Relationship Between Protein Biomarkers in Cerebrospinal Fluid and Alzheimer&Apos;s Disease in Patients With Depression

Institut Investigacio Sanitaria Pere Virgili50 enrolled

Overview

It is currently accepted that depression during midlife is a risk factor for Alzheimer's disease (AD). Furthermore, several prospective population studies have demonstrated that depression is an independent risk factor for incident dementia of different types (e.g. vascular, mixed, Alzheimer's disease). However, it is not clear, what are the mechanisms that link depression and dementia, and if depression can be a prodromal manifestation of AD. There are also studies that suggest that depression could be an initial sign of AD. Objective: 1. Demonstrate that late life depression (over 60 years of age) constitutes the first manifestation of AD. 2. Define by rating scales and life stressors have differential risk profiles evolutionary AD. 3. To study the relationship between the subtypes of depression and CSF biomarkers, neurophycological test and evolution to AD.

Groups of subjects: patients with recent apparition of late life depression without fulfilling the dementia criteria (Global Deterioration Scale, GDS, stages 1, 2 and 3). A longitudinal, prospective population study with two years follow-up. A cohort of will be included in the study. The patient's depression will be defined and categorized according to its severity (Yesavage Scale), whether it's endogenous or reactive (Holmes and Rahe scale) and taking into account the patient's medical history of depression. There will be a prospective follow-up of conversion to dementia (starting from GDS Stage 4). It will be considered that dementia corresponds to AD if the biological markers of LCR present typical changes of AD at the moment of inclusion (Beta amyloid low and P-tau high). It will be studied if there's any correlation between the clinically defined depression types and a high risk of progression to dementia and especially to AD.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Alzheimer's Disease

Medical Language ↔ Plain English

Inclusion Criteria: * \>= 60 years. * GDS (Reisberg Gobal Dementia Scale) of 2 to 3. * Geriatric Depression Scale of Yesavage \>=12. * History of previous depressive episodes resolved, but the emotional situation 15 months before inclusion, necessarily have to be normal. Exclusion Criteria: * Established dementia of any cause, or secondary degenerative dementia of any origin * Primary diagnosis of cognitive impairment with psychiatric illness (schizophrenia , bipolar disorder, personality disorders ... ) * Dual diagnosis of chronic depression, dysthymia more than 15 months duration, or major depression with psychotic or atypical symptoms * Neuroimaging with significant chronic vascular involvement * To take drugs with known side effects on cognition and it is suspected that the neuropsychological deficits. * Moderate or severe sensory deprivation or functional illiteracy in the neuropsychological study can not be performed * Neoplastic diseasesContraindication to performing a lumbar puncture

Outcomes

Primary Outcomes

Analysis of cerebrospinal fluid

Measure alterations in amyloid AB 1-42, total tau protein and phosphorylated tau protein, in pg/ml. Those alterations will be correlated with the evolution to dementia at final visit (after 24 months +/- 5 days)

Time frame: between the second and the fifth day after inclusion visit

Secondary Outcomes

Conversion to dementia

Measure increases scores in Global Dementia Scale (GDS), considering no dementia GDS from 1 until 3, and evolution to dementia GDS form 3 until 6

Time frame: first measure at inclusion visit and second measure at final visit (after 24 months +- 5 days).

Depression subtypes

classify the type of depression by scores in two scales. One of them is Yesavage with scores between 11-17 corresponding with "low depression" and scores between 18-30 with "major depression". the second ones is Vital Stressors Scale of Holmes and Rahe which define adaptative depression as scores upper than 150 and non adaptative depression as scores between 0 and 150. Subtype of depression will be correlated with posterior evolution to dementia at final visit (after 24 months +/- 5 days)

Time frame: at basal visit