Abstract
Background and purpose: Cerebral microinfarcts (CMIs) are associated with cognitive impairment and dementia. CMIs might affect cognitive performance through disruption of cerebral networks. We investigated in memory clinic patients whether cortical CMIs are clustered in specific brain regions and if presence of cortical CMIs is associated with reduced white matter (WM) connectivity in tracts projecting to these regions.Methods:164 memory clinic patients with vascular brain injury with a mean age of 72 ± 11 years (54% male) were included. All underwent 3 tesla MRI, including a diffusion MRI and cognitive testing. Cortical CMIs were rated according to established criteria and their spatial location was marked. Diffusion imaging-based tractography was used to reconstruct WM connections and voxel based analysis (VBA) to assess integrity of WM directly below the cortex. WM connectivity and integrity were compared between patients with and without cortical CMIs for the whole brain and regions with a high CMI burden.Results:30 patients (18%) had at least 1 cortical CMI [range 1–46]. More than 70% of the cortical CMIs were located in the superior frontal, middle frontal, and pre- and postcentral brain regions (covering 16% of the cortical surface). In these high CMI burden regions, presence of cortical CMIs was not associated with WM connectivity after correction for conventional neuroimaging markers of vascular injury. WM connectivity in the whole brain and WM voxels directly underneath the cortical surface did not differ between patients with and without cortical CMIs.Conclusion:Cortical CMIs displayed a strong local clustering in highly interconnected frontal, pre- and postcentral brain regions. Nevertheless, WM connections projecting to these regions were not disproportionally impaired in patients with compared to patients without cortical CMIs. Alternative mechanisms, such as focal disturbances in cortical structure and functioning, may better explain CMI associated cognitive impairment.
Highlights
Cerebral microinfarcts (CMIs) are small (
We have previously reported that presence of CMIs in memory clinic patients with vascular brain injury is associated with other neuroimaging markers of vascular injury, a diagnosis of vascular dementia and reduced performance in multiple cognitive domains [4]
Patients were included in the cohort if they presented with cognitive complaints at the memory clinic, and had evidence of vascular brain injury on MRI, operationalized as: [1] white matter hyperintensities (WMHs) with a Fazekas scale grade ≥ 2 [16]; [2] ≥ 1 lacunar or non-lacunar infarcts; [3] ≥ 1 cerebral microbleeds; [4] ≥ 1 intracerebral hemorrhage(s) or [5] Fazekas scale grade 1 combined with ≥ 2 vascular risk factors [15]
Summary
Both pathology and MRI studies have found a consistent association between CMI presence and cognitive impairment, after adjustments for the presence of co-occurring Alzheimer’s disease [3] and conventional neuroimaging markers of vascular injury [4,5,6,7]. Several manifestations of cerebral small vessel disease (SVD), such as white matter hyperintensities (WMHs), lacunes, and cerebral microbleeds have been suggested to affect cognitive functioning by disruption of the WM network [8,9,10,11,12]. We investigated in memory clinic patients whether cortical CMIs are clustered in specific brain regions and if presence of cortical CMIs is associated with reduced white matter (WM) connectivity in tracts projecting to these regions
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