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Articles by Kathleen A. Welsh- Bohmer
Total Records ( 5 ) for Kathleen A. Welsh- Bohmer
  Richard Mayeux , Christiane Reitz , Adam M. Brickman , Mary N. Haan , Jennifer J. Manly , M. Maria Glymour , Christopher C. Weiss , Kristine Yaffe , Laura Middleton , Hugh C. Hendrie , Lauren H. Warren , Kathleen M. Hayden , Kathleen A. Welsh- Bohmer , John C.S. Breitner and John C. Morris
  In this article, the challenges faced by several noted population studies for Alzheimer dementia in operationalizing current clinical diagnostic criteria for Alzheimer‘s disease (AD) have been reviewed. Differences in case ascertainment, methodological biases, cultural and educational influences on test performance, inclusion of special populations such as underrepresented minorities and the oldest old, and detection of the earliest symptomatic stages of underlying AD have been considered. Classification of Alzheimer dementia may be improved by the incorporation of biomarkers for AD if the sensitivity, specificity, and predictive value of the biomarkers are established and if they are appropriate for epidemiological studies, as may occur should a plasma biomarker be developed. Biomarkers for AD could also facilitate studies of the interactions of various forms of neurodegenerative disorders with cerebrovascular disease, resulting in ”mixed dementia“.
  Rima Kaddurah- Daouk , Steve Rozen , Wayne Matson , Xianlin Han , Christine M. Hulette , James R. Burke , P. Murali Doraiswamy and Kathleen A. Welsh- Bohmer
  Background Metabolomics, the global science of biochemistry, provides powerful tools to map perturbations in the metabolic network and enables simultaneous quantification of several metabolites to identify metabolic perturbances that might provide insights into disease. Methods In this pilot study, we took a targeted electrochemistry-based metabolomics approach where liquid chromatography followed by coulometric array detection enables quantification of over 30 metabolites within key neurotransmitter pathways (dopamine and serotonin) and pathways involved in oxidative stress. Results Using samples from postmortem ventricular cerebrospinal fluid (15 Alzheimer's disease [AD] and 15 nondemented subjects with autopsy-confirmed diagnoses) and by using regression models, correlations, Wilcoxon rank-sum tests, and t-tests we identified alterations in tyrosine, tryptophan, purine, and tocopherol pathways in patients with AD. Reductions in norepinephrine and its related metabolites were also seen, consistent with previously published data. Conclusions These data support further investigation of metabolomics in larger samples of clinical AD as well as in those with preclinical disease for use as biomarkers.
  Michelle M. Mielke , Jeannie-Marie Leoutsakos , Chris D. Corcoran , Robert C. Green , Maria C. Norton , Kathleen A. Welsh- Bohmer , JoAnn T. Tschanz and Constantine G. Lyketsos
  Background Observational studies suggest that cholinesterase inhibitors and/or memantine may delay clinical progression of Alzheimer‘s disease (AD) in 40% of individuals taking the medications. Given this response and existence of side effects, we sought to quantify medication use and benefits in a population-based study of incident AD cases. Methods The Cache County Dementia Progression Study enrolled and followed a cohort of 327 incident AD cases for a maximum of 9 years. Drug exposure was expressed using a persistency index (PI), calculated as total years of drug use divided by total years of observation. Linear mixed-effects models examined PI, and interactions with sex and apolipoprotein E (APOE) as predictors of clinical progression on the Mini-Mental State Examination and Clinical Dementia Rating-Sum of Boxes. Results A total of 69 participants (21.1%) reported having ever used cholinesterase inhibitors or memantine. There was a strong three-way interaction between PI, sex, and time. Among women, a higher PI (i.e., greater duration of use) of cholinesterase inhibitors was associated with slower progression on the Mini-Mental State Examination and Clinical Dementia Rating-Sum of Boxes, particularly among those with an APOE ɛ4 allele. In contrast, higher PI was associated with faster progression in males. Conclusion A low percentage of individuals with AD in the community are taking cholinesterase inhibitors or memantine. This study suggests that women, particularly those with an APOE ɛ4 allele, may benefit the most from these medications. With the newly approved increased dose of donepezil, it will be imperative to determine whether a higher dose is needed in men or whether other factors warrant consideration.
