Regional leukoaraiosis and cognition in non-demented older adults
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Frontal lobe-executive functions are heavily dependent on distal white matter connectivity. Even with healthy aging there is an increase in leukoaraiosis that might interrupt this connectivity. The goal of this study is to learn 1) the location, depth, and percentage of leukoaraiosis in white matter among a sample of non-demented older adults and 2) associations between these leukoarioasis metrics and composites of cognitive efficiency (processing speed, working memory, and inhibitory function), and episodic memory. Participants were 154 non-demented older adults (age range 60–85) who completed a brain MRI and neuropsychological testing on the same day. Brain MRIs were segmented via Freesurfer and white matter leukoaraiosis depth segmentations was based on published criteria. On average, leukoaraiosis occupied 1 % of total white matter. There was no difference in LA distribution in the frontal (1.12%), parietal (1.10%), and occipital (0.95%) lobes; there was less LA load within the temporal lobe (0.23%). For cortical depth, leukoaraiosis was predominantly in the periventricular region (3.39%; deep 1.46%, infracortical 0.15%). Only increasing frontal lobe and periventricular leukoaraiosis were associated with a reduction in processing speed, working memory, and inhibitory function. Despite the general presence of LA throughout the brain, only frontal and periventricular LA contributed to the speeded and mental manipulation of executive functioning. This study provides a normative description of LA for non-demented adults to use as a comparison to more disease samples.
KeywordsBrain aging Hyperintensities White matter alterations Frontal lobes Executive function Episodic memory
Margaret E Wiggins, Jared Tanner, Nadine Schwab, Samuel J Crowley, Loren P Hizel, Ilona Schmalfuss, Babette Brumback, David J Libon, Kenneth Heilman, and Catherine C Price declare that they have no conflicts of interest.
We sincerely thank the research participants involved in this investigation. This work was supported by the National Institute of Neurological Disorders and Stroke (R01NS082386); and the National Institute of Nursing Research (R01NR01481).
Compliance with ethical standards
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, and the applicable revisions at the time of the investigation. Informed consent was obtained from all patients for being included in the study.
- Amici, S., Ogar, J., Brambati, S. M., Miller, B. L., Neuhaus, J., Dronkers, N. L., & Gorno-Tempini, M. L. (2007). Performance in specific language tasks correlates with regional volume changes in progressive aphasia. Cognitive and Behavioral Neurology, 20(4), 203–211. https://doi.org/10.1097/WNN.0b013e31815e6265.CrossRefGoogle Scholar
- Brandt, J., & Benedict, R. H. B. (2001). Hopkins verbal learning test—Revised. Professional manual. Lutz, FL: Psychological Assessment Resources, Inc..Google Scholar
- Brandt, J., Spencer, M., & Folstein, M. (1988). The telephone interview for cognitive status. Neuropsychiatry, Neuropsychology, and Behavioral Neurology, 1(2), 111–117.Google Scholar
- Brickman, A. M., Provenzano, F. A., Muraskin, J., Manly, J. J., Blum, S., Apa, Z., et al. (2012). Regional white matter hyperintensity volume, not hippocampal atrophy, predicts incident Alzheimer disease in the community. Archives of Neurology, 69(12), 1621–1627. https://doi.org/10.1001/archneurol.2012.1527.CrossRefGoogle Scholar
- Devanand, D. P., Pradhaban, G., Lui, X., Khandji, A., De Santi, S., Segal, S., et al. (2007). Hippocampal and entorhinal atrophy in mild cognitive impairment prediction of Alzheimer disease. Neurology, 68(11), 828–836. https://doi.org/10.1212/01.wnl.0000256697.20968.d7.CrossRefGoogle Scholar
- Erkinjuntti, T., Inzitari, D., Pantoni, L., Wallin, A., Scheltens, P., Rockwood, K., Roman, G. C., Chui, H., & Desmond, D. W. (2000). Research criteria for subcortical vascular dementia in clinical trials. Journal of Neural Transmission, 59, 23–30.Google Scholar
