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Aim: To investigate whether there is a topographical and temporal pattern of index and recurrent intracerebral hemorrhages (ICH) in Dutch-type hereditary Cerebral Amyloid Angiopathy (D-CAA) to increase our understanding on CAA-related ICH development. Methods: We included patients with DNA confirmed D-CAA or a history with ≥1 lobar ICH and ≥1 first-degree relative with D-CAA. Topographical pattern was studied by location (proportion frontal/parietal/temporal/occipital; infra/supratentorial and occurrence ratios relative to lobe volume) and volume of index and recurrent ICHs were determined on CT. Temporal pattern was examined by time between recurrent ICHs was retrieved from medical records. Results: We included 72 patients with D-CAA (mean age at index ICH 55 years) with in total 214 ICH. The median follow-up time was 7 years (range 0.8 to 28 years). All ICH were lobar and supratentorial. The index ICH was most frequently located in the occipital lobe (34% vs. 22% in the other three lobes; with index ICH occurrence ratios relative to lobe volume of 1.9 for occipital, 1.0 for temporal, 1.2 for parietal, and 0.5 for frontal, p = 0.001). In 16/47 (34%) patients with multiple ICH, the second ICH was located in the same lobe as the index ICH. The median time-interval between subsequent ICH was #1-2 ICH 27 months, #2-3 ICH 14 months, and #3-4 ICH 7 months (p = 0.6) There was no difference in volume between index and recurrent ICHs. Conclusions: We found that index and recurrent ICHs in D-CAA have a preference for the occipital lobe and are least frequent in the frontal lobe, which adds to the existing knowledge of histopathological studies on amyloid load in CAA. Surprisingly, there was no acceleration in time nor gradual increase of hematoma volume between subsequent ICHs. [ABSTRACT FROM AUTHOR]

Peak width of skeletonized mean diffusivity (PSMD) is an emerging diffusion-MRI based marker to study subtle early alterations to white matter microstructure. We assessed PSMD over the clinical continuum in Dutch-type hereditary CAA (D-CAA) and its association with other CAA-related MRI-markers and cognitive symptoms. We included (pre)symptomatic D-CAA mutation-carriers and calculated PSMD from diffusion-MRI data. Associations between PSMD-levels, cognitive performance and CAA-related MRI-markers were assessed with linear regression models. We included 59 participants (25/34 presymptomatic/symptomatic; mean age 39/58 y). PSMD-levels increased with disease severity and were higher in symptomatic D-CAA mutation-carriers (median [range] 4.90 [2.77–9.50]mm2/s × 10−4) compared with presymptomatic mutation-carriers (2.62 [1.96–3.43]mm2/s × 10−4) p = <0.001. PSMD was positively correlated with age, CAA-SVD burden on MRI (adj.B [confidence interval] = 0.42 [0.16–0.67], p = 0.002), with number of cerebral microbleeds (adj.B = 0.30 [0.08–0.53], p = 0.009), and with both deep (adj.B = 0.46 [0.22–0.69], p = <0.001) and periventricular (adj.B = 0.38 [0.13–0.62], p = 0.004) white matter hyperintensities. Increasing PSMD was associated with decreasing Trail Making Test (TMT)-A performance (B = −0.42 [−0.69–0.14], p = 0.04. In D-CAA mutation-carriers microstructural white matter damage is associated with disease phase, CAA burden on MRI and cognitive impairment as reflected by a decrease in information processing speed. PSMD, as a global measure of alterations to the white matter microstructure, may be a useful tool to monitor disease progression in CAA. [ABSTRACT FROM AUTHOR]

