- PROJECT 1 Presently, there can be considerable uncertainty in the clinical diagnosis of the common neurodegenerative pathological dementia syndromes [AD, LBD and FTD] antemortem because of clinical heterogeneity (wherein the dementia underlying pathology does not match the clinical syndrome), subtle symptoms early in the disease process, and frequent occurrence of mixed dementias. The central aim of this proposal is to develop a methodology that uses the wealth of clinical, imaging and pathology data collected in past and current ADRC funding cycles to improve the antemortem prediction of the dementia pathology and long-term clinical outcomes in new incoming patients. Our working hypothesis is that an individual subject's cognitive performance can be approximately modeled based on the subjects multi-modal imaging scans which are surrogates of pathology, cognitive reserve, MRI evidence of CVD and demographics. Based on this hypothesis, we plan to integrate clinical, pathology and imaging information on about 370+ demented patients with autopsy diagnosis and at least one imaging exam available before death from the past and current ADRC cycles and use this information for diagnosis and prognosis of new incoming patients. The overall methodology which we will create will operate as follows: 1) identify the patients ("matched subjects") in our database who match the new incoming patient based on the multi-modal images, cognitive reserve, vascular disease and demographics and 2) use the matched subjects to aid in the diagnosis and prognosis of the new patient.

Public Health Relevance

- PROJECT 1 What are the pathologies underlying the clinical dementia syndrome in this patient? is the principal question that clinicians would like to answer when faced with a demented patient. What is my prognosis? is a major question a patient or caregiver asks once they are given their dementia diagnosis. The goal of the Project 1 proposal is to build software that precisely answers these two questions by building large databases of dementia subjects with clinical, antemortem imaging and pathology assessment at autopsy.

Agency
National Institute of Health (NIH)
Type
Specialized Center (P50)
Project #
2P50AG016574-16
Application #
8676251
Study Section
Special Emphasis Panel (ZAG1)
Project Start
Project End
Budget Start
Budget End
Support Year
16
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
City
Rochester
State
MN
Country
United States
Zip Code
55905
Tosto, Giuseppe; Bird, Thomas D; Bennett, David A et al. (2016) The Role of Cardiovascular Risk Factors and Stroke in Familial Alzheimer Disease. JAMA Neurol 73:1231-1237
Karch, Celeste M; Ezerskiy, Lubov A; Bertelsen, Sarah et al. (2016) Alzheimer's Disease Risk Polymorphisms Regulate Gene Expression in the ZCWPW1 and the CELF1 Loci. PLoS One 11:e0148717
Ma, Li; Allen, Mariet; Sakae, Nobutaka et al. (2016) Expression and processing analyses of wild type and p.R47H TREM2 variant in Alzheimer's disease brains. Mol Neurodegener 11:72
Kantarci, Kejal; Lowe, Val J; Lesnick, Timothy G et al. (2016) Early Postmenopausal Transdermal 17β-Estradiol Therapy and Amyloid-β Deposition. J Alzheimers Dis 53:547-56
Zheng, Honghua; Liu, Chia-Chen; Atagi, Yuka et al. (2016) Opposing roles of the triggering receptor expressed on myeloid cells 2 and triggering receptor expressed on myeloid cells-like transcript 2 in microglia activation. Neurobiol Aging 42:132-41
Staubo, Sara C; Aakre, Jeremiah A; Vemuri, Prashanthi et al. (2016) Mediterranean diet, micronutrients and macronutrients, and MRI measures of cortical thickness. Alzheimers Dement :
Labbé, Catherine; Heckman, Michael G; Lorenzo-Betancor, Oswaldo et al. (2016) MAPT haplotype diversity in multiple system atrophy. Parkinsonism Relat Disord 30:40-5
McCutcheon, Sarah T; Han, Dingfen; Troncoso, Juan et al. (2016) Clinicopathological correlates of depression in early Alzheimer's disease in the NACC. Int J Geriatr Psychiatry 31:1301-1311
Forrester, Sarah N; Gallo, Joseph J; Smith, Gwenn S et al. (2016) Patterns of Neuropsychiatric Symptoms in Mild Cognitive Impairment and Risk of Dementia. Am J Geriatr Psychiatry 24:117-25
Day, Gregory S; Musiek, Erik S; Roe, Catherine M et al. (2016) Phenotypic Similarities Between Late-Onset Autosomal Dominant and Sporadic Alzheimer Disease: A Single-Family Case-Control Study. JAMA Neurol 73:1125-32

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