- Email: [email protected]
A SENSITIVE FUNCTIONAL EARLY MARKER FOR AD: OLFACTORY FUNCTIONAL CONNECTIVITY
P838
Poster Presentations: P4
atrophy has not been well defined. In order to determine the relationship between Ab and atrophy, we compared the performance of the usual dichotomization of cerebrospinal fluid (CSF) Ab to identify subjects as Ab+ and Ab- with a trilinear spline model of CSF Ab. Methods: 183 subjects with mild cognitive impairment and 108 cognitively normal controls with baseline CSF A b and up to 4 years of longitudinal MRI data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) were analyzed using mixed-effects regression. Piecewise-linear splines were used to evaluate the nonlinear nature of the association between A b and regional atrophy and to identify points of acceleration of atrophy with respect to A b. Several parameterizations of A b were compared using likelihood ratio tests. Periods of acceleration of atrophy in which subjects transition from A b negativity to A b positivity were estimated from the spline models and tested for significance. Results: Spline models resulted in better fits for many temporal and parietal regions compared with the dichotomous models. The trilinear model showed that periods of acceleration of atrophy varied greatly by region with early changes seen in the insula, amygdala, precuneus, hippocampus, and other temporal regions, occurring prior to the clinical threshold for A b positivity. Conclusions: The use of piecewise-linear splines provides an improved model of the nonlinear association between A b and regional atrophy in regions implicated in the progression of Alzheimer’s disease. P4-138
A SENSITIVE FUNCTIONAL EARLY MARKER FOR AD: OLFACTORY FUNCTIONAL CONNECTIVITY
Prasanna Karunanayaka1, Qing X. Yang2, Jianli Wang1, Megha Vasavada1, Paul Eslinger1, Robet McHugh1, 1Penn State Hershey College of Medicine, Hershey, Pennsylvania, United States; 2Penn State Hershey College of Medicine, Hershey, Pennsylvania, United States. Contact e-mail: qyang@ psu.edu Background: AD has marked decline in olfaction at a very early stage [1, 2].The relationship between functional deficits and underlying AD pathology remains undefined. In this study, we identified the primary olfactory network (PON) and its relationship with the cognitively-related functional network, i.e. default mode network (DMN) using olfactory fMRI and independent component analysis (ICA). Methods: 12 AD subjects (mean age ¼ 73.7 yrs), 19 aMCI (mean age ¼ 72.8 yrs), and 36 CN (mean age ¼ 69.5 years) were administered the University of Pennsylvania Smell Identification Test (UPSIT) [3] and studied using olfactory fMRI. The olfactory stimulation paradigm includes a visual cue "smell?" synchronized with interleaved odor and no-odor conditions (Fig. 1). G roup ICA was performed by combining all three groups [2, 4] prior to applying the ICA algorithm. Responsiveness (average correlation) of each network to odor stimulation
events was calculated throughout the olfactory paradigm. Results: Fig. 2a shows each group IC map of the PON, including the primary olfactory cortex (POC), amygdala, hippocampus, insula, striatum, and putamen. Fig. 2b shows the IC map of DMN derived from the same olfactory fMRI paradigm. Both IC maps exhibit prominent deterioration in aMCI and AD groups, following a similar descending trend observed in the UPSIT scores and PON responsiveness (Fig. 3). Most interestingly, while the responsiveness of PON in aMCI is significantly lower than CN and different from AD under no-odor conditions, the aMCI group showed the same level of responsiveness in AD under the odor condition. This indicates that olfactory functional degeneration, detected by the odor stimulation, is significantly deteriorated as early as the aMCI stage. This potentially provides a sensitive marker in detection of AD functional degeneration in the MCI stage and potentially earlier. Conclusions: The fMRI paradigm provided a simple straightforward method for detecting functional degeneration of the olfactory and DMN networks in AD and aMCI. Evident deterioration in the responsiveness of the PON and DMN is demonstrated in aMCI and AD, providing neural substrate of AD clinical presentation and an objective marker for early diagnosis.
Fig. 2. Two IC networks found during olfactory fMRI stimulation in Healthy Controls (HC), aMCI and AD subjects. The IC1 activation map encompasses the PON (POC, amygdala, hippocampus). The IC2 map encompassed the DMN (PCC, IPL, ventral medial prefrontal cortex).
