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Biomedical subjects

S D Edland

Publications and source records attributed to S D Edland.

At least 19 recordsLinked to original sources
PubMed2005

Coronary artery bypass grafting is not a risk factor for dementia or Alzheimer disease.

OBJECTIVE: To study coronary artery bypass grafting (CABG) as a risk factor for dementia and Alzheimer disease (AD) using a case-control design. METHODS: The authors used the records-linkage system of the Rochester Epidemiology Project to ascertain incident cases of dementia in Rochester, MN, for the 5-year period 1990 to 1994. The authors defined dementia and AD using the criteria of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV). Each case was individually matched by age (+/-1 year) and sex to a person drawn randomly from the same population, and free of dementia in the index year (year of onset of dementia in the matched case). RESULTS: Among 557 dementia cases, 24 (4.3%) had undergone a CABG prior to the onset of dementia with a median lag time of 5.5 years (range = 0.1 to 15.9). Among 557 controls, 28 subjects (5.0%) had undergone a CABG prior to the index year with a median lag time 3.9 years (range = 0.1 to 12.3); OR = 0.85 (95% CI = 0.49 to 1.49; p = 0.57) for dementia and OR = 0.78 (95% CI = 0.39 to 1.56; p = 0.48) for AD. The findings did not change after adjustment for education. The perioperative courses of cases and controls were comparable. Analyses including only the 481 cases of dementia with presumed neurodegenerative or cerebrovascular etiology were also negative. CONCLUSIONS: This population-based case-control study suggests that coronary artery bypass grafting is not a major risk factor for dementia overall, or for Alzheimer disease.

Adult↗
PubMed2004

1H MR spectroscopy in common dementias.

OBJECTIVE: To determine the 1H MR spectroscopic (MRS) findings and intergroup differences among common dementias: Alzheimer disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB), and frontotemporal lobar degeneration (FTLD). METHODS: The authors consecutively recruited 206 normal elderly subjects and 121 patients with AD, 41 with FTLD, 20 with DLB, and 8 with VaD. The 1H MRS metabolite ratio changes in common dementias were evaluated with respect to normal and also differences among the common dementias. RESULTS: N-acetylaspartate (NAA)/creatine (Cr) was lower than normal in patients with AD, FTLD, and VaD. Myo-inositol (mI)/Cr was higher than normal in patients with AD and FTLD. Choline (Cho)/Cr was higher than normal in patients with AD, FTLD, and DLB. There were no metabolite differences between patients with AD and FTLD or between patients with DLB and VaD. NAA/Cr was lower in patients with AD and FTLD than DLB. MI/Cr was higher in patients with AD and FTLD than VaD. MI/Cr was also higher in patients with FTLD than DLB. CONCLUSIONS: NAA/Cr levels are decreased in dementias that are characterized by neuron loss, such as AD, FTLD, and VaD. MI/Cr levels are elevated in dementias that are pathologically characterized by gliosis, such as AD and FTLD. Cho/Cr levels are elevated in dementias that are characterized by a profound cholinergic deficit, such as AD and DLB.

Acetylcholine↗
PubMed2004

The incidence of frontotemporal lobar degeneration in Rochester, Minnesota, 1990 through 1994.

The records-linkage system of the Rochester Epidemiology Project was used to ascertain incident cases of frontotemporal lobar degeneration (FTLD) in Rochester, MN, from 1990 through 1994. Four cases of FTLD were identified (all women); two were confirmed neuropathologically. All were of the behavioral-dysexecutive type and had onset before age 70. The incidence rates (new cases per 100,000 person-years) were 2.2 for ages 40 to 49, 3.3 for ages 50 to 59, and 8.9 for ages 60 to 69. For comparison, the corresponding rates for Alzheimer disease were 0.0, 3.3, and 88.9.

Adult↗
PubMed2003

Insulin degrading enzyme (IDE) genetic variants and risk of Alzheimer's disease: evidence of effect modification by apolipoprotein E (APOE).

