- Email: [email protected]
DIVERSITY OF ODORANT IDENTIFICATION IMPAIRMENT IN PATIENTS WITH ALZHEIMER DISEASE
P360
Poster Presentations: Sunday, July 16, 2017
Results: In discovery and validation phases, 14 peptide biomarkers for MCI and AD were identified by 2D-mLCMALDI-TOF/MS, and, among them, 8 peptide biomarkers showed diagnostic potential for both MCI and AD in multicenter clinical studies by LC-MS/MS assay. The combinations of 3 biomarker peptides achieved an area under the curve of 0.86 (sensitivity 82%, specificity 80%) in MCI vs. NDC, and 0.89 (sensitivity 84%, specificity 84%) in AD vs. NDC, respectively. Individuals with lower MMSE scores had significantly elevated levels of the biomarker peptides. These peptides were derived from the proteins of complement system, fibrinolysis system and actin-binding protein family. Furthermore, levels of these peptides in the brain of definite AD and NDC subjects were analyzed by LC-MS/MS and immunochemistry against peptidespecific antibodies. The biomarker peptides were actually present in the brain and, in AD vs. NDC, differences of their levels in the hippocampus coincided with those in serum. Conclusions: The circulating peptides are potential biomarkers for MCI and AD in clinical use. The LC-MS/MS blood test system for peptide biomarkers is a powerful tool for early diagnostics for cognitive impairment.
P1-285
DIVERSITY OF ODORANT IDENTIFICATION IMPAIRMENT IN PATIENTS WITH ALZHEIMER DISEASE
Yumi Umeda-Kameyama1, Shinya Ishii1, Masashi Kameyama2,3, Kenji Kondo4, Atsushi Ochi4, Tatsuya Yamasoba4, Sumito Ogawa1, Masahiro Akishita1, 1The University of Tokyo, Tokyo, Japan; 2Keio University, Tokyo, Japan; 3Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan; 4The University of Tokyo, Tokyo, Japan. Contact e-mail: [email protected] Background: Patients with Alzheimer disease (AD) are reported to have olfactory dysfunction. However, the specific substrates of the olfactory disability and the precise nature of the olfactory decline in AD are not fully understood. Methods: One hundred consecutive patients (30 men, 70 women, 65 to 93 years old, 12 Normal, 28 with amnestic mild cognitive impairment (aMCI), 60 with AD), who admitted to the Department of Geriatric Medicine, The University of Tokyo Hospital for evaluation of cognitive impairment were enrolled. All participants underwent olfactory function testing using an odor stick identification test for Japanese (OSIT-J) and Mini-Mental State Examination (MMSE). Results: OSIT-J score was significantly correlated with recall. We classified OSIT-J odorants into three groups. Vulnerable odorants were difficult to identify with normal aging. Cognitive odorants showed a decline in correctness with cognitive status. Persistent odorants were identified even by AD patients. We made a “cognitive subset” in OSIT-J consisting of six odorants (Perfume, Rose, Japanese cypress (hinoki), Curry, India ink and Town gas), each of which showed a significant decline in correctness with dementia progression. The “cognitive subset” showed significantly better discriminatory power of cognitive status than the “non-cognitive subset”, which consisted of the six remaining items in OSIT-J. The ability to identify Town gas odorant was found to be decreased early at the aMCI stage, while Curry, Sweaty socks and Roasted garlic could be detected in over 45% of AD patients. Conclusions: The olfactory ability of other odorants declined with aging or AD. The “cognitive subset” consisting of six odorants in OSIT-J would provide a more convenient and effective biomarker for diagnosing
dementia in daily clinical settings. A deficit in the ability to detect the smell of town gas could be a threat for society.
