Cerebral Hypoperfusion Generates Cortical Watershed Microinfarcts in Alzheimer Disease

Suter, Oda-Christina; Sunthorn, Thanomphone; Kraftsik, Rudolf; Straubel, Joel; Darekar, Pushpa; Khalili, Kamel; Miklóssy, Judith

doi:10.1161/01.str.0000024523.82311.77

Cited by 204 publications

(194 citation statements)

References 37 publications

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“…This result may have direct clinical relevance. Accumulation of small cortical cysts is involved in pathologies that lead to cognitive decline in humans (40,41). Recent studies highlight a critical role for small microinfarctions in the cerebral cortex, which are distinct from subcortical lacunae that originate from a blockade in deep penetrating vessels.…”

Section: Discussionmentioning

confidence: 99%

Topological basis for the robust distribution of blood to rodent neocortex

Blinder¹,

Shih²,

Rafie³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

169

224

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The maintenance of robust blood flow to the brain is crucial to the health of brain tissue. We examined the pial network of the middle cerebral artery, which distributes blood from the cerebral arteries to the penetrating arterioles that source neocortical microvasculature, to characterize how vascular topology may support such robustness. For both mice and rats, two features dominate the topology. First, interconnected loops span the entire territory sourced by the middle cerebral artery. Although the loops comprise <10% of all branches, they maintain the overall connectivity of the network after multiple breaks. Second, >80% of offshoots from the loops are stubs that end in a single penetrating arteriole, as opposed to trees with multiple penetrating arterioles. We hypothesize that the loops and stubs protect blood flow to the parenchyma from an occlusion in a surface vessel. To test this, we assayed the viability of tissue that was sourced by an individual penetrating arteriole following occlusion of a proximal branch in the surface loop. We observed that neurons remained healthy, even when occlusion led to a reduction in the local blood flow. In contrast, direct blockage of a single penetrating arteriole invariably led to neuronal death and formation of a cyst. Our results show that the surface vasculature functions as a grid for the robust allocation of blood in the event of vascular dysfunction. The combined results of the present and prior studies imply that the pial network reallocates blood in response to changing metabolic needs.anastomoses | imaging | networks | stroke | vasculature

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Section: Discussionmentioning

confidence: 99%

Topological basis for the robust distribution of blood to rodent neocortex

Blinder¹,

Shih²,

Rafie³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

169

224

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“…Thirteen studies (41%) diagnosed the patients primarily on neuropathological criteria (Esiri et al, 1997;Olichney et al, 1997;Suter et al, 2002;Rossi et al, 2004;Del Ser et al, 2005;Yip et al, 2005;Haglund et al, 2006;Isojima et al, 2006;Kö vari et al, 2007;Longstreth et al, 2009;Okamoto et al, 2009;De Reuck et al, 2011a, b). The most commonly used neuropathological criteria for AD were the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) (Mirra et al, 1991) and the Braak criteria (Braak and Braak, 1991).…”

Section: Characteristics Of the Included Studiesmentioning

confidence: 99%

“…The remaining studies had a more limited brain coverage, that is, only the four lobes (Okamoto et al, 2009) or the temporal, parietal and frontal lobes combined with deep gray matter (Olichney et al, 1997;Gold et al, 2007;Kö vari et al, 2007;Santos et al, 2009). One study focused on the watershed areas (Suter et al, 2002), another study only on one midtemporal, and one midparietal section (Haglund et al, 2006) (see Supplementary Table 2). A brain slice thickness for macroscopic examination of 10 mm was most common (14 studies, 44%).…”

Section: Review On Cerebral Microinfarctsmentioning

confidence: 99%

“…Eight studies concerned patients with AD (Erkinjuntti et al, 1988;Suter et al, 2002;Yip et al, 2005;Isojima et al, 2006;Kö vari et al, 2007;Brayne et al, 2009;Okamoto et al, 2009;De Reuck et al, 2011b), with a total sample size of 409 patients (range 5 to 105). Microinfarcts were detected in 20% to 100% of the patients, with a weighted average of 43%.…”

Section: Frequencymentioning

confidence: 99%

“…The remaining studies mentioned the number of microinfarcts per patient more precisely: 0 to 4 in patients with different types of dementia (Erkinjuntti et al, 1988); a mean of six microinfarcts (range 1 to 37) in 14 patients with severe CAA and 3 (range 1 to 6) in 7 patients with mild CAA (Soontornniyomkij et al, 2010); 1 to 4 per watershed zone area (Suter et al, 2002).…”

Section: Review On Cerebral Microinfarcts M Brundel Et Almentioning

confidence: 99%

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Cerebral Microinfarcts: A Systematic Review of Neuropathological Studies

Brundel

Bresser

Dillen

et al. 2012

J Cereb Blood Flow Metab

238

207

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Vascular cognitive impairment is an umbrella term for cognitive dysfunction associated with and presumed to be caused by vascular brain damage. Autopsy studies have identified microinfarcts as an important neuropathological correlate of vascular cognitive impairment that escapes detection by conventional magnetic resonance imaging (MRI). As a frame of reference for future highresolution MRI studies, we systematically reviewed the literature on neuropathological studies on cerebral microinfarcts in the context of vascular disease, vascular risk factors, cognitive decline and dementia. We identified 32 original patient studies involving 10,515 people. The overall picture is that microinfarcts are common, particularly in patients with vascular dementia (weighted average 62%), Alzheimer's disease (43%), and demented patients with both Alzheimer-type and cerebrovascular pathology (33%) compared with nondemented older individuals (24%). In many patients, multiple microinfarcts were detected. Microinfarcts are described as minute foci with neuronal loss, gliosis, pallor, or more cystic lesions. They are found in all brain regions, possibly more so in the cerebral cortex, particularly in watershed areas. Reported sizes vary from 50 lm to a few mm, which is within the detection limit of current high-resolution MRI. Detection of these lesions in vivo would have a high potential for future pathophysiological studies in vascular cognitive impairment.

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