Alzheimer’s disease is the most common neurodegenerative disease. The prevalence of the disease increases with age and reaches 15-20% in subjects over 80 years.
Numbers are destined to grow: 7.7 million of new cases are diagnosed each year (a new case in 3 seconds) and the mean average survival time after diagnosis is now over 10 years.
Alzheimer’s disease starts with minor memory problems. During the disease, these and deficits in other cognitive domainsare exacerbated and can lead the patient not only to a severe disorientation in time, space and towards people, but also to neglect their personal safety, hygiene and nutrition.
The disease progresses until the total loss of autonomy and complete dependence on family members or other caregivers.
Therefore, Alzheimer’s disease is a priority in the global agenda.
Unfortunately, there are no drugs able to stop or reverse the disease so far. All available treatments aim at limiting its symptoms or slowing progression for a few months.
Scientific research has shown that thepathological processes of the disease can precedemany years, destroying cells and nerve circuits. This can happen thanks to the plastic reorganization aptitudes of the brain that uses resources from the “neural reserve” to replace damaged circuits.
Hence, there is a “prodromal” stage of disease during which symptoms are absent or very blurred.
Interceptor focuses on the diagnosis of this stage.
The diagnosis of the prodromal stage
In recent years the most frequent research approach is to develop a very early pharmacological intervention on the initial stages of the disease, when the symptoms are minimal.
This is why more attention has been paid to the identification of those biomarkers that allow the predictionof conversion to Alzheimer’s disease. Biomarkers evaluation supports neuropsychological tests in those subjects with mild cognitive impairment, individuals with a higher risk of developing Alzheimer’s disease (about 735,000 people in Italy).
Neuropsychological tests remain the main pillar of diagnosis.
Roughly 50% of people with a mild impairment of cognitive functions remain stable or revert to normality for the rest of their lives. The remaining half progresses to a form of dementia within 3-5 years from the diagnosis of MCI.
This is the scenario where the Italian Medicines Agency and a group of dementia experts have planneda series of activities with two objectives.
First: be ready to start all the currently available therapies as soon as possible.
Second: managing the occurrence of the arrival on the market of one or more drugs potentially capable of preventing or treating Alzheimer’s disease.
In the next few years, experimental researches of many dozens of new drugs potentially able to slow down / stop Alzheimer’s willterminate.
Many of them will be effective only in the “prodromal” stage of the disease, characterized by the condition of Mild Cognitive Impairment (MCI).
The project numbers
Six markers selected on the basis of the scientific evidencewill be evaluated during the study.
The goal is to determine which markers have the best combination of sensitivity and specificity to predict the conversion of MCIto Alzheimer’s disease.
The benefits for the economy and for the healthcare systemare evident.
There are 600,000 cases of Alzheimer disease in Italy (about half of all the various forms of dementia).
There are 1,200,000 cases of patients suffering from dementia.
Alzheimer‘s is not the only dementia, but it is the most common and accounts for about 50% of the total.
Roughly 3 million of people are directly or indirectly involved in the assistance of their loved ones.
Estimates of the social and health costs of Alzheimer’s disease suggest a total of about 6 billion.
All the patients will be evaluated on the basis of 6 biomarkers:
- Some neuropsychological tests
- The dosage of specific proteins in the Cerebrospinal fluid samples
- Positron emission tomography (PET) for the study of cerebral glucose metabolism and genetic analysis
- The evaluation of the electroencephalographic (EEG) indexes for brain connectivity
- Volumetric magnetic resonance, especially for hippocampal structures (that play a central role in episodic memory ).Residues of the biological samples taken will be kept in a dedicated Biorepository at the IRCCS “Carlo Besta” Neurological Institute of Milan.
The DNA will be stored at + 4 ° C, while the plasma, the serum and the liquor in liquid nitrogen at a temperature between -150 ° C and -196 ° C.These methods allow the correct preservation of samples for an indefinite amount of time and in optimal conditions, in consideration of any further analysis should emerge in the future due to new, innovative biomarkers, not known at the beginning of the study but potentially relevant to the achievement of its objectives.Patients will be followed for 42 months in order to collect all necessary data which will then be statistically analyzed. The result will be the identification of the biomarker, or combinations of biomarkers, which will be able to predict, with greater precision, the progression towards the disease.
The final objective is to be ready to identify the population of MCI subjects at higher risk of progression towards Alzheimer’s disease.
These results will allow the development of an organizational model for the distribution of new drugs, aligning the current therapies and procedures with the new knowledge.
The aim is also to avoid exposing to the treatment and to its potential adverse reactions, subjects that most probably would not benefit from it.
This precaution will therefore guarantee the sustainability of the system.
After 42 months, conversion to Alzheimer’s disease will be evaluated, as well as patients who will remain in a stable condition and those who will have a reversion to the normal cognitive profile.
Subjects with MCI converting to other forms of dementia will be considered separately.
In addition, the biomarker and/or the set of biomarkers will be evaluated to predict this progression with the best accuracy.
The ratio cost/benefitof the biomarker or of the set of biomarkers will be evaluated in terms of prediction of progression, their financial sustainability, availability on the national territory and non-invasive for patients.