Insulin degrading enzyme (IDE) is a protease that degrades insulin and the beta-amyloid peptide implicated in Alzheimer's disease (AD). We reexamined data on five previously reported IDE polymorphisms stratifying the analysis by the presence or absence of an apolipoprotein E (APOE) epsilon4 allele. Three IDE variants were associated with AD within epsilon4-negative subjects (genotype exact test P-values < or =0.02). A haplotype containing the minor variant at each of these sites represented an estimated 4.2% of case haplotypes versus 12.3% of control haplotypes among epsilon4-negative subjects. Lack of this minor haplotype may be predictive of AD, potentially explaining some fraction of disease within subjects without the APOE epsilon4 risk allele. Confirmation of this finding with a larger sample of cases and controls is warranted.

Aged↗
PubMed2002

Total intracranial volume: normative values and lack of association with Alzheimer's disease.

A larger premorbid brain is hypothesized to provide neuronal reserve against AD. Using MRI data from ongoing studies of normal aging and AD, the authors tested this hypothesis. Mean total intracranial volume was 15.8 cm(3) smaller for cases among women (n = 121 normal and 104 AD; p = 0.24) and 10.1 cm(3) larger for cases among men (n = 63 normal and 62 AD; p = 0.59). These differences are small and nonsignificant, suggesting that head size per se is not a critical determinant of AD.

Aged↗
PubMed2002

Antemortem MRI findings correlate with hippocampal neuropathology in typical aging and dementia.

OBJECTIVES: To assess the diagnostic specificity of MRI-defined hippocampal atrophy for AD among individuals with a variety of pathologically confirmed conditions associated with dementia as well as changes attributable to typical aging, and to measure correlations among premortem MRI measurements of hippocampal atrophy, mental status examination performance, and the pathologic stage of AD. METHODS: An unselected series of 67 individuals participating in the Mayo Alzheimer's Disease Research Center/Alzheimer's Disease Patient Registry who had undergone a standardized antemortem MRI study and also postmortem examination were identified. Hippocampal volumes were measured from antemortem MRI. Each postmortem specimen was assigned a pathologic diagnosis and in addition, the severity of AD pathology was staged using the method of Braak and Braak. RESULTS: Individuals with an isolated pathologic diagnosis of AD, hippocampal sclerosis, frontotemporal degeneration, and neurofibrillary tangle--only degeneration usually had substantial hippocampal atrophy, while those with changes of typical aging did not. Among all 67 subjects, correlations (all p < 0.001) were observed between hippocampal volume and Braak and Braak stage (r = -0.39), between hippocampal volume and Mini-Mental State Examination (MMSE) score (r = 0.60), and between MMSE score and Braak and Braak stage (r = -0.41). CONCLUSIONS: Hippocampal atrophy, while not specific for AD, was a fairly sensitive marker of the pathologic AD stage (particularly among subjects with isolated AD pathology [r = -0.63, p = 0.001]) and consequent cognitive status.

Aged↗
PubMed2001

Neuropsychological test performance in a cognitively intact sample of older Japanese American adults.

The purpose of this paper was to present population-based data showing the effects of age on cognitive test performance in a sample of older Japanese American adults. In addition, the relative effects of education, gender, and primary spoken language were compared to effects that have been reported in the literature for majority culture older adults. Subjects included 201 non-demented Japanese American adults age 70 and older currently enrolled in the Kame Project, a prospective study of aging and dementia in King County, WA. Cognitive tests included the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological assessment battery, WAIS-R Digit Span and Digit Symbol subtests, Trail Making Test, Purdue Pegboard, and Finger Tapping. Older age was associated with significantly (p<0.05) lower scores on all tests; less than high school education was associated with lower scores on all tests except Digit Span, Finger Tapping, and the Purdue Pegboard. Women and English-speaking participants scored higher than men and Japanese speakers on various tests of memory, attention, and visuomotor ability. These data reinforce the importance of using appropriately corrected norms when interpreting results of cognitive screening tests with minority culture older adults.

