This 71-year-old woman, with poorly controlled chronic hypertension, had impaired executive function (eMethods) and was found to have état criblé on MRI, with enlarged perivascular spaces (ePVSs) circumscribed to the basal ganglia but no lacunar lesions (Figure, A). We document in this IRB-approved study the arrangement of a vessel in the core of ePVSs, formerly described at autopsy but not in vivo,1 using a 7T Siemens MRI scanner, at a resolution of 148 µm (Figure, B and C; eMethods). Cognitive impairment associated with état criblé has been attributed to lacunar brain disease or Alzheimer changes.2 However, this patient had a negative amyloid PET and decreased metabolism bilaterally in striatum (Figure, D), the region with the most pronounced état criblé, but not in the cortex, therefore differing from neurodegenerative dementias, such as Alzheimer disease or frontotemporal dementia, and supporting the role of the vascular changes in the genesis of executive function impairment.
Figure. 7T MRI and [18F]fluorodeoxyglucose PET.
(A) Axial, (B) coronal, and (C) sagittal basal ganglia sections, showing arterioles as black dots surrounded by light CSF (arrows). (D) PET of control (left) and patient (center), with decreased metabolism in highlighted areas (right), compared with 35 controls (eMethods). SUVR = standard uptake value ratio.
Acknowledgment
The control FDG PET data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). Data collection and sharing for the ADNI project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (NIH Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the NIH (fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.
Appendix. Coinvestigators
| Coinvestigators are listed at Neurology.org/N. |
Author Contributions
E.L. Weil: drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data; study concept or design; analysis or interpretation of data. Q. Finn: drafting/revision of the manuscript for content, including medical writing for content; study concept or design; analysis or interpretation of data. A.M. Eid: drafting/revision of the manuscript for content, including medical writing for content; analysis or interpretation of data. C. Karmonik: drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data; analysis or interpretation of data. B. Pascual: drafting/revision of the manuscript for content, including medical writing for content; study concept or design; analysis or interpretation of data. J.C. Masdeu: drafting/revision of the manuscript for content, including medical writing for content; major role in the acquisition of data; study concept or design; analysis or interpretation of data.
Study Funding
The Graham, Harrison, and Nantz Funds from the Houston Methodist Foundation were the main sources of funding. Funding for ADNI and the list of investigators are included in the supplementary material.
Disclosure
The authors report no relevant disclosures. Go to Neurology.org/N for full disclosures.
References
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