- Email: [email protected]
COMPARING ATROPHY PATTERNS IN EARLY CLINICAL STAGES ACROSS DISTINCT PHENOTYPES OF ALZHEIMER'S DISEASE
Oral Sessions: O5-01: Neuroimaging: Differentiation Between Subtypes of Dementia
P289
Table 1 Demographics and clinical characteristics Controls
Early onset AD
CDR
0
0.5
N Age Sex (%male) Education (yr) MMSE Scanner type (% 3T) UCSF/VUMC TIV (L)
84 6567 48 1762 2961 51 55/29 1.5660.16
40 6467 53 1663 2563 60 20/20 1.6060.17
logopenic variant PPA
Posterior cortical atrophy
1
0.5
1
0.5
1
50 6467 50 1662 2163 64 15/35 1.5960.16
37 6668 57 1763 2564 68 20/17 1.5960.18
28 6468 43 1662 1964 79 15/13 1.5560.17
27 6468 44 1562 2562 56 10/17 1.6560.14
52 6166 39 1562 2164 69 14/38 1.5460.16
CDR ¼ clinical dementia rating, AD ¼ Alzheimer’s disease, PPA ¼ Primary progressive aphasia, TIV ¼ Total intracranial volume. involvement of left anteromedial temporal lobe, medial prefrontal cortex, inferior longitudinal fasciculus, uncinate fasciculus and forceps minor, were observed in the PiB-negative group. Conclusions: Alzheimer’s disease pathology accounts for a high proportion of patients presenting with anomia, difficulty repeating sentences and phonological errors. Highly asymmetric MRI findings and preserved spatial perceptual skills, suggest that AD pathology is absent. In such instances, a progranulin gene mutation should be suspected. O5-01-05
COMPARING ATROPHY PATTERNS IN EARLY CLINICAL STAGES ACROSS DISTINCT PHENOTYPES OF ALZHEIMER’S DISEASE
Manja Lehmann1, Brendan I. Cohn-Sheehy2, Yolande Pijnenburg3, William Seeley4, Bart van Berckel5, Bruce Miller6, Manja Lehmann7, Maria-Luisa Gorno-Tempini6, Joel H. Kramer8, Wiesje M. van der Flier9, Howard Rosen10, Philip Scheltens11, William Jagust12, Frederik Barkhof3, Gil Dan Rabinovici6, 1UCSF Memory and Aging Center, London, United Kingdom; 2Memory and Aging Center, University of California, San Francisco, Jagust Lab, University of California, Berkeley, California, United States; 3VU Medical Center, Amsterdam, Netherlands; 4UCSF MAC, San Francisco, California, United States; 5VU Medical Center, Amsterdam, Netherlands; 6UCSF Memory & Aging Center, San Francisco, California, United States; 7UCSF MAC, San Francisco, California, United States; 8 Memory Clinic, UCSF, San Francisco, California, United States; 9VU Medical Center, Amsterdam, Netherlands; 10University of California, San Francisco, San Francisco, California, United States; 11VU Medical Center, Amsterdam, Netherlands; 12University of California, Berkeley, Berkeley, California, United States. Contact e-mail: [email protected] Background: It has been proposed that temporoparietal regions are selectively vulnerable across clinical variants of Alzheimer’s disease (AD). However, since few studies included patients at the pre-dementia stage, it is unclear whether different clinical phenotypes of AD arise from focal structural alterations in the earliest disease stage and converge in temporoparietal cortex later on, or vice versa. In this study we used clinical dementia rating (CDR) scores
as proxy for disease severity to study progression of atrophy patterns in three different variants of AD. Methods: 234 patients with early-onset AD (EOAD, mainly amnestic and dysexecutive deficits), logopenic variant primary progressive aphasia (lvPPA, language variant) and posterior cortical atrophy (PCA, visual variant) with CDR scores of 0.5 (N¼104) or 1 (N¼130) were recruited from the UCSF and VUMC memory clinics (Table 1). In addition, we included a well-matched healthy control group (n¼84). Structural T1 weighted images were analyzed using voxel-based morphometry (VBM) in SPM8. We performed voxelwise contrasts between the different AD variants (both for CDR 0.5 and 1) and the control group. The VBM model included age, sex, total intracranial volume, MRI field strength (1.5T or 3T) and clinical center as nuisance variables. Results are displayed at p<0.05 (FWE-corrected). Results: At CDR 0.5, the different AD variants showed relatively distinct patterns of atrophy (see Figure 1). EOAD patients mainly had medial temporal lobe involvement, while lvPPA and PCA were affected most in left temporoparietal regions and right visual association cortex, respectively. At CDR 1, these atrophy patterns extended into the temporo-parietal cortex in EOAD, left anterior lateral temporal regions in lvPPA and the precuneus in PCA. The different variants converged at this stage in lateral temporoparietal cortex, as well as in the medial temporal lobes. Conclusions: Our crosssectional results indicate that brain atrophy is syndrome-specific in early disease stages, and converges in temporoparietal cortex and medial temporal lobes as the disease progresses. These findings provide insight into mechanisms that drive heterogeneity in AD, and have implications for early detection of atypical (or non-amnestic) AD variants using MRI. O5-01-06
