Association of Memory Impairment with Concomitant Tau Pathology in Patients with Cerebral Amyloid Angiopathy.

OBJECTIVE Relying on tau-PET imaging, this cross-sectional study explored whether memory impairment is linked to the presence of concomitant tau pathology in subjects with Cerebral Amyloid Angiopathy (CAA). METHODS Forty-six subjects with probable CAA underwent a neuropsychological examination and an MRI for quantification of structural markers of cerebral small vessel disease. A subset of these subjects also completed a [11C]-PiB (n=39) and [18F]-flortaucipir (n=40) PET for in-vivo estimation of amyloid and tau burden, respectively. Subjects were classified as amnestic or non-amnestic based on neuropsychological performance. Statistical analyses were performed to examine differences in cognition, structural markers of cerebral small vessel disease, and amyloid- and tau-PET retention between amnestic and non-amnestic CAA subjects. RESULTS: Probable CAA subjects with an amnestic presentation displayed a globally more severe profile of cognitive impairment, smaller hippocampal volume (p<0.001), and increased tau-PET binding in regions susceptible to Alzheimer's Disease neurodegeneration (p=0.003), as opposed to their non-amnestic counterparts. Amnestic and non-amnestic subjects did not differ on any other MRI markers, nor on amyloid-PET binding. In a generalized linear model including all evaluated neuroimaging markers, tau-PET retention (s=-.85, p=0.001) and hippocampal volume (s=.64 p=0.01) were the only significant predictors of memory performance. The cognitive profile of CAA subjects with an elevated tau-PET retention was distinctly characterized by a significantly lower performance on the Memory domain (p=0.004). CONCLUSIONS These results suggest that the presence of objective memory impairment in subjects with probable CAA could serve as a marker for underlying tau pathology. CLASSIFICATION OF EVIDENCE This study provides Class II evidence that tau-PET retention is related to the presence of objective memory impairment in subjects with CAA.