New developments in the diagnosis and treatment of Alzheimer’s disease

There are no other diseases – even cancers – that send chills down the spines of older people than Alzheimer’s disease (AD) and other dementias. 

Every year, there are about 10 million new cases. Someone in the world is diagnosed with them every three seconds, and there are over 55 million people around the world who live with these conditions. This figure is expected to almost double every two decades, with an estimated 78 million in 2030 and 139 million in two decades later. There are an estimated 150,000 Alzheimer’s patients in Israel. 

Yet, exciting new things are happening in this neurological field – and they offer good news: For example, a promising new monoclonal antibody that clears amyloid – a protein found in our brains and bodies that sticks together and forms tangles that become plaques in the brain – and cleans them out of the insides of vessels in the brain. 

Another encouraging development is the development of biomarkers that can diagnose some of the diseases that cause cognitive decline and treat them in time. As dementia can result from clogged blood vessels in the brain; uncontrolled hypertension and diabetes; a lack of physical and brain exercises such as puzzles and crosswords; a diet of over-processed food, and even a shortage of vitamin B12 – it’s important to start this process early. Not all dementias involve Alzheimer’s. 

Prof. David Tanne, director of the Stroke and Cognition Institute at Haifa’s Rambam Health Care Campus and immediate past president of the Israeli Neurological Association, worked last week with Prof. Judith Aharon-Peretz, chairman of the advisory committee of EMDA – the Israel Alzheimer’s Disease Association, giving a Rambam patient a first dose of Lecanemab, the new drug approved last year by the US Food and Drug Administration after 18 months of clinical trials on 1,700 patients in the US, Japan, and elsewhere. 

Tanne noted that the new drug was accepted for the “Accelerated Approval” (fast-track) pathway, under which the FDA can okay medications for serious disorders where there is an unmet medical need and a drug is shown to have an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients.

So far, Lecanemab has been found to delay the advance of Alzheimer’s by several months. It is given as treatment only to patients at the beginning of the disorder – and not yet included in Israel’s basket of health services. Before Rambam, Tel Aviv Sourasky Medical Center has given it to 50 Alzheimer’s patients. 

“Lecanemab is infused via a vein once every two weeks in our day hospital,” Tanne told The Jerusalem Post.  

“It’s truly exciting because this drug is the first treatment ever that shows a clear slowing of decline in Alzheimer’s disease. It targets and influences the underlying disease process of AD instead of only treating its symptoms. We have to see how long it has to be given to be effective. We will be able to see the reduced amyloid in the brain’s vessels only via an MRI scan.” 

He noted that there are many causes of dementia – and Alzheimer’s is only one of them.

“A huge revolution is upon us, as neuropathological changes can now be diagnosed via biomarkers in the blood and spinal fluid even when there are no symptoms and decades before they would appear. This will alter the public’s understanding of dementia from an advanced condition to early changes in the brain. There is a somewhat higher risk for dementia among descendants of patients, but it’s not a genetic disease. So many environmental and lifestyle factors are involved.”

Fighting the disease itself

Until now, there have been several drugs including an Israeli-invented one developed by Israel Prize winner Prof. Marta Weinstock-Rosin of the Hebrew University’s School of Pharmacy-Institute for Drug Research in the Faculty of Medicine, for her drug called Exelon. However, while it improves memory and shows a decline in some patients’ symptoms, it does not fight the disease itself. 

AHARON-PERETZ, of Rambam and also of Haifa’s Technion-Israel Institute of Technology, is a behavioral neurologist who studies the underlying mechanisms of neurocognitive disorders and is an expert in the diagnosis and management of dementia. She founded Haifa’s Cognitive Neurology Institute and fellowship program, and her interests include behavioral neurology, Alzheimer’s disease, frontotemporal dementia, vascular dementia, and cognitive impairment resulting from Parkinson’s disease.

She said that the world’s Alzheimer’s Association, whose guidelines are respected and followed by brain scientists around the world, had just created a great deal of excitement in the world’s neurology community: “After years of deliberations in three different and separate working groups, it has created and published new official criteria for diagnosing AD. This is a revolution in the diagnosis of the disease, which involves the progress, growth, and expansion of brain changes leading to the later appearance of clinical symptoms such as memory loss, disorientation, problems with planning or organization, and mental confusion that worsen with time,” she continued. 

“The innovation in publishing updated international guidelines for diagnosing AD and determining its various stages is in the combination between basing the clinical diagnosis that is sometimes inaccurate, and basing the diagnosis also on the process,” Aharon-Peretz noted.

 The international criteria for diagnosing Alzheimer’s and for determining the severity of the disease have been amended – from a clinical diagnosis only, to one based also on biological markers, similar to the diagnosis of other diseases such as cancer, heart disease, and diabetes.”

This international body dedicated to the treatment, support, and research of the disease included these new criteria for the diagnosis and characterization of the disease and for determining its degrees of severity in three different and separate working groups.

The revised criteria define Alzheimer’s as a biological process that begins with the appearance of changes occurring in the brain – another preliminary stage for the emergence of memory and thinking problems, Aharon-Peretz explained. 

“The international association said its research indicates that the progression and expansion of the changes in the brain lead to the later appearance of clinical symptoms including memory impairment and a variety of other symptoms that worsen slowly and gradually. However, the clinical symptoms, which are usually observed in Alzheimer’s patients, may also be caused by other conditions, so that their clinical diagnosis alone is not sufficient for an accurate characterization that it is AD,” she added.

Doctors recognize that there are differences between the causes of disease, as in cancer, and the clinical signs, Aharon-Peretz continued. “In the brain, there are biological changes and signs of AD. The pathology is identified better today. Biomarkers are 100% accurate without conducting a brain biopsy. Since dementias are caused by numerous other conditions, some of these can be treated early with lifestyle changes and medications to protect brain health. Fewer than 60% of dementias are caused by AD.” 

The innovation in the publication of the updated international guidelines for diagnosing the disease and determining its various stages is in the combination between basing the clinical diagnosis, which, as mentioned, is sometimes inaccurate, and basing the diagnosis also on the process.

Prof. Yoav Chapman, chairman of the Israel Neurology Society who heads the neurology department at Sheba Medical Center, concluded: “The importance of publishing the new global criteria for diagnosing Alzheimer’s disease should not be overstated. A bridge has actually been opened between the groundbreaking scientific research to diagnose the disease and the innovative clinical treatment."

"We actually went from describing general characteristics of a memory disorder, spatial orientation, and other cognitive symptoms to a deeper understanding of the disease and mapping its causes. Surely this process will lead to better patient care. In many research laboratories in the world, including in Israel, the best minds are working on cracking the disease and finding drugs to reverse it. This is an exciting time for us neurologists. Neurology is changing at a rapid pace before our eyes.”