PubMed Health⌕ Search

Biomedical subjects

K A Welsh-Bohmer

Publications and source records attributed to K A Welsh-Bohmer.

At least 19 recordsLinked to original sources
PubMed2006

Conversion to dementia from mild cognitive disorder: the Cache County Study.

OBJECTIVE: To examine 3-year rates of conversion to dementia, and risk factors for such conversion, in a population-based sample with diverse types of cognitive impairment. METHODS: All elderly (aged 65 or older) residents of Cache County, UT, were invited to undergo two waves of dementia screening and assessment. Three-year follow-up data were available for 120 participants who had some form of mild cognitive impairment at baseline. Of these, 51 had been classified at baseline with prodromal Alzheimer disease (proAD), and 69 with other cognitive syndromes (CS). RESULTS: Three-year rates of conversion to dementia were 46% among those with cognitive impairment at baseline. By comparison, 3.3% without impairment converted to dementia in the interval. Among converters, AD was the most common type of dementia. In individuals with at least one APOE epsilon4 allele, those with proAD or CS exhibited a 22- to 25-fold higher risk of dementia than cognitively unimpaired individuals (vs 5- to 10-fold higher risk in those without epsilon4). CONCLUSIONS: Individuals with all types of mild cognitive impairment have an elevated risk of dementia over 3 years, more so in those with an APOE epsilon4 allele. These results suggest value in dementia surveillance for broad groups of cognitively impaired individuals beyond any specific category, and utility of APOE genotyping as a prognostic method.

Aged↗
PubMed2006

Exploring the association of glyceraldehyde-3-phosphate dehydrogenase gene and Alzheimer disease.

BACKGROUND: Previous linkage studies have shown that chromosome 12 harbors susceptibility genes for late-onset Alzheimer disease (LOAD). However, association studies of several candidate genes on this chromosome region have produced ambiguous results. A recent study reported the association between the glyceraldehyde-3-phosphate dehydrogenase (GAPD) gene on chromosome 12p and the risk of LOAD. METHODS: The authors conducted family-based and case-control association studies in two independent LOAD data sets on 12 single-nucleotide polymorphisms (SNPs) in the GAPD gene and its paralogs. RESULTS: No association was found of the GAPD gene with LOAD in the family-based data set, but marginal evidence of association was seen in the later-onset subgroup when age at onset was stratified. The SNP rs2029721 in one GAPD pseudogene was also found to be associated with risk for LOAD in the unrelated case-control data set (p = 0.003). CONCLUSIONS: The GAPD gene and its pseudogene may play a role in the development of late-onset Alzheimer disease. However, the effect, if any, is likely to be limited.

Aged↗
PubMed2006

Lack of association between UBQLN1 and Alzheimer disease.

Alzheimer disease (AD) is heterogeneous and complex with a strong genetic diathesis. It is the most common cause of dementia affecting the elderly. Linkage studies [Kehoe et al., 1999; Hum Mol Genet 8: 237-245]; [Pericak-Vance et al., 2000; Exp Gerontol 35: 1343-1352]; [Myers et al., 2002; Am J Med Genet 114: 235-244]; [Blacker et al., 2003; Hum Mol Genet 12: 23-32] identified chromosome 9q as a region containing a possible AD candidate gene. Functional protein studies [Mah et al., 2000; J Cell Biol 151: 847-862]; [Ko et al., 2002; J Biol Chem 277: 35386-35392] identified the UBQLN1 gene on chromosome 9q that encodes ubiquilin as a likely candidate for a role in late-onset AD pathogenesis. A recent family-based study by [Bertram et al., 2005; N Engl J 352: 884-894] reported genetic association and expression evidence for a putative AD risk allele of an intronic single nucleotide polymorphism (SNP) within the UBQLN1 gene. In this study, we comprehensively assessed whether any of seven polymorphisms located across the UBQLN1 gene are associated with AD in another large family-based data set and an independent case-control data set. We found no significant association of AD risk with any of the seven SNPs genotyped (including those SNPs previously reported by Bertram et al.) in either the family-based or case-control data set. Age-specific analyses and analyses conditional on Apolipoprotein E (ApoE) genotype and sex also revealed no significant associations to AD risk in either data set. Using age at onset (AAO) as a quantitative trait revealed a modest age modifying association; however, the results were inconsistent between the data sets. Our results suggest that UBQLN1 variants do not increase risk for AD in these data.

