- Email: [email protected]
VISUAL CONTRAST SENSITIVITY IS ASSOCIATED WITH AMYLOID AND TAU DEPOSITION
P154
Poster Presentations: Saturday, July 15, 2017
associations between both self and informant ECog scores and [18F] Flortaucipir SUVR were observed (Figure 1). Notably, the selfbased memory concerns were associated with tau load predominantly in the frontal cortex and medial temporal regions, while the informant-based concerns were more strongly associated with precuneus and lateral parietal tau load (Figure 1C). However, informant-based concerns were associated with more widespread regions than self-based concerns on voxel-wise analysis (Figure 1B). Conclusions: The association between subjective concerns and tau deposition suggests an important role of tau pathology in the early stages of disease and that involvement of different brain regions underlie the phenomena detected by the ECog scale. Future longitudinal studies will help to elucidate the timing and source of cognitive concern presentation relative to disease and pathological progression.
IC-P-214
pal, entorhinal, and mean temporal volumes were also evaluated, pre-adjusted for age, sex, and ICV and z-scored within the sample. A z-score of -1 was considered positive. ROC curves were calculated to determine the optimal CCI-12 cutoff to provide 80% sensitivity, 80% specificity, or balanced sensitivity/specificity. Analyses with an AUC>0.6 were further considered and the median scores for the three cutoffs were calculated. These cutoffs were then applied to the ADNI significant memory concern (SMC) participants to determine sensitivity to conversion, biomarkers, and cognition. Results: ROC curves for MMSE, RAVLT immediate and delayed, entorhinal volume, and conversion had AUC>0.6. The median CCI-12 cutoff scores for 80% sensitivity, 80% specificity, and balanced sensitivity/specificity were 20, 28, and 23, respectively. When applied to ADNI, these cutoffs showed a trend for reduced MMSE (20 only) and faster 2-year mean temporal lobe atrophy rates (Fig1, p0.13). Conclusions: Optimal cutoffs to define SCD are dependent on the intended use of the measure. For example, in screening for SCD, a more sensitive cutoff may be desirable, while screening for biomarker-positive prodromal AD might require a higher cutoff. Use of the informant version of the CCI will also enhance specificity. This report provides preliminary evidence for cutoffs on the CCI-20, but future studies in larger cohorts are needed to firmly establish optimal cutoffs.
OPTIMIZING COGNITIVE CHANGE INDEX CUTOFFS BASED ON COGNITIVE DECLINE AND BIOMARKER POSITIVITY IN COGNITIVELY NORMAL OLDER ADULTS
Shannon L. Risacher1,2, John D. West1,2, Brenna C. McDonald1,2, Eileen F. Tallman1,2, Bradley S. Glazier1,2, Sujuan Gao1,2, Steve Brown1,2, Liana G. Apostolova1,2, Jared R. Brosch1,2, Martin R. Farlow1,2, Frederick W. Unverzagt1,2, Andrew J. Saykin1,2, the Alzheimer’s Disease Neuroimaging Initiative (ADNI), 1Indiana Alzheimer Disease Center, Indianapolis, IN, USA; 2Indiana University School of Medicine, Indianapolis, IN, USA. Contact e-mail: [email protected] Background: The presence of subjective cognitive decline (SCD) is thought to be an AD risk factor. However, defining SCD is difficult due to uncertainty regarding proper instruments and the level of concerns needed. Thus, we sought to establish optimal cutoffs for defining SCD based on the 20-item Cognitive Change Index (CCI-20). Methods: 178 cognitively normal older adults (CN) from the Indiana Alzheimer Disease Center underwent cognitive testing, including the CCI-20. Of these, 102 had cognitive testing from three years prior and 82 had an MRI within three years of the CCI-20. The sum of the first 12 items measuring episodic memory was used (CCI-12). Dependent variables included conversion and performance on and 3-year preceding longitudinal change in the MMSE, RAVLT (immediate/ delayed), pre-adjusted for demographics and z-scored using amyloid-negative CNs from ADNI (n¼79). Cortical, hippocam-
IC-P-215
VISUAL CONTRAST SENSITIVITY IS ASSOCIATED WITH AMYLOID AND TAU DEPOSITION
Shannon L. Risacher1,2, Darrell WuDunn2, John D. West1,2, Brenna C. McDonald1,2, Eileen F. Tallman1,2, Karmen K. Yoder1,2, Bradley S. Glazier1,2, Sujuan Gao1,2, Steve Brown1,2, Liana G. Apostolova1,2, Jared R. Brosch1,2, Martin R. Farlow1,2, Frederick W. Unverzagt1,2, Andrew J. Saykin1,2, 1Indiana Alzheimer Disease Center, Indianapolis, IN, USA; 2Indiana University School of Medicine, Indianapolis, IN, USA. Contact e-mail: [email protected] Background: Visual contrast sensitivity has been shown to be
impaired in patients with prodromal and clinical Alzheimer’s disease (AD). The utility of this technique as a biomarker is predicated on the ability of the measure to reflect AD-related pathology, both in clinical and preclinical stages. Thus, the goal of this study was to evaluate the relationship between contrast sensitivity and amyloid and tau deposition. Methods: 30 participants from the Indiana Alzheimer Disease Center (IADC), including 25 cognitively normal
