- Email: [email protected]
FUNCTIONAL AND STRUCTURAL DEGENERATIONS OF THE CENTRAL OLFACTORY SYSTEM IN AD AND MCI: AN EARLY MARKER
P50
Poster Presentations: IC-P
significantly worse than Stage 0 on challenging tests of memory for names (FNAME p¼0.042) and occupations (FNAME p¼0.033), 2 nd list learning on the Memory Capacity Test (MCT DR, p¼0.017), executive function (working memory WM, p¼0.016; Letter Number Sequencing LNSq , p¼0.027) and naming (BNT p¼0.026). Stage 2 performed significantly worse than Stage 0 on more standard memory tests such as the Free and Cued Selective Reminding Test (FRsrt p¼0.015; FCsrt p¼0.010) and worse than Stage 1 on challenging memory (MCT IR p¼0.029, MCT DR p¼0.009 and MCT CR p¼0.002) and executive function tests (LNSq p¼0.001, Trails A p¼0.034 and WM p¼0.042). SNAP performed similar to Stage 0 on standard and challenging memory tests but worse on executive tests (fluency, p¼0.031, WM p¼0.012, and LNSq p¼0.030). Conclusions: These findings suggest that subtle cognitive changes are associated with different biomarker stages in CN older adults.Amyloidosis is associated with impairment on both challenging memory and executive tests. Neurodegeneration is associated with more executive dysfunction than memory. The combination of amyloidosis and neurodegeneration results in more significant decline in memory and executive performance. IC-P-088
FUNCTIONAL AND STRUCTURAL DEGENERATIONS OF THE CENTRAL OLFACTORY SYSTEM IN AD AND MCI: AN EARLY MARKER
Qing X. Yang1, 1Penn State College of Medicine, Hershey, Pennsylvania, United States. Background: AD pathology is first found in the olfactory areas and olfactory deficits are prevalent in the early AD and MCI patients (1-4). These provide an opportunity for determining the direct relationship between pathological changes in the site of early degeneration and the associated functional deficit. Studying such a relationship has been difficult and confounded with neurocognitive variables. Our objective is to understand the olfactory deficits occurring in the early AD and develop diagnostic tools for early detection, monitoring and understanding the functional-pathological processes of AD. Methods: Sixty-three subjects including 15 AD, 21 MCI and 27 age-matched CN were studied with cognitive tests, the University of Pennsylvania Smell Identification Test (UPSIT) and fMRI using an olfactory stimulation paradigm in Fig. 1. The regions of interest (ROI) including the primary olfactory cortex (POC) and hippocampus were manually segmented on MRI T1 images for each subject using fslview and then SPM 8 was used to analyze the fMRI data. Results: The relationship of olfactory activation change and the local atrophy was quantified using the ratio of the activated volumes and the volumes of the POC and hippocampus. Shown in Fig. 2, MCI and AD had more than two-fold reduction in percent activated volume compared to the CN group in both the hippocampus and the POC. The MCI showed nearly the same level of deficit in percent activated volume as the AD group. The percent volume activated was reduced in both groups by up to 55.4% for the hippocampus and by up to 52.2% for the POC. Significant brain atrophy was observed in the hippocampus (P < 0.0001) and the POC (P < 0.001). Both MCI and AD subjects had significantly smaller hippocampus (P < 0.0001) and POC (P ¼ 0.001) than the CN group. The volumes of the two brain structures were positively correlated among the three cohorts (r ¼ 0.55, P < 0.0001). Conclusions: Olfactory fMRI detected earlier functional changes in the MCI group than behavioral and volumetric measurement in POC and hippocampus. Olfactory fMRI has potential to aid early diagnosis of AD and MCI.
Fig 1. Olfactory fMRI paradigm. The above cycles 4x. The 4 lavender concentrations are presented 3x each. Every time “Smell?” appears on the screen the subject must respond yes if they smell lavender and no if they do not.
Fig. 2. Percent activated volume and volumes of the bilateral hippocampus and primary olfactory cortex (POC) (mean 6 standard error). The percent activated volume in the hippocampus (A) and POC (B) in MCI and AD subjects was decreased by more than 50 percent than that of the CN. The hippocampus (C) and POC (D) were significantly smaller in volume in both MCI and AD compared to CN.
