Proximity to parental age at onset of Alzheimer's indicates an increased risk of developing the disease in women

Researchers from the Barcelonaβeta Brain Research Center (BBRC) have detected that the proximity to the parental age at onset of Alzheimer's disease symptoms is related, in women, to a greater accumulation of the beta protein amyloid, which is one of the characteristic lesions of the disease. The study has the support of the “la Caixa” Foundation, and has been published in the scientific journal Neurology.

The work was carried out on 290 participants (63% women, 37% men) without cognitive impairment from the Alfa Study, which is one of the largest research infrastructures in the world for the prevention of Alzheimer's. The participants are mostly descendants of people with Alzheimer's and are between 45 and 75 years of age.

To carry out the study, participants completed a series of clinical questionnaires, cognitive tests, a lumbar puncture, an MRI, and a positron emission tomography. All of these tests were performed to confirm whether proximity to the parental age at onset of Alzheimer's disease symptoms was associated with an increased load of beta amyloid protein and with other biomarkers of neural damage, and to assess the role of non-modifiable risk factors, such as age, sex and genetics, and modifiable factors, such as years of schooling, and mental and vascular health.

Parental age as a risk factor in women

Accumulation of beta amyloid protein can begin to develop up to 20 years before the onset of clinical symptoms of the disease. The presence of plaques of this protein in the brain exponentially increases the risk of suffering cognitive impairment and, therefore, of entering the clinical phase of Alzheimer's disease. However, there are people who despite having these plaques, will never develop symptoms.

The results of the study indicate, as a group, that the participants with the highest accumulation of beta amyloid protein were women over 60 years of age and that they were close to 7 to 8 years before the age at which one of their parents began to show cognitive problems. In the case of having two affected parents, the accumulation of the protein was even higher. Furthermore, these effects were independent of whether the participants were carriers of the APOE-Ɛ4 genotype, which also increases the risk of developing the disease.

As stated by the main researcher of the study, Dr. Eider Arenaza-Urquijo, “the parental age at onset of Alzheimer's symptoms is a simple variable to collect that can be very useful in order to enrich clinical prevention trials, since, along with other measures, people who have a higher risk of developing the disease can be selected”. In this sense, she adds, "we may be able to detect earlier the accumulation of amyloid pathology in women with this and other risk factors for the disease, and allow them to benefit from prevention programs”.

Regarding the association of parental age at onset of symptoms and other biomarkers of neural damage, the researchers found no significant results.

Anxiety and depression, another risk factor

Regarding the role of modifiable risk factors, the BBRC team did find an outstanding association: as participants got older and without distinction by sex, those with a history of anxiety or depression had a lower hippocampus volume, which is one of the brain areas that first atrophy in Alzheimer's disease. According to the study's first author, "this result suggests that anxiety and depression may decrease brain resilience". For this reason, she adds, "taking care of mental health is especially important in people with a family history of Alzheimer’s”.

This finding is in line with recent studies on mental health and Alzheimer's –in which Dr. Arenaza-Urquijo has also participated– which point out that negative thinking and stress can also increase the risk of developing the disease.

Towards personalized detection of Alzheimer's risk

Dr. José Luis Molinuevo, scientific director of the BBRC Alzheimer's Prevention Program, highlights that “this work provides us with novel information to add to the family history to more accurately identify people who may be at higher risk of developing Alzheimer's. The future involves the development of personalized prevention programs through the detection of risk factors for the disease that each person presents, in order to propose individualized prevention strategies and improve the selection of candidates for Alzheimer's prevention clinical trials".

The study has also had the participation of researchers from the University of Gothenburg, University College London, and with the collaboration of the CIBER for Fragility and Healthy Aging, and the CIBER for Bioengineering, Biomaterials and Nanomedicine.