Poster Presentations: Saturday, July 15, 2017
older adults (CN), 4 patients with mild cognitive impairment (MCI), and 1 AD patient underwent frequency doubling technology (FDT-2) to assess contrast sensitivity and [18F]Florbetapir PET scans. Both duration of the iterative FDT exam and mean contrast sensitivity were evaluated. Eighteen of the participants also underwent [18F]Flortaucipir PET scans. PET scans were processed using standard techniques and intensity-normalized to the whole cerebellum ([18F]Florabetapir) or cerebellar crus ([18F]Flortaucipir). The associations between contrast sensitivity and both [18]Florbetapir standardized uptake values with a reference region (SUVR) and [18F]Flortaucipir SUVR were evaluated at a voxel-wise level, covaried for age, sex, and diagnosis when appropriate, and displayed at a threshold of p<0.001 (uncorrected) and minimum cluster size (k)¼100 voxels. Mean SUVR from target regions of interest was also extracted, and associations between the regional amyloid and tau measures and contrast sensitivity were assessed using a linear regression model. Results: Significant associations between contrast sensitivity and both amyloid (Figure 1A) and tau (Figure 1B) deposition were observed. The associations remained significant when diagnosis was included as a covariate. When the evaluation was restricted to CNs, significant clusters remained for the association with tau, and at a trend-level for amyloid. Regional associations showed similar patterns of association (Figure 1C and 1D, p<0.01). Conclusions: These findings suggest that visual contrast sensitivity may be associated with two hallmarks of AD, amyloid and tau deposition, perhaps even at preclinical stages. Future studies evaluating longitudinal change in contrast sensitivity over time and/or the ability of contrast sensitivity measures to predict future cognitive decline will provide evidence for use of this tool as an inexpensive, non-invasive biomarker for AD.
IC-P-216
COMPARING IMAGING PHENOTYPES OF AMNESTIC EARLY VERSUS LATE-ONSET AMYLOID-NEGATIVE MILD COGNITIVE IMPAIRMENT AND DEMENTIA ADNI SUBJECTS
Eddie Stage Jr.1, Meredith Phillips1, Victor Hugo Canela1, Tugce Duran1, Naira Goukasian2, Gil D. Rabinovici3, Bradford C. Dickerson4, Maria C. Carrillo5, Susan de Santi6, Shannon L. Risacher1, Andrew J. Saykin1, Liana G. Apostolova1, 1Indiana University School of
P155
Medicine, Indianapolis, IN, USA; 2University of California, Los Angeles, Los Angeles, CA, USA; 3University of California San Francisco, San Francisco, CA, USA; 4Harvard Medical School, Boston, MA, USA; 5 Alzheimer’s Association, Chicago, IL, USA; 6Piramal Imaging Inc., Boston, MA, USA. Contact e-mail: [email protected] Background: Approximately 5% of dementia patients develop
symptoms before the age of 65 (EO). EO dementia (DEM) is believed to have a more aggressive disease course than late onset (LO-DEM). A proportion of patients with Alzheimer’s disease (AD)-like presentation do not show evidence of amyloid pathology, leading to their classification as Suspected Non-Alzheimer’s Pathophysiology (SNAP). Methods: We analyzed the available ADNI MRI and FDG-PET data of 34 amyloid-negative amnestic EO (29 MCI and 5 DEM), 83 amyloid-negative amnestic LO (64 MCI and 19 DEM) and 212 amyloid-negative cognitively normal (CN) subjects (Table 1 and Table 2). Amyloid negative status was determined using an 18F-AV-45 amyloid PET standard uptake value ratio (SUVR) < 1.17 normalized to whole cerebellum. In order to study the extent of disease involvement, we compared the MRI and FDG-PET data of EO and LO to the CN group using linear regression in SPM8, controlling for age, gender, and education. Additionally, in the MRI analyses, we controlled for intracranial volume and scan type. FWE correction for multiple comparisons was applied. Results: Demographic and amyloid burden comparisons of the diseased groups to CN can be seen in Table 1 and Table 2. Direct comparisons of EO and LO showed the expected significant difference in age (MCI and DEM p<0.001) and age at
Poster Presentations: Saturday, July 15, 2017
associations between both self and informant ECog scores and [18F] Flortaucipir SUVR were observed (Figure 1). Notably, the selfbased memory concerns were associated with tau load predominantly in the frontal cortex and medial temporal regions, while the informant-based concerns were more strongly associated with precuneus and lateral parietal tau load (Figure 1C). However, informant-based concerns were associated with more widespread regions than self-based concerns on voxel-wise analysis (Figure 1B). Conclusions: The association between subjective concerns and tau deposition suggests an important role of tau pathology in the early stages of disease and that involvement of different brain regions underlie the phenomena detected by the ECog scale. Future longitudinal studies will help to elucidate the timing and source of cognitive concern presentation relative to disease and pathological progression.
