Crowdsourced estimation of cognitive decline and resilience in Alzheimer's disease.
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ABSTRACT:
SUBMITTER: Allen GI
PROVIDER: S-EPMC5474755 | biostudies-literature | 2016 Jun
REPOSITORIES: biostudies-literature
Publications
Crowdsourced estimation of cognitive decline and resilience in Alzheimer's disease.
Allen Genevera I GI Amoroso Nicola N Anghel Catalina C Balagurusamy Venkat V Bare Christopher J CJ Beaton Derek D Bellotti Roberto R Bennett David A DA Boehme Kevin L KL Boutros Paul C PC Caberlotto Laura L Caloian Cristian C Campbell Frederick F Chaibub Neto Elias E Chang Yu-Chuan YC Chen Beibei B Chen Chien-Yu CY Chien Ting-Ying TY Clark Tim T Das Sudeshna S Davatzikos Christos C Deng Jieyao J Dillenberger Donna D Dobson Richard J B RJ Dong Qilin Q Doshi Jimit J Duma Denise D Errico Rosangela R Erus Guray G Everett Evan E Fardo David W DW Friend Stephen H SH Fröhlich Holger H Gan Jessica J St George-Hyslop Peter P Ghosh Satrajit S SS Glaab Enrico E Green Robert C RC Guan Yuanfang Y Hong Ming-Yi MY Huang Chao C Hwang Jinseub J Ibrahim Joseph J Inglese Paolo P Iyappan Anandhi A Jiang Qijia Q Katsumata Yuriko Y Kauwe John S K JS Klein Arno A Kong Dehan D Krause Roland R Lalonde Emilie E Lauria Mario M Lee Eunjee E Lin Xihui X Liu Zhandong Z Livingstone Julie J Logsdon Benjamin A BA Lovestone Simon S Ma Tsung-Wei TW Malhotra Ashutosh A Mangravite Lara M LM Maxwell Taylor J TJ Merrill Emily E Nagorski John J Namasivayam Aishwarya A Narayan Manjari M Naz Mufassra M Newhouse Stephen J SJ Norman Thea C TC Nurtdinov Ramil N RN Oyang Yen-Jen YJ Pawitan Yudi Y Peng Shengwen S Peters Mette A MA Piccolo Stephen R SR Praveen Paurush P Priami Corrado C Sabelnykova Veronica Y VY Senger Philipp P Shen Xia X Simmons Andrew A Sotiras Aristeidis A Stolovitzky Gustavo G Tangaro Sabina S Tateo Andrea A Tung Yi-An YA Tustison Nicholas J NJ Varol Erdem E Vradenburg George G Weiner Michael W MW Xiao Guanghua G Xie Lei L Xie Yang Y Xu Jia J Yang Hojin H Zhan Xiaowei X Zhou Yunyun Y Zhu Fan F Zhu Hongtu H Zhu Shanfeng S
Alzheimer's & dementia : the journal of the Alzheimer's Association 20160411 6
Identifying accurate biomarkers of cognitive decline is essential for advancing early diagnosis and prevention therapies in Alzheimer's disease. The Alzheimer's disease DREAM Challenge was designed as a computational crowdsourced project to benchmark the current state-of-the-art in predicting cognitive outcomes in Alzheimer's disease based on high dimensional, publicly available genetic and structural imaging data. This meta-analysis failed to identify a meaningful predictor developed from eithe ...[more]
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Project description:Introduction: Functional imaging studies have demonstrated the recruitment of additional neural resources as a possible mechanism to compensate for age and Alzheimer's disease (AD)-related cerebral pathology, the efficacy of which is potentially modulated by underlying structural network connectivity. Additionally, structural network efficiency (SNE) is associated with intelligence across the lifespan, which is a known factor for resilience to cognitive decline. We hypothesized that SNE may be a surrogate of the physiological basis of resilience to cognitive decline in elderly persons without dementia and with age- and AD-related cerebral pathology.Methods: We included 85 cognitively normal elderly subjects or mild cognitive impairment (MCI) patients submitted to baseline diffusion imaging, liquor specimens, amyloid-PET and longitudinal cognitive assessments. SNE was calculated from baseline MRI scans using fiber tractography and graph theory. Mixed linear effects models were estimated to investigate the association of higher resilience to cognitive decline with higher SNE and the modulation of this association by increased cerebral amyloid, liquor tau or WMHV. Results: For the majority of cognitive outcome measures, higher SNE was associated with higher resilience to cognitive decline (p-values: 0.011-0.039). Additionally, subjects with higher SNE showed more resilience to cognitive decline at higher cerebral amyloid burden (p-values: <0.001-0.036) and lower tau levels (p-values: 0.002-0.015).Conclusion: These results suggest that SNE to some extent may quantify the physiological basis of resilience to cognitive decline most effective at the earliest stages of AD, namely at increased amyloid burden and before increased tauopathy.
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Project description:BackgroundPast research has focused on risk factors for developing dementia, with increasing recognition of "resilient" people who live to old age with intact cognitive function despite pathological features of Alzheimer's disease (AD).ObjectiveTo evaluate demographic factors, mid-life characteristics, and non-AD neuropathology findings that may be associated with cognitive resilience to AD pathology.MethodsWe analyzed data from 276 autopsy cases with intermediate or high levels of AD pathology from the Adult Changes in Thought study. We defined cognitive resilience as having Cognitive Abilities Screening Instrument scores ≥86 within two years of death and no clinical dementia diagnosis; non-resilient people had dementia diagnoses from AD or other causes before death. We compared mid-life characteristics, demographics, and additional neuropathology findings between resilient and non-resilient people. We used multivariable logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for being resilient compared to not being resilient adjusting for demographic and neuropathology factors.ResultsWe classified 68 (25%) people as resilient and 208 (75%) as not resilient. A greater proportion of resilient people had a college degree (50%) compared with non-resilient (32%, p = 0.01). The odds of being resilient were significantly increased among people with a college education (OR = 2.01, 95% CI = 1.01-3.99) and significantly reduced among people with additional non-AD neuropathology findings such as hippocampal sclerosis (OR = 0.28, 95% CI = 0.09-0.89) and microinfarcts (OR = 0.34, 95% CI = 0.15-0.78).ConclusionIncreased education and absence of non-AD pathology may be independently associated with cognitive resilience, highlighting the importance of evaluating co-morbid factors in future research on mechanisms of cognitive resilience.
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