A new study below [1].
I think that a lot of men on ADT are concerned about the impact on brain function. Is the decline permanent?
One of the problems with ADT is the emergence or worsening of symptoms of the metabolic syndrome. Many men develop a pre-diabetic condition, if not type 2 diabetes itself. Certainly insulin resistance.
There are over 400 papers on PubMed for <Alzheimer's[title] diabetes[title]>. This is from one in April [2]:
"The brain is an organ in which energy metabolism occurs most intensively and glucose is an essential and dominant energy substrate. There have been many studies in recent years suggesting a close relationship between type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) as they have many pathophysiological features in common. The condition of hyperglycemia exposes brain cells to the detrimental effects of glucose, increasing protein glycation and is the cause of different non-psychiatric complications. Numerous observational studies show that not only hyperglycemia but also blood glucose levels near lower fasting limits (72 to 99 mg/dL) increase the incidence of AD, regardless of whether T2DM will develop in the future. As the comorbidity of these diseases and earlier development of AD in T2DM sufferers exist, new AD biomarkers are being sought for etiopathogenetic changes associated with early neurodegenerative processes as a result of carbohydrate disorders." [2]
From the new paper:
"Large-scale life span neuroimaging datasets show functional communication between brain regions destabilizes with age, typically starting in the late 40s, and that destabilization correlates with poorer cognition and accelerates with insulin resistance. Targeted experiments show that this biomarker for brain aging is reliably modulated with consumption of different fuel sources: Glucose decreases, and ketones increase the stability of brain networks." [1]
...
"Our data provide evidence that, starting at around the age of 47 y, the stability of brain networks begins to degrade with age, with the most dramatic changes occurring around the age of 60 y. Since glucose hypometabolism remains one of the hallmark clinical features of dementia and its prodrome, we hypothesized that the network destabilization seen with aging might reflect the earliest stages of latent metabolic stress. Thus, we tested whether diets with different energetic yield might modulate network stability even in a younger population expected to be decades prior to any overt symptoms of age-based cognitive impairment. While glucose is normally considered to be the brain’s default fuel, β-hydroxybutyrate metabolism increases by 27% the Gibbs free energy change for ATP compared to glucose. Consistent with that advantage, our results showed that even in younger (<50 y) adults, dietary ketosis increased overall brain activity and stabilized functional networks."
***
In previous posts, I have discussed the paradox in PCa that elevated glucose levels do not increase the risk of PCa, but elevated insulin does. Diabetics (poor glucose control) have a lower risk of PCa once the pancreatic beta cells that produce insulin begin to burn out.
Many of us have some degree of insulin resistance at diagnosis. The body responds by producing higher levels of insulin (akin to talking louder to a deaf person).
A Mediterranean diet (40% fat) has been proven to be heart-healthy (another concern of PCa patients, who have a higher rate of cardio events even without ADT). And now it seems that low-fat / high-carb diets are to be avoided, due to the physical deterioration that results in cognitive decline.
{Skim through the full paper, there are lots of interesting bits.)
-Patrick
CRPC - causes and prevention of 
