Browsing by Author "Santulli, Robert B."

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    Cholinergic Enhancement of Brain Activation in Mild Cognitive Impairment during Episodic Memory Encoding
    (Frontiers Media, 2013-09-17) Risacher, Shannon L.; Wang, Yang; Wishart, Heather A.; Rabin, Laura A.; Flashman, Laura A.; McDonald, Brenna C.; West, John D.; Santulli, Robert B.; Saykin, Andrew J.; Radiology and Imaging Sciences, School of Medicine
    Objective: To determine the physiological impact of treatment with donepezil (Aricept) on neural circuitry supporting episodic memory encoding in patients with amnestic mild cognitive impairment (MCI) using functional magnetic resonance imaging (fMRI). Methods: Eighteen patients with MCI and 20 age-matched healthy controls (HC) were scanned twice while performing an event-related verbal episodic encoding task. MCI participants were scanned before treatment and after approximately 3 months on donepezil; HC were untreated but rescanned at the same interval. Voxel-level analyses assessed treatment effects on activation profiles in MCI patients relative to retest changes in non-treated HC. Changes in task-related connectivity in medial temporal circuitry were also evaluated, as were associations between brain activation, task-related functional connectivity, task performance, and clinical measures of cognition. Results: At baseline, the MCI group showed reduced activation during encoding relative to HC in the right medial temporal lobe (MTL; hippocampal/parahippocampal) and additional regions, as well as attenuated task-related deactivation, relative to rest, in a medial parietal lobe cluster. After treatment, the MCI group showed normalized MTL activation and improved parietal deactivation. These changes were associated with cognitive performance. After treatment, the MCI group also demonstrated increased task-related functional connectivity from the right MTL cluster seed region to a network of other sites including the basal nucleus/caudate and bilateral frontal lobes. Increased functional connectivity was associated with improved task performance. Conclusion: Pharmacologic enhancement of cholinergic function in amnestic MCI is associated with changes in brain activation and functional connectivity during episodic memory processing which are in turn related to increased cognitive performance. fMRI is a promising biomarker for assessing treatment related changes in brain function.
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    Judgment in Older Adults with Normal Cognition, Cognitive Complaints, MCI, and Mild AD: Relation to Regional Frontal Gray Matter
    (Springer Nature, 2009) Rabin, Laura A.; Saykin, Andrew J.; West, John D.; Borgos, Marlana J.; Wishart, Heather A.; Nutter-Upham, Katherine E.; Flashman, Laura A.; Santulli, Robert B.; Radiology and Imaging Sciences, School of Medicine
    We investigated regional gray matter (GM) reduction as a predictor of judgment ability in 120 non-depressed older adults with varying degrees of cognitive complaints and/or impairment (including those with MCI and mild AD). Participants underwent neuropsychological assessment, including the Test of Practical Judgment (TOP-J), a recently developed instrument that evaluates judgment and problem solving related to safety, medical, social/ethical, and financial issues. Structural MR scanning included T1-weighted SPGR volumes acquired at 1.5 Tesla. We used voxel-based morphometry to analyze the relationship between GM density and TOP-J scores, controlling for age, education, gender, intracranial volume, verbal memory, and crystallized knowledge. Consistent with our hypothesis, judgment ability correlated with GM density in prefrontal regions (left inferior and superior frontal gyri). Findings extend previous observations of frontal involvement in higher-order cognitive abilities/executive functions and provide initial validation of the TOP-J's sensitivity to the integrity of these brain regions in individuals at risk for dementia.
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    Visual contrast sensitivity in Alzheimer's disease, mild cognitive impairment, and older adults with cognitive complaints
    (Elsevier, 2013) Risacher, Shannon L.; WuDunn, Darrell; Pepin, Susan M.; MaGee, Tamiko R.; McDonald, Brenna C.; Flashman, Laura A.; Wishart, Heather A.; Pixley, Heather S.; Rabin, Laura A.; Paré, Nadia; Englert, Jessica J.; Schwartz, Eben; Curtain, Joshua R.; West, John D.; O’Neill, Darren P.; Santulli, Robert B.; Newman, Richard W.; Saykin, Andrew J.; Radiology and Imaging Sciences, School of Medicine
    Deficits in contrast sensitivity (CS) have been reported in Alzheimer's disease (AD). However, the extent of these deficits in prodromal AD stages, including mild cognitive impairment (MCI) or even earlier, has not been investigated. In this study, CS was assessed using frequency doubling technology in older adults with AD (n = 10), amnestic MCI (n = 28), cognitive complaints without performance deficits (CC; n = 20), and healthy controls (HC; n = 29). The association between CS and cognition was also evaluated. Finally, the accuracy of CS measures for classifying MCI versus HC was evaluated. CS deficits were found in AD and MCI, while CC showed intermediate performance between MCI and HC. Upper right visual field CS showed the most significant difference among groups. CS was also associated with cognitive performance. Finally, CS measures accurately classified MCI versus HC. The CS deficits in AD and MCI, and intermediate performance in CC, indicate that these measures are sensitive to early AD-associated changes. Therefore, frequency doubling technology-based measures of CS may have promise as a novel AD biomarker.