Chronic inflammation is a major characteristic of the typical aging process. The view that the central nervous system is immunologically privileged, however, is challenged by evidence linking low level, chronic inflammation to neurologic injury, neurodegeneration, and cognitive dysfunction. The degree of risk posed by inflammation and the underlying mechanisms of injury remain unclear. The overarching goal of this proposal is to better define the impact of chronic inflammation on brain structure and function. We propose to study four potential downstream effects of chronic inflammation on the brain: 1) Alzheimer's-related changes; 2) white matter injury; 3) network connectivity; and 4) cognition. We will longitudinally study 150 functionally normal community-dwelling subjects over the age of 65 selected from on-going, well-characterized cohorts at UCSF. We will quantify chronic inflammation using several well established markers in serum, plasma, and cerebrospinal fluid. Innovative MRI and PET molecular neuroimaging methods will measure microstructural integrity of white matter tracts, functional connectivity networks, and Alzheimer's-related deposition of brain amyloid. Cerebrospinal fluid (CSF) obtained on a subset of cases will further our understanding of specific inflammatory profiles in the periphery and brain. The cognitive phenotype(s) associated with chronic inflammation will be defined using methods from cognitive neuroscience, and we will explore potential mechanisms by which chronic inflammation interacts with brain structure and function. Results from this project will potentially guide clinial trials and identify elderly subjects with treatable and reversible risks for adverse neurological and cognitive aging.
Chronic inflammation increases as we age, and has been independently linked to major age-related diseases, including neurodegeneration and cerebrovascular disease. The overarching goal of this proposal is to better define the longitudinal impact of chronic inflammation on brain structure and function in the elderly by employing imaging biomarkers of white matter injury and Alzheimer's disease. Because inflammation is potentially treatable, this study can contribute to public health by establishing te nature and mechanisms of brain changes, and identifying the best biomarkers of inflammation and neurological functioning for clinical trials.
|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|
|Casaletto, Kaitlin B; Staffaroni, Adam M; Elahi, Fanny et al. (2018) Perceived Stress is Associated with Accelerated Monocyte/Macrophage Aging Trajectories in Clinically Normal Adults. Am J Geriatr Psychiatry 26:952-963|
|Casaletto, K B; Elahi, F M; Fitch, R et al. (2018) A comparison of biofluid cytokine markers across platform technologies: Correspondence or divergence? Cytokine 111:481-489|
|Saloner, R; Casaletto, K B; Marx, G et al. (2018) Performance on a 1-week delayed recall task is associated with medial temporal lobe structures in neurologically normal older adults. Clin Neuropsychol 32:456-467|
|Staffaroni, Adam M; Brown, Jesse A; Casaletto, Kaitlin B et al. (2018) The Longitudinal Trajectory of Default Mode Network Connectivity in Healthy Older Adults Varies As a Function of Age and Is Associated with Changes in Episodic Memory and Processing Speed. J Neurosci 38:2809-2817|
|Whitwell, Jennifer L; Höglinger, Günter U; Antonini, Angelo et al. (2017) Radiological biomarkers for diagnosis in PSP: Where are we and where do we need to be? Mov Disord 32:955-971|
|Casaletto, K B; Marx, G; Dutt, S et al. (2017) Is ""Learning"" episodic memory? Distinct cognitive and neuroanatomic correlates of immediate recall during learning trials in neurologically normal aging and neurodegenerative cohorts. Neuropsychologia 102:19-28|
|Yokoyama, Jennifer S; Marx, Gabe; Brown, Jesse A et al. (2017) Systemic klotho is associated with KLOTHO variation and predicts intrinsic cortical connectivity in healthy human aging. Brain Imaging Behav 11:391-400|
|Alioto, Andrea G; Kramer, Joel H; Borish, Sarah et al. (2017) Long-term test-retest reliability of the California Verbal Learning Test - second edition. Clin Neuropsychol 31:1449-1458|
|Parthasarathy, Vishnu; Frazier, Darvis T; Bettcher, Brianne M et al. (2017) Triglycerides are negatively correlated with cognitive function in nondemented aging adults. Neuropsychology 31:682-688|
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