- Email: [email protected]
ANTERIOR COMMISSURE: NEUROANATOMIC AND COGNITIVE CORRELATES IN A POPULATION-BASED STUDY
Poster Presentations: Sunday, July 24, 2016
APOE e4 genotype and family history were controlled for statistical analysis. Results: In preclinical AD stage 1, significantly increased DBSI cellularity fraction was observed on the right side of the cerebral peduncle (Fig. 1A) and the right side of the anterior limb of internal capsule (Fig. 1B), suggesting the presence of neuroinflammation. CSF level of YKL-40, correlated with the DBSI total WM neuroinflammation index (r¼0.69, p<0.005) (Fig. 2). This finding is consist with DBSI being a noninvasive measure of WM neuroinflammation. Conclusions: In this study, DBSI detected the early presence of WM neuroinflammation in preclinical AD stage 1, and positively correlated with the CSF levels of YKL-40, a marker of gliosis/neuroinflammation. DBSI holds great promise as a potential novel, noninvasive and non-radioactive means to quantify neuroinflammation and study its role in AD pathogenesis and progression.
P1-276
ANTERIOR COMMISSURE: NEUROANATOMIC AND COGNITIVE CORRELATES IN A POPULATION-BASED STUDY
Hieab H.H. Adams1, Gennady V. Roshchupkin2, Wiro J. Niessen2, Meike W. Vernooij2, M Arfan Ikram2, 1Erasmus Medical Center, Rotterdam, Netherlands; 2Erasmus Medical Center, Rotterdam, Netherlands. Contact e-mail: [email protected] Background: The anterior commissure is the second largest commissural tract in the brain, but its relation to cognitive function and other brain regions remains poorly understood. Here, we systematically examine neuroanatomical and cognitive correlates of the anterior commissure in the largest study to date. Methods: The study population consisted of 4,745 participants from the population-based Rotterdam study. Magnetic resonance imaging was performed using a 1.5T scanner and included a high-resolution T1-weighted image. The anterior commissure was manually labelled on the mid-sagittal plane to calculate the cross-sectional area. Voxel-based morphometry was applied to identify cortical and subcortical grey matter regions that are putatively connected by the anterior commissure. Furthermore, the participants underwent a series of cognitive tests, for which we fit linear regressions models adjusting for age and sex (model 1), and additionally for intracranial volume (model 2) and total brain volume (model 3). Results: Mean age was 63.9 (SD 10.9) and 2,649
P523
Figure 1. Association between the anterior commissure and cortical and subcortical grey matter using voxel-based morphometry.
(55.5 %) were women. We found that the anterior commissure was significantly associated (p-value < 3.0 x 10-7) with voxels in the hippocampus, caudate, and various cortical regions (Figure 1). The anterior commissure was also associated with the cognitive tests, but most effects attenuated after adjusting for intracranial volume and total brain volume (Table 1). However, an inverse association with immediate recall remained strongly significant (p-value ¼ 9.8 x 10-7). Conclusions: A whole brain map reveals the relation of the anterior commissure to other brain structures. Furthermore, we find that its size is associated with cognitive performance, specifically on a test for verbal learning. The anterior commissure could be a specific biomarker for diseases that predominantly affect these brain areas and functions.
