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S C Waring

Publications and source records attributed to S C Waring.

24 records · Page 2Linked to original sources
PubMed1996

Predictive value of APOE genotyping in incipient Alzheimer's disease.

The Mayo Alzheimer's Disease Center/Alzheimer's Disease Patient Registry is a prospective, longitudinal project of aging and dementia in a community setting. Over 400 pairs of individuals have been studied through this project, and extensive data on clinical, radiological, neuropathological, and biological variables have been gathered. Previous case-control studies on this group of subjects have documented the role of the apolipoprotein E (APOE) epsilon 4 as a risk factor for dementia. Subsequent analyses between APOE and the age of the patients with dementia have shown that most of the epsilon 4 effect is manifest in subjects under 75 years of age. We have also used this patient resource to study a group of individuals who are at risk for dementia by virtue of having a significant memory impairment. We have designated these patients as having a mild cognitive impairment because they have abnormal memory function but do not reach criteria for dementia. Over the course of several years of follow-up, these subjects evolve to dementia at a rate of approximately 15% per year. The presence of an APOE epsilon 4 carrier status is the best predictor of subsequent development of dementia in these individuals. These studies indicate that APOE is an important risk factor for AD, and in patients with a mild cognitive impairment, APOE may be useful in predicting who is likely to progress to dementia.

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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

Amyotrophic lateral sclerosis and polio: is there an association?

Because polio and ALS are both manifestations of anterior horn cell disease, consideration of some etiologic or pathogenetic relationship continues to recur. Studies that show an association are infrequent and are greatly outnumbered by negative reports in spite of possible journal bias to report positive results. Our limited studies in Guam and Rochester, Minnesota, have added to the negative list, and support the conclusion that there is no etiologic association of these two distinct diseases. The role, if any, of nonparalytic polio and polio vaccines with respect to ALS is not clear. With such a high proportion of the population having antibodies to polio, it may not be feasible to differentiate ALS with respect to the presence or absence of polio antibodies. Although the results to date do not support a polio-ALS relationship, further long-term studies are desirable for both the classical and the Western Pacific forms of ALS with respect to past polio outbreaks and, for the future, the unknown effect of polio vaccines on the incidence of ALS.

Amyotrophic Lateral Sclerosis↗
PubMed1995

Apolipoprotein E status as a predictor of the development of Alzheimer's disease in memory-impaired individuals.

OBJECTIVE: The outcome of patients with mild cognitive impairment is not known, yet these patients present a difficult dilemma for the clinician. This study was designed to characterize the outcome of a group of patients with mild cognitive impairment and to determine whether the presence of the epsilon 4 allele on the apolipoprotein E gene (APOE) is a predictor of that outcome. DESIGN: A prospective, longitudinal inception cohort. SETTING: General community clinic. PARTICIPANTS: A consecutive sample of 66 patients who met criteria for a diagnosis of a mild cognitive impairment and who had at least one clinical reevaluation was identified from the Mayo Clinic Alzheimer's Disease Center/Alzheimer's Disease Patient Registry. INTERVENTIONS: We evaluated patients initially and at 12- to 18-month intervals up to 54 months using standard neurological and neuropsychological measures such as the Mini-Mental State Examination, the Dementia Rating Scale, the Wechsler Adult Intelligence Scale--Revised, the Wechsler Memory Scale--Revised, and the Free and Cued Selective Reminding Test. The APOE status of study patients was determined. MAIN OUTCOME MEASURE: The development of dementia as determined by the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition and the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria. RESULTS: Sixty-six individuals had been reevaluated once (mean of 18 months), 36 individuals twice (mean of 36 months), and 22 individuals on three occasions (mean of 54 months), with conversion rates to dementia at these intervals of 24%, 44%, and 55%, respectively. A multivariate Cox regression model demonstrated that possession of an APOE epsilon 4 allele was the strongest predictor of clinical outcome. CONCLUSIONS: These data suggest the following: (1) patients with mild cognitive impairment can be clinically defined, (2) many members of this group progress to Alzheimer's disease, and (3) APOE epsilon 4 allele status appears to be a strong predictor of clinical progression.

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PubMed1995

Guamanian neurodegenerative disease: investigation of the calcium metabolism/heavy metal hypothesis.

OBJECTIVE: There is a high prevalence of neurodegenerative disease (parkinsonism, dementia, and motor neuron disease) on the western Pacific island of Guam. We sought evidence in support of the hypothesis that these conditions are triggered by nutritional deficiencies of calcium and magnesium leading to secondary hyperparathyroidism that then facilitates the entry of calcium and toxic heavy metals into the brain. METHODS: We analyzed indices of calcium metabolism plus blood-serum, urine, nail, and hair heavy metal concentrations in 12 patients with Guamanian neurodegenerative disease and 12 Chamorro control subjects. RESULTS: All 12 patients with Guamanian neurodegenerative disease had normal values for serum total and ionized calcium, 25-hydroxyvitamin D, and 24-hour urine collections for calcium. Eleven of 12 patients had normal serum parathyroid hormone values and alkaline phosphatase levels. No patient had reduced serum phosphorus or magnesium values although a minority of patients and controls had low urinary magnesium concentrations. Median blood-serum and 24-hour urine collections for heavy metals (aluminum, arsenic, cadmium, copper, iron, lead, manganese, mercury, and zinc) were statistically similar in the patient and control groups except for a slight elevation of blood, but not urine, lead in the patient group. Concentrations of heavy metals in hair and nails were similar in the two groups. CONCLUSIONS: We could find no evidence in support of abnormalities of calcium metabolism or heavy metal absorption as a major causative factor in the development of neurodegenerative disease on the island of Guam.

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