White matter hyperintensities are associated with falls in older people with dementia
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White Matter Hyperintensities (WMHs) are associated with impaired gait, balance and cognition and increased fall risk in cognitively healthy older people. However, few studies have examined such relationships in older people with dementia. Understanding the role of WMHs in falls may assist in developing effective fall prevention strategies. We investigated the relationship between baseline WMHs, cognitive and sensorimotor function and prospective falls in older people with dementia. Twenty-eight community-dwelling older people with mild-moderate dementia (MMSE 11–23; ACE-R < 83) underwent magnetic resonance imaging and assessment of sensorimotor and cognitive (global and processing speed) function at baseline. WMHs, were quantified using a fully automated segmentation toolbox, UBO Detector (https://cheba.unsw.edu.au/group/neuroimaging-pipeline). Falls were ascertained prospectively for 12-months using monthly calendars with the assistance of carers. The median age of the participants was 83 years (IQR 77–86); 36% were female; 21 (75%) fell during follow-up. Using Generalized Linear Models, larger volumes of total WMHs were found to be significantly associated with poorer global cognitive and sensorimotor function. Using modified Poisson regression, total, periventricular and deep WMHs were each associated with future falls while controlling for age, sex, intracranial volume and vascular risk. Each standard deviation increase in total and periventricular WMH volume resulted in a 33% (RR 1.33 95%CI 1.07–1.66) and 30% (RR 1.30 95%CI 1.06–1.60) increased risk of falling, respectively. When the deep WMH volume z-scores were dichotomized at the median, individuals with greater deep WMH volumes had an 81% (RR 1.81 95% CI 1.02–3.21) increased risk of falling. WMHs were associated with poorer sensorimotor and cognitive function in people with dementia and total, periventricular and deep WMHs were associated with falls. Further research is needed to confirm these preliminary findings and explore the impact of vascular risk reduction strategies on WMHs, functional performance and falls.
KeywordsDementia Cognitive impairment Accidental falls White matter hyperintensities Leukoaraiosis Sensorimotor function
This work was supported by the Australian National Health and Medical Research Council (NHMRC) (grant number 455368) and the NHMRC Cognitive Decline Partnership Centre (grant number 9100000). This manuscript does not reflect the views of the NHMRC or funding partners. Dr. Morag Taylor is a NHMRC-Australian Research Council Dementia Research Development Fellow. A/Prof Kim Delbaere is a NHMRC Career Development Fellow. Prof Stephen Lord is a NHMRC Senior Principal Research Fellow.
Compliance with ethical standards
Conflict of interest
The Physiological Profile Assessment (FallScreen) is commercially available through Neuroscience Research Australia (NeuRA). Professor Henry Brodaty holds a position on the advisory board for Nutricia.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individuals, and their person responsible, included in the study.
- Altamura, C., Scrascia, F., Quattrocchi, C. C., Errante, Y., Gangemi, E., Curcio, G., Ursini, F., Silvestrini, M., Maggio, P., Beomonte Zobel, B., Rossini, P. M., Pasqualetti, P., Falsetti, L., & Vernieri, F. (2016). Regional MRI diffusion, white-matter hyperintensities, and cognitive function in Alzheimer's disease and vascular dementia. Journal of Clinical Neurology, 12(2), 201–208. https://doi.org/10.3988/jcn.2016.12.2.201.CrossRefGoogle Scholar
- Baezner, H., Blahak, C., Poggesi, A., Pantoni, L., Inzitari, D., Chabriat, H., Erkinjuntti, T., Fazekas, F., Ferro, J. M., Langhorne, P., O'Brien, J., Scheltens, P., Visser, M. C., Wahlund, L. O., Waldemar, G., Wallin, A., Hennerici, M. G., & On behalf of the LADIS Study Group. (2008). Association of gait and balance disorders with age-related white matter changes: The LADIS study. Neurology, 70(12), 935–942. https://doi.org/10.1212/01.wnl.0000305959.46197.e6.CrossRefGoogle Scholar
- Burton, E. J., McKeith, I. G., Burn, D. J., Firbank, M. J., & O'Brien, J. T. (2006). Progression of white matter Hyperintensities in Alzheimer disease, dementia with Lewy bodies, and Parkinson disease dementia: A comparison with normal aging. The American Journal of Geriatric Psychiatry, 14(10), 842–849. https://doi.org/10.1097/01.JGP.0000236596.56982.1c.CrossRefGoogle Scholar
- Delbaere, K., Close, J. C., Heim, J., Sachdev, P. S., Brodaty, H., Slavin, M. J., et al. (2010). A multifactorial approach to understanding fall risk in older people. Journal of the American Geriatrics Society, 58(9), 1679–1685. https://doi.org/10.1111/j.1532-5415.2010.03017.x.CrossRefGoogle Scholar
- Dickie, D. A., Ritchie, S. J., Cox, S. R., Sakka, E., Royle, N. A., Aribisala, B. S., Valdés Hernández, M. C., Maniega, S. M., Pattie, A., Corley, J., Starr, J. M., Bastin, M. E., Deary, I. J., & Wardlaw, J. M. (2016). Vascular risk factors and progression of white matter hyperintensities in the Lothian birth cohort 1936. Neurobiology of Aging, 42, 116–123. https://doi.org/10.1016/j.neurobiolaging.2016.03.011.CrossRefGoogle Scholar
