A Fascinating Lecture

I have been on the East Coast for a while, and I've been trying to catch up on a lot of stuff.  But something came up in the AD world yesterday that I want to share.

On July 27, 2019, UC San Francisco uploaded the video of a lecture from April 30, 2019.  Click here.  The core of the video was a presentation by Dr. Geroges Naasan, a neurologist at the UCSF Memory and Aging Center.  The title was Diagnosing Alzheimer's Disease. Much of the focus was on biomarkers used to diagnose AD, which required considerable knowledge of the brain and AD to understand them.  Some of what he presented was the result of very recent research.

It runs an hour and a half, but, depending on your interest, it may be worth your while.  I learned a lot, and it changed my understanding of several things.

Recall that the diagnosis of AD begins with measurement of memory/ cognition loss, but you can't conclude anything about the cause of the loss without looking at biomarkers.  The three biomarkers he discussed in the lecture were analysis of cerebrospinal fluid, PET scans, and MRI scans.

Something new I learned was that science has identified four different clinical syndromes that define how the disease will first be expressed.  It is not clear whether all will express as a case of the disease progresses to its end.  MRIs show that different parts of the brain are atrophying with the different syndromes.  They are:

• Memory syndrome.  This is our most familiar, but it is not universal, at least at the outset of the disease.  Learning and short term memory are impaired.

• Language syndrome.  This manifests as someone forgetting words and substituting other words that sound similar.  They showed a video of an interview with someone with this form of the disease in which the subject used words that sounded like the word he wanted to use but conveyed different meaning.  He seemed unaware he was substituting words.

• Visual syndrome.  He said that the eye can be considered an extension of the brain (my very bright ophthalmologist would agree), and symptoms of AD can express in changes in vision -- changes in the processing of information gathered through vision.  His description led me to believe this may explain the problem I had with driving in 2015 and early 2016.  I would look to see if there was a car or pedestrian where I wanted to go, but I would not see them.  (Fortunately nothing like this has recurred.)  I wonder if this explains the correlation of glaucoma with AD.   

• Frontal syndrome.  This involves atrophy of the prefrontal cortex (a feature of the brain peculiar to primates) which does a lot of things for humans.  Most notable for our purposes is its role in executive function.  Executive function is what orders your behavior.  Erosion of executive function may be reflected in inappropriate social behavior.  The distinction from frontal-temporal dementia (not usually considered AD) is ambiguous. 

One thing we discussed in an earlier post that he reinforced is that there can be a considerable increase in beta amyloid in the brain without obvious behavioral expression of the disease.  However, an abrupt increase in tau protein is almost always accompanied by measurable cognitive decline.

I had always read that elevated beta amyloid in cerebrospinal fluid is a biomarker for AD.  (Why I got a spinal tap during the insulin study.)  But they said that the biomarker is a decrease in amyloid in CSF because amyloids are being retained in the brain to form plaques.

Of course, the final diagnosis of AD is normally in the autopsy, but (as we said in Beating the Dementia Monster) very, very rarely a biopsy of brain tissue from a living subject may be performed.

Only humans develop AD.  Dogs may accumulate some beta amyloid, but there is no progress of dementia.  Rodents are studied when their genes have been edited to unnaturally develop a disorder that is an analog for AD.

I had (correctly) understood that PET scans are used to image the metabolism of glucose in the brain.  What I didn't know is that different tracers can be used to separately image tau protein and beta amyloid.   

I'm going to watch it again and see what I might have missed the first time.