Default mode network activation and prose recall performance

Poster Presentations: P3 Background: There is evidence that physical fitness positively effects brain activity patterns on functional MRI (fMRI) tasks in nondemented older adults. Individuals with Alzheimer’s Disease (AD) show abnormal patterns of brain activation when doing learning and memory tasks in fMRI. We investigated whether higher levels of physical fitness might positively mediate brain activation in both healthy elderly and AD individuals during a learning and memory fMRI paradigm. Methods: Twenty-three older adults (12 AD, 11 nondemented) completed maximal exercise testing and an fMRI session. Peak oxygen consumption (VO 2 peak) was used as a measure of cardiorespiratory fitness. Structural and functional imaging was performed. Functional imaging included a visual memory task which they were asked recall if they had seen an image in a set standardized indoor and outdoor visual scenes they were previously exposed to. BOLD images were rigid-body transformed to the first image, slice timing corrected (sinc-interpolation), normalized to MNI space, and smoothed using an 8mm FWHM Gaussian kernel. Group differences were explored and VO 2 peak was regressed against activation maps, controlling for age. Activation maps were masked to regions of high gray matter probability across each group and a threshold for significance was set at P<0.001, k>¼5 for these exploratory analyses. Results: Across all individuals, bilateral visual cortex fusiform gyrus and right dorsolateral prefrontal cortex were active during picture recall. Individuals without dementia showed increased activation in right temporal pole, hippocampus/ parahippocampus and left middle temporal lobe compared to individuals with AD during the recall task. In the nondemented group, better fitness (higher VO 2 peak) was associated with less activation of left middle temporal lobe during recall. In the AD group, better fitness was associated with less activation of left cerebellum during recall, a region previously reported to show increase activation in AD during recall tasks. Conclusions: Previous studies have identified associations between fitness levels and brain activation during cognitive tasks. Our results extend these findings to suggest that regional recruitment during visual recall may be modulated both by dementia and fitness level. These findings support further investigation of the effects of fitness and exercise training on memory in the earliest stages of dementia. P3-169

FUNCTIONAL NEUROIMAGING OF PROSE RECALL IN HEALTHY AND PATHOLOGICAL AGING

David Johnson1, Clarice Wang2, 1University of Kansas, Lawrence, Kansas, United States; 2University of Kansas, Kansas City, Kansas, United States. Background: Prose recall (e.g., Anna Thompson) has been suggested as a diagnostically sensitive test of episodic memory declines in AD; however, the neurocognitive process associated with failing recall in AD has not been defined. We use theories of discourse processing to map distinct patterns of brain activation during encoding and correlate activations with proposed cognitive mechanisms. Understanding subtle neurocognitive differences between healthy aging and very mild AD will provide insight into early stages of this brain disease. Methods: Healthy younger adults (YA), healthy older adults (HOA), and adults with very mild AD (AD; CDR¼0.5) were included in this study. We used a 3.0 Tesla head-only scanner to collect gradient echo blood oxygen level dependent (BOLD) scans during participants’ comprehension of two different prose genres, expository and narrative. All stories were binaurally presented. Identical stories were also presented in Korean, used as a baseline activation control for audition of similar speech sounds and patterns. Conclusions: We found both a significant age and dementia effect dependent on prose genre. Comprehension of expository prose discriminated young adults from healthy older adults. Comprehension of narrative prose discriminated healthy older adults from AD adults. Aging involves noncompensatory overrecruitment of cognitive control areas for long term memory and AD involves specific attentional deficits. This study further supports the sensitivity of a prose comprehension task as a diagnostic tool for AD. P3-170

DEFAULT MODE NETWORK ACTIVATION AND PROSE RECALL PERFORMANCE

Eric Vidoni1, David Johnson2, Cheryl Diao2, Robyn Honea2, Jeffrey Burns3, 1University of Kansas, Kansas City, Kansas, United States;

P511

2 University of Kansas, Lawrence, Kansas, United States; 3University of Kansas School of Medicine, Kansas City, Kansas, United States.