Adaptor Proteins, Signal Transducing↗
PubMed2005

An autosomal genomic screen for dementia in an extended Amish family.

Apolipoprotein E (APOE) is the only universally confirmed susceptibility gene for late-onset Alzheimer disease (LOAD), although many loci are believed to modulate LOAD risk. The genetic homogeneity of isolated populations, such as the Amish, potentially provide increased power to identify LOAD susceptibility genes. Population homogeneity in these special populations may reduce the total number of susceptibility genes contributing to the complex disorder, thereby increasing the ability to identify any one susceptibility gene. Dementia in the Amish is clinically indistinguishable from LOAD in the general population. Previous studies in the Amish demonstrated a significantly decreased frequency of the APOE-4 susceptibility allele, but significant familial clustering of dementia [M.A. Pericak-Vance, C.C. Johnson, J.B. Rimmler, A.M. Saunders, L.C. Robinson, E.G. D'Hondt, C.E. Jackson, J.L. Haines, Alzheimer's disease and apolipoprotein E-4 allele in an Amish population, Ann. Neurol. 39 (1996) 700-704]. These data suggested that a genetic etiology independent of APOE may underlie the dementia observed in this population. In the present analysis, we focused on a large, multiplex, inbred Amish family (24 sampled individuals; 10 of whom are affected). We completed a genomic screen to identify novel LOAD loci (n=316 genetic markers), using both model-dependent "affecteds-only" analysis (dominant and recessive) and model-independent affected relative pair analysis. Interesting results (lod>1.5 or p<0.01) were obtained for markers on eight chromosomes (2q, 5q, 6q, 7p, 8p, 8q, 11p, 18p, 18q, and 19q). The highest overall score was a multipoint lod score of 3.1 on chromosome 11p. Most regions we identified were not previously detected by genomic screens of outbred populations and may represent population-specific susceptibilities to LOAD. These loci are currently under further investigation in a study of LOAD including additional Amish families.

Alzheimer Disease↗
PubMed2004

Age effects of coronary artery bypass graft on cognitive status change among elderly male twins.

BACKGROUND: Research regarding long-term cognitive outcome following coronary artery bypass graft (CABG) is inconsistent, which may be due in part to differential genetic and environmental influences within most study samples. METHODS: The authors examined the effect of CABG on cognitive status change scores in members of the National Academy of Sciences-National Research Council Twins Registry of World War II veterans. Subjects were administered the modified Telephone Interview for Cognitive Status (TICS-m) at approximately 3-year intervals between 1990 and 2002 as part of an epidemiologic study of dementia. RESULTS: Based on co-twin control analyses using a repeated-measures analysis of variance matching twins discordant for CABG within the pair (n = 464 individuals) across three age categories (63 to 70, 71 to 73, 74 to 83), the authors found at follow-up that men who had CABG between ages 63 and 70 showed an increase in TICS-m scores and performed better than their co-twin who did not have the procedure. No significant differences were found within twin pairs for the older two age groups following CABG surgery. This age effect was replicated when comparing individuals positive for CABG surgery with nonfamilial, age- and education-matched controls who were negative for CABG. CONCLUSIONS: In this study of twin pairs who share many genetic and environmental risks for cerebrovascular problems, the results suggest that timing of the CABG procedure may be important to predicting positive cognitive outcomes.

Age Factors↗
PubMed2004

Dementia: the leading predictor of death in a defined elderly population: the Cache County Study.

