Expanding the spectrum of cerebral amyloid angiopathy: non-classical symptoms and the emerging iatrogenic subtype

Kaushik, K.

Expanding the spectrum of cerebral amyloid angiopathy: non-classical symptoms and the emerging iatrogenic subtype

Author(s):: Kaushik, K.

Published: 2025
Publication type: Doctoral Thesis

Abstract

This thesis aimed to identify non-classical symptoms associated with cerebral amyloid angiopathy (CAA) and investigate the disease consequences and burden as experienced by patients and reported by informants.

Part I, assessed the frequency and patterns of non-classical symptoms and HRQoL. We found that transient symptoms and headaches occur frequently, but are not associated with specific blood products visible on MRI. Informants of one-third to half of patients reported neuropsychiatric symptoms being present, which was linked to cognitive decline, but not radiological CAA-burden. Further, we found that CAA impacts emotional role functioning and factors related to social participation.

Part II investigates iatrogenic CAA (iCAA), a newly identified CAA-subtype. We described the frequency, clinical profile, radiological features and outcome of patients with presumed iCAA, which is thought de be a consequence of specific medical procedures and might be present in 45% of patients with young-onset CAA and in 4% of those fulfilling commonly used diagnostic criteria. Further, we described the first cases of a newly hypothesized transmission mechanism. Finally, we considered and scrutinized the ethical arguments concerning three disclosure-related questions regarding the iatrogenic CAA diagnosis, that arise due to the uncertainty regarding its etiology and prognosis, and the absence of disease-modifying treatments.

Cerebral amyloid angiopathyAmyloidCAAStrokeIntracerebral hemorrhagePrionsCerebral small vessel diseaseCognitive dysfunction

Defense date: 2025-02-12
Language: English
Supervisor(s): Wermer, M.J..H.; Terwindt, G.M.
Advisor(s): Etten, E.S. van
Committee member(s): Dekker, F.W.; Middelkoop, H.A.M.; Vries, M.C. de; Staals, J.; Schreuder, F.H.B.M.
Qualification: Ph.D.
Degree granting institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University, Leiden
hdl: 1887/4180270
ISBN(s): 9789465067810

Funding

Sponsorship: The research presented in this thesis was performed at the Department of Neurology of the Leiden University Medical Centre, Leiden, The Netherlands. The research in this thesis was supported by a grant from the Dutch Heart Foundation (Clinical Established Investigator grant 2016T86, granted to prof. dr. M.J.H. Wermer, paid to institution). Financial support by the Dutch Heart Foundation for publication of this thesis is gratefully acknowledged. Printing of this thesis was supported by Alzheimer Nederland (Amersfoort). Printing of this thesis was supported by Vakgroep Neurologie Reinier de Graaf Gasthuis (Delft).