Background: Different patterns of brain activity measured by fMRI (BOLD signal variation) in resting state older adults have been associated with cognitive impairment and Alzheimer’s disease (AD). Individuals with AD possess altered default mode network (DMN) activation and lower neuropsychological test performance, especially on measures of episodic memory. Episodic memory is typically measured by list learning tasks; however, recall for prose story (e.g., Anna Thompson) is a common index of episodic memory and has been shown to be very sensitive to detect early stage dementia. Methods: Eleven older adults completed an fMRI session and the Logical Memory of the WAIS was administered as part of a 1.5 hour Neuropsychological test battery at the University of Kansas Alzheimer Disease Center. Functional image processing was performed using Analysis of Functional Neuroimages. Functional imaging included a task-negative quiescent run with eyes closed. BOLD images were slice timing corrected, registered to the first volume, normalized to Talairach space, and smoothed using a 6mm FWHM Gaussian kernel. This signal was regressed across the brain after correcting for signal associated with motion parameters, deep white matter and CSF signal. The resulting residual BOLD signal was extracted from a 12mm sphere the precuneus and regressed across the whole brain. Resulting correlation maps were standardized and Goodness-of-Fit (GOF) with a DMN template was calculated. Results: After controlling for a between group age difference, Logical Memory scores significantly predicted both DMN activation and Group status (cognitively normal older adult controls and older adults with very mild dementia [CDR 0.5]). DMN activation in the controls was highly predictive of Logical Memory subtest performance (r¼.87) and this association was attenuated in individuals with very mild dementia (r¼.39). Between group tests revealed that these differences were significant (t[10]¼2.2, p<.05). Conclusions: Our preliminary results confirm that prose recall performance is a sensitive indicator of the dementia status and dementia-related differences in default mode network activation.

P3-171

A MULTIVARIATE GLUCOSE METABOLISM METRIC FOR PATIENT STRATIFICATION AND PREDICTION OF COGNITIVE DECLINE IN ALZHEIMER’S DISEASE CLINICAL TRIALS

Dawn Matthews1, Lisa Mosconi2, Ana S. Lukic3, Randolph Andrews4, Miles Wernick5, Mark Schmidt6, Stephen Strother7, 1Abiant, Inc. / ADMdx, Grayslake, Illinois, United States; 2Abiant, Inc. / ADM Diagnostics, Grayslake, Illinois, United States; 3ADM Diagnostics, LLC; Predictek, Inc., Chicago, Illinois, United States; 4Abiant, Inc / ADM Diagnostics, Grayslake, Illinois, United States; 5ADM Diagnostics, LLC, Predictek, Inc., Illinois Institute of Technology, Chicago, Illinois, United States; 6Janssen Research and Development, Beerse, Belgium; 7ADM Diagnostics, LLC, Predictek, Inc., Rotman Research Institute, Toronto, Ontario, Canada. Background: The variability of cognitive status and clinical progression in AD patient populations poses a major confound in clinical trials. While regional cerebral glucose metabolism (rCMglc) has been found to correlate with and predict clinical worsening in AD, the complexity of multi-region involvement and lack of consistent correlation across accepted cognitive metrics have limited its use as a biomarker. We show that a multivariate classifier approach can provide a single, interpretable biomarker of rCMglc that allows baseline stratification and prediction of subsequent cognitive deterioration. Methods: The FDG-PET scans, MMSE, CDR sum of box (CDRsb), and ADAS-11 scores of 55 AD patients from the ADNI database (76+7 yrs, 33M/22F) having 24 months of data were analyzed to assess relationships between baseline status and longitudinal progression. FDG-PET scans were sampled using automated regions of interest (ROI) for parietal cortex, posterior cingulate/precuneus, medial temporal cortex, hippocampal subregion (HIP), prefrontal cortex, lateral temporal cortex (LTL), and occipital cortex. Additionally, we applied an FDG-PET multivariate canonical variates (CV) classifier developed to characterize the progression from