Early detection of Alzheimer's is key to accessing new drugs that prolong life expectancy

Alzheimer's is the most prevalent neurodegenerative disease among the dementias. In fact, seven out of ten cases manifest in the same way, according to estimates by the Spanish Society of Neurology (SEN), who also warns more than 50% of cases that are still mild are undiagnosed and the average delay between the first symptoms and diagnosis is over two years.

This statistic can be extrapolated to Malaga, according to the scientific director of the Andalusian Institute of Neuroscience (IANEC), José María García-Alberca, who estimates that between between 15,000 and 20,000 people are affected in Malaga, and using the estimates of the SEN, it could be said that half of them are currently undiagnosed.

Detecting the disease in its early stages, i.e. in the early stages, or in its silent phase, years before it appears, will allow the new drugs (lecanemab and donanemab), which are about to be used in Spain, to slow down its progression. This will increase the life expectancy of those affected by it by three to five years, as well as providing a better quality of life.

The disease is closely linked to ageing and mainly affects people over the age of 65. It is Spain's ageing population that predicts a rise in dementia cases: from vascular dementia to Lewy body dementia or frontotemporal dementia, but above all, says Dr Raquel Sánchez del Valle, director of the SEN Behaviour and Dementia Study Group, Alzheimer's disease. It is undoubtedly one of the greatest global health challenges, so promoting early detection, slowing down its progression and prevention must be "spearheads" in the fight against the disease, she says.

Underdiagnosis is very high in Spain, says the SEN, especially in mild cases, with between 30% and 50% of people suffering from some form of dementia don't end up being formally diagnosed. Why does this happen? Firstly, the symptoms are often attributed, especially in the early stages, to absent-mindedness or signs of ageing, notably, the family of the person with Alzheimer's can downplay the importance of the situation; and lastly, the symptoms can overlap and be confused for other types of dementia.

Dr García-Alberca says that years ago the World Health Organization (WHO) estimated that 75% of mild cases were under-diagnosed, a figure that has now fallen to just over 50%. In fact, he points out, it is necessary to differentiate between the preclinical stage, where the first visible signs of the disease manifest, and the early progression, which can last for 20 to 25 years, before the onset of the acute stage. Today, this is possible with new technologies. The SEN, for example, highlights the great advances that have been made in imaging and biochemical diagnostic techniques, especially with the availability of blood markers that, with a simple analysis, can improve diagnosis rate accurately.

"Correctly diagnosing the disease means treatments can be incorporated earlier, also access to social and financial support and realistic future planning, brings many benefits to both patients and their families and carers. And it is now possible to make an accurate initial diagnosis, so we encourage identifying the symptoms of this disease, as to not be limited to generic dementia diagnoses, and not to attribute its symptoms to normal ageing," says Dr. Sánchez del Valle.

For García-Alberca, early diagnosis has two advantages. "The treatments don't cure Alzheimer's, but early medical intervention slows down the progression of the disease and improves symptoms. At the same time, you can decide how you live your life, if you need to make important decisions, 'How do I work with my loved ones'," he says.

Both the IANEC and the SEN recall that the European Medicines Agency (EMA) has already given Lecanemab and Donanemab a stamp of approval, two drugs to be applied in the early stages that modify the course of the disease. Administered intravenously, they reach the brain and eliminate excessive abnormal deposits of beta-amyloid protein, as the destruction of neural pathways is directly related to an excess of this, and another protein, tau. The initial deposits are produced in the brains of sufferers 20 to 25 years before "the most subtle symptoms begin". If diagnosed at the preclinical stage, these drugs can slow the progression of the disease by 27% (Lecanemab) and 40% (Donanemab), which means, in practice, an increase in life expectancy between three and five years, the doctor estimates. These drugs will soon be available in Spain.

"If the diagnosis is made in the silent phase, with those treatments that are coming, those affected will have the ability to reverse the symptons, or in some cases, even delay".

Carlos Cruz, head of the Neurology Department at the Hospital Universitario Virgen de la Victoria (Clinico) , also explained in April: "In terms of advances, we are at a relatively sweet spot: we hope to have two drugs by the end of the year or the beginning of next year. The first will be Lecanemab, which already affects the molecular structure of the disease, which wasn't possible until now, and is capable of altering the patient's trajectory. A trajectory in which the patient, between three and seven years, goes through all the stages until advanced dementia and then death. Now we are going to be able to prolong it for several years, three or five more years, and a good quality of life for the patient.

Nowadays, the diagnosis is made with a neuropsychological evaluation, explains Dr García-Alberca, tests that evaluate cognitive functions such as calculation or orientation which are, "as precise as a biological analysis". If the evaluation is negative, a neuroimaging test is ordered, an MRI which checks if the hippocampus has suffered some degree of atrophy and, finally, a blood test is carried out to rule out other dementias caused by hypothyroidism or a lack of vitamin B12.

Today, early diagnosis is possible. Firstly, an "extraordinary breakthrough" has been made by noting biomarkers in the blood, both beta-amyloid and tau. It can be said that with a simple prick it can be concluded if a person will suffer from Alzheimer's in the future, as these proteins have already been deposited in the brain. These biomarkers could be present in relatives of those who have it or for people who have a family history. "There are already public and private laboratories that do this," explains Dr García-Alberca, who adds: "The challenge is to diagnose at 20 or 25 years old. That is an early diagnosis; the preclinical phase is the silent phase.

Spinal taps are also performed to see if these biomarkers are in the cerebrospinal fluid, a very invasive test.

On the other hand, there are very advanced imaging tests, such as tau PET or amyloid PET, which also determine the presence of these proteins in the brain.

The public health system is gradually incorporating all these techniques, and they are already present in the private sector, but they are expensive.

As García-Alberca explains, "many cases go undiagnosed because the family agrees with what the doctor has said and, most of the time, a proper diagnosis will not be made".

The SEN, for its part, stresses that more than 100 new compounds are currently being investigated, which will broaden the diagnostic scope.

Recently, for instance, Lilly, mapEA and Alma-Care pointed out that waiting times, the lack of specialist training concerning the disease's pathology in primary care, and the minimal coordination between social, political and healthcare assistance, are some of the "main barriers" to early and accurate diagnosis of Alzheimer's disease in Andalucía.

As Lilly explained in a press statement, these projects aim to identify how to address the diagnosis, treatment and further supporting those with Alzheimer's disease in Spain, as well as to prepare the system to incorporate the latest therapies.