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Biomedical subjects

E Grober

Publications and source records attributed to E Grober.

At least 19 recordsLinked to original sources
PubMed2000

Occupational exposure to methyl isobutyl ketone causes lasting impairment in working memory.

The authors describe serial evaluations of a 44-year-old man who became cognitively impaired during a 6-year period of repeated exposure to high levels of methyl isobutyl ketone (MIBK). Neuropsychological tests administered six times over 10 years demonstrated a stable pattern of cognitive impairment. Dynamic imaging studies suggested persistent CNS dysfunction. The authors conclude that chronic, high-level, occupational MIBK exposure can cause a persistent cognitive syndrome best explained by impaired working memory.

Adult↗
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↗
PubMed2000

The relative frequency of "dementia of unknown etiology" increases with age and is nearly 50% in nonagenarians.

CONTEXT: With the recent change in pathological criteria for Alzheimer disease (AD), a group of patients has emerged who do not meet pathological criteria for any well-characterized degenerative dementias. Whether these unclassified patients have vascular dementia or some other form of dementia is not known. OBJECTIVE: To determine the clinical characteristics, pathological substrate, and relative frequency of dementia not caused by well-characterized degenerative dementias. DESIGN/SETTING: Clinicopathological study of a prospectively observed sample of elderly nondemented and demented subjects recruited from our urban community. METHODS: In our series of 128 subjects with prospective neuropsychological evaluations as well as neuropathology, we identified 35 clinically nondemented subjects and 20 demented patients who did not meet pathological criteria for well-characterized degenerative dementias such as AD or dementia with Lewy bodies. The 20 demented patients were grouped together under the term dementia of unknown etiology (DUE). We compared clinical, genetic, neuropsychological, pathological, and neurochemical characteristics of the nondemented group, patients with DUE, and 28 patients with AD and no other pathological abnormality. RESULTS: Mean age at death for patients with DUE was 89.1 +/- 5.8 years compared with 79.9 +/- 11.4 years for AD (P<.001). Patients with AD and DUE did not differ in sex, risk factors, apolipoprotein E genotype, neuropsychological features, or neurological features. Hippocampal sclerosis (in 11 patients with dementia and no controls) and leukoencephalopathy (in 7 patients with dementia and 1 control) were associated with cognitive impairment; other vascular markers were not. Dementia of unknown etiology accounted for 5% of all cases of dementia among patients dying in their 70s, 21% for patients dying in their 80s, and 48% for patients dying in their 90s. CONCLUSIONS: A significant percentage of demented patients older than 80 years do not meet pathological criteria for AD or dementia with Lewy bodies. Hippocampal sclerosis and leukoencephalopathy are common in these patients but rare in clinically nondemented subjects.

Aged↗
PubMed1998

Demographic influences on free and cued selective reminding performance in older persons.

This study evaluated the influence of age, gender, race, and education on learning and memory in older persons. Free and Cued Selective Reminding (FCSR) was administered to a community-based sample of 216 Caucasian and 50 African American seniors as part of a larger medical and neuropsychological battery. Although age, education, and gender influenced FCSR performance, race did not. The study suggests that memory performance is not influenced by race and that race-adjustment may not be necessary in the norming of memory tests.

Black or African American↗
PubMed1997

Learning and retention in preclinical and early Alzheimer's disease.

Accelerated forgetting has been proposed as the first sign in preclinical and early Alzheimer's disease (AD). The authors investigated learning and retention in participants who later developed AD with free and cued selective reminding (FCSR; H. Buschke, 1984; E. Grober & H. Buschke, 1987), a test that maximizes learning by inducing deep semantic processing and by controlling study and test conditions. AD patients in the preclinical stage recalled significantly fewer words than did matched control participants, indicating an impairment of learning; nonetheless, patients' retention was identical to that of control participants. A retention deficit was documented 3 years later for AD patients but not for control participants, whose retention was still perfect. Thus, a retention deficit is not present in preclinical AD when hallmark learning deficits can be documented. Detection of preclinical and very early AD may be best accomplished by using robust learning tests that control cognitive processing.

Aged↗
PubMed1997

Free and cued selective reminding and selective reminding in the elderly.

Free and Cued Selective Reminding (FCSR) differs from Selective Reminding (SR) because of a study procedure which controls cognitive processing and a reminding procedure which allows for cued recall. Performance on FCSR and SR was compared in two studies to determine which test produces better recall and to identify the factors that account for the superior recall. When the tests were administered to very elderly normal subjects using the standard clinical protocol, twice as many words were retrieved from long-term memory in FCSR than SR. The second experiment, which manipulated study and reminding conditions in a younger sample of normal elderly, suggests that the improvement in free recall was due to the study procedure and the method of reminding.

Aged↗
PubMed1996

Ethylene oxide neurotoxicity: a cluster of 12 nurses with peripheral and central nervous system toxicity.

