The goal of this R01 application is to investigate the relationships among late-life depression (LLD), cognitive impairment and progressive neurodegeneration with two imaging approaches: a novel PET ligand (Pittsburgh Compound-B;PiB) that binds to amyloid and volumetric MRI of white matter hyperintensities (WMH). The guiding hypothesis is that individuals who develop LLD have evolving cognitive impairments as a consequence of distinct underlying neuropathologic changes that frequently are expressed as Mild Cognitive Impairment (MCI). Amyloid and WMH are major neuropathologic features that lower brain reserve capacity, and in turn, increase risk of expressing clinical Alzheimer's disease. To pursue this goal, using the joint infrastructure of the University of Pittsburgh's Advanced Center for Intervention and Services Research for Late-Life Mood Disorders (MH071944) and the Alzheimer's Disease Research Center (AG05133), individuals with remitted depression will undergo PiB-PET imaging for amyloid pathology and MRI to determine WMH volume. We will study 100 remitted depressed subjects with a range of cognitive classifications (50 cognitively normal, 50 MCI) and follow them for 3 years with longitudinal clinical, cognitive and laboratory data collection through Dr. Butters'R01 (MH072947;""""""""Pathways Linking Late-Life Depression to MCI &Dementia""""""""). WMH and PiB-PET data from these subjects will be compared with similar data on 25 never-depressed non-amnestic MCI subjects gathered through the proposed research along with 75 never-depressed subjects with a range of cognitive classifications (50 cognitively normal, 25 amnestic MCI), collected under the auspices of two other funded awards (Program Project Grant AG025204 """"""""In Vivo PiB-PET Amyloid Imaging: Normals, MCI &Dementia"""""""" and MERIT Award AG025516 """"""""Brain Amyloid and Cognition in Normal Elderly""""""""). We will test a series of linked hypotheses that postulate the neuropathologic substrates of some of the pathways by which elderly, depressed patients develop cognitive impairment and lead some to Alzheimer's disease.

Public Health Relevance

This research study will gather information that will improve understanding of why elderly depressed individuals have an increased risk of developing dementia. To meet this goal we will study participants from related studies, with new brain scanning methods that detect cerebrovascular disease and amyloid, one of the key substances that accumulates in the brains of individuals with Alzheimer's disease. If we can better identify individuals at risk for developing specific types of dementia, such as Alzheimer's disease, then they can be candidates for treatment at the earliest disease stages, as new dementia treatments become available.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH080240-04
Application #
8235036
Study Section
Adult Psychopathology and Disorders of Aging Study Section (APDA)
Program Officer
Evans, Jovier D
Project Start
2009-04-14
Project End
2014-01-31
Budget Start
2012-02-01
Budget End
2013-01-31
Support Year
4
Fiscal Year
2012
Total Cost
$495,855
Indirect Cost
$168,558
Name
University of Pittsburgh
Department
Psychiatry
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Gildengers, Ariel G; Butters, Meryl A; Albert, Steven M et al. (2016) Design and Implementation of an Intervention Development Study: Retaining Cognition While Avoiding Late-Life Depression (ReCALL). Am J Geriatr Psychiatry 24:444-54
Koenig, Aaron M; DeLozier, Isaac J; Zmuda, Michelle D et al. (2015) Neuropsychological functioning in the acute and remitted States of late-life depression. J Alzheimers Dis 45:175-85
Rej, Soham; Begley, Amy; Gildengers, Ariel et al. (2015) Psychosocial Risk Factors for Cognitive Decline in Late-Life Depression: Findings from the MTLD-III Study. Can Geriatr J 18:43-50
Kalache, Sawsan M; Mulsant, Benoit H; Davies, Simon J C et al. (2015) The impact of aging, cognition, and symptoms on functional competence in individuals with schizophrenia across the lifespan. Schizophr Bull 41:374-81
Nascimento, Kenia Kelly Fiaux do; Silva, Kelly P; Malloy-Diniz, Leandro F et al. (2015) Plasma and cerebrospinal fluid amyloid-β levels in late-life depression: A systematic review and meta-analysis. J Psychiatr Res 69:35-41
Diniz, B S; Sibille, E; Ding, Y et al. (2015) Plasma biosignature and brain pathology related to persistent cognitive impairment in late-life depression. Mol Psychiatry 20:594-601
Dombrovski, A Y; Szanto, K; Clark, L et al. (2015) Corticostriatothalamic reward prediction error signals and executive control in late-life depression. Psychol Med 45:1413-24
Koenig, Aaron M; Butters, Meryl A; Begley, Amy et al. (2014) Response to antidepressant medications in late-life depression across the spectrum of cognitive functioning. J Clin Psychiatry 75:e100-7
Hall, Charles A; Reynolds 3rd, Charles F; Butters, Meryl et al. (2014) Cognitive functioning in complicated grief. J Psychiatr Res 58:20-5
Koenig, Aaron M; Butters, Meryl A (2014) Cognition in Late Life Depression: Treatment Considerations. Curr Treat Options Psychiatry 1:1-14

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