P1-277
OLDER HEALTHY PEOPLE HAVE INCREASED VASCULAR PERMEABILITY IN REGIONS SHOWING ‘OFF-TARGET’ [18F]AV-1451 UPTAKE
Belen Pascual, Elijah Rockers, Sahil Bajaj, Zhong Xue, Meixiang Yu, Christof Karmonik, Joseph C. Masdeu, Houston Methodist Hospital, Weill Cornell Medical College, Houston, TX, USA. Contact e-mail: bpascual@ houstonmethodist.org 18
Background: In older healthy subjects, [ F]AV-1451, which is
supposed to bind to hyperphosphorylated tau, also seems to bind to regions (putamen and other nuclei) known not to have abnormal tau deposition on neuropathology. Our aim is to determine whether apparently increased specific [18F] AV-1451 binding in areas unlikely to harbor hyperphosphorylated tau, such as the substantia nigra, globus pallidus and putamen, of older subjects could be related to greater
Table 1 Association between the anterior commissure and cognitive tests for memory, executive functioning, information processing, and fine motor speed. Model 1
Model 2
Model 3
Cognitive test
Beta (95% CI)
P
Beta (95% CI)
P
Beta (95% CI)
P
G-factor Letter-Digit Substitution Task Purdue Pegboard - both hands Purdue Pegboard - left hand Purdue Pegboard - right hand Stroop 1 - Reading Stroop 2 - Naming Stroop 3 - Interference Word Fluency Test Word Learning Test - Immediate recall Word Learning Test - Delayed recall
0.01 (0.00 - 0.02) 0.13 (0.04 - 0.22) 0.01 (-0.01 - 0.03) 0.04 (0.01 - 0.06) 0.04 (0.02 - 0.07) -0.03 (-0.08 - 0.02) -0.01 (-0.08 - 0.06) -0.44 (-0.76 - -0.12) 0.07 (-0.02 - 0.15) -0.24 (-0.34 - -0.14) 0.00 (-0.04 - 0.04)
0.094 0.007 0.449 0.003 0.001 0.209 0.708 0.006 0.123 2.1 3 10-6 0.971
0.01 (0.00 - 0.02) 0.12 (0.03 - 0.21) 0.01 (-0.02 - 0.03) 0.04 (0.01 - 0.06) 0.04 (0.01 - 0.07) -0.03 (-0.08 - 0.02) -0.01 (-0.08 - 0.06) -0.43 (-0.75 - -0.1l) 0.06 (-0.02 - 0.15) -0.24 (-0.34 - -0.14) 0.00 (-0.05 - 0.04)
0.140 0.011 0.511 0.006 0.002 0.247 0.847 0.008 0.148 1.8 3 10-6 0.851
0.00 (-0.01 - 0.01) 0.06 (-0.03 - 0.15) 0.00 (-0.03 - 0.02) 0.02 (0.00 - 0.05) 0.03 (0.01 - 0.06) -0.01 (-0.06 - 0.04) 0.03 (-0.04 - 0.10) -0.23 (-0.55 - 0.09) 0.03 (-0.06 - 0.11) -0.25 (-0.35 - -0.15) 0.00 (-0.05 - 0.04)
0.766 0.199 0.826 0.069 0.016 0.816 0.357 0.155 0.537 9.8 3 10-7 0.827
APOE e4 genotype and family history were controlled for statistical analysis. Results: In preclinical AD stage 1, significantly increased DBSI cellularity fraction was observed on the right side of the cerebral peduncle (Fig. 1A) and the right side of the anterior limb of internal capsule (Fig. 1B), suggesting the presence of neuroinflammation. CSF level of YKL-40, correlated with the DBSI total WM neuroinflammation index (r¼0.69, p<0.005) (Fig. 2). This finding is consist with DBSI being a noninvasive measure of WM neuroinflammation. Conclusions: In this study, DBSI detected the early presence of WM neuroinflammation in preclinical AD stage 1, and positively correlated with the CSF levels of YKL-40, a marker of gliosis/neuroinflammation. DBSI holds great promise as a potential novel, noninvasive and non-radioactive means to quantify neuroinflammation and study its role in AD pathogenesis and progression.
P1-276
ANTERIOR COMMISSURE: NEUROANATOMIC AND COGNITIVE CORRELATES IN A POPULATION-BASED STUDY
Hieab H.H. Adams1, Gennady V. Roshchupkin2, Wiro J. Niessen2, Meike W. Vernooij2, M Arfan Ikram2, 1Erasmus Medical Center, Rotterdam, Netherlands; 2Erasmus Medical Center, Rotterdam, Netherlands. Contact e-mail: [email protected] Background: The anterior commissure is the second largest commissural tract in the brain, but its relation to cognitive function and other brain regions remains poorly understood. Here, we systematically examine neuroanatomical and cognitive correlates of the anterior commissure in the largest study to date. Methods: The study population consisted of 4,745 participants from the population-based Rotterdam study. Magnetic resonance imaging was performed using a 1.5T scanner and included a high-resolution T1-weighted image. The anterior commissure was manually labelled on the mid-sagittal plane to calculate the cross-sectional area. Voxel-based morphometry was applied to identify cortical and subcortical grey matter regions that are putatively connected by the anterior commissure. Furthermore, the participants underwent a series of cognitive tests, for which we fit linear regressions models adjusting for age and sex (model 1), and additionally for intracranial volume (model 2) and total brain volume (model 3). Results: Mean age was 63.9 (SD 10.9) and 2,649
P523
Figure 1. Association between the anterior commissure and cortical and subcortical grey matter using voxel-based morphometry.
