08:06am Monday 06 July 2020

New approaches to finding treatments for Alzheimer's disease

The FINGER study led by Kivipelto involved 1,260 persons over 60 years of age who had a slightly elevated risk for memory disorders. One group of the study participants was given conventional lifestyle counselling, while the other received counselling related to nutrition and exercise, as well as cognitive training and support for the management of risk factors of cardiovascular diseases. A significant difference between the groups was observed in just two years’ time: the risk of declined cognitive performance was 31% higher in the control group than in the group receiving enhanced counselling.

“The objective is to transfer this model into health care practices. Our findings have attracted tremendous attention worldwide, and the WHO has already included the FINGER model into its recommendations,” Kivipelto said.

Novel interventions and drug research

Working as Professor in Clinical Geriatric Epidemiology at Karolinska Institutet and as Research Director of Neuroepidemiology at the University of Eastern Finland, Kivipelto presently coordinates the European MIND-AD project in which a similar intervention will be conducted among persons already suffering from mild cognitive impairment. Alongside enhanced lifestyle counselling, a nutrition supplement designed for the needs of the ageing brain will also be tested.

Although memory impairment can be slowed down, researchers haven’t been able to develop a drug that would target Alzheimer’s disease. “The past 30 years have witnessed more than 200 drug trials, but with no success. This means that we must do something differently,” Kivipelto says.

A novel approach is tried in the extensive EPAD project, in which research institutes and pharmaceutical companies collaborate. “A European-wide register of persons suitable for drug trials will be compiled, making it easier to test new drugs developed for memory disorders.  Different drug trials will have a shared control group, against which the efficiency of each drug will be compared. This makes it possible to quickly identify drugs that seem promising, and to focus further research on them.”

Test screens risk patients for further examination

A new testing method can identify memory patients who are likely to develop Alzheimer’s disease within one year. “The test is taken from a blood sample and it is 87% accurate,” said Ian Pike, Operative Manager of Proteome Sciences, a company in the field of biosciences.

The test is based on proteomics and it is a panel of ten proteins. Changes in their concentrations are indicators of a fast progression of the disease. According to Pike, this is significant especially for clinical trials, because the test makes it possible to select patients with the greatest risk of developing Alzheimer’s as participants to drug and other trials. The test has not yet been evaluated for early diagnosis in the general population.

“It is probable that in a few years’ time, we’ll have a test that can be used to chart the risk of persons who do not show any symptoms of memory diseases, and at that point I assume we will have treatments available, too.”

Focusing on early prevention and treatment

“Alzheimer’s disease is too big a challenge for anyone to tackle alone. We need extensive, international studies involving multiple institutes and patient cohorts,” said Johannes Streffer, leader of the EMIF-AD project.

The pan-European EMIF consortium will create a platform that combines patient and research data, and facilitates their use in research. The EMIF-AD sub-project combines research databases on Alzheimer’s disease in order to find new memory disorder biomarkers. “The focus of Alzheimer’s research has changed. Ten years ago, research focused on those already diagnosed with Alzheimer’s, whereas today the focus is on finding persons at risk of developing the disease, as well as on prevention.”

Working as Research Director at the pharmaceutical company Janssen Pharmaceutica, Streffer has been involved in developing immune based treatments for Alzheimer’s. According to him, trials carried out on the bapineuzumab antibodies that target harmful protein aggregations typical of the disease potentially haven’t led to a breakthrough, because they were tested on patients whose disease was too advanced. “I believe that we will be able to demonstrate the efficiency of new treatments when administered on time.”

PET scan shows amyloid aggregations in the brain

Imaging of structural and functional changes in the brain helps both in the diagnostics of memory diseases as well as in the monitoring of treatment response. In the future, imaging can play a role in the selection of a personalised treatment.

Professor Juha Rinne of Turku PET Centre said that positron emission tomography, i.e. PET scanning, can be used to study changes in, for example, the brain’s circulation, metabolism and mediator function.

“Nowadays, a PET scan can also detect the aggregation of β-amyloid and tau proteins, typical of Alzheimer’s disease, in the brain already at the early stage of the disease. These changes can start up to 20 years before any symptoms occur.”

“However, PET images have also shown that a surprisingly large share of patients do not have an amyloid aggregation in their brain. This means that it’s no use to expect an amyloid-targeting drug to work.”

According to Professor of Neurology, Dean Hilkka Soininen, PET scanning will become an increasingly important screening method, and it is also used in the EPAD project.

Text: Ulla Kaltiala Photos: Raija Törrönen


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