IC-P-089
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 College of Medicine, Hershey, Pennsylvania, United States. Contact e-mail: [email protected] 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). Group 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
Poster Presentations: IC-P
significantly worse than Stage 0 on challenging tests of memory for names (FNAME p¼0.042) and occupations (FNAME p¼0.033), 2 nd list learning on the Memory Capacity Test (MCT DR, p¼0.017), executive function (working memory WM, p¼0.016; Letter Number Sequencing LNSq , p¼0.027) and naming (BNT p¼0.026). Stage 2 performed significantly worse than Stage 0 on more standard memory tests such as the Free and Cued Selective Reminding Test (FRsrt p¼0.015; FCsrt p¼0.010) and worse than Stage 1 on challenging memory (MCT IR p¼0.029, MCT DR p¼0.009 and MCT CR p¼0.002) and executive function tests (LNSq p¼0.001, Trails A p¼0.034 and WM p¼0.042). SNAP performed similar to Stage 0 on standard and challenging memory tests but worse on executive tests (fluency, p¼0.031, WM p¼0.012, and LNSq p¼0.030). Conclusions: These findings suggest that subtle cognitive changes are associated with different biomarker stages in CN older adults.Amyloidosis is associated with impairment on both challenging memory and executive tests. Neurodegeneration is associated with more executive dysfunction than memory. The combination of amyloidosis and neurodegeneration results in more significant decline in memory and executive performance. IC-P-088
FUNCTIONAL AND STRUCTURAL DEGENERATIONS OF THE CENTRAL OLFACTORY SYSTEM IN AD AND MCI: AN EARLY MARKER
Qing X. Yang1, 1Penn State College of Medicine, Hershey, Pennsylvania, United States. Background: AD pathology is first found in the olfactory areas and olfactory deficits are prevalent in the early AD and MCI patients (1-4). These provide an opportunity for determining the direct relationship between pathological changes in the site of early degeneration and the associated functional deficit. Studying such a relationship has been difficult and confounded with neurocognitive variables. Our objective is to understand the olfactory deficits occurring in the early AD and develop diagnostic tools for early detection, monitoring and understanding the functional-pathological processes of AD. Methods: Sixty-three subjects including 15 AD, 21 MCI and 27 age-matched CN were studied with cognitive tests, the University of Pennsylvania Smell Identification Test (UPSIT) and fMRI using an olfactory stimulation paradigm in Fig. 1. The regions of interest (ROI) including the primary olfactory cortex (POC) and hippocampus were manually segmented on MRI T1 images for each subject using fslview and then SPM 8 was used to analyze the fMRI data. Results: The relationship of olfactory activation change and the local atrophy was quantified using the ratio of the activated volumes and the volumes of the POC and hippocampus. Shown in Fig. 2, MCI and AD had more than two-fold reduction in percent activated volume compared to the CN group in both the hippocampus and the POC. The MCI showed nearly the same level of deficit in percent activated volume as the AD group. The percent volume activated was reduced in both groups by up to 55.4% for the hippocampus and by up to 52.2% for the POC. Significant brain atrophy was observed in the hippocampus (P < 0.0001) and the POC (P < 0.001). Both MCI and AD subjects had significantly smaller hippocampus (P < 0.0001) and POC (P ¼ 0.001) than the CN group. The volumes of the two brain structures were positively correlated among the three cohorts (r ¼ 0.55, P < 0.0001). Conclusions: Olfactory fMRI detected earlier functional changes in the MCI group than behavioral and volumetric measurement in POC and hippocampus. Olfactory fMRI has potential to aid early diagnosis of AD and MCI.
Fig 1. Olfactory fMRI paradigm. The above cycles 4x. The 4 lavender concentrations are presented 3x each. Every time “Smell?” appears on the screen the subject must respond yes if they smell lavender and no if they do not.
Fig. 2. Percent activated volume and volumes of the bilateral hippocampus and primary olfactory cortex (POC) (mean 6 standard error). The percent activated volume in the hippocampus (A) and POC (B) in MCI and AD subjects was decreased by more than 50 percent than that of the CN. The hippocampus (C) and POC (D) were significantly smaller in volume in both MCI and AD compared to CN.
IC-P-089
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 College of Medicine, Hershey, Pennsylvania, United States. Contact e-mail: [email protected] 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). Group 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