You can’t treat something until you know it’s there. Currently, there’s no cure for Alzheimer’s disease (AD) but earlier diagnosis may lead to better understanding of how the disease inexorably progresses, which in turn may lead to prevention of AD and ultimately eradication of this horrific scourge. The latest breakthroughs in earlier diagnosis and even perhaps pre-diagnosis have involved lumbar punctures, brain MRIs, eye exams, and blood tests.
A 2024 study, performed across multiple medical centers in China and involving more than 1,300 volunteers, suggests tests which foretell AD may soon be a reality. The doctors involved in the inquiry performed serial spinal taps (a procedure during which a needle is introduced into the lower back and cerebrospinal fluid (CSF), the watery substance that bathes the spine and brain, is sampled). They repeated the spinal tap every few years for an entire score of years (between 2000 and 2020).
What did these intrepid researchers discover?
About 18 years before the onset of AD, those destined to be ravaged by that scourge displayed an increased level of a unique protein (amyloid-beta) in their CSF. Between 14 and 11 years prior to the clinical presentation of AD, the level of tau protein spiked in the CSF of those doomed to develop AD.
What’s more, the scientists performed serial MRIs on the volunteers.
A decade before suffering the brain havoc of AD, the MRIs of the predestined cohort demonstrated atrophy (wasting away) of a brain region called the hippocampus (a structure that is part of the limbic system and is crucial for memory formation and storage).
The Chinese researchers aren’t alone in exploring early diagnosis of AD via brain MRI. In 2021, Texan researchers developed an MRI that is so powerful that it can display what is going on inside of cells (as if it were a microscope). MRI strength is measured in Tesla (like the car). The typical MRI is between 1.5 and 3 Tesla. Everything is bigger in Texas, so the scientists used a 7 Tesla machine. Scientists using the new MRI can detect sub-cellular changes in the brains of people with early AD. Even before any symptoms have manifested, the doctors reported malfunctioning mitochondria (a part of the cell that generates energy) in the neurons (brain cells) of Alzheimer’s patients.
They say that the eyes are the window to your soul. In 2021, Japanese researchers reported that your eyes, specifically the retina (the back of your eye), may reveal whether you are at risk for developing AD. The scientists ophthalmologically evaluated thirty volunteers including fundus imaging by scanning laser ophthalmoscopy. They discovered that the retinas of those with AD had increased deposition of amyloid. Interestingly, even those with mild cognitive impairment (pre-Alzheimer’s) were found to have abnormal retinal amyloid deposition.
In 2023, Swedish researchers reported on a blood test that might provide an early warning for AD. The scientists followed 233 patients for about a decade and discovered a relationship between a specific type of glycan and AD. Glycans are sugar chains that may bind to proteins and affect their function (by changing shape). Some alterations of such proteins may result in autoimmune reactions and inflammation. In this cohort, an abnormally high level of glycan in the blood predicted the future development of AD. Interestingly, this same glycan may also be present in the cerebrospinal fluid (CSF). So, perhaps these Swedish scientists should collaborate with the Chinese scientists mentioned earlier.
In 2023, Australian scientists discovered that high cholesterol may be correlated with the future development of AD. Surprisingly, it was elevated HDL (the supposedly good cholesterol) which was the culprit. The researchers reviewed the medical records of more than 18,000 people. The group was composed of older adults who’d been followed for more than six years. The scientists reported that 850 (4.6 percent) of the volunteers were diagnosed with dementia during that time. On closer analysis of the participants diagnosed with dementia, the researchers discovered a correlation between high HDL-C (>80 mg/dL) and increased risk of cognitive issues. In fact, the risk to those with elevated HDL was 27 percent higher than those with lower cholesterol. The group most at risk was those who were older than 74 years.
We’ve discussed a bunch of diagnostic advances today. One question remains, though. There’s currently no cure for AD. Quite honestly, the available treatments aren’t even very effective. So, if you could go to the doctor and get a test that would predict whether you’ll develop AD, would you do it?
Marc Arginteanu is a neurosurgeon and author of Azazel’s Public House.
