Your search for: 'author:("Fagan, Anne")' has returned 19 results. (0.021s) Save search

Authors: Plotzker, Alan S. | Henson, Rachel L. | Fagan, Anne M. | Morris, John C. | Day, Gregory S.

Article Type: Research Article

Abstract: Background: Cerebral amyloid angiopathy with related inflammation (CAA-ri) is a rare age-associated disorder characterized by an inflammatory response to amyloid in cerebral blood vessels. CAA-ri is often treated with corticosteroids, but response to treatment is variable. Objective: To assess the relationship between clinical and paraclinical measures and outcomes in patients with CAA-ri treated with high doses of methylprednisolone. Methods: Longitudinal clinical course, and results from serum and cerebrospinal fluid (CSF) testing, electroencephalography, and neuroimaging were reviewed from 11 prospectively-accrued CAA-ri patients diagnosed, treated, and followed at Barnes Jewish Hospital (St. Louis, MO, USA). Magnetic resonance imaging (MRI) changes were quantified …using a scoring system validated in cases of amyloid related imaging abnormality (ARIA-E). Clinical outcomes were assessed as change in modified Rankin Scale (ΔmRS) from baseline to final assessment (median 175 days from treatment with high doses of methylprednisolone; range, 31–513). Results: Worse outcomes following methylprednisolone treatment were associated with requirement for intensive care unit admission (median ΔmRS, 5 versus 1.5; p  = 0.048), CSF pleocytosis (median ΔmRS 4.5 versus 1; p  = 0.04), or lower CSF Aβ40 at presentation (rho = –0.83; p  = 0.02), and diffusion restriction (median ΔmRS 4 versus 1.5; p  = 0.03) or higher late ARIA-E scores (rho = 0.70; p  = 0.02) on MRI, but not preexisting cognitive decline (median ΔmRS 2 versus 2; p  = 0.66). Conclusion: Clinical and paraclinical measures associated with outcomes may inform clinical counseling and treatment decisions in patients with CAA-ri. Baseline cognitive status was not associated with treatment responsiveness. Show more

Keywords: Alzheimer’s disease, amyloid-beta related angiitis, biomarkers, cerebral amyloid angiopathy, inflammation, treatment outcome

DOI: 10.3233/JAD-201299

Citation: Journal of Alzheimer's Disease, vol. 80, no. 1, pp. 133-142, 2021

Authors: Allison, Samantha L. | Fagan, Anne M. | Morris, John C. | Head, Denise

Article Type: Research Article

Abstract: Although several previous studies have demonstrated navigational deficits in early-stage symptomatic Alzheimer’s disease (AD), navigational abilities in preclinical AD have not been examined. The present investigation examined the effects of preclinical AD and early-stage symptomatic AD on spatial navigation performance. Performance on tasks of wayfinding and route learning in a virtual reality environment were examined. Comparisons were made across the following three groups: Clinically normal without preclinical AD (n  = 42), clinically normal with preclinical AD (n  = 13), and early-stage symptomatic AD (n  = 16) groups. Preclinical AD was defined based on cerebrospinal fluid Aβ42 levels below 500 pg/ml. Preclinical AD was …associated with deficits in the use of a wayfinding strategy, but not a route learning strategy. Moreover, post-hoc analyses indicated that wayfinding performance had moderate sensitivity and specificity. Results also confirmed early-stage symptomatic AD-related deficits in the use of both wayfinding and route learning strategies. The results of this study suggest that aspects of spatial navigation may be particularly sensitive at detecting the earliest cognitive deficits of AD. Show more

Keywords: Aging, allocentric, amyloid, caudate nucleus, egocentric, hippocampus

DOI: 10.3233/JAD-150855

Citation: Journal of Alzheimer's Disease, vol. 52, no. 1, pp. 77-90, 2016

Authors: Babulal, Ganesh M. | Johnson, Ann | Fagan, Anne M. | Morris, John C. | Roe, Catherine M.