WHITE MATTER HYPERINTENSITY PENUMBRA: A PASL STUDY
Nutta-on Promjunyakul1, David Lahna2, William D. Rooney2, Deniz Erten-Lyons3, Jeffrey Kaye2, Lisa C. Silbert2, 1Oregon Health and Science University, Portland, Oregon, United States; 2Oregon Health & Science University, Portland, Oregon, United States; 3Portland VA Medical Center and Oregon Health & Science University, Portland, Oregon, United States. Contact e-mail: [email protected] Background: White matter hyperintensities (WMH) are common with age and associated with cognitive impairment. WMHs are likely vascular in origin, yet the exact developmental process remains unclear. The aim of this study was to determine cerebral blood flow (CBF) values in the surrounding regions of WM injury, so that a penumbra, or "at risk" tissue surrounding the WM injury might be identified. Methods: Sixty-one cognitively intact elderly participants (mean age 84.8, CDR 0, MMSE 28.9) underwent 3T MRI FLAIR, MPRAGE and Q2TIPS pulsed arterial spin labeling (PASL). For each individual dataset, a custom-made algorithm was used to define WMH on FLAIR. To create a WMH layer mask, WMHs were used as seeds and 3dcalc was used to dilate each layer away from the WMHs by 1 voxel, for a total of 14 layers (Figure). CBF maps were linearly coregistered to the MPRAGE. The penumbra mask was then applied to the CBF map. Finally, the mean normal appearing white matter (NAWM) CBF of each layer of the periventricular (PV) and deep WMH was determined. The mean NAWM CBF was also calculated for each individual subject. Mean CBF was adjusted for age. Paired t-tests were
P289
Table 1 Demographics and clinical characteristics Controls
Early onset AD
CDR
0
0.5
N Age Sex (%male) Education (yr) MMSE Scanner type (% 3T) UCSF/VUMC TIV (L)
84 6567 48 1762 2961 51 55/29 1.5660.16
40 6467 53 1663 2563 60 20/20 1.6060.17
logopenic variant PPA
Posterior cortical atrophy
1
0.5
1
0.5
1
50 6467 50 1662 2163 64 15/35 1.5960.16
37 6668 57 1763 2564 68 20/17 1.5960.18
28 6468 43 1662 1964 79 15/13 1.5560.17
27 6468 44 1562 2562 56 10/17 1.6560.14
52 6166 39 1562 2164 69 14/38 1.5460.16
CDR ¼ clinical dementia rating, AD ¼ Alzheimer’s disease, PPA ¼ Primary progressive aphasia, TIV ¼ Total intracranial volume. involvement of left anteromedial temporal lobe, medial prefrontal cortex, inferior longitudinal fasciculus, uncinate fasciculus and forceps minor, were observed in the PiB-negative group. Conclusions: Alzheimer’s disease pathology accounts for a high proportion of patients presenting with anomia, difficulty repeating sentences and phonological errors. Highly asymmetric MRI findings and preserved spatial perceptual skills, suggest that AD pathology is absent. In such instances, a progranulin gene mutation should be suspected. O5-01-05
COMPARING ATROPHY PATTERNS IN EARLY CLINICAL STAGES ACROSS DISTINCT PHENOTYPES OF ALZHEIMER’S DISEASE
Manja Lehmann1, Brendan I. Cohn-Sheehy2, Yolande Pijnenburg3, William Seeley4, Bart van Berckel5, Bruce Miller6, Manja Lehmann7, Maria-Luisa Gorno-Tempini6, Joel H. Kramer8, Wiesje M. van der Flier9, Howard Rosen10, Philip Scheltens11, William Jagust12, Frederik Barkhof3, Gil Dan Rabinovici6, 1UCSF Memory and Aging Center, London, United Kingdom; 2Memory and Aging Center, University of California, San Francisco, Jagust Lab, University of California, Berkeley, California, United States; 3VU Medical Center, Amsterdam, Netherlands; 4UCSF MAC, San Francisco, California, United States; 5VU Medical Center, Amsterdam, Netherlands; 6UCSF Memory & Aging Center, San Francisco, California, United States; 7UCSF MAC, San Francisco, California, United States; 