Clues to Memory Impairment in Cerebral Amyloid Angiopathy

Amyloid beta peptide, computer illustration. This protein is the primary component of amyloid plagues in the brains of Alzheimers patients.
The researchers’ objective was to assess the neuroimaging features of patients with cerebral amyloid angiopathy, or CAA, with and without objective memory impairment using tau PET imaging.

Among patients with cerebral amyloid angiopathy (CAA), the presence of memory impairment may serve as a marker of tau pathology and medial temporal lobe integrity, according to study results published in Neurology.

Previous studies have shown that CAA, an angiopathy characterized by a buildup of amyloid proteins in leptomeningeal and cortical vessels, has a major role in the development of vascular cognitive impairment and dementia and is also a common feature of Alzheimer disease.

The objective of the current study was to assess the neuroimaging features of patients with CAA with and without objective memory impairment using tau positron emission tomography (PET) imaging.

The study included 46 patients with CAA who underwent neuropsychological assessment, 25 of whom had an amnestic CAA and 21 of whom had nonamnestic CAA. All patients completed magnetic resonance imaging (MRI) within 3 months of the neuropsychological evaluation to quantify small vessel disease.

A subgroup of included participants completed PET scans for in vivo estimation of amyloid ([11C]-Pittsburgh compound B amyloid-PET, n=39) and tau ([18F]-flortaucipir tau-PET, n=40) pathology.

Neuroimaging features of patients with CAA presenting with or without objective memory impairment were compared, as were demographic, clinical, and cognitive characteristics.

In patients with amnestic CAA, compared with those with nonamnestic CAA, tau-PET retention in regions susceptible to Alzheimer disease neurodegeneration was increased (P =.003), and the differences remained significant after controlling for MRI markers of cerebral small vessel disease, age, and sex (P =.01). After adjustment for age and sex, the normalized total hippocampal volume was lower among patients with amnestic CAA compared with patients with nonamnestic CAA (P <.001).

There were no significant differences between patients with amnestic and nonamnestic CAA on any other structural MRI markers or on amyloid-PET binding.

Comparing patients with CAA with a positive (21 participants) and a negative tau-PET (19 participants) showed a lower performance on the memory domain in the former, compared with the latter (P =.004), while performance on other cognitive domains did not differ significantly.

The study had several limitations, including the absence of of histopathology confirmation of the diagnosis of CAA and amyloid and tau pathology, small sample size, and potential selection bias because the study comprised patients with CAA with no history of intracerebral hemorrhage.

“Our study demonstrates that the presence of memory impairment in patients with CAA is a promising marker of tau pathology and medial temporal lobe integrity. In the absence of advanced neuroimaging technologies, this accessible clinical marker could provide relevant information on the severity and nature of underlying pathologic mechanisms in this heterogeneous population,” concluded the study researchers.


Schoemaker D, Charidimou A, Zanon Zotin MC, et al. Association of memory impairment with concomitant tau pathology in patients with cerebral amyloid angiopathy. Neurology. 2021;96(15):e1975-e1986. doi:10.1212/WNL.0000000000011745