Article Type: Short Communication

Abstract: We examined whether driving behavior can predict preclinical Alzheimer’s disease (AD). Data from 131 cognitively normal older adults with cerebrospinal fluid (CSF) and/or positron emission tomography (PET) biomarkers were examined with naturalistic driving behavior. Receiver operating characteristic curves were used to predict the highest 10%, 25%, and 50% of values for CSF tau/Aβ42 , ptau181 /Aβ42 , or amyloid PET. Six in vivo driving variables alone yielded area under the curves (AUC) from 0.64–0.82. Addition of age, Apolipoprotein ɛ 4, and neuropsychological measures to the models improved the AUC (0.81 to 0.90). Driving can be used as novel neurobehavioral marker …to identify presence of preclinical AD. Show more

Keywords: Aging drivers, Alzheimer’s disease, biomarkers, driving decline, preclinical

DOI: 10.3233/JAD-201294

Citation: Journal of Alzheimer's Disease, vol. 79, no. 3, pp. 1009-1014, 2021

Authors: Fagan, Anne M. | Csernansky, Cynthia A. | Morris, John C. | Holtzman, David M.

Article Type: Research Article

Abstract: Alzheimer's disease (AD) will likely become the greatest public health crisis in the United States within the next 2–3 decades if left unchecked. There are no proven treatments that delay the onset or prevent the progression of AD, although a few promising candidates are under development. Even the earliest clinical symptoms of AD are accompanied by, and likely due to, neuronal/synaptic dysfunction and/or cell death. Thus, it is critical to identify individuals with “preclinical AD”, prior to the development of clinical symptoms and concomitant neuronal loss, so new therapies will have the greatest clinical impact. At present, there are no …antecedent biomarkers that will identify individuals with preclinical AD, however ongoing investigations of “at risk” populations, including those with Mild Cognitive Impairment (MCI), presymptomatic individuals harboring known disease-causing familial AD mutations or carriers of the ε4 allele of apolipoprotein E are offering insights into possible biomarkers of early disease processes. To discover antecedent biomarkers of AD, a prospective, longitudinal study of middle-aged individuals with positive or negative family history of AD has been initiated at Washington University in St. Louis. The Adult Children Study provides an opportunity to discuss the challenges and goals for investigations of antecedent AD biomarkers. Show more

Keywords: Alzheimer's disease, amyloid-β, antecedent biomarkers, apolipoprotein E, cerebrospinal fluid, MCI, neuroimaging, PIB, plasma, preclinical AD

DOI: 10.3233/JAD-2005-8404

Citation: Journal of Alzheimer's Disease, vol. 8, no. 4, pp. 347-358, 2005

Authors: Babulal, Ganesh M. | Stout, Sarah H. | Head, Denise | Holtzman, David M. | Fagan, Anne M. | Morris, John C. | Roe, Catherine M.

Article Type: Research Article

Abstract: We examined whether neuropsychiatric symptoms (NPS) interact with cerebrospinal fluid (CSF) biomarkers (amyloid-β42 [Aβ42 ], tau, phosphorylated tau181 [ptau181 ], tau/Aβ42 , and ptau181 /Aβ42 ) of Alzheimer’s disease pathology to predict driving decline among cognitively-normal older adults (N  = 116) aged ≥65. Cox proportional hazards models examined time to receiving a rating of marginal or fail on the driving test. Age, education, and gender were adjusted in the models. Participants with more abnormal CSF (Aβ42 , tau/Aβ42 , ptau181 /Aβ42 ) and NPS were faster to receive a marginal/fail on the road test compared to those without NPS. NPS interact …with abnormal CSF biomarkers to impact driving performance among cognitively-normal older adults. Show more

Keywords: Alzheimer’s disease, cerebrospinal fluid, depression, neuropsychology, noncognitive outcomes, preclinical

DOI: 10.3233/JAD-170067

Citation: Journal of Alzheimer's Disease, vol. 58, no. 3, pp. 675-680, 2017

Authors: Wisch, Julie K. | Roe, Catherine M. | Babulal, Ganesh M. | Schindler, Suzanne E. | Fagan, Anne M. | Benzinger, Tammie L. | Morris, John C. | Ances, Beau M.

