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S L Glatt

Publications and source records attributed to S L Glatt.

At least 19 recordsLinked to original sources
PubMed1998

Gene-toxin interaction as a putative risk factor for Parkinson's disease with dementia.

We had previously examined environmental, sociodemographic and clinical variables as predictors for Parkinson's disease with dementia (PD + D) and found that lower educational attainment, greater motor impairment and advanced age at disease onset were more common in PD + D than in subjects with Parkinson's disease without dementia (PD-D). We now explore the hypothesis that genetic traits coupled with nongenetic factors may raise the risk of development of PD + D. The study cohort of 43 PD + D and 51 PD-D subjects was analyzed examining environmental, sociodemographic and clinical variables along with 3 candidate gene markers: poor debrisoquine metabolizer allele (CYP 2D6 29B+), monoamine oxidase B allele 1, and apolipoprotein E epsilon 4 allele. Variables were initially entered into a multivariate model singly. Again lower education, age at onset and motor impairment appeared as predictors of PD + D while other variables (including allele status) failed to emerge as significant individual risk factors for dementia. We then examined environmental and genetic variables analyzed in tandem to look for potential variable interactions. Subjects who had pesticide exposure and at least 1 copy of the CYP 2D6 29B+ allele had 83% predicted probability of PD + D (stepwise logistic regression model: p = 0.0491). This case-control study provides preliminary evidence that a gene-toxin interaction may play an etiological role in PD + D. Further assessment of the role of these putative risk factors in incident dementia in PD is indicated.

Aged↗
PubMed1996

Risk of dementia among relatives of Alzheimer's disease patients in the MIRAGE study: What is in store for the oldest old?

Despite recent advances in the molecular genetics of Alzheimer's disease (AD), several fundamental questions concerning risk of illness are unresolved, namely, if Mendelian factors account for the incidence of the disease, and if AD is an inevitable consequence of the aging process. This study was designed to address these issues and other aspects of familial aggregation of the disorder. A consecutive sample of 1,694 patients who met criteria for a diagnosis of probable or definite AD were ascertained in 13 centers participating in the Multi-Institutional Research in Alzheimer Genetic Epidemiology (MIRAGE) project. Lifetime risk and age at onset of AD among various strata of 12,971 first-degree relatives was estimated using survival analysis procedures. The lifetime risk of AD in first-degree relatives was 39.0% +/- 2.1% by age 96 years. Age-specific risk of AD declined after age 90 and the data set included 61 apparently unaffected persons who survived to age 96 without becoming demented. Female relatives had a higher risk of AD than male relatives at all ages. By age 80, children of conjugal AD couples had a cumulative risk of 54%, 1.5 times greater than the sum of the risks to children having affected mothers or fathers, and nearly 5 times greater than the risk to children having normal parents. Children of affected fathers had a cumulative risk that was 1.4 times the corresponding risk to children of affected mothers. Risk assessment in early-onset and late-onset families, using various strategies for determining the age cut-off, yielded contradictory results. These data suggest the following: (1) the lifetime risk among relatives does not support a simple autosomal dominant inheritance pattern of disease; (2) women are innately more susceptible to AD than men; (3) the proportion of hereditary cases may be higher in men than women; (4) distinction between early- onset and late-onset forms of AD has little meaning in the absence of a biological marker; (5) the risk of AD decreases after age 90; and (6) AD therefore may not be an inevitable concomitant of the aging process, a conclusion that has profound implications for basic and applied AD research. The age- and sex-specific lifetime risks derived from this study are sufficiently robust to be a reliable source of information for counseling relatives of AD patients.

Age Factors↗
PubMed1995

Apolipoprotein E genotypes in Parkinson's disease with and without dementia.

The apolipoprotein E gene (Apo E) type 4 allele is a genetic risk factor influencing the development and age of onset of Alzheimer's disease. Because Parkinson's disease shares many characteristics of Alzheimer's disease, we studied the frequencies of Apo E genotypes in a cohort of 52 Parkinson's disease patients with dementia and 61 patients without dementia. Dementia was determined per National Institute of Neurological and Communicative Disorders and Stroke criteria and Mattis Dementia Rating Scale (DRS) < 126. Normal cognition was defined as DRS > 132. Apo E genotype and allele frequencies did not differ between demented and nondemented parkinsonian patients. Neither group's genotype and allele frequencies differed from that of a nondemented population of 78 controls. We conclude that the Apo E epsilon 4 allele influences neither the development of Parkinson's disease nor the dementia associated with Parkinson's disease.

Age of Onset↗
PubMed1995

Differentiation of the dementias of Alzheimer's and Parkinson's disease with the dementia rating scale.