8 Memory Clinic, UCSF, San Francisco, California, United States; 9VU Medical Center, Amsterdam, Netherlands; 10University of California, San Francisco, San Francisco, California, United States; 11VU Medical Center, Amsterdam, Netherlands; 12University of California, Berkeley, Berkeley, California, United States. Contact e-mail: [email protected] Background: It has been proposed that temporoparietal regions are selectively vulnerable across clinical variants of Alzheimer’s disease (AD). However, since few studies included patients at the pre-dementia stage, it is unclear whether different clinical phenotypes of AD arise from focal structural alterations in the earliest disease stage and converge in temporoparietal cortex later on, or vice versa. In this study we used clinical dementia rating (CDR) scores
as proxy for disease severity to study progression of atrophy patterns in three different variants of AD. Methods: 234 patients with early-onset AD (EOAD, mainly amnestic and dysexecutive deficits), logopenic variant primary progressive aphasia (lvPPA, language variant) and posterior cortical atrophy (PCA, visual variant) with CDR scores of 0.5 (N¼104) or 1 (N¼130) were recruited from the UCSF and VUMC memory clinics (Table 1). In addition, we included a well-matched healthy control group (n¼84). Structural T1 weighted images were analyzed using voxel-based morphometry (VBM) in SPM8. We performed voxelwise contrasts between the different AD variants (both for CDR 0.5 and 1) and the control group. The VBM model included age, sex, total intracranial volume, MRI field strength (1.5T or 3T) and clinical center as nuisance variables. Results are displayed at p<0.05 (FWE-corrected). Results: At CDR 0.5, the different AD variants showed relatively distinct patterns of atrophy (see Figure 1). EOAD patients mainly had medial temporal lobe involvement, while lvPPA and PCA were affected most in left temporoparietal regions and right visual association cortex, respectively. At CDR 1, these atrophy patterns extended into the temporo-parietal cortex in EOAD, left anterior lateral temporal regions in lvPPA and the precuneus in PCA. The different variants converged at this stage in lateral temporoparietal cortex, as well as in the medial temporal lobes. Conclusions: Our crosssectional results indicate that brain atrophy is syndrome-specific in early disease stages, and converges in temporoparietal cortex and medial temporal lobes as the disease progresses. These findings provide insight into mechanisms that drive heterogeneity in AD, and have implications for early detection of atypical (or non-amnestic) AD variants using MRI. O5-01-06
WHITE MATTER HYPERINTENSITY PENUMBRA: A PASL STUDY
Nutta-on Promjunyakul1, David Lahna2, William D. Rooney2, Deniz Erten-Lyons3, Jeffrey Kaye2, Lisa C. Silbert2, 1Oregon Health and Science University, Portland, Oregon, United States; 2Oregon Health & Science University, Portland, Oregon, United States; 3Portland VA Medical Center and Oregon Health & Science University, Portland, Oregon, United States. Contact e-mail: [email protected] Background: White matter hyperintensities (WMH) are common with age and associated with cognitive impairment. WMHs are likely vascular in origin, yet the exact developmental process remains unclear. The aim of this study was to determine cerebral blood flow (CBF) values in the surrounding regions of WM injury, so that a penumbra, or "at risk" tissue surrounding the WM injury might be identified. Methods: Sixty-one cognitively intact elderly participants (mean age 84.8, CDR 0, MMSE 28.9) underwent 3T MRI FLAIR, MPRAGE and Q2TIPS pulsed arterial spin labeling (PASL). For each individual dataset, a custom-made algorithm was used to define WMH on FLAIR. To create a WMH layer mask, WMHs were used as seeds and 3dcalc was used to dilate each layer away from the WMHs by 1 voxel, for a total of 14 layers (Figure). CBF maps were linearly coregistered to the MPRAGE. The penumbra mask was then applied to the CBF map. Finally, the mean normal appearing white matter (NAWM) CBF of each layer of the periventricular (PV) and deep WMH was determined. The mean NAWM CBF was also calculated for each individual subject. Mean CBF was adjusted for age. Paired t-tests were