Article Type: Research Article

Abstract: Background: Changes in resting state functional connectivity (rs-fc) occur in Alzheimer’s disease (AD), but few longitudinal rs-fc studies have been performed. Most studies focus on single networks and not a global measure of rs-fc. Although the amyloid tau neurodegeneration (AT(N)) framework is increasingly utilized by the AD community, few studies investigated when global rs-fc signature changes occur within this model. Objective: 1) Identify a global rs-fc signature that differentiates cognitively normal (CN) individuals from symptomatic AD. 2) Assess when longitudinal changes in rs-fc occur relative to conversion to symptomatic AD. 3) Compare rs-fc with amyloid, tau, and neurodegeneration biomarkers. Methods: …A global rs-fc signature composed of intra-network connections was longitudinally evaluated in a cohort of cognitively normal participants at baseline (n  = 335). Biomarkers, including cerebrospinal fluid (Aβ42 and tau), structural magnetic resonance imaging, and positron emission tomography were obtained. Results: Global rs-fc signature distinguished CN individuals from individuals who developed symptomatic AD. Changes occurred nearly four years before conversion to symptomatic AD. The global rs-fc signature most strongly correlated with markers of neurodegeneration. Conclusion: The global rs-fc signature changes near symptomatic onset and is likely a neurodegenerative biomarker. Rs-fc changes could serve as a biomarker for evaluating potential therapies for symptomatic conversion to AD. Show more

Keywords: Alzheimer’s disease, biomarkers, neuroimaging, observational studies

DOI: 10.3233/JAD-191039

Citation: Journal of Alzheimer's Disease, vol. 74, no. 4, pp. 1085-1095, 2020

Authors: Aschenbrenner, Andrew J. | Gordon, Brian A. | Fagan, Anne M. | Schindler, Suzanne E. | Balota, David A. | Morris, John C. | Hassenstab, Jason J.

Article Type: Research Article

Abstract: Background: Cerebrospinal fluid tau and neurofilament light (NfL) are two biomarkers of neurodegeneration in Alzheimer’s disease. Previous reports have shown that the influence of tau on cognitive decline depends on levels of amyloid burden whereas NfL predicts decline independently of amyloid. Most studies use a global cognitive composite as the primary outcome, and it is unknown if critical cognitive domain scores are similarly sensitive to rates of decline due to neurodegeneration. Objective: To examine the unique contribution of amyloid, tau, and NfL to rates of cognitive decline in multiple cognitive composites in a cognitively healthy, middle-aged to older adult cohort. …Methods: A total of 255 participants (55% female; mean age = 66.2 years, range = 42.5–86.7 years) completed CSF studies and serial cognitive assessments to measure global cognition, episodic memory, and attentional control. Linear mixed effects models were used to examine rates of change on each composite score as a function of baseline biomarker levels. Results: Total tau predicted decline in attention regardless of amyloid status, but the relationship to global cognition and episodic memory was dependent on amyloid, replicating prior literature. NfL predicted decline in attention and global cognition, but not memory, and this effect was independent of amyloid status. Conclusions: These findings suggest that NfL can be used to monitor cognitive decline in aging and Alzheimer’s disease and that an attentional control composite may be a better outcome for tracking general neurodegenerative effects on cognition. Show more

Keywords: Alzheimer’s disease, attention, cerebrospinal fluid, memory, neurofilament light

DOI: 10.3233/JAD-200018

Citation: Journal of Alzheimer's Disease, vol. 74, no. 4, pp. 1119-1129, 2020

Authors: Ingber, Adam P. | Hassenstab, Jason | Fagan, Anne M. | Benzinger, Tammie L.S. | Grant, Elizabeth A. | Holtzman, David M. | Morris, John C. | Roe, Catherine M.

