The Cortisol Hypothesis, which is the basis for Xanamem, is very strongly supported in this recent longitudinal research conducted on people without any initial dementia diagnosis. The FACT that damage to the brain and to certain cognitive functions is directly associated with elevated cortisol levels in a sample population informs me that some efficacy of Xanamem is likely to be present across the battery of cognitive tests for a mild alzheimers population. We still have to recognize the chicken vs egg ambiguity of not knowing whether cortisol elevation is a direct or indirect causal factor or is it a non-active side effect of some other processes. We will soon find out more when the results are released. Dr. Bill and others have referenced this study before.
I suspect Actinogen is on to something big and I suggest there is no other AD pipeline drug with its potential.
REPORTED OCTOBER 24, 2018
Circulating cortisol and cognitive and structural brain measures
Objective To assess the association of early morning serum cortisol with cognitive performance and brainstructural integrity in community-dwelling young and middle-aged adults without dementia.
Methods: We evaluated dementia-free Framingham Heart Study (generation 3) participants (mean age48.5 years, 46.8% men) who underwent cognitive testing for memory, abstract reasoning, visualperception, attention, and executive function (n = 2,231) and brain MRI (n = 2018) to assesstotal white matter, lobar gray matter, and white matter hyperintensity volumes and fractionalanisotropy (FA) measures. We used linear and logistic regression to assess the relations ofcortisol (categorized in tertiles, with the middle tertile as referent) to measures of cognition,MRI volumes, presence of covert brain infarcts and cerebral microbleeds, and voxel-basedmicrostructural white matter integrity and gray matter density, adjusting for age, sex, APOE, andvascular risk factors.
Results: Higher cortisol (highest tertile vs middle tertile) was associated with worse memory and visualperception, as well as lower total cerebral brain and occipital and frontal lobar gray mattervolumes. Higher cortisol was associated with multiple areas of microstructural changes(decreased regional FA), especially in the splenium of corpus callosum and the posterior coronaradiata. The association of cortisol with total cerebral brain volume varied by sex (p forinteraction = 0.048); higher cortisol was inversely associated with cerebral brain volume inwomen (p = 0.001) but not in men (p = 0.717). There was no effect modification by the APOE4genotype of the relations of cortisol and cognition or imaging traits.
Conclusion: Higher serum cortisol was associated with lower brain volumes and impaired memory inasymptomatic younger to middle-aged adults, with the association being evident particularly inwomen. Correspondence Dr.
[email protected] [email protected] Discussion: Our findings suggest that middle-aged and young–to–middle-aged adults in their 40s with higher serum cortisol concentrations (highest tertile) perform worse on tasks ofvisual perception, executive function, and attention and haveless gray matter (total and regional) compared to personswith moderate cortisol levels (middle tertile), with womenbeing potentially more susceptible to the influence of gluco-corticoids. Blood cortisol concentration was also associatedwith structural changes in white matter integrity. The circulating cortisol and cognitive and structural brain measures association of cortisol and cognitive functioning was in thesame direction as for the brain volumes. Our findings areconsistent with the concept that increasing levels of circulat-ing glucocorticoids are associated with worse cognitivefunctioning.
We observed that high levels of cortisol are associated withmicrostructural white matter injury in several tracts, particu-larly the corpus callosum, which has also been reported to beassociated with cortisol in other studies.13 Our findings alsoextend observations from prior studies on the association ofcortisol and white matter tracts,13 which are scarce and limitedby their small size and, for some, restricted to clinical settingswith the inclusion of individuals with extreme phenotypes ofcortisol42,43 or with depression.44 White matter integrity issignificantly associated with processing speed, which in turn isstrongly associated with higher general cognitive ability.45Thus, disruption of information transfer by white matterdamage could partially explain the impairments to cognitiveability associated with higher cortisol concentrations observedin our study. We did not observe any association of bloodcortisol levels and WMH. This may simply be related to thefact that WMH could be the final stage of progressive whitematter degeneration,29 a process that may not be sufficientlyadvanced in middle-aged individuals.
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