Depressive symptoms prevention

Depression and the absence of a stable partner can accelerate Alzheimer’s disease in people with genetic risk

Depressive symptoms accelerated the age of onset of dementia between 3 to 5 years. Single, widowed, separated presented cognitive impairment 3 years earlier.

Antioquia, Colombia - Depressive symptoms and the absence of a stable partner can accelerate the progression of Alzheimer's disease in people who carry a genetic mutation. In addition, adequate treatment and controls in people with thyroid problems help delay depressive symptoms, progression to dementia, and death.

These findings were reached by a team of researchers from the Universidad de Antioquia, Colombia, Universidad Nacional de Colombia, and Hamburg-Eppendorf University Medical Center, Germany, in a population with the "paisa mutation" or presenilin 1, E280A mutation carriers, for early-onset Alzheimer's disease. A disorder in which people lose memory and other brain functions, requiring help with all activities of daily living by the average age of 44 years. This study has been published in the recent issue of the Journal of Alzheimer's Disease.

The Neurosciences Group of Antioquia, from the faculty of medicine at Universidad de Antioquia, studied 190 Colombian people in a family study program whose father or mother died of Alzheimer's disease. These patients were followed for more than 20 years, from 1995 to 2015, observing the age at which they presented any symptoms of depression and when they started with memory loss. The main objective of the study was to determine if the presence of depressive symptoms, years of education, marital status, rural or urban place of residence, or medical history accelerated or delayed the onset of the disease.

Fieldwork in rural and remote area from Colombia
Caption: Fieldwork in rural and remote area from Colombia. Medical and neurological evaluation carried out by the researchers of the Neurosciences Group of the University of Antioquia (GNA), Colombia. 

The findings
People with Alzheimer's disease carriers of the "paisa mutation" with a history of depression deteriorate almost twice as fast compared to those who do not present depression. And in total, having depressive symptoms accelerated the age of onset of dementia between 3 to 5 years, depending on other genes involved. This fact means that these people worsened faster, promptly needing help in all activities of daily living, such as talking, walking, or eating.

On the other hand, marital status also seems to be involved in this rapid progression of the disease. People without a stable partner (single, widowed, separated); presented cognitive impairment 3 years earlier compared to those who were married or in a free union.

Within the medical history, it was found that individuals who suffered from thyroid but had treatment presented dementia later. Age was delayed between 5 to 9 years, and death was between 4 to 9 years, depending on the presence of other protective genes. This could be explained because it was also observed that adequately treated hypothyroidism could prevent early depressive symptoms in this same population.

Other risk factors associated with depression in this population may also impact the prognosis of Alzheimer's. For example, women presented depressive symptoms earlier than men.

"The role of depression in brain functioning has been related before, but the importance of this study was precisely to demonstrate that these symptoms, like the absence of a permanent partner, mainly accelerate the stage of dementia, which is the longest stage and exhausting for the caregiver and family. If this stage could be delayed a bit, we would greatly contribute to the patient's and caregiver's quality of life". Explains Dr. Natalia Acosta-Baena, the first author of this study.

The dementia stage is the most devastating stage of the disease. At this stage, more significant complications, risk of falls, hospitalizations, behavior problems, and a more substantial burden for the caregiver are generated. It is the longest stage with the most significant economic effects on families and the health system.

Depressive symptoms prevention

What comes next?
This study is expected to call for good clinical practices and management guidelines. Since although there is no curative treatment for this disease, preventing, detecting, and treating depressive symptoms before Alzheimer's disease begins could be essential for these people with genetic risk. It could help delay the onset of dementia and functional dependence and, consequently, impact the benefit of the patient, caregivers, and society. Taking care of thyroid problems and having good relationships could also mitigate the impact of Alzheimer's disease.

Additionally, all these results are crucial to evaluate drugs or other therapies for Alzheimer's, so more studies are required to validate these conclusions and identify interventions capable of modifying risk factors for progression and, in the best case, achieving primary prevention, that is, before the onset of the disease.

The follow-up of all these years of families affected with hereditary forms of Alzheimer's disease and other diseases that cause the death of neurons has been essential to understanding the causes, the expected evolution of the disease, and its triggers to one day find solutions to prevent or cure them. For this reason, the Neurosciences Group of the University of Antioquia invites all families affected by these disorders to join their research and follow-up programs. "The families affected alone will not be able to find a solution to these diseases, but researchers and scientists alone could not do it either, but together we can!". Says Dr. Francisco Lopera, director of the Neurosciences Group at the University of Antioquia.

About the "paisa mutation"
A mutation is the change of one molecule for another in our genes. The paisa mutation is native to Europe but is widely distributed in different regions of Antioquia, Colombia. Affected people have a change in a gene called Presenilin 1, where Glutamic acid is changed to Alanine at position 280 of the gene. This change is pathogenic, causing Alzheimer's disease before age 65, and can be transmitted to subsequent generations. The paisa mutation is known throughout the world for being the cause of Alzheimer's in a large number of families.

About Alzheimer's disease
Alzheimer's disease is a disease that causes the death of neurons, affecting the ability to memorize, think, behave socially, and fend for oneself. It can be divided into three successive, slowly progressive stages: The first is the stage before memory symptoms or preclinical stage, the stage in which cognitive deterioration begins, and finally, the dementia stage. This last stage of dementia produces disability and dependency, inevitably leading to death.

Researchers have studied for decades the causes of rapid disease progression. Other disease-modifying genes, such as the APOE gene, have been identified. However, it had not been possible to demonstrate other factors, such as depression or marital status, which were directly involved.

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Media contact

Grupo de Neurociencias de Antioquia, Facultad de Medicina, Universidad de Antioquia
Natalia Acosta-Baena

Title of paper
“Early Depressive Symptoms Predict Faster Dementia Progression in Autosomal-Dominant Alzheimer's Disease,” by Natalia Acosta-Baena, Carlos Mario Lopera-Gómez, Mario Cesar Jaramillo-Elorza, Lina Velilla-Jiménez, Carlos Andrés Villegas-Lanau, Diego Sepúlveda-Falla, Mauricio Arcos-Burgos, Francisco Lopera;  ( The article appears online in advance of the Journal of Alzheimer’s Disease, Volume # 92 Issue # 3 (FEBRUARY  2023) published by IOS Press.

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About the Journal of Alzheimer’s Disease
Now in its 26th year of publication, the Journal of Alzheimer’s Disease (JAD) is an international multidisciplinary journal to facilitate progress in understanding the etiology, pathogenesis, epidemiology, genetics, behavior, treatment, and psychology of Alzheimer’s disease. The journal publishes research reports, reviews, short communications, book reviews, and letters-to-the-editor. Groundbreaking research that has appeared in the journal includes novel therapeutic targets, mechanisms of disease, and clinical trial outcomes. JAD has a Journal Impact Factor of 4.160 according to Journal Citation Reports (Clarivate, 2022). The journal is published by IOS Press.

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IOS Press is an independent international scientific, technical, medical (STM) publishing house established in 1987 in Amsterdam. We produce around 90 journals and 70 books annually in a broad range of subject categories, primarily specializing in health and life sciences (including neurosciences, medical informatics, cancer research, and rehabilitation) and computer sciences (including artificial intelligence, data science, and semantic web). In addition, we offer specialized services that support scientific advancement.