The Latest Advancements in Alzheimer’s Disease

According to the Alzheimer’s Association’s report, an estimated 6.9 million Americans are living with Alzheimer’s disease in 2024, and this number is expected to continue to grow as the population of Americans age 65 or older is also increasing. June is a month dedicated to raising awareness about Alzheimer’s disease and to promoting brain health. In this article, we will focus on the following topics:

• The latest research on early signs of Alzheimer’s disease
• The influence of modern lifestyle on the disease
• Advances in diagnosis: amyloid PET
• Non-invasive devices to detect biomarkers
• Hope in promising new drugs

The latest research on early signs of Alzheimer’s

Before examining the latest advancements in Alzheimer’s disease, understanding how a brain with Alzheimer’s disease works is essential.

With aging, the brain undergoes certain changes:

• Both the brain’s weight and volume decrease. In fact, the main change associated with aging is not so much the loss of neurons, as a decrease in their size and number of connections.
• The brain regions linked to learning, memory, processing speed, or planning capacity are the most affected by aging.

A healthy older person may experience a certain decline in the ability to learn new things or have difficulty retrieving certain information, but in a brain with Alzheimer's disease, significant neuronal loss occurs, mainly related to the accumulation of:

• Beta-amyloid protein plaques
• Tau protein neurofibrillary tangles

These plaques and tangles affect the functioning and survival of neurons. In addition to generating toxicity processes, they interrupt the ability of neurons to communicate with each other, inevitably leading to their death.

Beta-amyloid plaques begin to form decades before the first symptoms appear, which makes research on the early signs of Alzheimer’s disease crucial because it can lead to more efficient prevention. A recent large-scale study of posterior cortical atrophy completed by an international team suggests this condition may predict Alzheimer’s. Early identification of these visual symptoms, which normally appear around 59 years of age, may have important implications for Alzheimer’s treatment, as patients with posterior cortical atrophy may be candidates for anti-amyloid therapies, like lecanemab or donanemab.

The influence of modern lifestyle on the disease

According to research carried out by the University of Southern California and published in the Journal of Alzheimer’s Disease, Alzheimer’s disease and related dementias are closely related to modern environments and lifestyles, as medical texts from 2,500 years ago rarely mention them.

Researchers not only studied ancient medical writings from ancient Greeks and Romans, but they also turned to an Indigenous people of the Bolivian Amazon, the Tsimane, who have a physically active, pre-industrial lifestyle. These people show minimal dementia, which suggests that environmental factors such as pollution and sedentary behavior may be important determinants of dementia risk.

Latest advances in diagnosis: amyloid PET

Early diagnosis of Alzheimer’s disease is essential to initiate treatment and slow down the cognitive decline. Despite the increasing use of positron emission tomography (PET) to measure the abnormal accumulation of amyloid beta protein plaques, evidence for its utility and cost-benefit ratio was limited, but for the first time there has been a randomized controlled clinical trial carried out to confirm the clinical utility of amyloid PET, says Juan Domingo Gispert, head of the BBRC Neuroimaging Research Group, who has led the center's participation in AMYPAD.

The findings demonstrated that performing amyloid PET early in the diagnostic workup (within 1 month) allowed 40% of memory clinic patients to receive an etiological diagnosis with very high diagnostic confidence after only 3 months. This is relevant because, as the trial concludes, a timely high-confidence diagnosis is critical to the success of disease-modifying therapies, especially anti-amyloid drugs, whose efficacy might decrease with advancing disease progression.

Noninvasive devices to detect biomarkers

In an effort to find noninvasive detection methods for degenerative brain disease, an international team of researchers has developed a non-invasive device that can detect biomarkers for Alzheimer's and Parkinson's diseases. The detection of three important amyloids is reported:

• Amyloid beta (Aβ)
• Tau (τ)
• α-Synuclein (αS)

Although the results of these experiments are promising, the challenges of brain-derived amyloid protein detection directly via bodily fluids are also acknowledged and research in this field has to continue.

Hope in promising new drugs

Anti-amyloid drugs represent a significant advance in Alzheimer’s research.

Immunotherapies

Immunotherapies are already used in medicine, for example in the treatment of some cancers. They target amyloid plaques in the brains of people with Alzheimer’s to help them break them down.

• The pharmaceutical companies Biogen and Eisai presented the results of the phase III study of their drug lecanemab during the Congress of Clinical Trials on Alzheimer's (CTAD). The study confirms that lecanemab reduces amyloid markers and has managed to slow down cognitive decline by 27% in patients in the early stages of the disease. It is therefore the first drug that would succeed in slowing cognitive decline, so it represents a significant advance in Alzheimer's research
• Donanemab made headlines with the release of the full results from a large final-stage trial in July 2023, which showed the drug successfully leads to the removal of amyloid from the brain. In the study, donanemab cleared amyloid plaques better than aducanumab (Aduhelm) and lecanemab (Leqembi), also newly emerging monoclonal antibodies, and reduced blood tau concentrations, but not in a key area of the brain
• Remternetug is the third of these promising amyloid immunotherapy drugs and is also made by Eli Lilly, who makes donanemab. It has been described as a second-generation immunotherapy because it is hoped to perform better than donanemab. The method of administration used in the trial, injections under the skin, is more practical and effective than intravenous drip. In this way, patients could use pens similar to the ones used with insulin and have it administered at home.

Hope lies in the mentioned advances in research, with the help of artificial intelligence to analyze the large quantities of data generated.

Caregivers and their challenges are certainly the other crucial part of Alzheimer’s. Caring for a person with this disease involves a team of specialized professionals but also loved ones who will need support and resources as the patient’s health declines. It’s important for caregivers to prioritize care of themselves and stay strong physically and emotionally.