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P1‐484: CHOLECYSTOKININ INCREASES GRAY MATTER AND GLUCOSE UPTAKE IN THE BRAIN, LEADING TO INCREASED COGNITIVE FUNCTION, BUT IS CORRELATED WITH AN ACCUMULATION OF TAU AND PTAU FORMATIONS
Author(s) -
Plagman Alexandra K.,
McLimans Kelsey E.,
Klinedinst Brandon Skylar,
Willette Auriel A.
Publication year - 2018
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.06.494
Subject(s) - cholecystokinin , medicine , endocrinology , parahippocampal gyrus , effects of sleep deprivation on cognitive performance , cerebrospinal fluid , hippocampus , alzheimer's disease neuroimaging initiative , psychology , voxel , dentate gyrus , cognition , neuroscience , oncology , chemistry , disease , cognitive impairment , receptor , temporal lobe , epilepsy , radiology
Background:Cholecystokinin (CCK) is a satiety hormone, released in the small intestines by the pancreas, but also found in substantial amounts in memory regions of the brain. CCK is highly expressed in the hippocampus, which is adversely affected in patients with Alzheimer’s Disease (AD). CCK may show protective associations for people with AD. Methods:CCK levels were studied in cerebrospinal fluid (CSF) in 303 subjects across the AD spectrum from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Voxel-wise regression was used to gauge CCK and regional GM and glucose metabolism associations. Levels were associated with biomarker and cognitive outcomes. Results: Per point increase in CCK, there was a 65% decreased in likelihood of being diagnosed with AD compared to cognitively normal (CN) or mild cognitive impairment (MCI). Higher CSF CCK was related to more GM in a large cluster of voxels (k1⁄413,036) primarily spanning the parahippocampal gyrus. CSF CCK was not associated with Ab1-42. However, higher levels of CCK were related to higher expression of tau (b6SE 1⁄4 37.85764.799, F1⁄462.237, p<0.001) and p-tau181 (b6SE 1⁄4 10.04661.630, F1⁄437.992, p<0.001). Higher CCK predicted better CDR-sob, ADAS-cog11, MMSE, and memory factor scores. Conclusions: Higher levels of CCK predicted better cognitive outcomes and more gray matter in memory-specific regions, yet were also related to more tau species deposition. These conflicting results may be explained by the role of CCK acting as a protectant against AD. We propose that as the disease is progressing, CCK levels increase in efforts to protect against further damage.