  Kathleen M. Hayden , Jill M. McEvoy , Colton Linnertz , Deborah Attix , Maragatha Kuchibhatla , Ann M. Saunders , Ann M. Saunders , Kathleen A. Welsh- Bohmer , Allen D. Roses and Ornit Chiba- Falek
  Introduction A highly polymorphic T homopolymer was recently found to be associated with late-onset Alzheimer‘s disease risk and age of onset. Objective To explore the effects of the polymorphic polyT tract (rs10524523, referred as ’523‘) on cognitive performance in cognitively healthy elderly individuals. Methods One hundred eighty-one participants were recruited from local independent-living retirement communities. Informed consent was obtained, and participants completed demographic questionnaires, a conventional paper-and-pencil neuropsychological battery, and the computerized Cambridge Neuropsychological Test Automated Battery (CANTAB). Saliva samples were collected for determination of the TOMM40 ’523‘ (S, L, VL) and the apolipoprotein E (APOE) (ɛ2, 3, 4) genotypes. From the initial sample of 181 individuals, 127 were eligible for the association analysis. Participants were divided into three groups based on ’523‘ genotypes (S/S, S/L-S/VL, and L/L-L/VL-VL/VL). Generalized linear models were used to evaluate the association between the ’523‘ genotypes and neuropsychological test performance. Analyses were adjusted for age, sex, education, depression, and APOE ɛ4 status. A planned subanalysis was undertaken to evaluate the association between ’523‘ genotypes and test performance in a sample restricted to APOE ɛ3 homozygotes. Results The S homozygotes performed better, although not significantly, than the S/L-S/VL and the VL/L-L/VL-VL/VL genotype groups on measures associated with memory (CANTAB Paired Associates Learning, Verbal Recognition Memory free recall) and executive function (CANTAB measures of Intra-Extra Dimensional Set Shift). Follow-up analysis of APOE ɛ3 homozygotes only showed that the S/S group performed significantly better than the S/VL group on measures of episodic memory (CANTAB Paired Associates Learning and Verbal Recognition Memory free recall), attention (CANTAB Rapid Visual Information Processing latency), and executive function (Digit Symbol Substitution). The S/S group performed marginally better than the VL/VL group on Intra-Extra Dimensional Set Shift. None of the associations remained significant after applying a Bonferroni correction for multiple testing. Conclusions Results suggest important APOE-independent associations between the TOMM40 ’523‘ polymorphism and specific cognitive domains of memory and executive control that are preferentially affected in early-stage Alzheimer‘s disease.
  Jeffrey N. Browndyke , Kelly Giovanello , Jeffrey Petrella , Kathleen Hayden , Ornit Chiba- Falek , Karen A. Tucker , James R. Burke and Kathleen A. Welsh- Bohmer
  Background Reliable blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) phenotypic biomarkers of Alzheimer‘s disease (AD) or mild cognitive impairment (MCI) are likely to emerge only from a systematic, quantitative, and aggregate examination of the functional neuroimaging research literature. Methods A series of random-effects activation likelihood estimation (ALE) meta-analyses were conducted on studies of episodic memory encoding operations in AD and MCI samples relative to normal controls. ALE analyses were based on a thorough literature search for all task-based functional neuroimaging studies in AD and MCI published up to January 2010. Analyses covered 16 fMRI studies, which yielded 144 distinct foci for ALE meta-analysis. Results ALE results indicated several regional task-based BOLD consistencies in MCI and AD patients relative to normal control subjects across the aggregate BOLD functional neuroimaging research literature. Patients with AD and those at significant risk (MCI) showed statistically significant consistent activation differences during episodic memory encoding in the medial temporal lobe, specifically parahippocampal gyrus, as well superior frontal gyrus, precuneus, and cuneus, relative to normal control subjects. Conclusions ALE consistencies broadly support the presence of frontal compensatory activity, medial temporal lobe activity alteration, and posterior midline ”default mode“ hyperactivation during episodic memory encoding attempts in the diseased or prospective predisease condition. Taken together, these robust commonalities may form the foundation for a task-based fMRI phenotype of memory encoding in AD.
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