Cerebral microbleeds and amyloid pathology
Julie Elisabeth Oomens, Willemijn J. Jansen, Whitney M. Freeze, Nancy Nairi Maserejian, Frans R.J. Verhey, Stephanie J. B. Vos, Pieter Jelle Visser,- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
- Geriatrics and Gerontology
- Neurology (clinical)
- Developmental Neuroscience
- Health Policy
- Epidemiology
Abstract
Background
Cerebral microbleeds (CMBs) are common in the elderly population and are associated with cognitive decline. The aim of the current study was to examine the association between CMBs and cerebral amyloid pathology in cognitively unimpaired (CU) and cognitively impaired (CI) individuals included in the Amyloid Biomarker Study.
Method
We included 2550 CU and 1002 CI participants from 12 cohorts of the Amyloid Biomarker Study. Presence of amyloid pathology was determined based on Aß42 levels in CSF (n = 2873) or amyloid‐PET (n = 679) using data‐driven or center‐specific cutoffs. CMBs were assessed on in vivo MRI and were classified as present (≥1) or absent. The association of amyloid pathology with CMBs and its dependency on age, sex, APOE‐e4 carriership and hypertension was assessed using generalized‐estimating‐equations.
Result
Thirty‐seven percent of participants were amyloid positive, 38% were APOE‐e4 carrier, 54% were female, 30% had hypertension and 17% had CMBs (20% of the amyloid positive and 16% of the amyloid negative group, respectively). The mean age was 66.7 years (SD9.2). In CU participants, there was no association between amyloid pathology and CMBs. In CI individuals, CMB prevalence was associated with amyloid pathology depending on age (p = 0.044). At younger ages (<75 years), CMBs were more common in amyloid positive rather than amyloid negative participants while at older ages, amyloid negative participants had CMBs more often. However, the interaction between amyloid status and age became insignificant when hypertension was considered. CMB prevalence was associated with amyloid pathology depending on hypertension (p = 0.006). In CI participants without hypertension, CMBs were more common in those that were amyloid positive rather than amyloid negative. In CI participants with hypertension, there was no significant difference in CMB prevalence between the amyloid positive and negative groups (Figure 1). Sex and APOE‐e4 status did not affect the observed associations between amyloid pathology and CMBs in participants with CI.
Conclusion
CMB prevalence is associated with amyloid pathology and this association is dependent on hypertension. Knowledge on the background prevalence of CMBs considering AD biomarker and vascular risk factor status is needed to inform clinical trial design and safety evaluation of AD therapies.