. Association of Cerebral Microbleeds With Cognitive Decline and Dementia. JAMA Neurol. 2016 Aug 1;73(8):934-43. PubMed.


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  1. Whether cerebral microbleeds (CMBs) are associated with cognitive decline or not has long been debated. Akoudad et al. study the effects of number and location of CMBs on cognition in the population-based Rotterdam study. They suggest CMBs may be the missing link that bridges the vascular and amyloid hypotheses in Alzheimer’s disease.

    A thorough longitudinal neuropsychological test battery was used in the assessment of cognition, and a total of 4,841 patients were included in the analysis. Akoudad et al. found that a high CMB count (>4) is associated with cognitive decline, and that the presence of CMBs is associated with an increased risk of dementia. 

    Prior thorough studies on CMBs and cognition in general populations are scarce. Yet data so far suggest that CMBs indeed may be associated with cognitive decline. In memory clinic populations, CMBs have been shown to be associated with Aβ42 (Shams et al., 2016; Shams et al., 2016; Goos et al., 2012; Goos et al., 2009; Park et al., 2013), with more CMBs being associated with increased amyloid deposition in the brain. Further, CMBs have been shown to be associated with high age, high mortality, and a suggested decreased cognitive performance, although studies on the last point are discrepant (Goos et al., 2009; Shams et al., 2015; Pettersen et al., 2008; Chiang et al., 2015; Benedictus et al., 2015; Ye et al., 2015; van der Vlies et al., 2012; Wu et al., 2014). Cortical CMBs have also been shown to be associated with lower cerebral blood flow in cognitively normal individuals (Gregg et al., 2015). Finally, patients with subjective cognitive decline with white matter hyperintensities, another marker of small vessel disease, have been shown to be at increased risk of cognitive decline and clinical disease progression (Benedictus et al., 2015). 

    Associations with cognitive decline have likewise been seen in elderly populations. In the Rotterdam Scan Study, a prior report highlights the association between multiple CMBs and worse cognitive function (Poels et al., 2012). Multiple CMBs have been associated with a high global neuropsychiatric burden (Xu et al., 2016). In older participants, the total score of imaging small vessel disease markers has shown associations with lower general cognitive ability (Staals et al., 2015). Infratentorial CMBs have further shown an association with a loss in cognitive function (van Es et al., 2011). In the AGES-Reykjavik study it has been shown that multiple CMBs are associated with vascular cognitive impairment (Qiu et al., 2012). Lobar CMBs, and CMBs in general, have further been associated with executive function decline (Meier et al., 2014; Yamashiro et al., 2014). 

    In conclusion, many studies point to the fact that CMBs are associated with cognitive decline. This current study is among the most thorough in examining CMB burden and associations with cognition, corroborating previous data.


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    View all comments by Sara Shams
  2. The association between cortical microbleeds (CMB) and Alzheimer's disease is unexpected, though these findings lend support to vascular causes of Alzheimer's disease. The significance of small vessel disease findings such as CMBs on imaging studies in patients with memory complaints has been uncertain. These results suggest that clinicians need to pay attention to these types of lesions on imaging studies, as they may have treatable causes.

    In a cross-sectional study based in India, we did not find an association between CMB and Motoric Cognitive Risk syndrome, a pre-dementia state (Wang et al., 2015). We did, however, see an association between lacunar infarctions (another type of cerebral small vessel disease) in the frontal lobe and MCR syndrome. Most small vessel disease and cognition studies have been conducted in Western populations, and there may be regional or ethnic differences in the association between the types of cerebral small vessel diseases and cognition.


    . Cerebral Small Vessel Disease and Motoric Cognitive Risk Syndrome: Results from the Kerala-Einstein Study. J Alzheimers Dis. 2015;50(3):699-707. PubMed.

    View all comments by Joe Verghese

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  1. Microbleeds in the Brain Portend Dementia