(55.5 %) were women. We found that the anterior commissure was significantly associated (p-value < 3.0 x 10-7) with voxels in the hippocampus, caudate, and various cortical regions (Figure 1). The anterior commissure was also associated with the cognitive tests, but most effects attenuated after adjusting for intracranial volume and total brain volume (Table 1). However, an inverse association with immediate recall remained strongly significant (p-value ¼ 9.8 x 10-7). Conclusions: A whole brain map reveals the relation of the anterior commissure to other brain structures. Furthermore, we find that its size is associated with cognitive performance, specifically on a test for verbal learning. The anterior commissure could be a specific biomarker for diseases that predominantly affect these brain areas and functions.
P1-277
OLDER HEALTHY PEOPLE HAVE INCREASED VASCULAR PERMEABILITY IN REGIONS SHOWING ‘OFF-TARGET’ [18F]AV-1451 UPTAKE
Belen Pascual, Elijah Rockers, Sahil Bajaj, Zhong Xue, Meixiang Yu, Christof Karmonik, Joseph C. Masdeu, Houston Methodist Hospital, Weill Cornell Medical College, Houston, TX, USA. Contact e-mail: bpascual@ houstonmethodist.org 18
Background: In older healthy subjects, [ F]AV-1451, which is
supposed to bind to hyperphosphorylated tau, also seems to bind to regions (putamen and other nuclei) known not to have abnormal tau deposition on neuropathology. Our aim is to determine whether apparently increased specific [18F] AV-1451 binding in areas unlikely to harbor hyperphosphorylated tau, such as the substantia nigra, globus pallidus and putamen, of older subjects could be related to greater
Table 1 Association between the anterior commissure and cognitive tests for memory, executive functioning, information processing, and fine motor speed. Model 1
Model 2
Model 3
Cognitive test
Beta (95% CI)
P
Beta (95% CI)
P
Beta (95% CI)
P
G-factor Letter-Digit Substitution Task Purdue Pegboard - both hands Purdue Pegboard - left hand Purdue Pegboard - right hand Stroop 1 - Reading Stroop 2 - Naming Stroop 3 - Interference Word Fluency Test Word Learning Test - Immediate recall Word Learning Test - Delayed recall
0.01 (0.00 - 0.02) 0.13 (0.04 - 0.22) 0.01 (-0.01 - 0.03) 0.04 (0.01 - 0.06) 0.04 (0.02 - 0.07) -0.03 (-0.08 - 0.02) -0.01 (-0.08 - 0.06) -0.44 (-0.76 - -0.12) 0.07 (-0.02 - 0.15) -0.24 (-0.34 - -0.14) 0.00 (-0.04 - 0.04)
0.094 0.007 0.449 0.003 0.001 0.209 0.708 0.006 0.123 2.1 3 10-6 0.971
0.01 (0.00 - 0.02) 0.12 (0.03 - 0.21) 0.01 (-0.02 - 0.03) 0.04 (0.01 - 0.06) 0.04 (0.01 - 0.07) -0.03 (-0.08 - 0.02) -0.01 (-0.08 - 0.06) -0.43 (-0.75 - -0.1l) 0.06 (-0.02 - 0.15) -0.24 (-0.34 - -0.14) 0.00 (-0.05 - 0.04)
0.140 0.011 0.511 0.006 0.002 0.247 0.847 0.008 0.148 1.8 3 10-6 0.851
0.00 (-0.01 - 0.01) 0.06 (-0.03 - 0.15) 0.00 (-0.03 - 0.02) 0.02 (0.00 - 0.05) 0.03 (0.01 - 0.06) -0.01 (-0.06 - 0.04) 0.03 (-0.04 - 0.10) -0.23 (-0.55 - 0.09) 0.03 (-0.06 - 0.11) -0.25 (-0.35 - -0.15) 0.00 (-0.05 - 0.04)
0.766 0.199 0.826 0.069 0.016 0.816 0.357 0.155 0.537 9.8 3 10-7 0.827