Preventive neurologist Dr Richard Isaacson stared at the numbers on the fax in astonishment. Blood biomarkers of telltale signs of early Alzheimer鈥檚 disease in the brain of his patient, 55-year-old entrepreneur Simon Nicholls, had all but disappeared in a mere 14 months.
鈥淚 had to catch my breath. It was a complete shock: The blood tests on his brain had normalized,鈥 said Isaacson, director of research at the Institute for Neurodegenerative Diseases in Boca Raton, Fla.
Was this stunning result the work of some new miracle drug designed to combat dementia? Not at all. This is a story of old-fashioned grit and determination.
鈥淪imon was on a mission, as if the Grim Reaper was peering over his shoulder. He was going to kick ass and take names,鈥 Isaacson said.
Nicholls reduced his risk of developing Alzheimer鈥檚 via lifestyle changes recommended by Isaacson, including diet, exercise, reducing stress and optimizing sleep, along with a few strategically chosen supplements and medications prescribed by his cardiologist.
鈥淚 was very worried,鈥 Nicholls told CNN Chief Medical Correspondent Dr. Sanjay Gupta in his new documentary, 鈥淭he Last Alzheimer鈥檚 Patient,鈥 which is airing on 鈥淭he Whole Story with Anderson Cooper.鈥
鈥淚 have a three-year-old son and an eight-year-old son. It鈥檚 really important for me, as I get older, to try and be there for them in the future,鈥 he said. 鈥淭here are many (changes) in lifestyle you can do to hopefully push the disease backwards and give yourself more time, which is all we need until we find a cure.鈥
Unlucky genes
When it came to genetics and dementia, Nicholls had drawn the short straw. He carried two copies of the one from each parent, which may increase the risk of developing Alzheimer鈥檚 at least tenfold.
鈥淪adly, my mum passed away from what we think is Alzheimer鈥檚 in her 70s,鈥 Nicholls said. 鈥淔or the last 10 years of her life, she just sat in a chair, rocking, while on about 14 medications. I鈥檇 much rather have a longer health span and then just go quickly.鈥
Not everyone with one or even two copies of APOE4 develops Alzheimer鈥檚, however, creating a tantalizing opportunity. Can a person diminish their genetic risk for Alzheimer鈥檚 via lifestyle and various medical interventions, especially if started early, before too much damage is done?
Isaacson, who also has a family history of Alzheimer鈥檚, believes the answer is yes. He began the in New York City in 2013 before moving his program to Florida in 2021. His has shown that following a dozen or more lifestyle interventions, when practiced 60 per cent or more of the time, can improve cognitive function, .
Today, scientists around the world are also investigating the impact on cognition of such lifestyle changes as a healthy plant-based diet, stress reduction, strength training, aerobic exercise and quality sleep habits 鈥 behaviors that Isaacson and his team outlined in a recent review published in Nature.
鈥淚 don鈥檛 use the term 鈥榬everse.鈥 I don鈥檛 know what reverse means when it comes to the field of Alzheimer鈥檚,鈥 Isaacson said. 鈥淏ut the results we鈥檝e seen with Simon and some other patients in our research are extremely exciting.鈥
How the heart and the brain are intertwined
Alzheimer鈥檚 isn鈥檛 the only pathway to a life of dwindling memory and the inability to think, plan and interact with loved ones.
the second most common type of dementia after Alzheimer鈥檚 disease, can be caused by atherosclerosis, a buildup of plaque in the arteries that can lead to heart attacks, stroke, blood clots and more, all of which can further damage the body and brain.
Poor hearts and their consequences can run rampant in a family over generations, a fact Nicholls knew all too well.
鈥淢y whole family had endless heart attacks, resulting in my grandfather on my mother鈥檚 side dying around age 50,鈥 he said. 鈥淢y mother had three heart attacks, the first at age 50, then a triple bypass before she went on to develop dementia.鈥
Carrying an APOE4 gene further increases the as well as dementia, experts say.
鈥淢y sister had three heart attacks, and when I was 40, I was told that I had atherosclerosis, with a ridiculously massive coronary artery calcium score of like 1,500 and occlusions in about 96 per cent of my arteries.鈥 A normal coronary artery calcium score is zero.
For a man in the prime of his life, the news was crushing. Doctors tried to use lifestyle changes and statins to reverse the plaque buildup but finally resorted to surgery, opening three of Nicholls鈥 arteries with stents. He also began using an injectable drug called evolocumab, designed to boost the liver鈥檚 ability to remove 鈥渂ad鈥 , or LDL, from the body.
鈥業t was time to turn to my brain鈥
Slowly, Nicholls鈥 heart condition began to improve, but the bad news didn鈥檛 end there. A brain scan found telltale signs of vascular damage in Nicholls鈥 brain, which occurs when the tiniest blood vessels are starved of oxygen.
鈥淭he doctors said I had too many white matter lesions. I told myself that since I now had my heart more or less under control, it was time to turn to my brain,鈥 Nicholls said.
In January 2023, Nicholls became participant No. 34 in a novel clinical trial at Isaacson鈥檚 Florida centre. The trial is designed to uncover cognitive risk factors and counter them with a personalized plan of attack. (Full disclosure: I am participant No. 20 in the same trial; you can .)
鈥淭he overall goal of the study is democratize access to preventive neurology care by eventually using at-home blood testing to cost-effectively reach the most people,鈥 Isaacson said.
As part of the trial, Nicholls underwent a battery of tests, including a unique blood test that can track and other hallmark biomarkers for Alzheimer鈥檚 disease and other degenerative conditions. Deposits of amyloid can begin accumulating in the brain decades before symptoms begin, .
