It is broadly acknowledged that the onset of dementia in Alzheimer’s disease (AD) may be modifiable by the management of risk factors. While several recent guidelines and multidomain intervention trials on prevention of cognitive decline address lifestyle factors and risk diseases, such as hypertension and diabetes, a special reference to the established risk factor of depression or depressive symptoms is systematically lacking. In this article we review epidemiological studies and biological mechanisms linking depression with AD and cognitive decline. We also emphasize the effects of antidepressive treatment on AD pathology including the molecular effects of antidepressants on neurogenesis, amyloid burden, tau pathology, and inflammation. We advocate moving depression and depressive symptoms into the focus of prevention of cognitive decline and dementia. We constitute that early treatment of depressive symptoms may impact on the disease course of AD and affect the risk of developing dementia and we propose the need for clinical trials.

BackgroundLate-life depression (LLD) is one of the most prevalent mental disorders in old age. It is associated with various adverse outcomes and frequent use of health care services thereby remaining a serious public health concern. Compared with depression in early adulthood, most treatment options of LLD are less effective. Psychotherapy may be particularly beneficial for LLD due to specific psychological conditions in old age and a low risk of side effects. Although cognitive behavioural therapy (CBT) is highly established and effective in depression in young and mid-life there is only a limited number of small studies on CBT in LLD. An LLD-specific CBT has not yet been compared to an active, but unspecific supportive psychological intervention in a multicentre trial.MethodsHere we present the design of the CBTlate trial, which is a multicentre, randomized, observer-blinded, active-controlled, parallel group trial. CBTlate aims at including 248 patients with LLD of both genders at 7 sites in Germany. The purpose of the study is to test the hypothesis that a 15-session individually-delivered CBT specific for LLD is of superior efficacy in reducing symptoms of depression in comparison with a supportive unspecific intervention (SUI) of the same quantity. The intervention includes 8 weeks of individual treatment sessions twice per week and a follow-up period of 6 months after randomization. The primary end point is the severity of depression at the end of treatment measured by the self-rated 30-item Geriatric Depression Scale (GDS). Secondary endpoints include depressive symptoms at week 5 and at follow-up (6 months after randomization). Additional secondary endpoints include the change of depressive symptoms assessed with a clinician-rating-scale and a patient reported outcome instrument for major depressive disorder, anxiety symptoms, sleep, cognition, quality of life, and overall health status from baseline to end-of treatment and to end of follow-up. Add-on protocols include MRI and the collection of blood samples.DiscussionThis study is the first multicentre trial of a specific CBT intervention for LLD compared to an unspecific supportive psychological intervention administered in a specialist setting. It has important implications for developing and implementing efficient psychotherapeutic strategies for LLD and may be a significant step to broaden treatment options for people suffering from LLD.Trial registrationClinicalTrials.gov (NCT03735576, registered on 24 October 2018); DRKS (DRKS00013769, registered on 28 June 2018).