Fig. 3. (a). Behavioral scores for the smell function (UPSIT scores) in HC, MCI and AD. (b). The PON network responsiveness in respective cohorts for odor and no-odor conditions. * Two-sample t-test (p< 0.05) P4-139
RESTING STATE FUNCTIONAL CONNECTIVITY OF EXECUTIVE NETWORK PREDICTS THE PERFORMANCE OF COGNITIVE FUNCTION
Rakesh Balachandar1, Srikala Bharath2, John P. John3, Jitender Saini2, Keshava Kumar1, Himanshu Joshi1, Subramonium Aiyappan1, Shilpa Sadanand1, Preeti Sinha1, Mathew Varghese2, 1National Institute of Mental Health and Neurosciences, Bangalore, India; 2National Institute of Mental Health And Neuroscieces, Bangalore, India; 3National Institute of Mental Health And Neurosciences, Bangalore, India. Contact e-mail: [email protected]
Fig. 1. The bars of different height represent different odor intensities. The odor presentation is synchronized with visual cues. Each visual cue (“smell?”) is a condition in the four-intensity paradigm and interleaved with (and without) odor stimulation epochs. Prior to fMRI scanning, all subjects were trained to keep the respiration rate and volume consistent.
Background: Executive dysfunction arising from involvement of prefrontal cortex is one of the hallmarks of early Alzheimer’s disease (AD). Restingstate functional connectivity (RSFC) of brain refers to interregional synchrony of low frequency fluctuations of functional magnetic resonance imaging (fMRI) blood oxygen-level dependent signal acquired during resting state. Multiple large scale spatially distributed networks can be defined by such synchronous activity of brain during rest. Executive network (EN) is one such resting-state network that comprises of brain regions critical for executive functioning (medial prefrontal cortex and paracingulate regions). These brain regions have been shown to be activated during performing task-based fMRI paradigms involving executive functions. Disruption of RSFC involving EN is reported among early stages of AD. Verbal fluency task (VFT) is commonly used for assessing executive function. Rest-fMRI is advantageous, as the interpretation is not confounded by differences in task performance and active participation. This study explores the role of RSFC of EN on VFT performance in a group of patients
Poster Presentations: P4
atrophy has not been well defined. In order to determine the relationship between Ab and atrophy, we compared the performance of the usual dichotomization of cerebrospinal fluid (CSF) Ab to identify subjects as Ab+ and Ab- with a trilinear spline model of CSF Ab. Methods: 183 subjects with mild cognitive impairment and 108 cognitively normal controls with baseline CSF A b and up to 4 years of longitudinal MRI data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) were analyzed using mixed-effects regression. Piecewise-linear splines were used to evaluate the nonlinear nature of the association between A b and regional atrophy and to identify points of acceleration of atrophy with respect to A b. Several parameterizations of A b were compared using likelihood ratio tests. Periods of acceleration of atrophy in which subjects transition from A b negativity to A b positivity were estimated from the spline models and tested for significance. Results: Spline models resulted in better fits for many temporal and parietal regions compared with the dichotomous models. The trilinear model showed that periods of acceleration of atrophy varied greatly by region with early changes seen in the insula, amygdala, precuneus, hippocampus, and other temporal regions, occurring prior to the clinical threshold for A b positivity. Conclusions: The use of piecewise-linear splines provides an improved model of the nonlinear association between A b and regional atrophy in regions implicated in the progression of Alzheimer’s disease. P4-138
A SENSITIVE FUNCTIONAL EARLY MARKER FOR AD: OLFACTORY FUNCTIONAL CONNECTIVITY
