Presence of Microinfarcts at Autopsy is Associated with Increased Rate of Gray Matter Atrophy on Antemortem MRI (P4.017)

OBJECTIVE: To investigate whether the presence of microinfarcts at autopsy is associated with an increased rate of global and regional gray matter atrophy on antemortem MRI. BACKGROUND: Microinfarcts are a common pathology identified at autopsy and are associated with cognitive impairment and dementia in the elderly. They are not visible on conventional antemortem MRI, therefore they are not assessed in vivo. Contribution of this common pathology to brain atrophy rates in older adults is unknown. DESIGN/METHODS: We retrospectively identified cases (n=13) with one or more microinfarcts at autopsy and controls with no microinfarcts (n=13) matched on age, sex, APOE4 status, MMSE score, and pathologic diagnosis of Alzheimer’s disease (AD) to the cases. All subjects had to have serial MRI up to 3.5 years before death. Rates of whole brain atrophy and ventricular expansion were calculated using the boundary shift integral method. Voxel-wise gray matter atrophy rates were determined using Tensor Based Morphometry-Symmetric Diffeomorphic Image Normalization. Group differences were displayed using two-sided t-tests in SPM5 thresholded at p<0.001. RESULTS: Rate of whole brain atrophy was higher (p=0.004) in cases with microinfarcts compared to controls with no microinfarcts at autopsy. Rate of ventricular volume increase showed a similar trend (p=0.089) in cases with microinfarcts. Voxel-wise analysis revealed greater rates of atrophy in the posterior cingulate gyrus, precuneus, and focal areas in the temporal lobe neocortex in cases with microinfarcts compared to controls with no microinfarcts. CONCLUSIONS: Microinfarcts are associated with an increased rate of brain atrophy independent of AD pathology particularly in the posterior cingulate gyrus and precuneus, which are the connectivity hubs and highly perfused areas of the brain. Effects of microinfarcts should be taken into account when using brain atrophy rates as a pure measure of AD pathology, even in the absence of overt infarcts. Study Supported by: P50-AG016574, U01-AG006786), R01-AG040042, R01-AG011378, RO1-AG041851, Robert H. and Clarice Smith and Abigail van Buren Alzheimer Disease Research Program Disclosure: Dr. Raman has nothing to disclose. Dr. Senjem has nothing to disclose. Dr. Gunter has nothing to disclose. Dr. Przybelski has nothing to disclose. Dr. Vemuri has nothing to disclose. Dr. Murray has nothing to disclose. Dr. Boeve has received research support from Cephalon, Inc., Allon Therapeutics, and GE Healthcare. Dr. Knopman has received personal compensation for activities with Eli Lilly & Company and TauRx Pharmaceuticals. Dr. Knopman has received personal compensation in an editorial capacity for Neurology. Dr. Knopman has received research support from Janssen and Baxter. Dr. Petersen has received personal compensation for activities with Pfizer, Inc., and Janssen Alzheimer9s Immunotherapy. Dr. Petersen has received royalty payments from Oxford University Press. Dr. Parisi has nothing to disclose. Dr. Dickson has received personal compensation for activities with Neotope, Inc. as a consultant. Dr. Jack has received personal compensation for activities with Janssen, Eisai Inc., General Electric, Johnson & Johnson, and Eli Lilly & Co. Dr. Jack has received research support from Pfizer Inc., Allon, and Baxter. Dr. Kantarci has received research support from Pfizer Inc., Jannsen Alzheimer immunotherapy, and Takeda Global Research & Development Center.