Early-Stage MRI Volumetric Differences in White Matter Hyperintensity and Temporal Lobe Volumes between Autopsy-Confirmed Alzheimer's Disease, Cerebral Small Vessel Disease, and Mixed Pathologies

Abstract

Introduction: Alzheimer's disease (AD) and cerebral small vessel disease (CVSD) both contribute to age-related cognitive decline but can be difficult to clinically distinguish at early stages. At mild cognitive impairment (MCI), we investigated brain MRI volumetric differences in white matter hyperintensities (WMH), frontal and temporal lobe volumes between neuropathologically defined groups of cerebral arteriolosclerosis alone (pARTE), AD alone (pAD), and mixed (ADARTE). Methods: From the National Alzheimer's Coordinating Center, we defined neuropathology groups of pARTE (n = 18), pAD (n = 36), and ADARTE (n = 55) who had MRI brain volumetrics within 1 year of clinical evaluation with Clinical Dementia Rating score of 0.5, corresponding to MCI. We included moderate-to-severe arteriolosclerosis and/or ABC score 2-3 for AD, after excluding other major neuropathologies. We compared WMH and frontal and temporal lobe volumes between neuropathology groups using regression analysis. Results: Adjusted regression models show AD-related groups associated with less WMH when compared to pARTE (pAD adjusted odds ratio (aOR) (95% confidence interval [CI]): 0.94 (0.90-0.98); ADARTE aOR (95% CI): 0.96 (0.93-0.99)). The mixed pathology group, but not pAD, had smaller right temporal lobe volumes than pARTE (pAD aOR [95% CI]: 0.86 [0.74-1.00]; ADARTE aOR [95% CI]: 0.83 [0.72-0.96]). There were no differences in frontal lobe volumes. Discussion/Conclusions: Findings from this neuropathologically confirmed cohort suggest volumetric differences in WMH and temporal lobe volumes between AD- and CVSD-related MCI. Moreover, our results suggest a differential atrophy susceptibility of the right versus left temporal lobe to the additive effect of AD and vascular pathologies.