Prasanna Karunanayaka1, Qing X. Yang2, Jianli Wang1, Megha Vasavada1, Paul Eslinger1, Robet McHugh1, 1Penn State Hershey College of Medicine, Hershey, Pennsylvania, United States; 2Penn State Hershey College of Medicine, Hershey, Pennsylvania, United States. Contact e-mail: qyang@ psu.edu Background: AD has marked decline in olfaction at a very early stage [1, 2].The relationship between functional deficits and underlying AD pathology remains undefined. In this study, we identified the primary olfactory network (PON) and its relationship with the cognitively-related functional network, i.e. default mode network (DMN) using olfactory fMRI and independent component analysis (ICA). Methods: 12 AD subjects (mean age ¼ 73.7 yrs), 19 aMCI (mean age ¼ 72.8 yrs), and 36 CN (mean age ¼ 69.5 years) were administered the University of Pennsylvania Smell Identification Test (UPSIT) [3] and studied using olfactory fMRI. The olfactory stimulation paradigm includes a visual cue "smell?" synchronized with interleaved odor and no-odor conditions (Fig. 1). G roup ICA was performed by combining all three groups [2, 4] prior to applying the ICA algorithm. Responsiveness (average correlation) of each network to odor stimulation
events was calculated throughout the olfactory paradigm. Results: Fig. 2a shows each group IC map of the PON, including the primary olfactory cortex (POC), amygdala, hippocampus, insula, striatum, and putamen. Fig. 2b shows the IC map of DMN derived from the same olfactory fMRI paradigm. Both IC maps exhibit prominent deterioration in aMCI and AD groups, following a similar descending trend observed in the UPSIT scores and PON responsiveness (Fig. 3). Most interestingly, while the responsiveness of PON in aMCI is significantly lower than CN and different from AD under no-odor conditions, the aMCI group showed the same level of responsiveness in AD under the odor condition. This indicates that olfactory functional degeneration, detected by the odor stimulation, is significantly deteriorated as early as the aMCI stage. This potentially provides a sensitive marker in detection of AD functional degeneration in the MCI stage and potentially earlier. Conclusions: The fMRI paradigm provided a simple straightforward method for detecting functional degeneration of the olfactory and DMN networks in AD and aMCI. Evident deterioration in the responsiveness of the PON and DMN is demonstrated in aMCI and AD, providing neural substrate of AD clinical presentation and an objective marker for early diagnosis.
Fig. 2. Two IC networks found during olfactory fMRI stimulation in Healthy Controls (HC), aMCI and AD subjects. The IC1 activation map encompasses the PON (POC, amygdala, hippocampus). The IC2 map encompassed the DMN (PCC, IPL, ventral medial prefrontal cortex).
Fig. 3. (a). Behavioral scores for the smell function (UPSIT scores) in HC, MCI and AD. (b). The PON network responsiveness in respective cohorts for odor and no-odor conditions. * Two-sample t-test (p< 0.05) P4-139
RESTING STATE FUNCTIONAL CONNECTIVITY OF EXECUTIVE NETWORK PREDICTS THE PERFORMANCE OF COGNITIVE FUNCTION
Rakesh Balachandar1, Srikala Bharath2, John P. John3, Jitender Saini2, Keshava Kumar1, Himanshu Joshi1, Subramonium Aiyappan1, Shilpa Sadanand1, Preeti Sinha1, Mathew Varghese2, 1National Institute of Mental Health and Neurosciences, Bangalore, India; 2National Institute of Mental Health And Neuroscieces, Bangalore, India; 3National Institute of Mental Health And Neurosciences, Bangalore, India. Contact e-mail: [email protected]
Fig. 1. The bars of different height represent different odor intensities. The odor presentation is synchronized with visual cues. Each visual cue (“smell?”) is a condition in the four-intensity paradigm and interleaved with (and without) odor stimulation epochs. Prior to fMRI scanning, all subjects were trained to keep the respiration rate and volume consistent.
Background: Executive dysfunction arising from involvement of prefrontal cortex is one of the hallmarks of early Alzheimer’s disease (AD). Restingstate functional connectivity (RSFC) of brain refers to interregional synchrony of low frequency fluctuations of functional magnetic resonance imaging (fMRI) blood oxygen-level dependent signal acquired during resting state. Multiple large scale spatially distributed networks can be defined by such synchronous activity of brain during rest. Executive network (EN) is one such resting-state network that comprises of brain regions critical for executive functioning (medial prefrontal cortex and paracingulate regions). These brain regions have been shown to be activated during performing task-based fMRI paradigms involving executive functions. Disruption of RSFC involving EN is reported among early stages of AD. Verbal fluency task (VFT) is commonly used for assessing executive function. Rest-fMRI is advantageous, as the interpretation is not confounded by differences in task performance and active participation. This study explores the role of RSFC of EN on VFT performance in a group of patients