This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.This NIH-sponsored, 3-year, prospective longitudinal study will examine whether cognitively intact individuals with late-life major depression (LLMD) have increased plasma Abeta 42 levels and Abeta 42/Abeta 40 ratio at baseline. The study will also determine whether increased plasma Abeta 42 levels and Abeta 42/Abeta 40 ratio at baseline, as well as greater reductions in Abeta 42 during longitudinal follow-up, are associated with cognitive decline and/or conversion to Alzheimer's disease (AD). In addition, this study will also determine the relationships among plasma and CSF Abeta 42 levels, APOE genotype, baseline cognitive functioning and cognitive decline. If a relationship between plasma Abeta 42 levels and cognitive functioning in late-onset LLMD subjects is confirmed, then the determination of plasma Abeta 42 might be an easily obtainable marker to identify individuals with LLMD who may have prodromal AD. The study will target cognitively intact individuals with LLMD and with a first episode of depression at or after age 60 and who are presently on a stable dose of antidepressant. Since no marketed medications including antidepressants have been shown to influence plasma Abeta levels, no washout from these medications will be required. However, individuals on active treatment with medications with the potential to cause significant cognitive impairments including those having significant central anticholinergic effects and benzodiazepines will be required to undergo a 2-week washout. An initial MRI will be performed to exclude individuals with significant cerebrovascular disease. A total of 160 individuals will be prescreened annually during the first 2 years of the study. Of these individuals, it is estimated that 70 depressed individuals will be matched with an equal number of age-, sex-, education-, APOE e4 and non-e4 matched non-depressed controls. Eligible subjects will come to the site for a total of 9 visits, which will consist of prescreening visit, screening visit, baseline visit, and 2 visits for every annual follow-up at Years 1-3. Subjects who during the Prescreening visit are found to meet preliminary entry criteria for LLMD and those in the control group with the targeted APOE genotype will undergo further evaluations during the Screening Visit. The Screening visit will involve monitoring of vital signs, physical exam, ECG, routine laboratory tests including drug screen, and MRI to rule out any significant vascular brain pathology. Please note that subjects who have pacemakers, defibrillators, other implanted electronic devices or any other contraindications to an MRI will be excluded. All subjects who meet the study criteria after the Screening visit will be asked to come for the Baseline Visit. At this time, subjects will be requested to see their personal MD for washout of any non-allowable medications, if needed. During the Baseline visit, the following assessments will be done: vital signs, depression rating scale, mood rating scale, and a neuropsychological test battery. Blood will be drawn for determination of plasma Abeta 40 and Abeta 42 at this visit and annually thereafter. In a subset of subjects who agree, a lumbar puncture procedure will be performed on another day as part of Visit 3 to collect CSF for Abeta 40 and Abeta42 determination. Dr. Thomas Wisniewski will perform the lumbar puncture at the NYU Medical Center/Bellevue GCRC. Subjects will be asked to return for annual assessments, which will occur at 1-year 1 month of the preceding annual visit and will be divided into 2 sessions. With the exception of APOE genotyping, the diagnostic interview (SCID) and MRI, the same evaluations will be repeated during the annual visit. The lumbar puncture will only be repeated on the 2nd visit of the 3rd Year follow-up.
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