Journal Article↗
PubMed2000

Polymorphisms at the Werner locus: II. 1074Leu/Phe, 1367Cys/Arg, longevity, and atherosclerosis.

Werner syndrome (WS) is a progeroid syndrome caused by autosomal recessive null mutations at the WRN locus. The WRN gene encodes a nuclear protein of 180 kD that contains both exonuclease and helicase domains. WS patients develop various forms of arteriosclerosis, particularly atherosclerosis, and medial calcinosis. The most common cause of death in Caucasian subjects with WS is myocardial infarction. Previous studies have identified specific polymorphisms within WRN that may modulate the risk of atherosclerosis. Population studies of the 1074Leu/Phe and 1367Cys/Arg polymorphisms were undertaken to evaluate the role of WRN in atherogenesis. Frequencies of the 1074Leu/Phe polymorphisms in Finnish and Mexican populations revealed an age-dependent decline of 1074Phe/Phe genotype. In Mexican newborns, but not in Finnish newborns, the 1074Leu/Phe and 1367Cys/ Arg polymorphisms were in linkage disequilibrium. Among coronary artery disease subjects, there was a tendency for the 1074Phe allele to be associated with coronary stenosis in a gene dose-dependent manner. Furthermore, the 1367Arg/Arg genotype predicted a lower degree of coronary artery occlusion, as measured by NV50, when compared to the 1367Cys/Cys or 1367Cys/Arg genotypes. However, these tendencies did not achieve statistical significance. Samples from Mexican patients with ischemic stroke showed a trend of haplotype frequencies different from that in a control group of Mexican adults. These data support the hypothesis that WRN may mediate not only WS, but may also modulate more common age-related disorders and, perhaps, a basic aging process.

Adult↗
PubMed1999

Polymorphisms at the Werner locus: I. Newly identified polymorphisms, ethnic variability of 1367Cys/Arg, and its stability in a population of Finnish centenarians.

The Werner syndrome gene (WRN) encodes a novel helicase of 1,432 amino acids. Homozygous mutations, all of which result in the truncation of the protein, lead to Werner syndrome. However, little is known about the role of WRN in "normal" aging. We have identified four missense polymorphisms and four conservative polymorphsims in WRN gene. A single study showed that a polymorphism at amino acid 1367 Cys(TTG)/ Arg(CTG) is associated with a variation in risk of myocardial infarction among a Japanese population. The 1367 Cys/Arg polymorphism was examined during aging in three different populations: Finnish, Mexican, and North American. The frequencies of 1367 Cys were higher than those of 1367 Arg in all the populations examined, though the frequencies varied among populations. The frequency of the 1367 Arg allele, thought to be protective against myocardial infarction in a Japanese population, was approximately three times higher in the North American and Finnish adult populations. When newborns and centenarians were compared within the Finnish population, no differences were observed in the proportions of 1367 Cys/Arg across age groups. Within the Finnish population, we confirmed a significant decrease of the APOE epsilon2 allele and an increase in the epsilon4 allele in newborn infants compared with centenarians. Thus, unlike the APOE polymorphism, there is no evidence of an association of this WRN polymorphism with longevity.

Adult↗
PubMed1999

Estimation and sample design in prevalence surveys of dementia.

Population prevalence rates of dementia using stratified sampling have previously been estimated using two methods: standard weighted estimates and a logistic model-based approach. An earlier study described this application of the model-based approach and reported a small computer simulation comparing the performance of this estimator to the standard weighted estimator. In this article we use large-scale computer simulations based on data from the recently completed Kame survey of prevalent dementia in the Japanese-American residents of King County, Washington, to describe the performance of these estimators. We found that the standard weighted estimator was unbiased. This estimator performed well for a sample design with proportional allocation, but performed poorly for a sample design that included large strata that were lightly sampled. The logistic model-based estimator performed consistently well for all sample designs considered in terms of the extent of variability in estimation, although some modest bias was observed.

Aged↗
PubMed1999

Longitudinal decline in measured firefighter single-breath diffusing capacity of carbon monoxide values. A respiratory surveillance dilemma.