- Fuster, J. M. (1985). The prefrontal cortex, mediator of cross-temporal contingencies. Human Neurobiology, 4(3), 169–179.Google Scholar
- Hachinski, V. C., Potter, P., & Merskey, H. (1986). Leuko-araiosis: An ancient term for a new problem. Le Journal Canadien des Sciences Neurologiques, 13, 533–534.Google Scholar
- Heaton, R., Miller, W., Taylor, M., & Grant, I. (2004). Revised comprehensive norms for an expanded Halstead-Reitan battery: Demographically adjusted neuropsychological norms for African American and Caucasian adults. Lutz, FL: Psychological Assessment Resources, Inc..Google Scholar
- Jenkinson, M., Bannister, P., Brady, M., & Smith, S. (2002) Improved optimization for the robust and accurate linear registration and motion correction of brain images. Neuroimage, 17, 825–841.Google Scholar
- Junqué, C., Jesús, P., Vandrell, P., Bruna, O., Jódar, M., Ribas, J., et al. (1990). Leuko-araiosis on magnetic resonance imaging and speed of mental processing. Archives of Neurology, 47(2), 151–156. https://doi.org/10.1001/archneur.1990.00530020047013.CrossRefGoogle Scholar
- Lamar, M., Price, C. C., Giovannetti, T., Swenson, R., & Libon, D. J. (2009/2010). The dysexecutive syndrome associated with ischaemic vascular disease and related subcortical neuropathology: A Boston process approach. Behavioral Neurology, 22, 53–62. https://doi.org/10.3233/BEN-2009-0237.CrossRefGoogle Scholar
- Lezak, M. D., Howieson, D., Bigler, E., & Tranel, D. (2012). Neuropsychological Assessment (5th Ed.). New York: Oxford University press.Google Scholar
- Liao, D., Cooper, L., Cai, J., Toole, J. F., Bryan, N. R., Hutchinson, R. G., & Tyroler, H. A. (1996). Presence and severity of cerebral white matter lesions and hypertension, its treatment, and its control. The ARIC Study. Stroke, 27, 2262–2270. https://doi.org/10.1161/01.STR.27.12.2262.CrossRefGoogle Scholar
- Libon, D., Price, C. C., Giovannetti, T., Swenson, R., Bettcher, B. M., Heilman, K., & Pennisi, A. (2008). Linking MRI hyperintensities with patterns of neuropsychological impairment: Evidence for a threshold effect. Stroke, 39, 806–813. https://doi.org/10.1161/STROKEAHA.107.489997.CrossRefGoogle Scholar
- Price, C. C., Jefferson, A. L., Merino, J. G., Heilman, K. M., & Libon, D. J. (2005). Subcortical vascular dementia: Integrating neuropsychological and neuroradiologic data. Neurology, 65(3), 376–382. https://doi.org/10.1212/01.wnl.0000168877.06011.15.CrossRefGoogle Scholar
- Price, C. C., Tanner, J. J., Schmalfuss, I. M., Brumback, B., Heilman, K. M., & Libon, D. J. (2015). Dissociating statistically-determined Alzheimer’s disease/vascular dementia neuropsychological syndromes using white and gray Neuroradiological parameters. Journal of Alzheimer’s Disease, 48(3), 833–847.CrossRefGoogle Scholar
- Spilt, A., Goekoop, R., Westendorp, R. G., Blauw, G. J., de Craen, A. J., & van Buchem, M. A. (2006). Not all age-related white matter hyperintensities are the same: A magnetization transfer imaging study. American Journal of Neuroradiology, 27(9), 1964–1968.Google Scholar
- Tabert, M. H., Manly, J. J., Lui, X., Pelton, G. H., Rosenblum, S., Jacobs, M., et al. (2006). Neuropsychological prediction of conversion to Alzheimer disease in patients with mild cognitive impairment. Archives of General Psychiatry, 63(8), 916–924. https://doi.org/10.1001/archpsyc.63.8.916.CrossRefGoogle Scholar
- Tomimoto, H., Ohtani, R., Wakita, H., Lin, J. X., Ihara, M., Miki, Y., et al. (2006). Small artery dementia in Japan: Radiological differences between CADASIL, leukoaraiosis and Binswanger's disease. Dementia and Geriatric Cognitive Disorders, 21(3), 169–169. https://doi.org/10.1159/000090677.CrossRefGoogle Scholar
- Tosto, G., Zimmerman, M. E., Hamilton, J. L., Carmichael, O. T., & Brickman, A. M. (2015). The effect of white matter hyperintensities on neurodegeneration in mild cognitive impairment. Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, 11(12), 1510–1519. https://doi.org/10.1016/j.jalz.2015.05.014.CrossRefGoogle Scholar
- Wechsler, D. (1997). Wechsler memory scale (WMS-III) (Vol. 14). San Antonio, TX: Psychological corporation.Google Scholar