Helmet T Karim1, Dana L Tudorascu2, Ann Cohen1, Julie C Price3, Brian Lopresti4, Chester Mathis4, William Klunk5, Beth E Snitz6, Howard J Aizenstein7. 1. Department of Psychiatry (HTK, DLT, AC, HJA), University of Pittsburgh, Pittsburgh, PA. 2. Department of Psychiatry (HTK, DLT, AC, HJA), University of Pittsburgh, Pittsburgh, PA; Department of Internal Medicine (DLT), University of Pittsburgh, Pittsburgh, PA; Department of Biostatistics (DLT), University of Pittsburgh, Pittsburgh, PA. 3. Department of Radiology (JCP), Massachusetts General Hospital, Boston, MA. 4. Department of Radiology (BL, CM, WK), University of Pittsburgh, Pittsburgh, PA. 5. Department of Radiology (BL, CM, WK), University of Pittsburgh, Pittsburgh, PA; Department of Neurology (WK, BES), University of Pittsburgh, Pittsburgh, PA. 6. Department of Neurology (WK, BES), University of Pittsburgh, Pittsburgh, PA. 7. Department of Psychiatry (HTK, DLT, AC, HJA), University of Pittsburgh, Pittsburgh, PA; Department of Bioengineering (HJA), University of Pittsburgh, Pittsburgh, PA. Electronic address: aizen@pitt.edu.
Abstract
INTRODUCTION: In cognitively healthy older adults, amyloid-beta (Aβ) burden is associated with greater activity on task-based functional magnetic resonance imaging. Higher levels of functional activation are associated with other factors along with amyloid and the authors investigated these relationships as well as how they relate to Aβ in cognitively healthy older adults. METHODS: The authors recruited cognitive healthy older adults (N = 50) from the Pittsburgh community that underwent extensive cognitive batteries, activation during a working memory (digit symbol substitution task, DSST), positron emission tomography scan for Pittsburgh Compound B (PiB, measuring amyloid), and other demographic measures. The authors tested the association between DSST activation and global PiB, neurocognitive batteries, and education. RESULTS: The authors found that the DSST robustly activated expected structures involved in working memory. The authors found that greater global Aβ deposition was associated with greater DSST activation in the right calcarine, precuneus, middle temporal as well as the left insula and inferior frontal gyrus. The authors also found that greater education was associated with lower DSST activation - however this was not significant after adjusting for Aβ. DISCUSSION: Greater amyloid was associated with greater activation, which may represent compensatory activation. Greater education was associated with lower activation, which may represent more efficient activation (i.e., less activation for the same task). After adjusting for amyloid, education was not significantly associated with activation suggesting that during the preclinical stage amyloid is the primary determinant of activation. Further, activation was not associated with cognitive function. Compensatory activation in the preclinical stage may help maintain cognitive function.
INTRODUCTION: In cognitively healthy older adults, amyloid-beta (Aβ) burden is associated with greater activity on task-based functional magnetic resonance imaging. Higher levels of functional activation are associated with other factors along with amyloid and the authors investigated these relationships as well as how they relate to Aβ in cognitively healthy older adults. METHODS: The authors recruited cognitive healthy older adults (N = 50) from the Pittsburgh community that underwent extensive cognitive batteries, activation during a working memory (digit symbol substitution task, DSST), positron emission tomography scan for Pittsburgh Compound B (PiB, measuring amyloid), and other demographic measures. The authors tested the association between DSST activation and global PiB, neurocognitive batteries, and education. RESULTS: The authors found that the DSST robustly activated expected structures involved in working memory. The authors found that greater global Aβ deposition was associated with greater DSST activation in the right calcarine, precuneus, middle temporal as well as the left insula and inferior frontal gyrus. The authors also found that greater education was associated with lower DSST activation - however this was not significant after adjusting for Aβ. DISCUSSION: Greater amyloid was associated with greater activation, which may represent compensatory activation. Greater education was associated with lower activation, which may represent more efficient activation (i.e., less activation for the same task). After adjusting for amyloid, education was not significantly associated with activation suggesting that during the preclinical stage amyloid is the primary determinant of activation. Further, activation was not associated with cognitive function. Compensatory activation in the preclinical stage may help maintain cognitive function.
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