Article Type: Research Article

Abstract: Background: The influence of reserve variables and Alzheimer’s disease (AD) biomarkers on cognitive test performance has been fairly well-characterized. However, less is known about the influence of these factors on “non-cognitive” outcomes, including functional abilities and mood. Objective: We examined whether cognitive and brain reserve variables mediate how AD biomarker levels in cognitively normal persons predict future changes in function, mood, and neuropsychiatric behavior. Methods: Non-cognitive outcomes were examined in 328 individuals 50 years and older enrolled in ongoing studies of aging and dementia at the Knight Alzheimer Disease Research Center (ADRC). All participants were cognitively normal at baseline (Clinical …Dementia Rating [CDR] 0), completed cerebrospinal fluid (CSF) and structural neuroimaging studies within one year of baseline, and were followed for an average of 4.6 annual visits. Linear mixed effects models explored how cognitive reserve and brain reserve variables mediate the relationships between AD biomarker levels and changes in function, mood, and neuropsychiatric behavior in cognitively normal participants. Results: Education levels did not have a significant effect on predicting non-cognitive decline. However, participants with smaller brain volumes exhibited the worst outcomes on measures of mood, functional abilities, and behavioral disturbance. This effect was most pronounced in individuals who also had abnormal CSF biomarkers. Conclusions: The findings suggest that brain reserve plays a stronger, or earlier, role than cognitive reserve in protecting against non-cognitive impairment in AD. Show more

Keywords: Alzheimer’s disease, biomarkers, cognitive reserve, dementia

DOI: 10.3233/JAD-150478

Citation: Journal of Alzheimer's Disease, vol. 52, no. 3, pp. 1055-1064, 2016

Authors: Okereke, Olivia I. | Xia, Weiming | Irizarry, Michael C. | Sun, Xiaoyan | Qiu, Wei Q. | Fagan, Anne M. | Mehta, Pankaj D. | Hyman, Bradley T. | Selkoe, Dennis J. | Grodstein, Francine

Article Type: Research Article

Abstract: Identifying biomarkers of Alzheimer's disease (AD) risk will be critical to effective AD prevention. Levels of circulating amyloid-β (Aβ) 40 and 42 may be candidate biomarkers. However, properties of plasma Aβ assays must be established. Using five different protocols, blinded samples were used to assess: intra-assay reproducibility; impact of EDTA vs. heparin anticoagulant tubes; and effect of time-to-blood processing. In addition, percent recovery of known Aβ concentrations in spiked samples was assessed. Median intra-assay coefficients of variation for the assay protocols ranged from 6–24% for Aβ40 , and 8–14% for Aβ42 . There were no systematic differences in reproducibility by …collection method. Plasma concentrations of Aβ (particularly Aβ42 ) appeared stable in whole blood kept in ice packs and processed as long as 24 hours after collection. Recovery of expected concentrations was modest, ranging from −24% to 44% recovery of Aβ40 , and 17% to 61% of Aβ42 . In conclusion, across five protocols, plasma Aβ40 and Aβ42 levels were measured with generally low error, and measurements appeared similar in blood collected in EDTA versus heparin. While these preliminary findings suggest that measuring plasma Aβ40 and Aβ42 may be feasible in varied research settings, additional work in this area is necessary. Show more

Keywords: Alzheimer's disease, amyloid, assay reliability, biomarker, quality control

DOI: 10.3233/JAD-2009-0948

Citation: Journal of Alzheimer's Disease, vol. 16, no. 2, pp. 277-285, 2009

Authors: Ting, Simon Kang Seng | Benzinger, Tammie | Kepe, Vladimir | Fagan, Anne | Coppola, Giovanni | Porter, Verna | Hecimovic, Silva | Chakraverty, Suma | Alvarez-Retuerto, Ana Isabel | Goate, Alison | Ringman, John M.

Article Type: Short Communication

Abstract: Mutations in PSEN1 are the most common cause of autosomal dominant familial Alzheimer's disease (FAD). We describe an African-American woman with a family history consistent with FAD who began to experience cognitive decline at age 50. Her clinical presentation, MRI, FDG-PET, and PIB-PET scan findings were consistent with AD and she was found to have a novel I238M substitution in PSEN1. As this mutation caused increased production of Aβ42 in an in vitro assay, was not present in two population databases, and is conserved across species, it is likely to be pathogenic for FAD.

Keywords: African, Alzheimer's disease, amyloid-β42, autosomal dominant, familial, gamma-secretase, in vitro, PIB-PET, presenilin-1, PSEN1

DOI: 10.3233/JAD-131844

Citation: Journal of Alzheimer's Disease, vol. 40, no. 2, pp. 271-275, 2014