OBJECTIVE: To examine the relative risk and population attributable risk (PAR) of death with dementia of varying type and severity and other risk factors in a population of exceptional longevity. METHODS: Deaths were monitored over 5 years using vital statistics records and newspaper obituaries in 355 individuals with prevalent dementia and 4,328 without in Cache County, UT. Mean age was 83.3 (SD 7.0) years with dementia and 73.7 (SD 6.8) years without. History of coronary artery disease, hypertension, diabetes, and other life-shortening illness was ascertained from interviews. RESULTS: Death certificates implicated dementia as an important cause of death, but other data suggested a stronger association. Adjusted Cox relative hazard and PAR of death were higher with dementia than with any other illness studied. Relative hazard of death with dementia was highest at ages 65 to 74, but the high prevalence of dementia after age 85 resulted in 27% PAR among the oldest old. Mortality increased substantially with severity of dementia. Alzheimer disease shortened survival time most dramatically in younger participants, but vascular dementia posed a greater mortality risk among the oldest old. CONCLUSION: In this population, dementia was the strongest predictor of mortality, with a risk two to three times those of other life-shortening illnesses.

Aged↗
PubMed2001

Hormone replacement therapy and reduced cognitive decline in older women: the Cache County Study.

OBJECTIVE: To examine the association between postmenopausal hormone replacement therapy (HRT) and the trajectory of global cognitive change with age. METHODS: The Modified Mini-Mental State Examination (MMSE) was administered to a population sample of 2,073 nondemented, community-dwelling female residents of Cache County, UT, aged 65 and older. Current and past HRT and other medications at a baseline interview and at follow-up 3 years later were assessed. Between interviews, a telephone Women's Health Questionnaire was administered to assess initial exposure, duration, and recency of HRT. Generalized estimating equation marginal models were used to evaluate the cross-sectional and longitudinal relations of HRT and modified MMSE score. Also assessed were effects with multivitamins and calcium supplements as exposures likely to reflect a "healthy lifestyle" among HRT users. Model covariates included the presence of APOE epsilon4 alleles, age, education, concurrent depression, several chronic diseases, and self-perceived general health. RESULTS: Age, lower education, depression, and APOE epsilon4 were all associated with lower baseline modified MMSE scores. With these covariates in the model, lifetime HRT use was associated with better baseline modified MMSE scores and a slower rate of decline. Stratification by APOE genotype did not alter these effects. Apparent benefits with HRT were attenuated but remained significant after elimination of scores from participants with incident dementia. A significant interaction between age and HRT indicated the strongest effects in women aged 85 and older. Measures of age at initial use of HRT, duration, and recency of exposure did not improve the models. No effects were seen with the "healthy lifestyle" control exposures. CONCLUSIONS: In a population cohort of older women, lifetime HRT exposure was associated with improved global cognition and attenuated decline over a 3-year interval. Improvements were greatest in the oldest old.

Aged↗
PubMed2001

Positron emission tomography in evaluation of dementia: Regional brain metabolism and long-term outcome.

CONTEXT: Deficits in cerebral glucose utilization have been identified in patients with cognitive dysfunction attributed to various disease processes, but their prognostic and diagnostic value remains to be defined. OBJECTIVE: To assess the sensitivity and specificity with which cerebral metabolic patterns at a single point in time forecast subsequent documentation of progressive dementia. DESIGN, SETTING, AND PATIENTS: Positron emission tomography (PET) studies of [(18)F]fluorodeoxyglucose in 146 patients undergoing evaluation for dementia with at least 2 years' follow-up for disease progression at the University of California, Los Angeles, from 1991 to 2000, and PET studies in 138 patients undergoing evaluation for dementia at an international consortium of facilities, with histopathological diagnoses an average of 2.9 years later, conducted from 1984 to 2000. MAIN OUTCOME MEASURES: Regional distribution of [(18)F]fluorodeoxyglucose in each patient, classified by criteria established a priori as positive or negative for presence of a progressive neurodegenerative disease in general and of Alzheimer disease (AD) specifically, compared with results of longitudinal or neuropathologic analyses. RESULTS: Progressive dementia was detected by PET with a sensitivity of 93% (191/206) and a specificity of 76% (59/78). Among patients with neuropathologically based diagnoses, PET identified patients with AD and patients with any neurodegenerative disease with a sensitivity of 94% and specificities of 73% and 78%, respectively. The negative likelihood ratio of experiencing a progressive vs nonprogressive course over the several years following a single negative brain PET scan was 0.10 (95% confidence interval, 0.06-0.16), and the initial pattern of cerebral metabolism was significantly associated with the subsequent course of progression overall (P<.001). CONCLUSION: In patients presenting with cognitive symptoms of dementia, regional brain metabolism was a sensitive indicator of AD and of neurodegenerative disease in general. A negative PET scan indicated that pathologic progression of cognitive impairment during the mean 3-year follow-up was unlikely to occur.

