinical phase of dementia.

Aged↗
PubMed1990

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↗
PubMed1989

Diffuse Lewy body disease: light and electron microscopic immunocytochemistry of senile plaques.

The nature of senile plaques (SP) in 27 cases of diffuse Lewy body disease (LBD) was investigated using immunocytochemistry and antibodies to beta amyloid protein synthetic peptides (BetaSP), ubiquitin (UBQ), paired helical filaments (PHF; Ab39) and a 68-kDa protein in Alzheimer brains (Alz50). Lewy bodies were present in widespread areas of the neocortex of all cases and were more easily detected with ubiquitin immunocytochemistry than with conventional stains. All cases had neocortical SP, but only six cases had neocortical neurofibrillary tangles (NFT). SP were very numerous in most cases and were usually "pale", "diffuse" or "very primitive" plaques with thioflavin S fluorescent microscopy. SP in diffuse LBD were immunostained with BetaSP. Several cases had extensive amyloid angiopathy that was also immunoreactive with BetaSP. SP in diffuse LBD were characterized by amyloid deposits with few or no neuritic elements that could be detected with thioflavin S, Bielschowsky's stain or double staining with BetaSP and Bodian's silver stain. They differed from plaques in Alzheimer's disease by lack of PHF-type neurites that could be stained with Ab39. In diffuse LBD, SP contained PHF-type neurites only in areas coexistent with NFT. Some SP had round, granular neurites that were immunoreactive with UBQ, but weakly argyrophilic with Bodian's stain and nonfluorescent with thioflavin S. Diffuse LBD lacked significant neuritic change in the neuropil that could be detected with UBQ, Ab39 and Alz50. The latter finding is a characteristic feature that distinguishes Alzheimer's disease from diffuse LBD.

Aged↗
PubMed1989

Neuropsychological characteristics of subjects with and without neocortical Alz-50 immunoreactivity.

We performed quantitative histopathology and Alz-50 staining on 8 non-demented and 16 demented subjects who had received yearly neuropsychological evaluations as part of prospective studies of dementia. Of the 8 non-demented subjects, four had begun to show signs of cognitive decline on serial neuropsychological testing. These subjects showed marked decline on the Fuld Object Memory Evaluation, a test of recent memory. Scores on IQ tests and the Blessed test of orientation, memory, and concentration showed fluctuations but not consistent declines. These old-old, retired subjects were called "cognitively impaired" but not demented because they did not show decline in activities of daily living or social interactions. Five of the non-demented subjects had numerous cortical senile plaques and met standard pathological criteria for Alzheimer's disease (AD), but only one of the five was Alz-50 positive. That subject had shown the most consistent decline on neuropsychological scores. Ten of 11 clinically demented subjects with pathological evidence of AD were Alz-50 positive. All five clinically demented subjects with non-Alzheimer dementias on pathological examination were Alz-50 negative. Alz-50 may stain plaques found in AD, but not stain plaques which accompany aging. The cognitive impairment found in the Alz-50 negative subjects may be age-associated and not indicate early AD.

Aging↗
PubMed1988

Clinico-pathologic studies in dementia: nondemented subjects with pathologically confirmed Alzheimer's disease.

We compared neuropsychological findings in 28 longitudinally evaluated elderly subjects with their postmortem neuropathology, including senile plaque and neurofibrillary tangle counts from standardized sections. Nine of the subjects were not demented when evaluated just prior to their death. Numerous cortical senile plaques and other changes of Alzheimer's disease (AD) occurred in six of nine nondemented old-old subjects. Five of these six subjects had shown decline on yearly neuropsychological tests but their cognitive impairment was too mild to meet clinical criteria for dementia. Whereas cortical senile plaque count did not distinguish well between demented and nondemented subjects, every subject with numerous cortical neurofibrillary tangles was demented. The nondemented subjects with Alzheimer pathology may have had "preclinical" AD, or numerous cortical plaques may occur in some elderly subjects who would never develop clinical dementia.

Aged↗
PubMed1988

Screening for dementia by memory testing.

Enhanced cued recall provides a simple and clinically useful memory test for identifying dementia in the elderly. Because this test induces semantic processing and coordinates encoding and retrieval for maximum recall, genuine memory deficits due to impairment of specific memory processes can be distinguished from apparent memory deficits due to use of inefficient strategies or impairment of other cognitive processes. Since genuine memory deficits in the elderly are usually associated with dementia, their identification is highly predictive of clinical dementia. The present study validates the use of enhanced cued recall as a screening test for dementia in 70 aged subjects. All but one person with a pure amnesia were correctly classified. Enhanced cued recall correctly classified 97% of the 120 subjects in this and the previous study. Enhanced cued recall shows learning not revealed by free recall, providing more accurate measurement of memory, and distinguishes demented from nondemented elderly more accurately than either free recall or recognition.

Aged↗
PubMed1988

Alzheimer's disease. A double-labeling immunohistochemical study of senile plaques.