鈥淪imon鈥檚 first test came back with a score of 70. Anything over 58 was positive for amyloid in the brain,鈥 Isaacson said. 鈥淭he results backed up the amyloid PET scan Simon had taken in 2019, where I could see the plaque in his brain.鈥
10,000 steps a day: 鈥業鈥檓 very consistent鈥
Nicholls needed to loose weight, so he began taking tirzepatide (the active ingredient in the medications and ), one of the newer injectable drugs that suppress appetite by stimulating hormones that control blood sugar levels.
At the same time, Nicholls was encouraged to step up his physical activity by incorporating strength training three times a week while adding 45 to 60 minutes a day of zone 2 exercise, in which you briskly , jog or cycle at 60-to-70 per cent of your heart rate.
鈥淚 love going for a walk every morning at sunrise for an hour and a half with a podcast. I get in 10,000 steps or more every day. I鈥檓 very consistent,鈥 Nicholls said. 鈥淚 also do a very slow full-body workout with weights three times a week for an hour鈥檚 time.鈥
Avoiding sugar, artificial sweeteners, alcohol and ultraprocessed foods is a must, as is following a such as the
鈥淲hen I first saw Simon, he had a bit of a middle, like most guys in their 50s,鈥 Isaacson said. 鈥淲hen I saw him at nine weeks, I did a double take. He was totally buff, ripped even.
鈥淲ithin those nine weeks, he had lost 21 pounds, about 80 per cent of that fat, and put on muscle, which was excellent,鈥 Isaacson added. 鈥淚 almost didn鈥檛 recognize him.鈥
The weight loss and increased muscle mass lowered Nicholls鈥 fasting blood sugar levels, ending his march toward diabetes, while some tweaks to his cholesterol medications further optimized his good and bad cholesterol numbers.
In August 2023, it was time to repeat the blood test for amyloid. By then, the company that administers the tests had added a measurement for tau, another key hallmark sign of Alzheimer鈥檚, frontal lobe dementia and Lewy body disease.
鈥淪imon鈥檚 amyloid probability score on the new APS2 test had dropped to 53, which was phenomenal,鈥 Isaacson said. 鈥淏ut he was still positive, as anything between 48 and 100 is considered to reflect a high probability of amyloid brain plaques on a brain scan.鈥
'Turn on the screws'
Now that the big concerns of cholesterol, insulin, diet, exercise and fat mass were addressed, it was time 鈥渢o turn on the screws,鈥 Isaacson said, with personalized recommendations based on Nicholls鈥 biology.
鈥淲e optimized Simon鈥檚 omega-3 fatty acid levels, which is especially important for people with APOE 蔚4, as they need more omega-3. We also added B complex vitamins to control elevated homocysteine in his blood,鈥 Isaacson said. 鈥淗owever, we would not give B complex vitamins to anyone who did not have higher homocysteine levels.鈥
Elevated homocysteine, which is an amino acid used by the body to make protein, is a risk factor for brain atrophy, cognitive impairment and dementia. A September 2010 randomized controlled trial found that supplementation slowed brain atrophy in people with mild cognitive impairment.
In the meantime, Nicholls, an avid researcher who loves to read medical journals, was adding some interventions of his own.
鈥淚 have steam and sauna rooms in my home, I do a lot of that. I love it,鈥 he said. 鈥淚鈥檝e tried cold water plunges, and I have lists of things to do I get from podcasts, from walking to sleeping to gratitude to yoga to sleep routines.
鈥淏ut there鈥檚 one thing I do that Dr. Isaacson doesn鈥檛 agree with: I get stem cell injections twice a year,鈥 Nicholls added. 鈥淪adly, I have arthritis in my hands, and that definitely feels better when I use stem cells, and I like to think they may be helping my brain, as well.鈥
There was one more big issue to tackle: Nicholls鈥 sleep, which have shown can hasten and
With business around the world, Nicholls is a frequent flyer with 鈥渢errible sleep鈥 due to jet lag and insomnia. 鈥淚鈥檓 also a worrier type of person,鈥 he confessed.
Adding a sleep medication approved for insomnia helped, 鈥渂ut Simon really needs to tackle his sleep by improving his sleep hygiene with a more regular sleep schedule,鈥 Isaacson said.
An unbelievable result
On Halloween 2023, the next APS2 score arrived. Amazingly, Nicholls had reduced the amount of amyloid and tau in his blood to 40: He was testing negative in blood for signs of 础濒锄丑别颈尘别谤鈥檚.
Shocked and amazed, Isaacson remained skeptical. 鈥淚 was very cautious. You know, promise not to overpromise. I needed to retest.鈥
A few days before Christmas, the repeat test results arrived. When it too was a negative finding of 40, Isaacson decided to tell Nicholls in person.
鈥淒r. Isaacson drove all the way from Boca Raton to Miami excited, very happy,鈥 Nicholls said. 鈥淲e walked on a beach together, and we were ecstatic that we鈥檇 actually been able go from positive to negative for amyloid.鈥
Although Nicholls is ecstatic about the improvements, he鈥檚 also very humble about his efforts to improve his health.
鈥淚鈥檓 really not all that compliant. To comply is just horrendously difficult, right? Of course I want to have a beer or a hamburger or something stupid. I love gummy bears and eating crappy food,鈥 he said.
鈥淚t鈥檚 helped that I have some great doctors to help me, but to be honest, my biggest motivator are my children,鈥 Nicholls added. 鈥淚鈥檇 love to see my sons get married and have their own kids, and to do that, I have to put in the work to stay the way I am now.鈥