Ethylene oxide (EO) is commonly used to sterilize heat-sensitive products used by hospital patients and personnel. Ethylene chlorohydrin (EC), a by-product, is considered highly toxic. We report a cluster of 12 operating-room nurses and technicians who developed symptoms after a 5-month exposure to high levels of EO and EC in disposable surgical gowns. All patients reported a rash on the wrist where contact was made with the gowns, headaches, and hand numbness with weakness. Ten of 12 patients complained of memory loss. Neurologic evaluation revealed neuropathy on examination in nine of the 12 patients, elevated vibration threshold in four of nine, abnormal pressure threshold in 10 of 11, atrophy on head MRI in three of 10, and neuropathy on conduction studies in four of 10. Neuropsychological testing demonstrated mild cognitive impairment in four of six patients. Sural nerve biopsy in the most severely affected patient showed findings of axonal injury. Several patients in this group display signs of peripheral and CNS dysfunction following exposure to EO. Possible mechanisms of neurotoxicity include direct exposure of peripheral nerves through cutaneous absorption and central involvement through inhalation and vascular dissemination. The frequency of central and peripheral nervous system symptoms, supported by objective testing in these EO-exposed patients, suggests other healthcare personnel may be at similar risk.

Adult↗
PubMed1994

Hippocampal sclerosis: a common pathological feature of dementia in very old (> or = 80 years of age) humans.

In a neuropathological study of 81 brains of prospectively studied subjects of 80 years of age or older at the time of death, 13 cases (16%), including 4 men and 9 women, had hippocampal sclerosis (HpScl) affecting the vulnerable region of the hippocampus. In demented subjects of 80 years of age or older, the frequency of HpScl was even higher, 26%. Cases with HpScl had significantly fewer hippocampal senile plaques (SP) and neurofibrillary tangles (NFT) and parahippocampal NFT than cases without HpScl, but did not differ significantly in any of the other measured pathological parameters. Enzyme-linked analysis of synaptic protein immunoreactivity in a subset of 33 cases demonstrated significant decreases in the hippocampus, but not in frontal, temporal, parietal or parahippocampal cortices. All but 1 of the cases with HpScl had Blessed information, memory and concentration scores (BIMC) of 8 or more, and all were considered to be demented. In some patients memory disturbance was disproportionate to deficits in other cognitive areas. All but 4 of the cases with HpScl had many non-neuritic, amyloid plaques in the neocortex meeting NIA criteria for Alzheimer's disease (AD); however, given the advanced age of the subjects, amyloid plaques were considered to represent age-related cerebral amyloid deposition ("pathological aging") in most cases. Only 3 cases had both many SP and NFT in multiple cortical regions consistent with AD. Another case had brain stem and cortical Lewy bodies consistent with diffuse Lewy body disease (DLBD). A few ballooned neurons were present in the limbic cortices in 3 cases, including one case of dementia with argyrophilic grains (DAG) in limbic and orbital frontal and temporal cortices. The 8 cases without AD, DLBD or DAG included 4 cases in which no other obvious cause of dementia was detected and 4 cases in which HpScl was accompanied by either multiple cerebral infarcts or leukoencephalopathy, or both, that could have contributed to dementia. Patients with HpScl had risk factors, clinical signs and post-mortem pathological findings of cardiovascular disease, but due to the high prevalence of these conditions in very old humans, no significant correlation with HpScl was detected. This study demonstrates that HpScl is a common post-mortem finding in demented, but not normal, elderly subjects. It may contribute to. or be a marker for, the increased risk of dementia in subjects with documented cardiovascular disease or a history of myocardial infarction.

Aged↗
PubMed1993

Pathological markers associated with normal aging and dementia in the elderly.

We investigated the associations of pathological markers of Alzheimer's disease (AD) and diffuse Lewy body disease as well as possible markers of vascular dementia with cognitive function in a sample of 20 nondemented and 35 demented subjects (median age of both groups, 88 years) who had been studied prospectively for 4.0 +/- 2.1 years. Very old demented subjects almost always had nonneuritic senile plaques, but over half had no neuritic senile plaques and little other AD pathology. Five subjects had cortical Lewy bodies; all were demented. We propose that hippocampal sclerosis, leukoencephalopathy, and multiple lacunae are possible markers of vascular dementia. When grouped together, these markers were significantly associated with dementia and occurred in 40% of demented subjects. As the relative frequency of neuritic markers of AD (and possibly AD itself) declines in the tenth decade, vascular dementia may become an increasingly important type of dementia.

Aged↗
PubMed1992

Skill learning and repetition priming in Alzheimer's disease.

While perceptual-motor learning occurs normally in Alzheimer's disease (AD) patients, their ability to acquire the skill of reading transformed text has not been well delineated. AD patients and matched controls were timed as they read two blocks of words presented in mirror image. Control subjects displayed both skill learning and repetition priming, whereas AD patients displayed only repetition priming. Skill learning in AD patients was associated with their ability to complete verbal analogies. They displayed the expected impairment in recognition for the words from the mirror reading task. The failure of AD patients to acquire the mirror reading skill can be understood through a task analysis and may reflect an underlying deficit in abstract reasoning that precludes the development of appropriate pattern analyzing strategies needed to transform rotated text.

