Depression and Pre-Clinical Dementia

Research Paper Title

A cross-national study of depression in preclinical dementia: A COSMIC collaboration study.


Depression commonly accompanies Alzheimer’s disease, but the nature of this association remains uncertain.


Longitudinal data from the COSMIC consortium were harmonized for eight population-based cohorts from four continents. Incident dementia was diagnosed in 646 participants, with a median follow-up time of 5.6 years to diagnosis. The association between years to dementia diagnosis and successive depressive states was assessed using a mixed effect logistic regression model. A generic inverse variance method was used to group study results, construct forest plots, and generate heterogeneity statistics.


A common trajectory was observed showing an increase in the incidence of depression as the time to dementia diagnosis decreased despite cross-national variability in depression rates.


The results support the hypothesis that depression occurring in the preclinical phases of dementia is more likely to be attributable to dementia-related brain changes than environment or reverse causality.


Carles, S., Carriere, I., Reppermund, S., Davin, A., Guaita, A., Vaccaro, R., Ganguli, M., Jacobsen, E.P., Beer, J.C., Riedel-Heller, S.G., Roehr, S., Pabst, A., Haan, M.N., Brodarty, H., Kochan, N.A., Trollor, J.N., Kim, K.W., Han, J.W., Suh, S.W., Lobo, A., De La Camara, C., Lobo, E., Lipnicki, D.M., Sachdev, P.S., Ancelin, M-L., Ritchie, K. & for Cohrot Studies of Memory in an International Consortium (COSMIC). (2020) A cross-national study of depression in preclinical dementia: A COSMIC collaboration study. Alzheimer’s & Dementia. doi: 10.1002/alz.12149. Online ahead of print.

Causes of Mental Illness

Currently, mental illness is thought to be caused by a complex interaction of factors, including the following:

  • Hereditary;
  • Biologic (physical factors);
  • Psychologic; and/or
  • Environmental (including social and cultural factors).

Research has shown that for many mental health disorders, heredity plays a part. Often, a mental health disorder occurs in people whose genetic make-up makes them vulnerable to such disorders. This vulnerability, combined with life stresses, such as difficulties with family or at work, can lead to the development of a mental disorder.

Also, many experts think that impaired regulation of chemical messengers in the brain (neurotransmitters) may contribute to mental health disorders.

Brain imaging techniques, such as magnetic resonance imaging (MRI) and positron emission tomography (PET), often show changes in the brains of people with a mental health disorder.

Thus, many mental health disorders appear to have a biologic component, much like disorders that are considered neurologic (such as Alzheimer disease).

However, whether the changes seen on imaging tests are the cause or result of the mental health disorder is unclear.