OBJECTIVE: We performed a systematic review and meta-analyses to assess the evidence for genetic associations with brain microbleeds (BMBs). METHODS: We sought all published studies of the association between any genetic polymorphism and BMBs studied in a total of >100 people. We critically appraised studies, and calculated pooled odds ratios (ORs) using the generic inverse variance fixed effects method. We used I² and χ² statistics to assess heterogeneity, and fail-safe N estimates to assess the robustness of our results. RESULTS: Only the APOE ε2/3/4 polymorphism had been studied in >100 people (10 studies, 7,351 participants). Compared with people with the ε3/ε3 genotype, carriers of the ε4 allele (ε4+) were statistically significantly more likely to have BMBs in any location (ε4+ vs ε3/ε3: pooled OR 1.22, 95% confidence interval [CI] 1.05-1.41, p = 0.01). For strictly lobar BMBs, this association appeared slightly stronger (ε4+ vs ε3/ε3: pooled OR 1.35, 95% CI 1.10-1.66, p = 0.005). The association of ε4+ genotypes with strictly lobar BMBs was reasonably robust to potential publication and reporting biases. CONCLUSIONS: Given the known associations of APOE alleles with lobar intracerebral hemorrhage and cerebral amyloid angiopathy, these findings support the concept that strictly lobar BMBs may be an imaging biomarker of cerebral amyloid angiopathy.
OBJECTIVE: We performed a systematic review and meta-analyses to assess the evidence for genetic associations with brain microbleeds (BMBs). METHODS: We sought all published studies of the association between any genetic polymorphism and BMBs studied in a total of >100 people. We critically appraised studies, and calculated pooled odds ratios (ORs) using the generic inverse variance fixed effects method. We used I² and χ² statistics to assess heterogeneity, and fail-safe N estimates to assess the robustness of our results. RESULTS: Only the APOE ε2/3/4 polymorphism had been studied in >100 people (10 studies, 7,351 participants). Compared with people with the ε3/ε3 genotype, carriers of the ε4 allele (ε4+) were statistically significantly more likely to have BMBs in any location (ε4+ vs ε3/ε3: pooled OR 1.22, 95% confidence interval [CI] 1.05-1.41, p = 0.01). For strictly lobar BMBs, this association appeared slightly stronger (ε4+ vs ε3/ε3: pooled OR 1.35, 95% CI 1.10-1.66, p = 0.005). The association of ε4+ genotypes with strictly lobar BMBs was reasonably robust to potential publication and reporting biases. CONCLUSIONS: Given the known associations of APOE alleles with lobar intracerebral hemorrhage and cerebral amyloid angiopathy, these findings support the concept that strictly lobar BMBs may be an imaging biomarker of cerebral amyloid angiopathy.
Authors: M Kim; H J Bae; J Lee; L Kang; S Lee; S Kim; J E Lee; K M Lee; B W Yoon; O Kwon; J S Koo; B K Kim Journal: Neurology Date: 2005-11-08 Impact factor: 9.910
Authors: M O McCarron; J A Nicoll; J Stewart; J W Ironside; D M Mann; S Love; D I Graham; D Dewar Journal: J Neuropathol Exp Neurol Date: 1999-07 Impact factor: 3.685
Authors: John M Ringman; Michael C Sachs; Yan Zhou; Sarah E Monsell; Jeffrey L Saver; Harry V Vinters Journal: JAMA Neurol Date: 2014-07-01 Impact factor: 18.302
Authors: Sabrina Schilling; Anita L DeStefano; Perminder S Sachdev; Seung Hoan Choi; Karen A Mather; Charles D DeCarli; Wei Wen; Peter Høgh; Naftali Raz; Rhoda Au; Alexa Beiser; Philip A Wolf; José Rafael Romero; Yi-Cheng Zhu; Kathryn L Lunetta; Lindsay Farrer; Carole Dufouil; Lewis H Kuller; Bernard Mazoyer; Sudha Seshadri; Christophe Tzourio; Stéphanie Debette Journal: Neurology Date: 2013-07-16 Impact factor: 9.910
Authors: Anne F Wiegman; Irene B Meier; Nicole Schupf; Jennifer J Manly; Vanessa A Guzman; Atul Narkhede; Yaakov Stern; Sergi Martinez-Ramirez; Anand Viswanathan; José A Luchsinger; Steven M Greenberg; Richard Mayeux; Adam M Brickman Journal: J Neurol Sci Date: 2014-07-18 Impact factor: 3.181
Authors: Julius S Ngwa; Thomas V Fungwe; Oyonumo Ntekim; Joanne S Allard; Sheree M Johnson; Chimene Castor; Lennox Graham; Sheeba Nadarajah; Richard F Gillum; Thomas O Obisesan Journal: Dement Geriatr Cogn Disord Date: 2018-04-25 Impact factor: 2.959