Aged↗
PubMed2001

How proxies make decisions about research for patients with Alzheimer's disease.

We examined the proxy decision-making and informed consent processes for clinical research involving 49 patient-subjects with dementia in an outpatient setting by performing serial in-depth, structured, open-ended telephone interviews. Interviews were tape recorded and transcribed. Transcripts were then coded and analyzed. Although in all cases proxy consent was obtained for research from a legally authorized representative, proxies reported considerable ambiguity regarding who made the decision to participate in research, or to what degree the decision was that of the proxy or of the patient. Reasons proxies gave for participating in research included: hope of direct or indirect benefits to the patient, caregiver, or patient's descendents; desperation; trust in the investigator; belief in the goodness of research; and altruism. These reasons varied according to the type of research. For instance, in drug trials hope of direct benefit prevailed; in studies not evaluating a potential therapy more altruistic concerns predominated. Being a proxy decision maker for research can be burdensome. The degree of burden related to making a decision to participate in research seems influenced by a number of intersecting factors, most importantly, the risk and nature of the study, the extent to which patients were able to participate in the decision, and the duration and severity of dementia. Proxy decision-making concerning participation in research for patients with dementia can be a difficult task. The process might be improved by emphasizing that proxy consent is being sought because the nature of the patient's underlying medical condition can preclude the ability to make meaningful decisions. In addition, clinical researchers should recognize that giving proxy consent might place additional burdens on caregivers and discuss this explicitly when proxy consent is solicited.

Aged↗
PubMed2000

Documented head injury in early adulthood and risk of Alzheimer's disease and other dementias.

BACKGROUND: The association between antecedent head injury and AD is inconsistent. OBJECTIVE: To examine the association between early adult head injury, as documented by military hospital records, and dementia in late life; and to evaluate the interaction between head injury and APOE epsilon4 as risk factors for dementia. METHODS: The study had a population-based prospective historical cohort design. It included men who were World War II Navy and Marine veterans, and were hospitalized during their military service with a diagnosis of either a nonpenetrating head injury or another unrelated condition. In 1996 to 1997, military medical records were abstracted to document the occurrence and details of closed head injury. The entire sample was then evaluated for dementia and AD using a multistage procedure. There were 548 veterans with head injury and 1228 without head injury who completed all assigned stages of the study. The authors estimated risk of dementia, specifically AD, using proportional hazards models. RESULTS: Both moderate head injury (hazard ratio [HR] = 2.32; CI = 1.04 to 5.17) and severe head injury (HR = 4.51; CI = 1.77 to 11.47) were associated with increased risk of AD. Results were similar for dementia in general. The results for mild head injury were inconclusive. When the authors stratified by the number of APOE epsilon4 alleles, they observed a nonsignificant trend toward a stronger association between AD and head injury in men with more epsilon4 alleles. CONCLUSIONS: Moderate and severe head injuries in young men may be associated with increased risk of AD and other dementias in late life. However, the authors cannot exclude the possibility that other unmeasured factors may be influencing this association.

Aged↗
PubMed2000

Dementia diagnoses from clinical and neuropsychological data compared: the Cache County study.

