PI: Charles DeCarli, MD
Contact person: John Olichney [email protected]
Contact method: please contact site directly
VRADB Application required for sample access? No
Study Description
The NIA-funded UC Davis Alzheimer’s Disease Center (ADC) is the coherent synthesis of two sites, one is located at the VA Outpatient Clinic in Martinez, and the second is located at the University of California, Davis Medical Center (UCDMC) in Sacramento. The geographic dispersion of these two sites, separated by nearly 70 miles, affords a broad subject catchment area extending from San Francisco to the Sierra Foothills and Santa Clara to Sonoma. This geographical diversity also fosters the recruitment of large numbers of elderly persons who are highly diverse with regard to racial and ethnic composition, educational attainment, and other socio-economic factors. The ADC has multicultural staff with many years of experience in community outreach and a successful track record for recruiting African American, Hispanic and other ethnic minorities into its longitudinal cohort.
Consisting of 6 Cores (Administrative, Clinical, Database and Statistics, Neuropathology, Neuroimaging, Education and Information Transfer) the UCD ADC approach to supporting ongoing research is based on the belief that AD exists within the wider context of other factors that affect cognitive function. A variety of protective and risk conditions exist and combine to result in widely varying trajectories of cognitive aging. Understanding the sources for this heterogeneity is a central issue to research that has both scientific significance and clinical relevance, including relevance for potential treatment. Unraveling the multiple deleterious and protective factors that ultimately determine the variance in course of cognitive function with advancing age, however, remains an enormous challenge. To meet this challenge, the Clinical Core developed methods to enhance subject diversity amongst the participants within the longitudinal cohort of the UCD ADC leading to recruitment of a highly diverse study population that varies across multiple dimensions. Approximately 50% of our multi-ethnic cohort has cognitive impairment (dementia or MCI), while most of the others carry risk factors to develop cognitive decline (e.g. diabetes, other vascular risk factors) . Our center has a wide range of expertise, including in the early detection of AD using neuroimaging and other biomarkers, predicting cogntive decline and dementia in patients with MCI, clinical treatment trials, clinical assessment and treatment of dementia, biostatistics, structural and functional Magnetic Resonance imaging. We also maintain close collaborative relationships with the other Northern California centers specializing in AD research: UC San Francisco, UC Berkeley, and Stanford University.
Subjects:
We currently follow 527 participants in our Longitudinal Cohort with annual assessments. At entry, 35% had a diagnosis of Mild Cognitive Impairment (MCI), and ~50% were cognitively normal. Most recent assessments have yielded diagnoses of Alzheimer’s disease in 130 persons, 25 have other dementia etiologies, and 118 have MCI. Approximately 50% are Caucasian Non-Hispanic, 20% are Hispanic and 20% African American. The mean MMSE score in our cohort is 24. Approximately 75% have consented for Brain Autopsy. We have banked biospecimens on over 900 participants (n = 908 as of 3/1/2013).
Material available:
Serum, Plasma (EDTA) and DNA (Isolated from peripheral blood: RNA could also be extracted).
Collection method:
Subjects were consented at one of the three UC Davis ADC sites (Sacramento, Martinez VA, Mather VA). Blood is drawn by venipuncture. Serum tubes are left to sit for 0.5 to 1 hour to clot, then placed on ice. Plasma tubes are placed immediately on ice. One plasma tube is sent the UC Davis Medical Center Clinical Laboratory for determination of ApoE genotype. One plasma tube is set aside for isolation of genomic DNA (Qiagen max-prep). Remaining serum and plasma tubes are centrifuged at 4 deg C within 4 hours of collection.
Storage:
Serum, plasma, and DNA are stored at -80 deg C.
Other measurements availalbe for this cohort:
We have collected research structural MRI studies in over 650 participants, and nearly all of our current longitudinal cohort has received at least one Brain MRI. Most participants receive post-mortem neuropathological assessments. Over 100 persons in our longitudinal cohort have received amyloid imaging studies, predominantly with PiB tracer administered by Dr. Bill Jagust’s PET Lab at Lawrence Berkeley National Laboratory. We have extensive longitudinal neuropsychological data on our cohort, including the UDS and SENAS batteries.
Related Publications:
Bergt C, Nakano T, Ditterich J, DeCarli C, Eiserich JP. Oxidized plasma
high-density lipoprotein is decreased in Alzheimer's disease. Free Radical
Biology and Medicine 41:1542-1547, 2006.
Haan MN, Miller JW, Aiello AE, Whitmer RA, Jagust WJ, Mungas DM, Allen LH,
Green R. Homocysteine, B vitamins and incidence of dementia and cognitive
impairment: results from the Sacramento Area Latino Study on Aging.
American Journal of Clinical Nutrition 85:511-517, 2007. PMID: 17284751
Garrod MG, Green R, Allen LH, Mungas DM, Jagust WJ, Haan MN, Miller JW. The
fraction of total plasma vitamin B12 bound to transcobalamin correlates
with cognitive function in elderly Latinos with depressive symptoms.
Clinical Chemistry 54:1210-1217, 2008. PMID: 18451312
Jun G, Naj AC, Beecham GW, ... Alzheimer’s Disease Genetics Consortium*,
... Younkin SG. Meta-analysis confirms CR1, CLU, and PICALM as Alzheimer
disease risk loci and reveals interactions with APOE genotypes. Archives of
Neurology 67:1473-1484, 2010. PMID: 20697030 (*The UC Davis Alzheimer's
Disease Center is a member of the Alzheimer’s Disease Genetics Consortium)
Naj AC, Jun G, Beecham GW, ... DeCarli C, ... Ellis WG, ... Miller JW, ...
Schellenberg GD. Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are
associated with late-onset Alzheimer's disease. Nature Genetics 43:436-441,
2011. PMID: 21460841
Coppola G, Chinnathambi S, Lee JJ, ... Alzheimer's Disease Genetics
Consortium*, ... Geschwind DH. Evidence for a role of the rare p.A152T
variant in MAPT in increasing the risk for FTD-spectrum and Alzheimer's
diseases. Human Molecular Genetics 21:3500-3512, 2012. PMID: 22556362 (*The
UC Davis Alzheimer's Disease Center is a member of the Alzheimer’s Disease
Genetics Consortium)
Allen M, Zou F, Chai HS, ... Alzheimer’s Disease Genetics Consortium*, ...
Ertekin-Taner N. Novel late-onset Alzheimer’s disease loci variants
associate with brain gene expression. Neurology 79:221-228, 2012. PMID:
22722634 (*The UC Davis Alzheimer's Disease Center is a member of the
Alzheimer’s Disease Genetics Consortium)
Jun G, Vardarajan BN, Buros J, ... Alzheimer’s Disease Genetics
Consortium*, ... Farrer LA. Comprehensive search for Alzheimer disease
susceptibility loci in the APOE region. Archives of Neurology 69:1270-1279,
2012. PMID: 22869155 (*The UC Davis Alzheimer's Disease Center is a member
of the Alzheimer’s Disease Genetics Consortium)
Zou F, Chai HS, Younkin CS, ... Alzheimer’s Disease Genetics Consortium*,
... Ertekin-Taner N. Brain expression genome-wide association study (eGWAS)
identifies human disease-associated variants. PLoS Genetics 8:e1002707,
2012. PMID: 22685416 (*The UC Davis Alzheimer's Disease Center is a member
of the Alzheimer’s Disease Genetics Consortium)