Cholecystokinin (CCK) is a satiety hormone that is highly expressed in brain regions like the hippocampus. CCK is integral for maintaining or enhancing memory, and thus may be a useful marker of cognitive and neural integrity in participants with normal cognition, mild cognitive mpairment (MCI), and Alzheimer's disease (AD). CSF CCK levels were examined in 287 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Linear or voxel-wise regression was used to examine associations between CCK, regional gray matter (GM), CSF AD biomarkers, and cognitive outcomes. Briefly, higher CCK was related to a decreased likelihood of having MCI or AD, better global and memory scores, and more GM volume primarily spanning posterior cingulate cortex, parahippocampal gyrus, and medial prefrontal cortex. CSF CCK was also strongly related to higher CSF total tau (R2=0.339) and p-tau181 (R2=0.240), but not Aβ1-42. Tau levels partially mediated CCK and cognition associations. In conclusion, CCK levels may reflect compensatory protection as AD pathology progresses.
Background: Fluid intelligence (FI) involves abstract problem-solving without prior knowledge. Greater age-related FI decline increases Alzheimer’s disease (AD) risk, and recent studies suggest that certain dietary regimens may influence rates of decline. However, it is uncertain how long-term food consumption affects FI among adults with or without familial history of AD (FH) or APOE4 (ɛ4). Objective: Observe how the total diet is associated with long-term cognition among mid- to late-life populations at-risk and not-at-risk for AD. Methods: Among 1,787 mid-to-late-aged adult UK Biobank participants, 10-year FI trajectories were modeled and regressed onto the total diet based on self-reported intake of 49 whole foods from a Food Frequency Questionnaire (FFQ). Results: Daily cheese intake strongly predicted better FIT scores over time (FH-: β= 0.207, p < 0.001; ɛ4–: β= 0.073, p = 0.008; ɛ4+: β= 0.162, p = 0.001). Alcohol of any type daily also appeared beneficial (ɛ4+: β= 0.101, p = 0.022) and red wine was sometimes additionally protective (FH+: β= 0.100, p = 0.014; ɛ4–: β= 0.59, p = 0.039). Consuming lamb weekly was associated with improved outcomes (FH-: β= 0.066, p = 0.008; ɛ4+: β= 0.097, p = 0.044). Among at risk groups, added salt correlated with decreased performance (FH+: β= –0.114, p = 0.004; ɛ4+: β= –0.121, p = 0.009). Conclusion: Modifying meal plans may help minimize cognitive decline. We observed that added salt may put at-risk individuals at greater risk, but did not observe similar interactions among FH- and AD- individuals. Observations further suggest in risk status-dependent manners that adding cheese and red wine to the diet daily, and lamb on a weekly basis, may also improve long-term cognitive outcomes.
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