Can We Treat Alzheimers 20 years early?

Clinical neurologist-Reisa Sperling 1.Is a clinical neurologist, a neuroimaging researcher. 2.Is a leading force in the movement towards earlier diagnosis and treatment of Alzheimer’s disease.

The iceberg By the time that the symptoms of Alzheimer’s disease have percolated up to the surface where recognize it as Alzheimer’s disease dementia that process has been going on in the brain for 10 maybe even twenty years and we can’s see what’s underneath the surface.

Mild cognitive impairment(MCI): Mild cognitive impairment causes cognitive changes that are serious enough to be noticed by the individuals experiencing them or to other people, but the changes are not severe enough to interfere with daily life or independent function. Dementia: when people have lots of memory difficulty and make eventually progress where they can’t feed themselves work and dressed themselves or where they can recognize the person sitting next to them has been their spouse for thirty or forty years and unfortunately this stage at the disease where we are typically doing our clinical trials where there’s already been year irreversible brain. Mild cognitive impairment: at the stage mild cognitive impairment not all of these individuals will progress towards Alzheimer’s disease and in fact not all of them have AD as the cost of their memory impairment but yet we know this is a significant risk factor in 15 percent of them will

Unfortunately, even MCI might already be too late due to the fact that about fifty to seventy percent of central neurons are damaged. As a result, we must go further to the preclinical stage. However, this stage is quiet hard to recognize, cuz there’s no symptoms for us to see it clinically.

While symptoms of dementia can vary greatly, at least two of the following core mental functions must be significantly impaired to be considered dementia: Dementia 1.Memory 2.Communication and language 3.Ability to focus and pay attention 4.Reasoning and judgment 5.Visual perception

LET’S PLAY A SMALL GAME

How do we detect AD in the living brain?

Biomarkers for us to detect: amyloid beta What’s Amyloid Beta denotes peptides of 36–43 amino acids that are crucially involved in Alzheimer's disease as the main component of the amyloid plaques found in the brains of Alzheimer patients.  The normal function of Aβ is not well understood.

You can see on the top row is when a typical normal older individual looks like so they don’t have any amyloid where at least not much in the brain that we can detect all about blue is . The pink and yellow part on the bottom row indicates that the cortex is filled with amyloid plaques, and these parts are associated with our thinking and memories

So even people that act normal with amyloid plaques in their their brains, the recent models suggest that its about 15 yrs from the time they might develop amyloid plaques in their brain to the time they develop AD dementia. Its just like having cholesterol plaques in our hearts years before we develop a heart attack. Fortunately, with the aid of functional MRI and other means, we find out that people who were amyloid-positive but still remain normal have already malfunctioning in their brain, which means we get to detect alzhemeir’s disease before symptoms appear.

Why would we want to detect AD more than a decade before dementia? Think about what happens when we wait to treat diseases only after symptoms are evident. Why would we want to detect AD more than a decade before dementia? What we must do is to treat AD much much early so as to bend the curve that ends up with dementia. Symptomatic therapy is what we treat AD now, however, it doesn’t actually bend the curve. DISEASE MODIFYING therapy is the vital key to success. Alzheimer's disease starts long before anyone would notice; previous studies have shown an effect on the brain 10-15 years before symptoms. It is only after enough brain cells have died that the signs of dementia begin to appear - some regions of the brain will have lost up to 20% of their brain cells before the disease becomes noticeable.

Antibody reduction of amyloid burden: solanezumab Quotes from newspaper articles: upnext

In two previous clinical trials, solanezumab did not successfully slow the progression of dementia in a group of patients with moderate Alzheimer's disease. however, people with the mildest form of Alzheimer's seemed to improve on the drug. “Combined across the two studies, that subgroup [of people with the mildest form of Alzheimer's] had an estimated 34 percent slowing of cognitive decline,” she says. “If we could make that happen 10 years earlier, as in the A4 trial, we could prevent dementia in a substantial number of people.” Based on that effect, and the fact that the drug appeared to be safe and well tolerated in patients, the researchers felt confident that the compound merited additional testing.

“We don't know whether solanezumab—or any treatment—will be more effective in the early stages of the disease than after symptoms emerge,” says John C. Morris, MD, FAAN, director of the Charles F. and Joanna Knight Alzheimer's Disease Research Center at Washington University in St. Louis, who is a member of the Neurology Now editorial advisory board. “But the evidence suggests that it may have a better chance if we administer it before the symptoms appear, while the brain cells are still intact.” Regardless of the outcome of the A4 study, Dr. Sperling is confident that she and her colleagues will learn plenty from the 3,000 PET scans they will be collecting during the trial. “We will learn about the genetic and lifestyle risk factors that help predict amyloid buildup. We'll also understand the factors that tell us whether someone is going to progress toward Alzheimer's dementia, or be resilient and progress more slowly.”

SO LET’S TAKE A LITTLE REVIEW

Thanks for your attention