OBJECTIVE: To validate a neuropsychological algorithm for dementia diagnosis. METHODS: We developed a neuropsychological algorithm in a sample of 1,023 elderly residents of Cache County, UT. We compared algorithmic and clinical dementia diagnoses both based on DSM-III-R criteria. The algorithm diagnosed dementia when there was impairment in memory and at least one other cognitive domain. We also tested a variant of the algorithm that incorporated functional measures that were based on structured informant reports. RESULTS: Of 1,023 participants, 87% could be classified by the basic algorithm, 94% when functional measures were considered. There was good concordance between basic psychometric and clinical diagnoses (79% agreement, kappa = 0.57). This improved after incorporating functional measures (90% agreement, kappa = 0.76). CONCLUSIONS: Neuropsychological algorithms may reasonably classify individuals on dementia status across a range of severity levels and ages and may provide a useful adjunct to clinical diagnoses in population studies.

Aged↗
PubMed2000

APOE and AD concordance in twin pairs as predictors of AD in first-degree relatives.

OBJECTIVE: To examine the independent effects of the APOE genotype (APOE) and concordance for AD in twin pairs on the occurrence of AD in first-degree relatives. BACKGROUND: Studies of twins have been undertaken to investigate the influence of genes in a variety of conditions, including AD. A previous study, performed before reports linking APOE to AD, demonstrated an increase in AD among first-degree relatives of twins concordant for AD compared with relatives of discordant twins. METHODS: In a sample of 94 twin pairs the authors examined the association between concordance for AD within the twin pair and family history of AD among first-degree relatives of twins. They then examined the extent to which the presence of the APOE epsilon4 allele in the twin pair explains the association between concordance for AD within the twin pair and family history of AD. RESULTS: Concordance among twins was associated with increased risk of AD among relatives (logrank test, chi2 = 12.558; p = 0.0004), and the presence of at least one APOE epsilon4 allele in each member of the twin pair is also associated with increased risk of AD among family members (logrank test, chi2 = 7.712; p = 0.0055). CONCLUSIONS: APOE genotype explains much but not all of the association between concordance among twins and increased familial risk of AD.

Age of Onset↗
PubMed2000

Prevalence of depression and its treatment in an elderly population: the Cache County study.

BACKGROUND: Previous estimates of the prevalence of geriatric depression have varied. There are few large population-based studies; most of these focused on individuals younger than 80 years. No US studies have been published since the advent of the newer antidepressant agents. METHODS: In 1995 through 1996, as part of a large population study, we examined the current and lifetime prevalence of depressive disorders in 4,559 nondemented individuals aged 65 to 100 years. This sample represented 90% of the elderly population of Cache County, Utah. Using a modified version of the Diagnostic Interview Schedule, we ascertained past and present DSM-IV major depression, dysthymia, and subclinical depressive disorders. Medication use was determined through a structured interview and a "medicine chest inventory." RESULTS: Point prevalence of major depression was estimated at 4.4% in women and 2.7% in men (P= .003). Other depressive syndromes were surprisingly uncommon (combined point prevalence, 1.6%). Among subjects with current major depression, 35.7% were taking an antidepressant (mostly selective serotonin reuptake inhibitors) and 27.4% a sedative/hypnotic. The current prevalence of major depression did not change appreciably with age. Estimated lifetime prevalence of major depression was 20.4% in women and 9.6% in men (P<.001), decreasing with age. CONCLUSIONS: These estimates for prevalence of major depression are higher than those reported previously in North American studies. Treatment with antidepressants was more common than reported previously, but was still lacking in most individuals with major depression. The prevalence of subsyndromal depressive symptoms was low, possibly because of unusual characteristics of the population.

Age Factors↗
PubMed2000

Relation between informant-rated personality and clinician-rated depression in patients with memory disorders.

