Diet and Dementia - A New Study

Alrighty.  You might have noticed I've slowed down on the blogging a tad this month.  Well, there's sunshine and vitamin D to collect, and lots of social engagements (here in the Northeast U.S. we seem to do everything for the whole year in the summer).  Also, ever since I started doing crossfit, I have needed more time to admire myself in the mirror (see Melissa's comment).

Today's music is on the… cheesy classical side.  I'm feeling a little Spanish summer on the Mediterranean right now.  Just go with it (as always, right click in new tab): Concerto De Aranjuez Adagio.  

Paleoland events:  Turns out I'm the blog of the week at Latest In Paleo!  Also, "fantastic."  (Surely you jest, I mean, really?  Tell me more…thanks Angelo!)   AND very excited that  next week I will join the ranks of Stephan Guyenet, Kurt Harris, and Chris Masterjohn to participate in a Healthy Skeptic Podcast with Chris Kresser and Danny Roddy.  Chris asks me to ask you if you have any questions for me.  You can post them here on my blog, or if the Blogger comment system is too much of a deterrent (you are not the first - 20/20 hindsight would lead me to Wordpress…), then I'm told Chris is also going to post and you can ask a question over there.  If there is something I can't answer, I will surely dodge or turn it around on you just like any practiced therapist.

Now, the Science.  A new paper came out in the JAMA Archives of Neurology.  The Archives are always going to be pretty much a first tier journal in any specialty, and it is important to keep abreast of them.

Here's the paper:  Diet Intervention and Cerebrospinal Fluid Biomarkers in Amnestic Mild Cognitive Impairment.

The design:  20 healthy 69 y/os and 29 68 y/os with amnestic-type mild cognitive impairment were randomized to either a HIGH diet or an isocaloric LOW diet for four weeks.  The HIGH diet was 45% fat (25% saturated fat), 35-40% high glycemic carbohydrates, and 15-20% protein.  The LOW diet was 25% fat (7% saturated fat), 55-60% carbohydrate, and 15-20% protein.  The diets were designed by a nutritionist and the food was delivered twice weekly to the participants.  There is no more information about the diets, but I have emailed the corresponding author to ask for more details (um, were the deliveries kinda like Jenny Craig mirowaveable meals or whole food?  Is it sugar or starch?  Is the saturated fat animal fat, coconut oil?  What about the trans fats? You know, all those gory but vitally important details.)  All participants were free of major psychiatric or neurologic disorders other than mild cognitive impairment, and were free of kidney disease, diabetes, COPD, cardiac disease, alcoholism, and no one was on cholesterol-lowering medication (where did they find these 68 year/olds not on statins? Oh, Seattle.)

I quote: "The length of time participants consumed the HIGH diet was restricted due to safety considerations." My goodness!  Safety considerations!  What were they giving them?  Surely not something so horrific as coconut cream or steak… well, thus far we don't know what they were giving them.  I mean, I have to give the researchers huge kudos for examining diet and the brain at all!  But let's have a look at the results, shall we?

The participants received cognitive testing, oral glucose tolerance testing, blood collection, and a lumbar puncture before and in the fourth week of the diet.  Insulin, glucose, and blood lipids were measured, as well as CSF amyloid beta protein (a couple of types), tau protein, apolipoprotein E, and F2-isoprostanes (omega-6 derived marker of inflammation and oxidative stress).

Okay.  So the HIGH diet increased insulin resistance (measured as insulin area under the curve, which is nice), and the LOW diet decreased it (far more so in the healthy controls than the mild cognitive impairment folks, which is interesting).  On the HIGH diet, LDL went up by 20 points in the MCI patients and less than 10 points in the healthy controls.  LDL dropped 20 points on the LOW diet  in MCI folks and 15 points in the controls.  Not surprisingly, HDL went down on the LOW diet (by 4 points in controls and 8 points in MCIs) and up on the HIGH diet (about 4 points for both).   For some weird reason, the researchers used LDL/HDL ratio instead of the more standard total cholesterol/HDL ratio, and that went down in the LOW folks and up in the HIGH folks.

With respect to cognitive testing, everything was a wash except some mild improvement in "delayed visual memory" scores that were better on the LOW group than in the HIGH group.

In controls, CSF amyloid protein went down on the LOW group and up in the HIGH group.  In the MCI folks, amyloid went up in the LOW group (which would fit the general model that amyloid beta is a last ditch desperate substitute for cholesterol in those with a dementing process going on) and remained the same in the HIGH group (the authors interpreted this as pathology was already advanced in the MCI group so dietary interventions couldn't make it much worse).  CSF ApoE in controls stayed the same in the control LOW group and increase in the MCI group (again - ApoE drags cholesterol into the brain - likely to increase on a low fat diet if the brain is fat-starved) - ApoE went down in both control and MCI groups on the HIGH diet (the authors considered this to be a bad sign for the HIGH diet.  I'm not so sure.  If you need more ApoE, the inefficient ApoE4 will be found wanting…)  CSF insulin dropped in the controls on the LOW and HIGH diets - in the MCI folks insulin increased on the LOW and stayed the same on the HIGH.  Since low CSF insulin is associated with Alzheimer's, the researchers considered low insulin bad.  F2-Isoprostanes decreased in both groups on the LOW diet and increased in controls on the HIGH diet (but not in MCI folks).

Yeah. I don't know what to make of it either.  The authors seemed to think it was a ringing endorsement for the LOW diet.  "For healthy adults, the HIGH diet moved CSF biomarkers in a direction that may characterize a presymptomatic stage of [Alzheimer's disease]… the AD biomarkers were unaffected by the HIGH diet for adults with [mild cognitive impairment], possibly because more extreme intervention is needed to exacerbate already-exant pathologic processes."  And, shucks, if the HIGH diet was all industrially-fried pork rinds and chocolate cake with hydrogenated frosting, I wouldn't doubt it.

We'll see if more information comes from my email (I hope so!).  Otherwise, I think this study serves as another example to show that diet is important, but that research is pointed in the direction of macronutrients rather than the quality of the food, thus we can't really make useful conclusions.

(This paper also states that cholesterol does not cross the blood brain barrier in a healthy brain - Seneff et al suggest that transcytosis of LDL across the BBB is conclusively proven in this paper.)