The senile plaque is one of the histopathologic changes that characterizes Alzheimer's disease and the aging brain. The histopathology of senile plaques was studied using double-labeling immunohistochemistry and lectin histochemistry with thioflavin S fluorescent microscopy in 9 cases of Alzheimer's disease, 2 nondemented elderly individuals, and 3 individuals with non-Alzheimer primary degenerative dementias. Every plaque that was visualized with thioflavin also had amyloid, but not all thioflavin-positive plaques contained neurites that could be recognized with specific monoclonal antibodies to paired helical filament, tau, or neurofilament epitopes. Some neurofilament-positive neurites were not visualized with thioflavin, but almost all tau-positive neurites were colabeled with thioflavin. Microglia were associated with most plaques. Most plaques were also surrounded by fibrous astrocytes. These results suggest that amyloid may be the common feature that defines senile plaques, but that other elements may be more specific for Alzheimer's disease, because extensive neuritic degeneration was seen only in Alzheimer brains and not in either nondemented elderly individuals with senile plaques or in non-Alzheimer dementia cases.

Alzheimer Disease↗
PubMed1988

Clinical experience with COP-1 in multiple sclerosis.

COP-1 is one of a series of polypeptide preparations developed to stimulate myelin basic protein (MBP), a natural component of the myelin sheath. MBP in Freund's complete adjuvant induces experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). In saline, MBP suppresses EAE. This is the rationale for the use of COP-1 in MS.

Adult↗
PubMed1987

A pilot trial of Cop 1 in exacerbating-remitting multiple sclerosis.

Cop 1 is a random polymer (molecular weight, 14,000 to 23,000) simulating myelin basic protein. It is synthesized by polymerizing L-alanine, L-glutamic acid, L-lysine, and L-tyrosine. It suppresses but does not induce experimental allergic encephalomyelitis, an animal model of multiple sclerosis. It is not toxic in animals. In a double-blind, randomized, placebo-controlled pilot trial, we studied 50 patients with the exacerbating-remitting form of multiple sclerosis, who self-injected either 20 mg of Cop 1 dissolved in 1 ml of saline or saline alone daily for two years. Six of 23 patients in the placebo group (26 percent) and 14 of 25 patients in the Cop 1 group (56 percent) had no exacerbations (P = 0.045). There were 62 exacerbations in the placebo group and 16 in the Cop 1 group, yielding two-year averages of 2.7 and 0.6 per patient, respectively. Among patients who were less disabled on entry (Kurtzke disability score, 0 to 2), there were 2.7 exacerbations in the placebo group and 0.3 in the Cop 1 group over two years. Among patients who were more affected (Kurtzke disability score, 3 to 6), there was an average of 2.7 exacerbations in the placebo group and 1.0 in the Cop 1 group. Over two years, less disabled patients taking Cop 1 improved an average of 0.5 Kurtzke units; those taking placebo worsened an average of 1.2 Kurtzke units. More disabled patients worsened by 0.3 (Cop 1 group) and 0.4 (placebo group) unit. Irritation at injection sites and rare, transient vasomotor responses were observed as side effects. These results suggest that Cop 1 may be beneficial in patients with the exacerbating-remitting form of multiple sclerosis, but we emphasize that the study is a preliminary one and our data require confirmation by a more extensive clinical trial.

Adult↗
PubMed1987

Diffuse Lewy body disease. Neuropathological and biochemical studies of six patients.

Post-mortem pathological and biochemical studies are reported on six patients with progressive dementia. The characteristic pathological finding was neurofilament-containing cytoplasmic inclusions in cortical and subcortical neurons. The clinical and pathological findings were consistent with so-called diffuse Lewy body disease. The patients had variable changes of the Alzheimer type, with five of six patients displaying "plaques only" Alzheimer's changes. Biochemical studies showed profound decreases in neocortical choline acetyltransferase (ChAT) activities that correlated with marked neuronal loss in the basal nucleus of Meynert. ChAT activities were normal in the hippocampus in three patients who also had no significant Alzheimer type hippocampal changes. All patients had decreased cortical somatostatin-like immunoreactivity. Our observations suggest that dementia in diffuse Lewy body disease bears biochemical similarities to Alzheimer's disease, in that biochemical markers for both intrinsic cortical neurons and ascending cholinergic neurons are affected.

Aged↗
PubMed1981

Choline chloride fails to improve cognition of Alzheimer's disease.

Seven mildly to moderately demented patients with Alzheimer's disease were treated with either placebo or choline chloride (50, 100 and 200 mg/kg/24 hrs) in a double blind, crossover study. Detailed psychometric analysis was carried out at the end of each two-week period of drug or placebo administration. No subjects showed significant overall improvement at any dose level despite more than a doubling of the baseline plasma choline level.

Aged↗
PubMedDate not supplied

Memory and mental status correlates of modified Braak staging.

We assessed the relationships of performance on memory and mental status tests and neuropathologic stage of Alzheimer's disease as defined by Braak and Braak in 29 patients from a prospective clinicopathologic series. We predicted that memory changes would occur at an earlier Braak stage than mental status changes. Staging was accomplished by matching the topographic distribution of neurofibrillary lesions detected with tau immunocytochemistry to the best fitting diagram published by Braak and Braak. Higher Braak stages were associated with decrements in performance on both memory and mental status tests. As predicted, memory performance declined from stages II to III and mental status did not decline until stages III to IV. The association between memory and Braak stage was unchanged after adjusting for neocortical senile plaques, whereas adjustments for Braak stage eliminated the association between cognitive functioning and amyloid burden. We conclude that Braak staging provides a useful summary of Alzheimer's disease neuropathology, which is associated with both memory and mental status performance.

Aged↗