IC-P-214
pal, entorhinal, and mean temporal volumes were also evaluated, pre-adjusted for age, sex, and ICV and z-scored within the sample. A z-score of -1 was considered positive. ROC curves were calculated to determine the optimal CCI-12 cutoff to provide 80% sensitivity, 80% specificity, or balanced sensitivity/specificity. Analyses with an AUC>0.6 were further considered and the median scores for the three cutoffs were calculated. These cutoffs were then applied to the ADNI significant memory concern (SMC) participants to determine sensitivity to conversion, biomarkers, and cognition. Results: ROC curves for MMSE, RAVLT immediate and delayed, entorhinal volume, and conversion had AUC>0.6. The median CCI-12 cutoff scores for 80% sensitivity, 80% specificity, and balanced sensitivity/specificity were 20, 28, and 23, respectively. When applied to ADNI, these cutoffs showed a trend for reduced MMSE (20 only) and faster 2-year mean temporal lobe atrophy rates (Fig1, p0.13). Conclusions: Optimal cutoffs to define SCD are dependent on the intended use of the measure. For example, in screening for SCD, a more sensitive cutoff may be desirable, while screening for biomarker-positive prodromal AD might require a higher cutoff. Use of the informant version of the CCI will also enhance specificity. This report provides preliminary evidence for cutoffs on the CCI-20, but future studies in larger cohorts are needed to firmly establish optimal cutoffs.
OPTIMIZING COGNITIVE CHANGE INDEX CUTOFFS BASED ON COGNITIVE DECLINE AND BIOMARKER POSITIVITY IN COGNITIVELY NORMAL OLDER ADULTS
Shannon L. Risacher1,2, John D. West1,2, Brenna C. McDonald1,2, Eileen F. Tallman1,2, Bradley S. Glazier1,2, Sujuan Gao1,2, Steve Brown1,2, Liana G. Apostolova1,2, Jared R. Brosch1,2, Martin R. Farlow1,2, Frederick W. Unverzagt1,2, Andrew J. Saykin1,2, the Alzheimer’s Disease Neuroimaging Initiative (ADNI), 1Indiana Alzheimer Disease Center, Indianapolis, IN, USA; 2Indiana University School of Medicine, Indianapolis, IN, USA. Contact e-mail: [email protected] Background: The presence of subjective cognitive decline (SCD) is thought to be an AD risk factor. However, defining SCD is difficult due to uncertainty regarding proper instruments and the level of concerns needed. Thus, we sought to establish optimal cutoffs for defining SCD based on the 20-item Cognitive Change Index (CCI-20). Methods: 178 cognitively normal older adults (CN) from the Indiana Alzheimer Disease Center underwent cognitive testing, including the CCI-20. Of these, 102 had cognitive testing from three years prior and 82 had an MRI within three years of the CCI-20. The sum of the first 12 items measuring episodic memory was used (CCI-12). Dependent variables included conversion and performance on and 3-year preceding longitudinal change in the MMSE, RAVLT (immediate/ delayed), pre-adjusted for demographics and z-scored using amyloid-negative CNs from ADNI (n¼79). Cortical, hippocam-
IC-P-215
VISUAL CONTRAST SENSITIVITY IS ASSOCIATED WITH AMYLOID AND TAU DEPOSITION
Shannon L. Risacher1,2, Darrell WuDunn2, John D. West1,2, Brenna C. McDonald1,2, Eileen F. Tallman1,2, Karmen K. Yoder1,2, Bradley S. Glazier1,2, Sujuan Gao1,2, Steve Brown1,2, Liana G. Apostolova1,2, Jared R. Brosch1,2, Martin R. Farlow1,2, Frederick W. Unverzagt1,2, Andrew J. Saykin1,2, 1Indiana Alzheimer Disease Center, Indianapolis, IN, USA; 2Indiana University School of Medicine, Indianapolis, IN, USA. Contact e-mail: [email protected] Background: Visual contrast sensitivity has been shown to be
impaired in patients with prodromal and clinical Alzheimer’s disease (AD). The utility of this technique as a biomarker is predicated on the ability of the measure to reflect AD-related pathology, both in clinical and preclinical stages. Thus, the goal of this study was to evaluate the relationship between contrast sensitivity and amyloid and tau deposition. Methods: 30 participants from the Indiana Alzheimer Disease Center (IADC), including 25 cognitively normal
Poster Presentations: Saturday, July 15, 2017