The Mattis Dementia Rating Scale (DRS) was used to distinguish between 50 dementia of the Alzheimer's type (DAT) and 50 Parkinson's disease (PD) subjects matched for age, education, and DRS total score. Despite a similar level of overall cognitive impairment, the DAT group earned significantly lower scores than did the PD group on the Memory subscale, while the PD group displayed lower scores than did the DAT subjects on the Construction subscale. Ajackknifed, stepwise, linear discriminant function using the five DRS subscales revealed that the Memory, Construction, and Initiation subtests significantly distinguished the groups. These results suggest qualitative differences in the dementias of DAT and PD patients and reveal that such differences can emerge on brief mental status examinations.

Aged↗
PubMed1995

Erythrocyte thiolmethyltransferase: another failed marker for Alzheimer's and Parkinson's diseases.

There are reports that patients with Parkinson's disease (PD) and Alzheimer's disease (AD) have reduced levels of thiolmethyltransferase (TMT) in erythrocyte membranes. TMT methylates thiols and thiocarbamates, thereby reducing their toxicity. We examined TMT levels in erythrocytes from patients with PD and AD and from age-matched controls. Specific activities of TMT were 564 +/- 199 U/mg protein in PD (n = 32), 513 +/- 118 in AD (n = 13), and 565 +/- 183 in controls (n = 35). There was no difference between any of the groups (p = 0.64). We failed to confirm TMT as a marker for neurodegenerative diseases or for this metabolic defect predisposing to susceptibility to neurotoxins.

Aged↗
PubMed1995

The influence of depression on cognition in Parkinson's disease: a pattern of impairment distinguishable from Alzheimer's disease.

Conflicting reports about the effects of depression on cognition in Parkinson's disease (PD) are difficult to interpret because they are based on small sample sizes and confound depression with other variables. We found that a sample of 45 PD patients with current depression was cognitively more impaired than a sample of 45 PD patients without current depression matched for age, education, gender, age at disease onset, disease duration, and disease severity. The domains of cognition impaired in the two PD groups (compared with 45 age-, education-, and gender-matched controls) overlapped considerably, but only the depressed PD group had impaired memory relative to the control group. Our comparison of 22 depressed PD patients and 22 Alzheimer's disease (AD) patients matched for over-all severity of cognitive impairment, age, education, and gender indicated that the depressed PD group performed significantly worse on visuoconstructive tasks and marginally worse on conceptualization tasks. In contrast, the AD group performed significantly worse than the depressed PD group on memory tasks. Together, our results suggest that depression has a negative impact on cognition (and, in particular, memory) in PD, and that the pattern of this cognitive impairment is distinguishable from that associated with AD.

Aged↗
PubMed1995

Influence of demographic variables on the Dementia Rating Scale.

Demographic characteristics influence many cognitive assessment tools. We evaluated the impact of age, education, and gender on the Dementia Rating Scale (DRS) in a sample of 212 normal people. Separate regression analyses revealed that age was the most potent demographic factor, whereas education and gender had little impact. However, the amount of variance accounted for by age was small (less than 20%). Clinical utility of age-adjusted DRS total score cut-offs was investigated in samples of Alzheimer's and Parkinson's disease patients. Hit rate analysis revealed greater sensitivity for a single cut-off value than age-corrected cut-off scores. Overall, these findings revealed the lack of a clinically meaningful relationship between demographic characteristics and DRS scores, suggesting that age, education, and gender can be ignored for interpretative purposes based on cut-off scores.

Aged↗
PubMed1992

Driving in Alzheimer's disease.

OBJECTIVE: To determine if the impaired mental skills in Alzheimer's Disease (AD) may adversely affect driving ability. DESIGN: Retrospective survey. SETTING: The Alzheimer's Clinic of the University of Kansas Medical Center. PATIENTS: We interviewed 67 AD patients and their families and compared them with 100 elderly, non-spousal controls. MEASURES: The questionnaire was designed to obtain information on their driving habits, with emphasis placed on whether they were still driving, and the number of accidents per year for the past 10 years. RESULTS: Forty-six of the AD subjects had stopped driving because of safety concerns expressed by the subjects, their families, or health care providers, and two had stopped for other reasons. Only two of the normal controls had stopped driving (P < 0.0001, Chi-square test). Over the past 3 years, the 19 AD subjects who were still driving had 263.2 motor vehicle accidents per million vehicle miles of travel compared with 14.3 for the controls (P < 0.002, Mann-Whitney U test) and 5.7 for the general driving population age > or = 55 years (P < 0.05, Students one group, two-tailed t test). CONCLUSION: This study suggests that a significant traffic safety problem exists in subjects with AD who continue to drive. Efforts should be directed to detect patients with AD whose driving presents a traffic safety problem.

Accidents, Traffic↗
PubMed1989

Alzheimer disease: quantitative analysis of I-123-iodoamphetamine SPECT brain imaging.