Background and Purpose: Data on health-related quality of life (HRQoL) and mood in cerebral amyloid angiopathy (CAA), a disease characterized by stroke and cognitive decline, are limited. We aimed to investigate the impacted domains of life, value-based HRQoL and the prevalence of depression and anxiety in patients with CAA., Methods: We conducted a cross-sectional study of patients with sporadic (s)CAA, lobar dominant mixed CAA and hypertensive arteriopathy (mixed CAA-HTA), or Dutch-type hereditary (D-)CAA, from prospective outpatient clinic cohorts. Participants completed four questionnaires: the EuroQoL 5 dimensions 5-level questionnaire (EQ-5D-5L; EQ-VAS for visual analogue scale; EQ-Index for index rating), the Short-Form 36 questionnaire (SF-36), the Center for Epidemiologic Studies-Depression scale (CES-D), and the Hospital Anxiety and Depression Scale (HADS; -D for depression and -A for anxiety subscales). The EQ-5D-5L assesses the domains mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The SF-36 domains are physical functioning, social functioning, physical role limitations, emotional role limitations, mental health, vitality, bodily pain, and general health perceptions. We compared age- and sex- adjusted HRQoL (SF-36 domain scores; EQ-VAS; EQ-Index) to the Dutch normative population, and estimated the prevalences of current depression (either: history of depression or current use of antidepressants, with high score on CES-D [≥16] and/or HADS-D [≥8]; or high score on both depression questionnaires) and anxiety (HADS-A ≥ 8)., Results: We included 179 patients: 77 with sCAA (mean age: 72 years, women: 36%), 31 with mixed CAA-HTA (68 years, women: 29%), and 71 with D-CAA (56 years, women: 52%, symptomatic: 35 [49%]). The SF-36 profiles of all patient groups were similar, negatively differing from the norm in emotional role functioning, social functioning and vitality. The EQ-VAS score of patients (mean [SD] sCAA: 76 [16], D-CAA: 77 [15]) was similar to the norm, as was the EQ-Index score. Fifteen patients with sCAA (23%; 95% confidence interval [CI] 13%-33%), seven with mixed CAA-HTA (27%; 95% CI 10%-44%) and eight with D-CAA (14%; 95% CI 5%-22%) were noted as having depression. The prevalences of anxiety and depression were equivalent., Conclusions: We found that CAA influenced emotional role functioning and aspects linked to social engagement consistently across its subtypes. One quarter of patients exhibited depressive or anxiety symptoms. Recognizing these impacted domains could enhance overall well-being., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Objective: Elevated levels of anti-amyloid-β (anti-Aβ) autoantibodies in cerebrospinal fluid (CSF) have been proposed as a diagnostic biomarker for cerebral amyloid angiopathy-related inflammation (CAA-RI). We aimed to independently validate the immunoassay for quantifying these antibodies and evaluate its diagnostic value for CAA-RI., Methods: We replicated the immunoassay to detect CSF anti-Aβ autoantibodies using CSF from CAA-RI patients and non-CAA controls with unrelated disorders and further characterized its performance. Moreover, we conducted a literature review of CAA-RI case reports to investigate neuropathological and CSF evidence of the nature of the inflammatory reaction in CAA-RI., Results: The assay demonstrated a high background signal in CSF, which increased and corresponded with higher total immunoglobulin G (IgG) concentration in CSF (r sp  = 0.51, p = 0.02). Assay levels were not elevated in CAA-RI patients (n = 6) compared to non-CAA controls (n = 20; p = 0.64). Literature review indicated only occasional presence of B-lymphocytes and plasma cells (i.e., antibody-producing cells), alongside the abundant presence of activated microglial cells, T-cells, and other monocyte lineage cells. CSF analysis did not convincingly indicate intrathecal IgG production., Interpretation: We were unable to reproduce the reported elevation of anti-Aβ autoantibody concentration in CSF of CAA-RI patients. Our findings instead support nonspecific detection of IgG levels in CSF by the assay. Reviewed CAA-RI case reports suggested a widespread cerebral inflammatory reaction. In conclusion, our findings do not support anti-Aβ autoantibodies as a diagnostic biomarker for CAA-RI., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)