Memory impairment is a clinical marker of tau pathology in cerebral amyloid angiopathy

Abstract

AbstractBackgroundCerebral Amyloid Angiopathy (CAA) shows a high comorbidity with Alzheimer’s Disease (AD). Nonetheless, CAA is an independent neuropathological disorder, and over half of CAA cases present without AD‐related tau pathology. Differentiating CAA patients with or without concomitant tau pathology could have important implications for therapeutic approaches. We aimed to determine whether memory impairments in CAA are indicative of underlying tau pathology.MethodThis study included 29 patients fulfilling criteria for mild cognitive impairment (MCI) and probable CAA. Subjects underwent a neuropsychological evaluation, a MRI, and PET scans for in‐vivo estimation of amyloid ([11C]– PiB) and tau ([18F]‐AV‐1451) burden. Structural markers of small vessel disease, total brain volume and hippocampal volume were quantified on MRI images. [11C]‐PiB specific binding was expressed as distribution volume ratios (DVR) and [18F]‐AV‐1451 specific binding as standardized uptake value ratio (SUVR), using the cerebellar cortex as the reference region. CAA subjects were classified as “amnestic” or “non‐amnestic” based on neuropsychological performance. Groups were contrasted on demographic features and quantified MRI markers. Between‐group voxel‐wise comparisons of SUVR [18F]‐AV‐1451 and DVR [11C]‐PiB maps were performed. Mean [18F]‐AV‐1451 SUVR in areas of group differences was extracted for each subject and correlated to memory performance.ResultIn our sample, 14 CAA subjects were classified as “amnestic”, and 15 as “non‐amnestic”. Amnestic and non‐amnestic subjects did not differ in age, education, or sex representation. Groups did not differ on any MRI markers of small vessel disease, nor in total brain volume (p>0.05, for all). However, amnestic subjects showed smaller hippocampal volume (F(1,28)=5.65, p<0.05). Voxel‐wise comparison of DVR [11C]‐PiB maps did not reveal any differences between amnestic and non‐amnestic CAA. Comparison of SUVR [18F]‐AV‐1451 maps revealed significant increase in tau PET binding in several regions for amnestic subjects (Figure 1). Mean tau PET binding in these regions was correlated with memory performance (r=‐0.68, p<0.001), and hippocampal volume (r=‐0.44, p<0.05), after accounting for age.ConclusionAmnestic CAA subjects present higher tau PET binding, and smaller hippocampal volume than non‐amnestic CAA. Our results suggest that memory impairments in CAA are related to tau pathology and medial temporal lobe neurodegeneration, consistent with the presence of concomitant AD.