Seattle firefighters participate in a voluntary annual medical surveillance program including measurements of ventilatory capacity (FVC and FEV1) and single-breath diffusing capacity of carbon monoxide (DLCO). From 1989 to 1996, average % predicted DLCO (Crapo) for all participating firefighters declined from 94.4% (95% confidence interval [CI]: 93.4% to 95.5%) to 87.3% (95% CI: 86.2% to 88.3%), with no significant change in average FVC or FEV1. A random-effects regression model based on data from 812 firefighters with at least two annual sets of DLCO measurements showed the expected associations between DLCO and age, height, gender, race, ventilatory capacity, and smoking. In addition, two important temporal changes were observed, including, for an average firefighter, a large mean decline in DLCO of -1.02 ml/min/mm Hg associated with year of measurement, and a relatively smaller decline of -0.006 ml/min/mm Hg associated with number of fires fought. Although the stability of ventilatory capacity over time is reassuring, the marked temporal decline in diffusing capacity among this population of firefighters raises issues of concern. Interpretation of the observed decline poses a dilemma in terms of the reliability and efficacy of diffusing capacity as a screening tool, in whether DLCO is subject to unacceptable technical variability or whether it might provide more sensitive detection of early adverse respiratory effects of smoke inhalation.

Adult↗
PubMed1999

The cognitive abilities screening instrument (CASI): data from a cohort of 2524 cognitively intact elderly.

OBJECTIVES: To describe the effects of age and education for the Cognitive Abilities Screening Instrument (CASI), a 25-item test of cognitive function. DESIGN: Cross-sectional descriptive study of the initial enrollment in a community-based prospective cohort study. PARTICIPANTS: A total of 2524 cognitively intact older adults over age 65 who were members of a major health maintenance organization, and who consented to participate in a longitudinal study. MEASUREMENTS: Summary scores for the CASI are given in the form of mean, median and percentile distributions specific for age and educational level. RESULTS: Based upon maximum likelihood analyses, age and education were significant (p<0.0001) predictors of total CASI score. Increased age and lower education were associated with a lower CASI score, as well as an increased spread in score distribution. Gender was also significantly related (p<0.01) to total CASI, with women having a slightly higher distribution of scores. Mean total scores ranged from CASI=82.2 (SD=9.0) in subjects aged 90-95 who had less than a high school degree to CASI=94.8 (SD=3. 8) in subjects aged 65-69 with at least a high school education. CONCLUSIONS: Like most cognitive screening instruments, performance on the CASI in non-demented persons is influenced by age and education. The reference values for 5-year age categories described in this article should be useful for clinicians and research investigators when using the CASI as a measure of cognitive function.

Aged↗
PubMed1998

Accelerated decline in apolipoprotein E-epsilon4 homozygotes with Alzheimer's disease.

BACKGROUND: The apolipoprotein E-epsilon4 (APOE-epsilon4) allele is a powerful genetic risk factor for the development of Alzheimer's disease (AD). AD patients who are APOE-epsilon4 homozygotes have an earlier age at onset, increased amyloid burden, and decreased acetylcholine levels--findings that suggest differences in disease severity or rate of progression. Studies of genotype differences in rate of decline, however, have produced negative results that may be due to methodologic biases. The current study examined rate of decline in the largest sample of APOE-genotyped AD patients for whom longitudinal cognitive data have been reported. METHODS: Newly diagnosed patients with probable AD (n = 201) comprised four genotype groups: epsilon2/3 (n = 14), epsilon3/3 (n = 75), epsilon3/4 (n = 82), and epsilon4/4 (n = 30). The Dementia Rating Scale (DRS) was administered at baseline and then annually for 1 to 6 years (mean, 2.5 years). For each subject, a DRS slope was calculated reflecting annual rate of decline. Rate of decline as measured by DRS slope differed according to genotype, with the effect modified by DRS score (p < 0.014). At the mean DRS score observed in our sample (DRS = 105), the epsilon4/4 group had an increased rate of decline (11.9 points per year) relative to the epsilon2/3 (5.8 points per year; p < 0.003), epsilon3/3 (9.3 points per year; p < 0.076), and epsilon3/4 (9.6 points per year; p < 0.055) groups. At a lower DRS score (DRS = 80), even larger differences were observed among genotypes; the epsilon4/4 group had a increased rate of decline (22.2 points per year) relative to the epsilon2/3 (9.7 points per year; p < 0.0006), epsilon3/4 (15.8 points per year; p < 0.020), and epsilon3/3 (18.2 points per year; p < 0.173) groups. The epsilon2/3 group had a significantly slower rate of decline than all other groups at DRS scores of 80 or 105. CONCLUSIONS: APOE-epsilon4 homozygosity is associated with a faster rate of cognitive decline, whereas the epsilon2 allele slows disease progression. These findings suggest that APOE plays a mechanistic role in the progression of AD, and is not simply related to disease onset.