older adults (CN), 4 patients with mild cognitive impairment (MCI), and 1 AD patient underwent frequency doubling technology (FDT-2) to assess contrast sensitivity and [18F]Florbetapir PET scans. Both duration of the iterative FDT exam and mean contrast sensitivity were evaluated. Eighteen of the participants also underwent [18F]Flortaucipir PET scans. PET scans were processed using standard techniques and intensity-normalized to the whole cerebellum ([18F]Florabetapir) or cerebellar crus ([18F]Flortaucipir). The associations between contrast sensitivity and both [18]Florbetapir standardized uptake values with a reference region (SUVR) and [18F]Flortaucipir SUVR were evaluated at a voxel-wise level, covaried for age, sex, and diagnosis when appropriate, and displayed at a threshold of p<0.001 (uncorrected) and minimum cluster size (k)¼100 voxels. Mean SUVR from target regions of interest was also extracted, and associations between the regional amyloid and tau measures and contrast sensitivity were assessed using a linear regression model. Results: Significant associations between contrast sensitivity and both amyloid (Figure 1A) and tau (Figure 1B) deposition were observed. The associations remained significant when diagnosis was included as a covariate. When the evaluation was restricted to CNs, significant clusters remained for the association with tau, and at a trend-level for amyloid. Regional associations showed similar patterns of association (Figure 1C and 1D, p<0.01). Conclusions: These findings suggest that visual contrast sensitivity may be associated with two hallmarks of AD, amyloid and tau deposition, perhaps even at preclinical stages. Future studies evaluating longitudinal change in contrast sensitivity over time and/or the ability of contrast sensitivity measures to predict future cognitive decline will provide evidence for use of this tool as an inexpensive, non-invasive biomarker for AD.
IC-P-216
COMPARING IMAGING PHENOTYPES OF AMNESTIC EARLY VERSUS LATE-ONSET AMYLOID-NEGATIVE MILD COGNITIVE IMPAIRMENT AND DEMENTIA ADNI SUBJECTS
Eddie Stage Jr.1, Meredith Phillips1, Victor Hugo Canela1, Tugce Duran1, Naira Goukasian2, Gil D. Rabinovici3, Bradford C. Dickerson4, Maria C. Carrillo5, Susan de Santi6, Shannon L. Risacher1, Andrew J. Saykin1, Liana G. Apostolova1, 1Indiana University School of
P155
Medicine, Indianapolis, IN, USA; 2University of California, Los Angeles, Los Angeles, CA, USA; 3University of California San Francisco, San Francisco, CA, USA; 4Harvard Medical School, Boston, MA, USA; 5 Alzheimer’s Association, Chicago, IL, USA; 6Piramal Imaging Inc., Boston, MA, USA. Contact e-mail: [email protected] Background: Approximately 5% of dementia patients develop
symptoms before the age of 65 (EO). EO dementia (DEM) is believed to have a more aggressive disease course than late onset (LO-DEM). A proportion of patients with Alzheimer’s disease (AD)-like presentation do not show evidence of amyloid pathology, leading to their classification as Suspected Non-Alzheimer’s Pathophysiology (SNAP). Methods: We analyzed the available ADNI MRI and FDG-PET data of 34 amyloid-negative amnestic EO (29 MCI and 5 DEM), 83 amyloid-negative amnestic LO (64 MCI and 19 DEM) and 212 amyloid-negative cognitively normal (CN) subjects (Table 1 and Table 2). Amyloid negative status was determined using an 18F-AV-45 amyloid PET standard uptake value ratio (SUVR) < 1.17 normalized to whole cerebellum. In order to study the extent of disease involvement, we compared the MRI and FDG-PET data of EO and LO to the CN group using linear regression in SPM8, controlling for age, gender, and education. Additionally, in the MRI analyses, we controlled for intracranial volume and scan type. FWE correction for multiple comparisons was applied. Results: Demographic and amyloid burden comparisons of the diseased groups to CN can be seen in Table 1 and Table 2. Direct comparisons of EO and LO showed the expected significant difference in age (MCI and DEM p<0.001) and age at