Description (from grant):
A consortium of five studies was established to examine potential risk and protective factors that influence vulnerability to AD, including: gender, genetics, cognitive reserve, physical activity, personality, depression and vascular risk factors. The extensive longitudinal clinical and cognitive data, and rich biomarker collection from the consortium sites offer a unique opportunity to address these important issues.
The Preclinical AD Consortium was established in 2014 to accelerate understanding of the preclinical phase of AD. While each of these studies has federal funding to support the longitudinal collection of clinical, cognitive, genetic and biomarker data among individuals who were cognitively normal when first enrolled, it is understood that it is essential to combine their data together in order to address some of the most challenging questions related to the evolution of AD during its earliest phases. One of the primary goals of these studies has been to identify individuals at greatest risk for progression in order to facilitate early intervention. However, these studies have also been gathering information relevant to risk and protective factors that may influence vulnerability to disease. These factors are challenging to study because the effect of any one risk factor may be modest and large sample sizes are needed in order to examine potential interactions of effects, particularly as they pertain to biomarkers of disease. This application provides the unique opportunity to leverage the data prospectively collected by five ongoing studies of preclinical AD to examine a range of risk and protective factors that may influence risk for progression from normal cognition to mild cognitive impairment. We are also proposing additional biomarker assays (in blood and cerebrospinal fluid) and the generation of new genetic data, to address selected issues. The potential risk and protective factors the consortium is proposing to examine include: gender, genetics, cognitive reserve, physical activity, personality, depression and vascular risk factors. The consortium represented by this application, with its' extensive longitudinal clinical and cognitive data, and rich biomarker collection (including blood, CSF, MRI scans and PET scans) offers a unique opportunity to address these important issues.
Lin Z, Sur S, Liu P, Li Y, Jiang D, Hou X, Darrow J, Pillai JJ, Yasar S, Rosenberg P, Albert M, Moghekar A, Lu H. Blood-Brain Barrier Breakdown in Relationship to Alzheimer and Vascular Disease. Ann. Neurol. 2021 August;90(2):227-238. PMCID: PMC8805295.
Liu P, Jiang D, Albert M, Bauer CE, Caprihan A, Gold BT, Greenberg SM, Helmer KG, Jann K, Jicha G, Rodriguez P, Satizabal CL, Seshadri S, Singh H, Thompson JF, Wang DJJ, Lu H. Multi-vendor and multisite evaluation of cerebrovascular reactivity mapping using hypercapnia challenge. NeuroImage. 2021 December 15;245:118754. PMCID: PMC8783393.
Pettigrew C, Soldan A, Brichko R, Zhu Y, Wang MC, Kutten K, Bilgel M, Mori S, Miller MI, Albert M. Computerized paired associate learning performance and imaging biomarkers in older adults without dementia. Brain imaging and behavior. 2022 April;16(2):921-929. PubMed PMID: 34686968; PubMed Central PMCID: PMC9012682; DOI: 10.1007/s11682-021-00583-9.
Han H, Lin Z, Soldan A, Pettigrew C, Betz JF, Oishi K, Li Y, Liu P, Albert M, Lu H. Longitudinal Changes in Global Cerebral Blood Flow in Cognitively Normal Older Adults: A Phase-Contrast MRI Study. Journal of magnetic resonance imaging 2022; February 56(5):1538-1545. PubMed PMID: 35218111; PubMed Central PMCID: PMC9411265; DOI: 10.1002/jmri.28133.
Newton P, Tchounguen J, Pettigrew C, Lim C, Lin Z, Lu H, Moghekar A, Albert M, Soldan A; BIOCARD Research Team. Regional White Matter Hyperintensities and Alzheimer's Disease Biomarkers Among Older Adults with Normal Cognition and Mild Cognitive Impairment. J Alzheimers Dis. 2023;92(1):323-339. PMCID: PMC10041440.
Stouffer KM, Chen C, Kulason S, Xu E, Witter MP, Ceritoglu C, Albert MS, Mori S, Troncoso J, Tward DJ, Miller MI; Alzheimer’s Disease Neuroimaging Initiative. Early amygdala and ERC atrophy linked to 3D reconstruction of rostral neurofibrillary tau tangle pathology in Alzheimer's disease. Neuroimage Clin. 2023;38:103374. doi: 10.1016/j.nicl.2023.103374. Epub 2023 Mar 15. PMID: 36934675; PMCID: PMC10034129.
Lin Z, Lim C, Jiang D, Soldan A, Pettigrew C, Oishi K, Zhu Y, Moghekar A, Liu P, Albert M, Lu H. Longitudinal changes in brain oxygen extraction fraction (OEF) in older adults: Relationship to markers of vascular and Alzheimer's pathology. Alzheimers Dement. 2023 Feb;19(2):569-577. PMCID: PMC10838398
Xu F, Liu D, Zhu D, Hillis AE, Bakker A, Soldan A, Albert MS, Lin DDM, Qin Q. Test-retest reliability of 3D velocity-selective arterial spin labeling for detecting normal variations of cerebral blood flow. NeuroImage. 2023 May 1;271:120039. PMID: 36931331; PMCID: PMC10150252.
Rani N, Alm KH, Corona-Long CA, Speck CL, Soldan A, Pettigrew C, Zhu Y, Albert M, Bakker A. Tau PET burden in Brodmann areas 35 and 36 is associated with individual differences in cognition in non-demented older adults. Front Aging Neurosci. 2023 Dec 14;15:1272946. PMCID: PMC10757623.
Gou Y, Golden WC, Lin Z, Shepard J, Tekes A, Hu Z, Li X, Oishi K, Albert M, Lu H, Liu P, Jiang D. Automatic Rejection based on Tissue Signal (ARTS) for motion-corrected quantification of cerebral venous oxygenation in neonates and older adults. Magn Reson Imaging. 2024 Jan;105:92-99. doi: 10.1016/j.mri.2023.11.008. Epub 2023 Nov 7. PubMed PMID: 37939974; PubMed Central PMCID: PMC10841989.
Liu P, Lin Z, Hazel K, Pottanat G, Xu C, Jiang D, Pillai JJ, Lucke E, Bauer CE, Gold BT, Greenberg SM, Helmer KG, Jann K, Jicha G, Kramer J, Maillard P, Mulavelil RM, Rodriguez P, Satizabal CL, Schwab K, Seshadri S, Singh H, Velarde Dediós ÁG, Wang DJJ, Kalyani RR, Moghekar A, Rosenberg PB, Yasar S, Albert M, Lu H. Cerebrovascular reactivity MRI as a biomarker for cerebral small vessel disease-related cognitive decline: Multi-site validation in the MarkVCID Consortium. Alzheimers Dement. 2024 Aug;20(8):5281-5289. PMCID: PMC11350011.
Sur S, Lin Z, Li Y, Yasar S, Rosenberg PB, Moghekar A, Hou X, Jiang D, Kalyani RR, Hazel K, Pottanat G, Xu C, Pillai JJ, Liu P, Albert M, Lu H. CO2 cerebrovascular reactivity measured with CBF-MRI in older individuals: Association with cognition, physical function, amyloid and tau proteins. J Cereb Blood Flow Metab. 2024 Sep;44(9):1618-1628. PMCID: PMC11532674.