Tuesday, May 6, 2014

Brain Atrophy in Cushing's Disease (Cognitive and Emotional changes on the brain)

"Brain Atrophy" is a scary term, right?  But I do use it.  When I say my memory is mush, or I get confused, can't remember things, can't focus, etc...I actually mean it!  It doesn't make me feel any better to know you forget names too.  ;)  I forget things like my own age, social security number, the age of my children (all of them at the same time), can't look from a phone book to the phone and remember a number, etc.  And if I get interrupted mid-sentence/story/thought, it's just gone...It won't come back for a good 5-50 minutes, so don't bother asking what I was saying!  I can't concentrate well enough to play simple songs on the piano or to even read a "for fun" book sometimes (when I used to play complicated pieces and read medical studies), can't concentrate well enough to feel safe driving (even in "Nowhere, Alaska"), and when I try to look at my options and think things through logically, I miss big, obvious things that someone else has to point out to me.  I say the wrong word ALL the time (Like "kitchen" instead of "bathroom" --my poor kids and husband!) and cannot be trusted to order food or make travel reservations alone because I mess things up royally.  It is a constant, ongoing problem...and I'm 33, not 66.


So when someone, presumably in an effort to make me feel better, won't allow that I do indeed have a real problem, it is actually irritating and I'll throw that term out there.  My body metabolizes bones and muscle, AND it shrinks my brain.  I WIN!  HA HA HA!  Oh....wait.  I am glad to be corrected when I make an obvious mistake, but PLEASE do it nicely.  It is hard enough living with the staggering effects of this disease all on it's own, I don't need it thrown in my face and laughed at too (Yes, this applies to you too, grammar Nazi's!  You know who you are!).  Forgive me if I cannot find the humor in it at times; I bet you'd find it hard too.  I do my best, but public humiliation shouldn't be expected to be funny to the person being humiliated.


Moving on to the medical side, here are some good excerpts from the article/study linked below:



"Cushing's disease is associated with brain atrophy and cognitive deficits. Excess glucocorticoids cause retraction and simplification of dendrites in the hippocampus, and this morphological change probably accounts for the hippocampal volume loss. Mechanisms by which glucocorticoids affect the brain include decreased neurogenesis and synthesis of neurotrophic factors, impaired glucose utilization, and increased actions of excitatory amino acids. In this review, the timing, pathology, and pathophysiology of the brain atrophy in Cushing's disease are discussed. The correlation of atrophy with cognitive deficits and its reversibility is also reviewed."


It makes real, visible changes in our brains.  Isn't THAT a comforting thought!  (Can you read my sarcasm?)  A friend and I were just discussing whether there was a possibility for this to help in faster diagnosis times.  Heaven knows we need that!


"Cognitive impairments are common in patients with Cushing's disease and are correlated with elevated cortisol levels. Starkman and coworkers[22] found cognitive deficits in several domains in patients with Cushing's disease, including verbal intellectual skills, learning, and memory. The largest decline in cognitive function in this study was found in measures of the verbal intelligence quotient and verbal learning and recall. These impairments are consistent with the clinical cognitive complaints reported by patients with Cushing's disease.[24] In contrast to dementia, delirium, and aging, which show increased vulnerability across visuospatial measures, verbal functions are most prominently affected in Cushing's disease. The deficits in verbal intellectual skills suggest involvement of the neocortex, whereas the impairments in verbal learning and recall are consistent with the increasingly accepted view that the hippocampus is especially vulnerable to the effects of glucocorticoids.[17,22,27,29]"


It's not just me!  And it is interesting to find that it is different in its presentation for Cushing's than for other causes of mental deficits.


"These data highlight the fact that the effects of glucocorticoids are not limited to the hippocampus-atrophy has been documented in the prefrontal cortex and other cortical areas.[1,12] It is also entirely possible that glucocorticoids affect specific areas of the brain differently. For example, in contrast to the dendritic atrophy observed in the hippocampus and prefrontal cortex, glucocorticoids increase dendritic growth in the amygdala.[12] "


Did you just read that?!?  So all those emotional changes that we blame on hormones alone, REALLY also are due to changes in the brain caused by the initial excess of cortisol (and the whole cascade of issues that stems from that --because really, all the hormones get thrown out of balance).  Can you think or fee" differently than your brain is wired to think and feel?  Recognizing the source could help dampen the effects thoughts and emotions can have on our lives, but we cannot simply chose to not think or feel that way, nor can we be expected to gain mastery over it.


"Primate studies using exogenous glucocorticoids show that hippocampal changes are present within 1 year of glucocorticoid exposure. Because of the often insidious onset of symptoms in Cushing's disease, no specific data on exposure duration and brain atrophy are available. Clinical investigations of exogenous glucocorticoid therapy show an exposure duration of as short as 2 to 6 months before changes in the brain and hippocampus are detected.[5,21] Cerebral cortical atrophy has been reported within 6 months of glucocorticoid exposure, even in children.[21] ...For example, Newcomer and colleagues[15] found deficits in verbal declarative memory after 4 days of cortisol exposure..."


Wow.  Seriously?  4 days to 6 months is all that is needed to make obvious changes to the brain.  No wonder it has gotten progressively worse over the past ?17? years...but most drastically in the past 3-4.  But don't worry, there IS some good news:


"Cerebral atrophy has been shown to be reversible in patients with Cushing's disease.[8] Following resection of adrenocorticotropin hormone-secreting pituitary adenomas, hippocampal formation volume has been shown to increase by as much as 10%.[23] The increase in hippocampal formation volume correlates with the magnitude of decrease in urinary free cortisol. In addition, improvements in memory correlate with decreases in cortisol levels as well as with increases in hippocampal formation volume.[9] Age has been identified as a significant factor that influences the speed of recovery. Younger patients regain and sustain their improvement in cognitive functioning more quickly than older subjects. These findings suggest that at least some of the deleterious effects of prolonged hyper-cortisolemia on cognitive functioning and hippocampal volume are reversible."

So, their findings suggest it can in fact be reversed, at least in part...and that it happens faster with younger patients.  I think we knew that anecdotally (that the young recovery from this disease faster, in general, than the old).  I'm hoping I hit cure/remission while young enough to recover on the quicker side...of course, I've also read articles stating that length of illness plays a large role in it as well.  But honestly, I'll take any improvement I can get and be happy for it! 


http://www.medscape.com/viewarticle/566312

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