Podium Presentations: Sunday, July 24, 2016
P191
convergence, the syndromes also showed increased similarity in their hypometabolic patterns with time. Altogether, our result suggests that FDG-PET is a sensitive biomarker for tracking disease progression in FTD. O1-07-04
LONGITUDINAL AMYLOID DEPOSITION AND HIPPOCAMPAL VOLUME IN SUSPECTED NONALZHEIMER PATHOPHYSIOLOGY AND PRECLINICAL ALZHEIMER’S DISEASE
Brian Andrew Gordon1,2, Tyler Blazey1, John C. Morris2,3, David M. Holtzman1,2,4, Anne M. Fagan2,3,4, Tammie L. S. Benzinger1,2, 1 Washington University in St. Louis School of Medicine, St. Louis, MO, USA; 2Knight Alzheimer’s Disease Research Center, St. Louis, MO, USA; 3 Washington University School of Medicine, St. Louis, MO, USA; 4Hope Center for Neurological Disorders, St. Louis, MO, USA. Contact e-mail:
[email protected] Background: Preclinical Alzheimer Disease (AD) can be staged us-
ing a two-factor model denoting the presence or absence of significant beta-amyloid (Ab +/-) accumulation and neurodegeneration (ND+/-). The National Institute of Aging and Alzheimer’s Association (NIA-AA) working group formalized this two factor model such that Stage 0 represents individuals with no pathology, Stage 1 is characterized by the presence of b-amyloidosis alone, Stages 2 and 3 (Stage 2+) by abnormal levels of both Ab and ND, and those with evidence of ND in the absence of b-amyloidosis, so-called suspected non-Alzheimer pathophysiology (SNAP). While prior work has examined how these stages predict the longitudinal risk of dementia, there is a dearth of work relating preclinical staging to longitudinal rates of biomarker accumulation. Methods: We examined 174 cognitively normal individuals (mean age 65.7, females¼93), with a clinical dementia rating (CDR) of 0 at baseline. Pathology was characterized with 11[C]Pittsburgh Compound B (PiB) PET, and hippocampal volume derived from MRI. A subset (n¼110) also had CSF measurements of tau and ptau181 at baseline. Participants were classified into baseline preclinical stages using PiB to denote abnormal Ab and then using either MRI or CSF to denote ND. All subjects had longitudinal measurements of PiB deposition and hippocampal volume (mean ¼ 4.1 years of follow-up). Results: The longitudinal rates of Ab accumulation and loss of hippocampal volume in SNAP individuals were indistinguishable from those without any sort of pathology at baseline (Stage 0) when using either hippocampal volume or CSF measures to denote ND. Later preclinical stages (Stages 1 and Stage 2+) had elevated Ab accumulation relative to other groups, and when defined using CSF biomarkers, Stage 2+ had accelerated hippocampal atrophy relative to the rest of the cohort. Conclusions: Rather than representing a neurodegenerative first pathway to AD, SNAP appears more likely
Figure 1.
Figure 2.
to capture inherent individual variability in brain structure or represent comorbid pathology. Low hippocampal volumes or elevated levels of tau and ptau181 measured cross-sectionally in the absence of elevated Ab may not accurately represent an ongoing neurodegenerative processes. More advanced preclinical stages have greater longitudinal Ab accumulation. O1-07-05
LONGITUDINAL PATTERNS OF CEREBRAL ATROPHY IN DISTINCT CLINICAL VARIANTS OF ALZHEIMER’S DISEASE
Gautam Tammewar1, Rik Ossenkoppele1,2, Brendan Cohn-Sheehy1, Zachary A. Miller1, Miguel Santos1, Averill Cantwell1, William W. Seeley3, Marilu Gorno-Tempini1, Joel Kramer1, Howard J. Rosen1, Bruce Miller1, Gil D. Rabinovici1,4, 1University of California San Francisco, San Francisco, CA, USA; 2VU University Medical Center, Amsterdam, Netherlands; 3University of California, San Francisco, San Francisco, CA, USA; 4Lawrence Berkeley National Laboratory, Berkeley, CA, USA. Contact e-mail:
[email protected] Background: Alzheimer’s disease (AD) can present with different
clinical phenotypes that show both distinct and overlapping patterns of neurodegeneration at baseline. We sought to compare longitudinal atrophy patterns across AD variants to better understand
