Late-onset depression represent a pre-clinical stage of alzheimer's dementia? A biomarker study

Dementia is a chronic, progressive syndrome with no treatment available, and the most common type related with age is the Alzheimer's type dementia. With the advances in knowledge and technology in the recent years, the pathology of Alzheimer's type dementia in the brain is now known to begin 20-30 years before the emergence of clinical symptoms. Alzheimer's disease is a high burden for both the society and the caregivers; numerous studies are carried out to diagnose Alzheimer's disease in the pre-clinical stages, especially before the neurodegeneration occurs. As suggested by the biomarker model of NIA-AA (the National Institute on Aging and Alzheimer's Association) in 2010, Alzheimer' disease progresses in a biphasic process. According to this model, in the first phase which has no neurodegeneration and clinical symptoms, biomarkers indicating the Amyloid β deposition are thought to become positive; while in the second phase biomarkers showing the neuronal injury and neurodegeneration become positive. In the light of these findings, new biomarkers are studied to detect the signs of the disease in the pre-clinical stage. The depressive disorders occuring for the first time in late adulthood (after 50-65 yo) are called as Late Onset Depression (LOD). Most of the LOD are accompanied by cognitive impairment. The cognitive impairment in LOD generally continues after the treatment of the depressive disorder, and most of the individuals with depression accompanied by cognitive impairment are found to develop dementia in longitudinal follow-ups. Upon these results LODs are thought to imply a pre-dementia clinical condition. With the new developments in the era of dementia diagnosis, studies exploring the relation of LOD and Alzheimer's disease using biomarkers have begun to be recruited. In this study we aimed to explore by various biomarkers whether LOD may represent a pre-clinical stage of Alzheimer's disease. Twentytwo elderly outpatients diagnosed with LOD and 14 patients with a diagnosis of dementia of Alzheimer's type followedup at Hacettepe University Psychiatry outpatient clinic were included in the study; detailed clinical examination and neuropsychological evaluation, plasma biomarkers and saliva biomarkers comprised of AB42, AB42/AB40 ratio, p-tau and t-tau measurements, structural neuroimaging (MRG) and molecular imaging (FDG-PET) were done in both groups. In a subset of LOD patients (n=8) a hypometabolism pattern and neuropsychological pattern compatible with Alzheimer's type dementia were found, but no statistically significant difference was found for plasma and saliva Aβ1-40, Aβ1-42, total tau and p tau measures between LOD and AD groups. In the light of these findings, it could be concluded that a subset of LOD patients could be representing an early stage of Alzheimer's disease; future studies with larger samples and investigating the longitudinal course of LOD patients would be helpful for solving the problem. Key words: late onset depression, Alzheimer's disease, biomarker