Posterior white matter hyperintensities are associated with reduced medial temporal lobe subregional integrity and long-term memory in older adults

Batool Rizvi¹, Mithra Sathishkumar¹, Soyun Kim¹, Freddie Márquez¹, Steven J Granger¹, Myra S Larson¹, Blake A Miranda¹, Martina K Hollearn¹, Liv McMillan¹, Bin Nan², Nicholas J Tustison³, Patrick J Lao⁴, Adam M Brickman⁴, Dana Greenia⁵, Maria M Corrada⁶, Claudia H Kawas⁷, Michael A Yassa⁸

Affiliations

¹ Center for the Neurobiology of Learning and Memory, University of California, Irvine, CA, USA; Department of Neurobiology and Behavior, University of California, Irvine, CA, USA.
² Center for the Neurobiology of Learning and Memory, University of California, Irvine, CA, USA; Department of Statistics, University of California, Irvine, Irvine, CA, USA.
³ Center for the Neurobiology of Learning and Memory, University of California, Irvine, CA, USA; Department of Neurobiology and Behavior, University of California, Irvine, CA, USA; Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA, USA.
⁴ Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA; Gertrude H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
⁵ Department of Neurology, School of Medicine, University of California, Irvine, CA, USA.
⁶ Department of Neurology, School of Medicine, University of California, Irvine, CA, USA; Department of Epidemiology, University of California, Irvine, CA, USA.
⁷ Center for the Neurobiology of Learning and Memory, University of California, Irvine, CA, USA; Department of Neurobiology and Behavior, University of California, Irvine, CA, USA; Department of Neurology, School of Medicine, University of California, Irvine, CA, USA.
⁸ Center for the Neurobiology of Learning and Memory, University of California, Irvine, CA, USA; Department of Neurobiology and Behavior, University of California, Irvine, CA, USA; Department of Neurology, School of Medicine, University of California, Irvine, CA, USA. Electronic address: michael.yassa@uci.edu.

PMID: 36586358
PMCID: PMC9830310
DOI: 10.1016/j.nicl.2022.103308

Posterior white matter hyperintensities are associated with reduced medial temporal lobe subregional integrity and long-term memory in older adults

Batool Rizvi et al. Neuroimage Clin. 2023.

. 2023:37:103308.

doi: 10.1016/j.nicl.2022.103308. Epub 2022 Dec 28.

Authors

Affiliations

¹ Center for the Neurobiology of Learning and Memory, University of California, Irvine, CA, USA; Department of Neurobiology and Behavior, University of California, Irvine, CA, USA.
² Center for the Neurobiology of Learning and Memory, University of California, Irvine, CA, USA; Department of Statistics, University of California, Irvine, Irvine, CA, USA.
³ Center for the Neurobiology of Learning and Memory, University of California, Irvine, CA, USA; Department of Neurobiology and Behavior, University of California, Irvine, CA, USA; Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA, USA.
⁴ Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA; Gertrude H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
⁵ Department of Neurology, School of Medicine, University of California, Irvine, CA, USA.
⁶ Department of Neurology, School of Medicine, University of California, Irvine, CA, USA; Department of Epidemiology, University of California, Irvine, CA, USA.
⁷ Center for the Neurobiology of Learning and Memory, University of California, Irvine, CA, USA; Department of Neurobiology and Behavior, University of California, Irvine, CA, USA; Department of Neurology, School of Medicine, University of California, Irvine, CA, USA.
⁸ Center for the Neurobiology of Learning and Memory, University of California, Irvine, CA, USA; Department of Neurobiology and Behavior, University of California, Irvine, CA, USA; Department of Neurology, School of Medicine, University of California, Irvine, CA, USA. Electronic address: michael.yassa@uci.edu.

PMID: 36586358
PMCID: PMC9830310
DOI: 10.1016/j.nicl.2022.103308

Abstract

White matter hyperintensities are a marker of small vessel cerebrovascular disease that are strongly related to cognition in older adults. Similarly, medial temporal lobe atrophy is well-documented in aging and Alzheimer's disease and is associated with memory decline. Here, we assessed the relationship between lobar white matter hyperintensities, medial temporal lobe subregional volumes, and hippocampal memory in older adults. We collected MRI scans in a sample of 139 older adults without dementia (88 females, mean age (SD) = 76.95 (10.61)). Participants were administered the Rey Auditory Verbal Learning Test (RAVLT). Regression analyses tested for associations among medial temporal lobe subregional volumes, regional white matter hyperintensities and memory, while adjusting for age, sex, and education and correcting for multiple comparisons. Increased occipital white matter hyperintensities were related to worse RAVLT delayed recall performance, and to reduced CA1, dentate gyrus, perirhinal cortex (Brodmann area 36), and parahippocampal cortex volumes. These medial temporal lobe subregional volumes were related to delayed recall performance. The association of occipital white matter hyperintensities with delayed recall performance was fully mediated statistically only by perirhinal cortex volume. These results suggest that white matter hyperintensities may be associated with memory decline through their impact on medial temporal lobe atrophy. These findings provide new insights into the role of vascular pathologies in memory loss in older adults and suggest that future studies should further examine the neural mechanisms of these relationships in longitudinal samples.

Keywords: Aging; Cerebrovascular disease; Hippocampus; Long-term memory; Small vessel disease.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

**Fig. 1**
**(A)**. Axial view of a FLAIR image with unlabeled WMH. **(B)**. Axial view of a FLAIR image with labeled WMH. **(C)**. Coronal view of a T2-weighted image with MTL segmentation from ASHS. PHC is not captured in this image slice.

**Fig. 2**
In all three scatterplots, cognitive status is color-coded, with cognitively unimpaired (CU) in blue and cognitively impaired (CI) in purple. **(A)** A scatterplot of the negative association between square root transformed occipital WMH and delayed recall. **(B).** A scatterplot of the negative association between square root transformed occipital WMH and BA36 volume (TIV adjusted ratio). **(C).** A scatterplot of the positive association between BA36 volume (TIV adjusted ratio) and delayed recall. Other significant associations found that were not involved in the mediation model (as seen in Fig. 3) can be found in Supplemental materials. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

**Fig. 3**
In this mediation model, there is an indirect effect where perirhinal cortex (BA36) volume mediates the relationship between occipital WMH and RAVLT delayed recall. Path a: b = −0.426, p = 0.0015; Path b: b = 2.4681, p = 0.0003; Path c’ (Direct effect): b = −0.8654, 95 % CIs [-2.8366, 1.1058]; Path ab (Indirect effect): b = −1.0523, 95 % CIs [−2.1835, −0.2328].

See this image and copyright information in PMC

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Posterior white matter hyperintensities are associated with reduced medial temporal lobe subregional integrity and long-term memory in older adults

Affiliations

Posterior white matter hyperintensities are associated with reduced medial temporal lobe subregional integrity and long-term memory in older adults

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous