Alzheimer’s disease (AD) primarily affects older adults.
In this report, we present the case of a 19-year-old male with gradual memory decline for 2 years and World Health Organization-University of California Los Angeles Auditory Verbal Learning Test (WHO-UCLA AVLT) results also showing memory impairment.
Positron emission tomography-magnetic resonance imaging with 18F fluorodeoxyglucose revealed atrophy of the bilateral hippocampus and hypometabolism in the bilateral temporal lobe.
Examination of the patient’s cerebrospinal fluid showed an increased concentration of p-tau181 and a decreased amyloid-β 42/40 ratio.
However, through whole-genome sequencing, no known gene mutations were identified.
Considering the above, the patient was diagnosed with probable AD.
This is interesting for quite a few reasons. The one that sticks out first, and consistent with the theme of the sub, is that we have this well established construct (Alzheimer’s Disease), with billions of research dollars being poured into the treatment and prevention of it, and we don’t have a hard definition of what it actually is.
It’s one of those clear examples of a carry over definition based purely on subjective observations that we’ve twisted and contorted to make fit into a consistent physiological class.
Are there a significant number of people with hippocampal atrophy and high tangle ratios that don’t have dementia like symptoms? ABSOLUTELY, in fact like half of all people over 80. Are there people with pretty clear dementia symptoms without these biomarkers? Absolutely, in fact nearly every all trisomy fits this description past a certain age.
So here we are, still using “probable alzheimer’s” because we still can’t actually define it because it’s a holdover definition from a time before we understood physiology at all. And that definition is based on behavior rather than physiology, meaning there could be many different routes to the same behavior, or no “abnormal” route at all.
This is also pretty interesting in that if it is “Alzheimer’s” pathology, it decouples quite a few assumed etiological classes and leaves us with immunological and metabolic roots.
What’s personally interesting about this I regularly score between 24-26 on MoCA, and psychiatrists always have to override in the notes “no cognitive impairment”. I’ve always been kind of notorious for forgetting what I was saying right in the middle of a sentence, and literally having no short term memory for anything without an external prosthetic.
The whole list of words, distraction, repeat words portion for example? I absolutely will not remember any of them even if I make a concerted effort to store them during the distraction if the distraction is long enough. I suppose the only real difference is that I have zero confidence that I’m correctly repeating back the words, which is apparently unusual for this level of wrongness.
As a teen I used to get constantly scolded for having “xxx iq but can’t remember to tie your shoes”. If I personally never had the opportunity to engage in more complex cognitive tasks, I likely would be completely indistinguishable from any other “level 2/3 autism” individual at that age.
So when I see stuff like this, where assumptions about function are based on arbitrary descriptors it gives me pause. It makes me wonder how much of the negative effect of dementia revolves around how we train ourselves and treat these conditions.
It makes me wonder why it’s still impossible to look at imaging and determine which are experiencing dementia and which are not based on the imaging alone. It makes me wonder why there are some 80 year olds with completely blown out ventricles that still have very good memory and “executive function”.
More than anything, it makes me wonder if we should be approaching this problem from a completely different direction, one which requires a redefinition of our assumptions about brain functions.
I spent a lot of time a few months ago reading about the experiences of individuals and families of individuals in memory care, and a few really distinct classes of experiences popped out. And from that, along the lines of dorsal vs. ventral mechanics, there seemed to be two major classes of experience.
The first were individuals who no longer had any prior context at all, they could not remember anything at all past a certain recency threshold. They were able to somewhat adaptively function, despite not really understanding the circumstances around them.
The second class seem to be individuals who have a really strong set of memories, particularly contextual memories, that degrade the more recent they are (essentially as metabolic disruption started making hippocampal stream writes less efficient). These are the ones that don’t seem to have a clue where they are, but are able to “create” an external world around them based on prior context.
Further, these two major sub classes generally have nearly intact salience until degeneration gets too acute (at which point they die pretty soon afterward). This suggests that we might be able to describe dementia as degraded valence, rather than being about “memory” itself.
It also gives a clear separation between “psychiatric” descriptions which have dementia like behavior, “imbalanced” valence vs. “degraded” valence because degraded valence can create an imbalance, resulting in overlapping symptoms.
For example, “Major Depressive Disorder” often shows up as indistinguishable from mild cognitive impairment on most scales. This may be because MDD is usually a dorsal stream nuke, a metabolic slowdown/shutdown of dorsal stream mechanics.
There’s been some success using stimulation to enhance cognitive performance in dementia patients, of nearly exactly the same type and effect as those with MDD. What if we could somehow provide an artificial boost to the degraded valence side in dementia patients, could that help resolve some of the issues? Or possibly even slow down the “normally” functioning valence areas, would that result in less metabolic folding issues?
There may be quite a few solutions for many of these cognitive problems that are hidden underneath the statistical blurring that occurs when we assume that “all brains work mostly the same”. If we don’t segregate dorsal/ventral/balanced types, when we do average them we get an inconsistent mess with results depending on how weighted our pool is by dorsal/ventral populations.
It’s my suspicion, and one of the reasons I started paying more attention to the raw data in most studies, is that by missing/misunderstanding that there are core top level brain phenotypes, we’ve been averaging away some of our best options, and applying literally the “opposite” treatment for what might be appropriate for certain individuals.