OBJECTIVE: The goal of this study was to examine the convergent validity of informant-rated changes in depressive and related personality traits with clinician-assessed depression in memory-disordered patients. BACKGROUND: Depressive symptoms are frequent complications in persons with dementias such as Alzheimer disease, and caregiver informants consistently report changes in depression and related neurotic traits on the NEO Personality Inventory (NEO-PI) in dementia patients. METHODS: In 78 patients undergoing evaluation of memory complaints at an Alzheimer disease clinic, depression was characterized by clinical diagnosis, a clinician-rated scale, and informant ratings of premorbid versus current depression, anxiety, vulnerability, and neuroticism on the NEO-PI. RESULTS: The diagnostic groups differed in meaningful patterns on the NEO-PI measures. Those with a diagnosis of major depression differed from never-depressed patients in all personality areas, although those with depressed mood differed only on NEO-PI depression. The clinician-rated depression scale correlated modestly with current personality and change from baseline personality. CONCLUSIONS: The NEO-PI provides a useful measure of informants' perspectives on depressive personality changes in patients with memory disorders but does not correspond fully with a clinical syndrome of depression.

Aged↗
PubMed2000

FDG PET imaging in patients with pathologically verified dementia.

UNLABELLED: The purpose of this study was to confirm with pathologic verification 2 beliefs related to Alzheimer's disease (AD): (a) the long-standing impression that bilateral temporo-parietal hypometabolism, as noted on FDG PET imaging, is the metabolic abnormality associated with Alzheimer's disease (AD) and (b) that the sensitivity, specificity, and diagnostic accuracy of the metabolic pattern of bilateral temporo-parietal hypometabolism allows differentiation between other degenerative causes of dementia. METHODS: Twenty two individuals (8 women, 14 men) with difficult-to-characterize memory loss or dementia (using standard clinical criteria), and who eventually received pathologic confirmation of diagnosis, were evaluated. FDG PET brain scans were obtained and visually graded by an experienced nuclear medicine physician as to the presence of classic bilateral temporo-parietal hypometabolism as seen in Alzheimer's type dementia. Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of the metabolic pattern of bilateral temporo-parietal hypometabolism were determined using pathologic diagnosis as the gold standard. RESULTS: The clinical diagnosis of possible or probable AD was determined as the primary cause of dementia in 12 patients. The sensitivity and specificity of the clinical diagnosis for probable AD were 63% and 100%, respectively. The sensitivity and specificity of the clinical diagnosis for possible and probable AD were 75% and 100%, respectively. The sensitivity, specificity, and diagnostic accuracy of bilateral temporo-parietal hypometabolism being associated with AD were 93%, 63%, and 82%, respectively. CONCLUSION: This study confirms that bilateral temporo-parietal hypometabolism is indeed the classic metabolic abnormality associated with AD. Furthermore, in individuals with dementia whose FDG PET scans indicated a metabolic pattern other than bilateral temporo-parietal hypometabolism, a cause of dementia other than AD should be suspected. These observations may be of clinical importance in differentiating dementia syndromes. The sensitivity, specificity, and diagnostic accuracy of FDG PET are acceptable as tests to be used in the evaluation of dementia and particularly to confirm the clinical suspicion of AD.

Aged↗
PubMed1999

Determining the cause of memory loss in the elderly. From in-office screening to neuropsychological referral.

Improved understanding of neurobehavior in normal aging, Alzheimer's disease, and late-life depression makes early detection of neurodegenerative conditions possible. Primary care physicians can screen patients' mental status and mood states with simple in-office tests. When screening results or the clinical picture is ambiguous or complex, neuropsychological evaluation is useful in making an early, reliable differentiation between dementia and normal aging. Early identification of neurologic problems provides an opportunity to enhance quality of life and long-term care. Medical interventions, such as a trial of donepezil hydrochloride (Aricept) or other memory-enhancing medications as they become available, can be started when results are likely to be optimal. Common coexisting problems (e.g., depression, falls) can be sought and managed. Additional important medical decisions (e.g., elective surgeries) may be considered differently when dementia is diagnosed early.

Aged↗