Population-Based Prevalence of Cerebral Cavernous Malformations in Older Adults: Mayo Clinic Study of Aging

Abstract

Importance: The prevalence of cerebral cavernous malformation (CCM) is unknown. Case ascertainment in most previous studies was based on autopsy data or clinical convenience samples, often without detailed clinical or radiologic information.

Objective: To determine the prevalence of CCM in a population-based sample of older adults.

Design, setting, and participants: This prospective imaging study included 4721 participants aged 50 to 89 years who were enrolled between January 1, 2004, and December 15, 2015, in the Mayo Clinic Study of Aging, a longitudinal, population-based study of residents of Olmsted County, Minnesota. An age- and sex-stratified sampling strategy was used to randomly select participants from Olmsted County using the medical records linkage system of the Rochester Epidemiology Project. Participants were invited to undergo brain magnetic resonance imaging (MRI). Of the 4721 participants, 2715 had an evaluable MRI. All images were reviewed by a board-certified neuroradiologist, and MRI reports were searched for the terms cavernous malformation, cavernous angioma, and cavernoma. Two vascular neurologists reviewed MRIs, and potential CCMs were classified using Zabramski classification. Medical records of the identified individuals with CCM were reviewed along with their demographic information, medical history, and any symptoms referable to the identified CCM lesion.

Main outcomes and measures: Prevalence of CCM and clinical and radiologic characteristics of study participants with CCM.

Results: Of the 2715 participants who underwent MRI scans, 12 (0.44%) had CCM. With the use of inverse probability weights to adjust for participation bias, the overall prevalence was 0.46% (95% CI, 0.05-0.86). The age-adjusted prevalence was found to be 0.61% (95% CI, 0-1.47) for the 50- to 59-year age group, 0.17% (95% CI, 0-0.50) for the 60- to 69-year age group, 0.45% (95% CI, 0.09-0.81) for the 70- to 79-year age group, and 0.58% (95% CI, 0-1.29) for the 80- to 89-year age group. The sex-adjusted prevalence was 0.41% (95% CI, 0-1.00) for women and 0.51% (95% CI, 0-1.07) for men. Observed frequencies were similar in men and women, with a slight male predominance. Of the 12 participants with CCM, 9 (75%) had a single Zabramski type 2 lesion in a supratentorial location. Only 1 participant (0.037%) was symptomatic from the CCM during the study period.

Conclusions and relevance: The findings and data from this study are important for determining the potential number of patients available for cohort studies and anticipated clinical trials in older patients with CCM.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Flemming reported serving as an unpaid scientific advisor for the Angioma Alliance. Dr Kantarci reported serving on the data safety monitoring board of Takeda Global Research & Development Center, Inc, as well as the data monitoring boards of Pfizer and Janssen Alzheimer Immunotherapy and being funded by grants R01 AG040042 (principal investigator [PI]), R21 NS066147 (PI), P50 AG44170/Project 2 (PI), P50 AG16574/Project 1 (PI), and R01 AG11378 (coinvestigator) from the National Institutes of Health (NIH). Dr Mielke reported serving as a paid consultant for Lysosomal Therapeutics, Inc, AbbVie, and Lilly; being funded by the NIH and the Michael J. Fox Foundation; and receiving unrestricted research grants from Biogen. Drs Roberts and Kremers reported being funded by the NIH. Dr Kremers also reported receiving research funding from AstraZeneca unrelated to cerebral cavernous malformations. Dr Knopman reported being deputy editor for Neurology; serving on a data safety monitoring board for Lilly Pharmaceuticals, Lundbeck Pharmaceuticals, and for the DIAN study; serving as a consultant to TauRx Pharmaceuticals; and having been an investigator in clinical trials sponsored by Baxter and Elan Pharmaceuticals, being an investigator in a clinical trial sponsored by TauRx, and receiving research support from the NIH. Dr Petersen reported serving on scientific advisory boards for Elan Pharmaceuticals, Wyeth Pharmaceuticals, and GE Healthcare and receiving research support from the National Institute on Aging. Dr Jack reported serving as a consultant for Janssen, Bristol-Meyers Squibb, General Electric, and Johnson & Johnson; being involved in clinical trials sponsored by Allon and Baxter, Inc; and receiving research support from Pfizer, Inc, the National Institute on Aging (AG11378 [PI], P50-AG16574 [coinvestigator], and U01-AG024904-01 [coinvestigator]), and the Alexander Family Alzheimer’s Disease Research Professorship of the Mayo Foundation. No other disclosures were reported.