Age of Onset↗
PubMed1997

Little evidence of reduced survival to adulthood of apoE epsilon4 homozygotes in Down's syndrome.

It has been proposed that homozygosity for the apolipoprotein E (apoE) epsilon4 allele decreases the probability of an individual with Down's syndrome (DS) surviving to adulthood. We performed a meta-analysis of 11 published DS series for which apoE genotype data were available. Seven epsilon4 homozygotes out of a total of 538 DS adults have been reported in the literature. This number is not significantly different from that expected based on the epsilon4 allele frequencies in the individual series (p = 0.72). We conclude that there is little evidence that epsilon4/epsilon4 genotype frequency is substantially reduced in DS adults.

Adolescent↗
PubMed1997

Association of a polymorphic variant of the Werner helicase gene with myocardial infarction in a Japanese population.

The Werner syndrome (WS) is a rare autosomal recessive progeroid syndrome characterized by the premature onset of multiple age-related disorders, including atherosclerosis, cancer, non-insulin-dependent diabetes mellitus (NIDDM), ocular cataracts and osteoporosis [Epstein et al., 1966]. The major cause of death (at a median age of 47) is myocardial infarction (MI) [Epstein et al., 1966]. The WS mutation involves a member (WRN) of the RecQ family of helicases and may perturb DNA replication, repair, recombination, transcription, or chromosomal segregation [Yu et al., 1996]. We now report data on 149 MI cases and age-matched controls suggesting that a polymorphic WRN variant is associated with increased risk for MI. Based on our data, homozygosity for a cysteine at amino acid 1367 (the most prevalent genotype) predicts a 2.78 times greater risk of MI (95% confidence intervals: 1.23 to 6.86). The variant was not significantly associated with NIDDM. The two alleles (cysteine vs. arginine) could influence helicase activity, turnover, macromolecular interactions or, alternatively, could be markers for haplotypes influencing WRN regulation or reflecting gene action at linked loci. However, given the caveats implicit in genetic association studies, it is imperative that the present results be replicated in independent populations.

Adult↗
PubMed1997

Consortium to establish a registry for Alzheimer's disease: development, database structure, and selected findings.

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) was funded in 1986 by the National Institute on Aging to develop standardized assessments for patients with Alzheimer's disease (AD). Since that time, CERAD has developed and evaluated clinical and neuropsychological test batteries, a neuroimaging protocol, and an assessment of the neuropathological findings of the brains of these patients at autopsy. Approximately 1,200 carefully screened patients with AD and 450 control subjects were evaluated using these instruments at 24 major medical centers around the United States. Annual follow-up observations of these subjects were made for up to eight years. Autopsy examinations of the brain were done in over half of the deceased cases and the clinical diagnosis of AD was confirmed in 85 percent of them. This article outlines the procedures used for identifying the clinical sites, the entry and annual evaluations of patients and control subjects, the collection and analysis of data at a central Methodology and Data Management Center, and evaluation of the CERAD measures. We also present selected data from the 50 or so peer-reviewed papers published to date, with particular emphasis on findings from African-American patients with AD, and related policy implications.

Aged↗