Aged↗
PubMed1992

Implicit and explicit memory in young, old, and demented adults.

Previous study of scopolamine and memory (Grober et al., 1989) showed that young adults given moderate or high doses of scopolamine maintained maximum cued recall in spite of a dose-dependent decrement in free recall when memory was assessed by cued selective reminding (CSR), a procedure which circumvents inattention and induces semantic processing. Intact recall by CSR indicates either that scopolamine impairs memory indirectly through effects on attention and information processing or that it impairs explicit memory but not implicit memory. In the present study which was done to determine if CSR reflects explicit or implicit memory, a free association test was used to estimate implicit memory after CSR was administered; explicit memory was estimated with a final trial of cued recall. Data from young, nondemented, and demented adults indicate that CSR reflects explicit memory supporting the interpretation of the previous study that scopolamine does not produce direct impairment of explicit memory.

Adolescent↗
PubMed1991

Dual-task performance in demented and nondemented elderly.

The present study examined the ability of demented and nondemented elderly subjects to divide their attention between recalling digits and judging the similarity of pairs of letters. Both groups showed substantial decrements in digit recall following distraction by letter matching. To identify the nature of the interference effect, digit recall was scored according to a strict criterion where preservation of the serial order of the digits was required (order-based recall), and a lenient criterion where preservation of digit order was not required (order-free recall). While both groups showed a comparable decrement in order-based recall due to the interfering task, order-free recall virtually eliminated the decrement for the nondemented group whereas substantial interference was still observed in the demented group. These results suggest that letter matching interferes with digit recall in nondemented elderly primarily by disrupting order information. In the case of demented elderly, letter matching disrupts the preservation of item information as well.

Aged↗
PubMed1991

Development and validation of a model for estimating premorbid verbal intelligence in the elderly.

In a preliminary effort to improve the early diagnosis of dementia, we developed a regression-based method for estimating premorbid intelligence measured by the ability to read irregular words from the American version of the Nelson Adult Reading Test (AMNART). Using errors on the AMNART and years of education, a model for predicting current verbal intelligence (VIQ) was developed in a sample of nondemented elderly. Double cross validation showed that the model had high accuracy and stability in estimating current VIQ in nondemented subjects. The model was then used to estimate premorbid VIQ in mildly demented subjects. Estimated premorbid IQ exceeded current IQ by at least 10 points and did not differ from that of nondemented subjects. Less than 10% of nondemented elderly had discrepancies that were as large. If intellectual decline predicts future functional loss and can be reliably measured using cross-sectional data, the requirement of functional impairment may be an unnecessary barrier to the early diagnosis of dementia.

Actuarial Analysis↗
PubMed1989

Brain white-matter changes in the elderly prone to falling.

Falls and impaired gait are a major source of morbidity in the elderly. Why some elderly become prone to falling is often unclear. We analyzed the gait, equilibrium, and brain computed tomography results of 40 elderly subjects without evidence of neurologic disease known to be associated with falls. Twenty of these subjects were prone to falling and the remaining 20 were nonfalling controls. These two groups were comparable in terms of age and sex (mean age, 83.3 years [SE, 1.7 years]). The group of fallers had significantly worse gait and equilibrium scores and a greater degree of white-matter hypodensity on computed tomography. White-matter hypodensity correlated with impaired gait and equilibrium scores but not with impaired performance on cognitive testing. This study reveals the association of white-matter disease with gait and balance impairment leading to falls in the elderly.

Accidental Falls↗
PubMed1989

Preservation of musical memory in Alzheimer's disease.

An 82 year old musician with Alzheimer's disease (AD) showed a preserved ability to play previously learned piano compositions from memory while being unable to identify the composer or titles of each work. He also showed a preserved ability to learn the new skill of mirror reading while being unable to recall or recognise new information. Both anterograde and retrograde procedural memory may be relatively spared in AD.

Aged↗
PubMed1988

Cognitive impairment and sensory loss associated with chronic low-level ethylene oxide exposure.

A 29-year-old college graduate worked for 10 years adjacent to an ethylene oxide (EtO) chemical sterilizer. When the sterilizer was closed, levels of EtO in the air around the sterilizer were 4.2 ppm (OSHA maximum level, 1 ppm). Seven years after beginning work with EtO, she experienced impaired memory, increased irritability, clumsiness, and falling. Three years later exposure ceased, and symptoms markedly improved over the next few months, but did not disappear entirely. Neurologic and neuropsychological exams 1 year after exposure ceased demonstrated emotional lability, impaired concentration, cognitive slowing, impaired recent and remote memory, and impaired thermal and vibratory sense in distal limbs. Her pattern of relatively preserved learning and profound forgetting distinguished her from most other subjects with memory disorders. No other causes for the condition were identified.

Adult↗
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↗