P1-286
VISUAL CONTRAST SENSITIVITY IS ASSOCIATED WITH AMYLOID AND TAU DEPOSITION
Shannon L. Risacher1,2, Darrell WuDunn2, John D. West1,2, Brenna C. McDonald1,3, 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, Fred Unverzagt1,2, Andrew J. Saykin1,2, 1Indiana Alzheimer Disease Center, Indianapolis, IN, USA; 2Indiana University School of Medicine, Indianapolis, IN, USA; 3Indiana University, 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 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
Poster Presentations: Sunday, July 16, 2017
Results: In discovery and validation phases, 14 peptide biomarkers for MCI and AD were identified by 2D-mLCMALDI-TOF/MS, and, among them, 8 peptide biomarkers showed diagnostic potential for both MCI and AD in multicenter clinical studies by LC-MS/MS assay. The combinations of 3 biomarker peptides achieved an area under the curve of 0.86 (sensitivity 82%, specificity 80%) in MCI vs. NDC, and 0.89 (sensitivity 84%, specificity 84%) in AD vs. NDC, respectively. Individuals with lower MMSE scores had significantly elevated levels of the biomarker peptides. These peptides were derived from the proteins of complement system, fibrinolysis system and actin-binding protein family. Furthermore, levels of these peptides in the brain of definite AD and NDC subjects were analyzed by LC-MS/MS and immunochemistry against peptidespecific antibodies. The biomarker peptides were actually present in the brain and, in AD vs. NDC, differences of their levels in the hippocampus coincided with those in serum. Conclusions: The circulating peptides are potential biomarkers for MCI and AD in clinical use. The LC-MS/MS blood test system for peptide biomarkers is a powerful tool for early diagnostics for cognitive impairment.
P1-285
DIVERSITY OF ODORANT IDENTIFICATION IMPAIRMENT IN PATIENTS WITH ALZHEIMER DISEASE
Yumi Umeda-Kameyama1, Shinya Ishii1, Masashi Kameyama2,3, Kenji Kondo4, Atsushi Ochi4, Tatsuya Yamasoba4, Sumito Ogawa1, Masahiro Akishita1, 1The University of Tokyo, Tokyo, Japan; 2Keio University, Tokyo, Japan; 3Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Tokyo, Japan; 4The University of Tokyo, Tokyo, Japan. Contact e-mail: [email protected] Background: Patients with Alzheimer disease (AD) are reported to have olfactory dysfunction. However, the specific substrates of the olfactory disability and the precise nature of the olfactory decline in AD are not fully understood. Methods: One hundred consecutive patients (30 men, 70 women, 65 to 93 years old, 12 Normal, 28 with amnestic mild cognitive impairment (aMCI), 60 with AD), who admitted to the Department of Geriatric Medicine, The University of Tokyo Hospital for evaluation of cognitive impairment were enrolled. All participants underwent olfactory function testing using an odor stick identification test for Japanese (OSIT-J) and Mini-Mental State Examination (MMSE). Results: OSIT-J score was significantly correlated with recall. We classified OSIT-J odorants into three groups. Vulnerable odorants were difficult to identify with normal aging. Cognitive odorants showed a decline in correctness with cognitive status. Persistent odorants were identified even by AD patients. We made a “cognitive subset” in OSIT-J consisting of six odorants (Perfume, Rose, Japanese cypress (hinoki), Curry, India ink and Town gas), each of which showed a significant decline in correctness with dementia progression. The “cognitive subset” showed significantly better discriminatory power of cognitive status than the “non-cognitive subset”, which consisted of the six remaining items in OSIT-J. The ability to identify Town gas odorant was found to be decreased early at the aMCI stage, while Curry, Sweaty socks and Roasted garlic could be detected in over 45% of AD patients. Conclusions: The olfactory ability of other odorants declined with aging or AD. The “cognitive subset” consisting of six odorants in OSIT-J would provide a more convenient and effective biomarker for diagnosing
dementia in daily clinical settings. A deficit in the ability to detect the smell of town gas could be a threat for society.
P1-286
VISUAL CONTRAST SENSITIVITY IS ASSOCIATED WITH AMYLOID AND TAU DEPOSITION
Shannon L. Risacher1,2, Darrell WuDunn2, John D. West1,2, Brenna C. McDonald1,3, 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, Fred Unverzagt1,2, Andrew J. Saykin1,2, 1Indiana Alzheimer Disease Center, Indianapolis, IN, USA; 2Indiana University School of Medicine, Indianapolis, IN, USA; 3Indiana University, 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 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