The theme of this ongoing R01 project is that risk factors for Alzheimer's disease (AD) are associated with presymptomatic changes in brain function that can be detected well in advance of symptom onset. Previously we studied an AD risk cohort known as the Wisconsin Registry for Alzheimer's Prevention (WRAP) and have shown functional MRI (fMRI) associated changes due to family history of AD and apolipoprotein E genotype. In this project we will investigate associations that may shed light on explanatory mechanisms of our previously observed findings by measuring amyloid burden using [C11]PiB, regional cerebral metabolic rate of glucose (rCMRglu) using [F18]fluoro-deoxyglucose (FDG) positron emission tomography (PET), neural function, rate of atrophy and ischemic lesion burden using MRI. Our prior study had a cross-sectional design;thus, a second major goal is to investigate the longitudinal course of brain change in a group of at risk subjects who were cognitively normal at baseline;some are now declining toward MCI. This proposed ongoing project represents a unique opportunity to comprehensively follow high-risk patients from cognitively normal to pre-MCI, and eventually to MCI and AD. Our studies are centered around three Specific Aims: A) to examine potential mechanisms (by way of association) of the BOLD risk effect we have observed in the prior funding period;B) To investigate longitudinal presymptomatic evolution of AD related brain changes and cognitive decline in people who are at high risk for AD, and determine whether PiB predicts decline in people at risk;C) Examine the direct relationship between brain changes and the best available known biomarkers consisting of CSF A242, t-tau and p-tau181. We will study 250 subjects longitudinally and use integrated path and regression analyses to accomplish these cross-sectional and longitudinal aims.
By the time a patient exhibits symptomatic dementia, devastating neural loss has already occurred, and the time window for most effective intervention already past. If a preclinical signal can be reliably observed and is predictive of cognitive decline, this will greatly strengthen the rationale for earlier intervention rather than waiting for symptomatic AD to present itself.
|Besser, Lilah; Kukull, Walter; Knopman, David S et al. (2018) Version 3 of the National Alzheimer's Coordinating Center's Uniform Data Set. Alzheimer Dis Assoc Disord 32:351-358|
|Betthauser, Tobey J; Cody, Karly A; Zammit, Matthew D et al. (2018) In vivo characterization and quantification of neurofibrillary tau PET radioligand [18F]MK-6240 in humans from Alzheimer's disease dementia to young controls. J Nucl Med :|
|Bettcher, Brianne M; Johnson, Sterling C; Fitch, Ryan et al. (2018) Cerebrospinal Fluid and Plasma Levels of Inflammation Differentially Relate to CNS Markers of Alzheimer's Disease Pathology and Neuronal Damage. J Alzheimers Dis 62:385-397|
|Zhou, Hao Henry; Singh, Vikas; Johnson, Sterling C et al. (2018) Statistical tests and identifiability conditions for pooling and analyzing multisite datasets. Proc Natl Acad Sci U S A 115:1481-1486|
|Clark, Lindsay R; Koscik, Rebecca L; Allison, Samantha L et al. (2018) Hypertension and obesity moderate the relationship between ?-amyloid and cognitive decline in midlife. Alzheimers Dement :|
|Swanson, Ashley; Wolf, Tovah; Sitzmann, Alli et al. (2018) Neuroinflammation in Alzheimer's disease: Pleiotropic roles for cytokines and neuronal pentraxins. Behav Brain Res 347:49-56|
|Johnson, Sterling C; Koscik, Rebecca L; Jonaitis, Erin M et al. (2018) The Wisconsin Registry for Alzheimer's Prevention: A review of findings and current directions. Alzheimers Dement (Amst) 10:130-142|
|Dougherty, Ryan J; Lindheimer, Jacob B; Stegner, Aaron J et al. (2018) An Objective Method to Accurately Measure Cardiorespiratory Fitness in Older Adults Who Cannot Satisfy Widely Used Oxygen Consumption Criteria. J Alzheimers Dis 61:601-611|
|Koscik, Rebecca L; Jonaitis, Erin M; Clark, Lindsay R et al. (2018) Longitudinal Standards for Mid-life Cognitive Performance: Identifying Abnormal Within-Person Changes in the Wisconsin Registry for Alzheimer's Prevention. J Int Neuropsychol Soc :1-14|
|Deming, Yuetiva; Dumitrescu, Logan; Barnes, Lisa L et al. (2018) Sex-specific genetic predictors of Alzheimer's disease biomarkers. Acta Neuropathol 136:857-872|
Showing the most recent 10 out of 122 publications