To enable a more quantitative diagnosis of senile dementia of the Alzheimer type (SDAT), the authors developed and tested a semiautomated method to define regions of interest (ROIs) to be used in quantitating results from single photon emission computed tomography (SPECT) of regional cerebral blood flow performed with N-isopropyl iodine-123-iodoamphetamine. SPECT/IMP imaging was performed in ten patients with probable SDAT and seven healthy subjects. Multiple ROIs were manually and semiautomatically generated, and uptake was quantitated for each ROI. Mean cortical activity was estimated as the average of the mean activity in 24 semiautomatically generated ROIs; mean cerebellar activity was determined from the mean activity in separate ROIs. A ratio of parietal to cerebellar activity less than 0.60 and a ratio of parietal to mean cortical activity less than 0.90 allowed correct categorization of nine of ten and eight of ten patients, respectively, with SDAT and all control subjects. The degree of diminished mental status observed in patients with SDAT correlated with both global and regional changes in IMP uptake.

Adult↗
PubMed1988

Understanding and treating multi-infarct dementia.

MID is a controversial entity responsible for at least 15 to 20 per cent of dementia in the elderly. Clinical manifestations include dementia with abrupt onset, step-wise progression, and focal neurologic signs and symptoms. Infarcts are scattered through the brain involving both subcortical and cortical regions secondary to hypertensive atherosclerotic cerebrovascular disease. Diagnosis is based on the presence of dementia with both cognitive and motor sequelae of stroke as suggested by an elevated "ischemic score." Neuro-imaging studies, while not particularly helpful in differential diagnosis, have identified a population with white matter hypodensity without clinical signs of dementia who may serve as a presymptomatic at-risk group, allowing for studies of the pathogenesis of stroke-related dementia. Management of the cognitive difficulties of MID is similar to that of other forms of dementia. Therapy is directed at patients with modalities that will reduce the likelihood of further vascular insults. This would include treatment of hypertension, cessation of smoking, avoidance of excessive alcohol intake, and use of aspirin for patients with atherothrombotic disease. Medical measures have been shown to be effective in reducing the occurrence of stroke. Further studies are needed to assess the benefits of these measures for MID exclusively.

Aged↗
PubMed1985

Senile gait. A distinct neurologic entity.

Neurologic disease may result in a variety of different gait abnormalities. Senile gait is a distinct neurologic disorder and signs of dysfunction of major neuroanatomic systems are absent. The clinical picture is variable. Senile gait is not directly associated with dementing illness and its anatomic basis is unknown. It does not appear related to hydrocephalus. It is a specific clinical entity related to the degeneration of the nervous system. Further studies are needed to better understand this condition and to develop therapeutic approaches.

Accidents↗
PubMed1982

Pergolide mesylate and idiopathic Parkinson disease.

We studied the effects of pergolide mesylate in an open trial of 23 patients with idiopathic Parkinson disease (PD). All had suffered from loss of efficacy or dose-limiting side effects on current antiparkinsonian regimens. On pergolide therapy, improvement, which was maintained for 6 months, was noted in some parkinsonian features in all 23 patients. All patients suffering from on-off phenomenon were helped by pergolide. Significant side effects were not encountered. Pergolide is useful in the treatment of PD.

Adolescent↗
PubMed1981

Cerebellar atrophy: relationship to aging and cerebral atrophy.

We studied the incidence of computed tomography evidence of cerebellar atrophy in 20 elderly patients with dementia, 20 age-matched controls, and 40 younger normal subjects. Cerebellar vermian atrophy was present in 6 of 20 demented patients, 7 of 20 elderly controls, and 1 of 40 younger controls. There was no other atrophy of infratentorial structures except for occasional enlargement of the cisterna magna and cerebellopontine angle cisterns. Vermian atrophy did not correlate with cerebral atrophy (enlargement of either lateral ventricles or cortical sulci). None of these patients had clinical signs of cerebellar dysfunction. Therefore, atrophy of the cerebellar vermis may occur selectively with aging, without atrophy of the cerebral cortex, and without clinical manifestations.

Adult↗
PubMed1981

Cerebellar atrophy demonstrated by computed tomography.

We studied 55 cases of cerebellar atrophy identified by computerized tomography. Atrophy was determined by subjective assessment and objective measurements (superior cerebellar cistern, fourth ventricle, and brainstem). Different patterns of cerebellar atrophy were related to clinical diagnoses. A high incidence of vermal atrophy was observed in primary cerebellar degeneration and chronic alcoholism. More than half the patients with alcoholism had hemispheral atrophy. Vermal atrophy and enlargement of superior cerebellar cisterns (but not hemispheral atrophy) were associated with carcinomatous cerebellar degeneration. Atrophy caused by chronic phenytoin usage showed a specific pattern of enlargement of the cisterna magna, cerebellopontine angle, and superior cerebellar cisterns. Supratentorial atrophy was increased significantly only in the alcoholics. In general, limb ataxia, dysarthria, and nystagmus were related to hemispheral but not to vermal atrophy.

Adult↗