The memory and thinking changes characteristic of Alzheimer disease (AD) are now known to be preceded by over a decade of brain amyloid deposition in cognitively normal older adults. The overarching goal of this renewal application is to characterize the indicators of the transition from cognitive normality to the earliest stages of symptomatic AD. However, the substantial heterogeneity in the cognitive abilities of older adults can blur this threshold. To address this concern, Project 1 proposes to identify the cognitive indicators (collected through Core B: Clinical) of the transition and to substantiate these cognitive markers with resting state functional connectivity MRI (rs-fcMRI;collected through Core E: Imaging). We hypothesize that the irreversible transition from cognitive normality to symptomatic AD can be detected by impairment in attentional control, impaired learning on cognitive measures and disruption in resting state networks (RSNs). To test this hypothesis, we propose the following Specific Aims: 1) To evaluate sensitive measures of cognitive performance as indicators of preclinical AD and as predictors of the development of symptomatic AD. 2) To evaluate alterations in RSNs using rs-fcMRI as indicators of preclinical AD and as predictors of the development of symptomatic AD. 3) To examine the relationship between the cognitive performance measures in SA1 with the RSN alterations in SA2, both cross-sectionally and longitudinally on the rate of change. 4) To relate the cognitive and rs-fcMRI findings in Project 1 with findings from all other Projects and Cores to develop a model that optimally characterizes the transition from cognitive normality to symptomatic AD. In particular, Project 1 findings will be examined in relation to the sleep variables and cerebrospinal fluid measures obtained in Project 2, genetic variants of AD progression in Project 3, volumetric and amyloid imaging data in Core E: Imaging, [and the molecular pathology of AD and markers of synaptic integrity and neuronal number (particularly in the relevant brain regions such as the dorsal anterior cingulate) obtained in Core D: Neuropathology]. .
As instructed by the funding opportunity announcement for this application (PAR-13-329), only the Overall component contains a project narrative. Cores and projects were instructed not to include this section.
|Su, Yi; Blazey, Tyler M; Snyder, Abraham Z et al. (2015) Partial volume correction in quantitative amyloid imaging. Neuroimage 107:55-64|
|Shim, Yong Soo; Yang, Dong-Won; Roe, Catherine M et al. (2015) Pathological correlates of white matter hyperintensities on magnetic resonance imaging. Dement Geriatr Cogn Disord 39:92-104|
|Wang, Li-San; Naj, Adam C; Graham, Robert R et al. (2015) Rarity of the Alzheimer disease-protective APP A673T variant in the United States. JAMA Neurol 72:209-16|
|Ghoshal, Nupur; Perry, Arie; McKeel, Daniel et al. (2015) Variably Protease-sensitive Prionopathy in an Apparent Cognitively Normal 93-Year-Old. Alzheimer Dis Assoc Disord 29:173-6|
|Hurth, Kyle; Tarawneh, Rawan; Ghoshal, Nupur et al. (2015) Whipple's disease masquerades as dementia with Lewy bodies. Alzheimer Dis Assoc Disord 29:85-9|
|Aschenbrenner, Andrew J; Balota, David A; Tse, Chi-Shing et al. (2015) Alzheimer disease biomarkers, attentional control, and semantic memory retrieval: Synergistic and mediational effects of biomarkers on a sensitive cognitive measure in non-demented older adults. Neuropsychology 29:368-81|
|Lim, Miranda M; Gerstner, Jason R; Holtzman, David M (2014) The sleep-wake cycle and Alzheimer's disease: what do we know? Neurodegener Dis Manag 4:351-62|
|Pizzie, Rachel; Hindman, Halley; Roe, Catherine M et al. (2014) Physical activity and cognitive trajectories in cognitively normal adults: the adult children study. Alzheimer Dis Assoc Disord 28:50-7|
|Fagan, Anne M; Xiong, Chengjie; Jasielec, Mateusz S et al. (2014) Longitudinal change in CSF biomarkers in autosomal-dominant Alzheimer's disease. Sci Transl Med 6:226ra30|
|Harari, Oscar; Cruchaga, Carlos; Kauwe, John S K et al. (2014) Phosphorylated tau-A?42 ratio as a continuous trait for biomarker discovery for early-stage Alzheimer's disease in multiplex immunoassay panels of cerebrospinal fluid. Biol Psychiatry 75:723-31|
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