Sex Differences in Onset and Progression of Cerebral Amyloid Angiopathy

Abstract

Background: Cerebral Amyloid Angiopathy (CAA) disease course is highly variable even in hereditary forms. Sex may be a possible modifying factor. We investigated biological sex differences in clinical disease course and magnetic resonance imaging-markers in sporadic (sCAA) and Dutch-type hereditary CAA (D-CAA). Methods: Patients with D-CAA and sCAA were included from hospital and research databases of the Leiden University Medical Center (2012–2020) and Massachusetts General Hospital (1994–2012). Key outcomes were: sex differences in symptomatic intracerebral hemorrhage (sICH) onset, recurrence and survival (analyzed using Kaplan Meier survival and regression analyses), and sex differences in magnetic resonance imaging-markers in D-CAA (explored using scatterplots), and in sCAA (investigated using regression analysis). Results: We included 136 patients with D-CAA (mean age 57 years, 56% women, 64% with previous sICH) and 370 patients with sCAA (mean age 76 years, 51% women, all with previous sICH). Men and women with D-CAA did not differ for sICH onset (median age 54 in men and 56 in women [ P =0.13]). Men with D-CAA had a slightly higher number of sICH compared with women (median 2 versus 1; adjusted RR, 1.5 [95% CI, 1.1–1.9]) and a shorter interval between the first and second sICH (median 1.8 years for men and 3.1 years for women, P =0.02). Men with sCAA had their first sICH at an earlier age (median 75 versus 78 years, respectively, P =0.003) and more lobar microbleeds (median 1 versus 0, P =0.022) compared with women with sCAA. No substantial differences were found in the other magnetic resonance imaging markers. Survival after first sICH was comparable between sexes for D-CAA ( P =0.12) and sCAA ( P =0.23). Conclusions: Men with CAA seem to have an earlier onset (sCAA) and more hemorrhagic disease course (sCAA and D-CAA) compared with women. Future studies are necessary to confirm these findings and determine the underlying role of sex-related factors.

Cerebral Amyloid Angiopathy: An Undeniable Small Vessel Disease

“…Sex may also play a key role in CAA progression. A study of patients with HCHWA-D and sCAA found that male sex and sCAA may be related to an earlier onset and longer course of CAA [ 12 ].…”

Non‐hemorrhagic imaging markers of cerebral amyloid angiopathy in memory clinic patients

“…We also found an independent association between female sex and the presence of non‐hemorrhagic CAA markers. Although in some population‐based studies, 37 cohorts of patients with CAA, 40 and memory clinic cohorts, 41 no association between sex and CSO‐EPVS burden was found, other studies have found an increased CSO‐EPVS burden in women with CAA 42 and a higher age‐related rate of increased EPVS in women 43 . Very little was found in the literature on the question of sex differences and the presence of the multispot pattern.…”

Sex and interferon gamma signaling regulate microglia migration in the adult mouse cortex in vivo

“…), our results showing sex differences in migratory responses to injury could have functional implications. Human studies are rather mixed but show that males diagnosed with cerebral amyloid angiopathy ( 87 ), mild cognitive impairment, or Alzheimer disease ( 88 ), have significantly more cerebral microbleeds than females ( 89 ), whereas females with small vessel disease have increased microbleed burden ( 90 ). In rodents, the picture appears more consistent where female mice exhibit more abundant microbleeds than males in mouse models of Alzheimer disease ( 91 ) or cerebral amyloid angiopathy ( 92 ).…”