- Lamb, S. E., Jorstad-Stein, E. C., Hauer, K., & Becker, C. (2005). Development of a common outcome data set for fall injury prevention trials: The prevention of falls network Europe consensus. Journal of the American Geriatrics Society, 53(9), 1618–1622. https://doi.org/10.1111/j.1532-5415.2005.53455.x.CrossRefGoogle Scholar
- Martin, K. L., Blizzard, L., Srikanth, V. K., Wood, A., Thomson, R., Sanders, L. M., & Callisaya, M. L. (2013). Cognitive function modifies the effect of physiological function on the risk of multiple falls--a population-based study. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 68(9), 1091–1097. https://doi.org/10.1093/gerona/glt010.CrossRefGoogle Scholar
- Mioshi, E., Dawson, K., Mitchell, J., Arnold, R., & Hodges, J. R. (2006). The Addenbrooke's cognitive examination revised (ACE-R): A brief cognitive test battery for dementia screening. International Journal of Geriatric Psychiatry, 21(11), 1078–1085. https://doi.org/10.1002/gps.1610.CrossRefGoogle Scholar
- Mirelman, A., Herman, T., Brozgol, M., Dorfman, M., Sprecher, E., Schweiger, A., Giladi, N., & Hausdorff, J. M. (2012). Executive function and falls in older adults: New findings from a five-year prospective study link fall risk to cognition. PLoS One, 7(6), e40297. https://doi.org/10.1371/journal.pone.0040297.CrossRefGoogle Scholar
- Ogama, N., Sakurai, T., Shimizu, A., & Toba, K. (2014). Regional white matter lesions predict falls in patients with amnestic mild cognitive impairment and alzheimer's disease. Journal of the American Medical Directors Association, 15(1), 36–41. https://doi.org/10.1016/j.jamda.2013.11.004.CrossRefGoogle Scholar
- Ramirez, J., McNeely, A. A., Scott, C. J. M., Stuss, D. T., & Black, S. E. (2014). Subcortical hyperintensity volumetrics in Alzheimer's disease and normal elderly in the Sunnybrook dementia study: Correlations with atrophy, executive function, mental processing speed, and verbal memory. Alzheimer's Research & Therapy, 6(4), 12. https://doi.org/10.1186/alzrt279.CrossRefGoogle Scholar
- Sarro, L., Tosakulwong, N., Schwarz, C. G., Graff-Radford, J., Przybelski, S. A., Lesnick, T. G., Zuk, S. M., Reid, R. I., Raman, M. R., Boeve, B. F., Ferman, T. J., Knopman, D. S., Comi, G., Filippi, M., Murray, M. E., Parisi, J. E., Dickson, D. W., Petersen, R. C., Jack Jr., C. R., & Kantarci, K. (2017). An investigation of cerebrovascular lesions in dementia with Lewy bodies compared to Alzheimer's disease. Alzheimer's & Dementia, 13(3), 257–266. https://doi.org/10.1016/j.jalz.2016.07.003.CrossRefGoogle Scholar
- Srikanth, V., Beare, R., Blizzard, L., Phan, T., Stapleton, J., Chen, J., Callisaya, M., Martin, K., & Reutens, D. (2009). Cerebral white matter lesions, gait, and the risk of incident falls: A prospective population-based study. Stroke, 40(1), 175–180. https://doi.org/10.1161/STROKEAHA.108.524355.CrossRefGoogle Scholar
- Taylor, M. E., Lord, S. R., Delbaere, K., Mikolaizak, A. S., & Close, J. C. T. (2012). Physiological fall risk factors in cognitively impaired older people: A one-year prospective study. Dementia and Geriatric Cognitive Disorders, 34(3–4), 181–189. https://doi.org/10.1159/000343077.CrossRefGoogle Scholar
- Taylor, M. E., Delbaere, K., Lord, S. R., Mikolaizak, A. S., Brodaty, H., & Close, J. C. (2014). Neuropsychological, physical, and functional mobility measures associated with falls in cognitively impaired older adults. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 69(8), 987–995. https://doi.org/10.1093/gerona/glt166.CrossRefGoogle Scholar
- Taylor, M. E., Lord, S. R., Delbaere, K., Kurrle, S. E., Mikolaizak, A. S., & Close, J. C. T. (2017). Reaction time and postural sway modify the effect of executive function on risk of falls in older people with mild to moderate cognitive impairment. The American Journal of Geriatric Psychiatry, 25(4), 397–406. https://doi.org/10.1016/j.jagp.2016.10.010.CrossRefGoogle Scholar
- van der Vlies, A. E., Staekenborg, S. S., Admiraal-Behloul, F., Prins, N. D., Barkhof, F., Vrenken, H., Reiber, J. H. C., Scheltens, P., & van der Flier, W. M. (2013). Associations between magnetic resonance imaging measures and neuropsychological impairment in early and late onset alzheimer's disease. Journal of Alzheimer's Disease, 35(1), 169–178. https://doi.org/10.3233/jad-121291.CrossRefGoogle Scholar
- van Straaten, E. C. W., Fazekas, F., Rostrup, E., Scheltens, P., Schmidt, R., Pantoni, L., Inzitari, D., Waldemar, G., Erkinjuntti, T., Mantyla, R., Wahlund, L. O., Barkhof, F., & on behalf of the LADIS Group. (2006). Impact of white matter hyperintensities scoring method on correlations with clinical data: The LADIS study. Stroke, 37(3), 836–840. https://doi.org/10.1161/01.str.0000202585.26325.74.CrossRefGoogle Scholar
- van Uden, I. W., van der Holst, H. M., Tuladhar, A. M., van Norden, A. G., de Laat, K. F., Rutten-Jacobs, L. C., et al. (2016). White matter and hippocampal volume predict the risk of dementia in patients with cerebral small vessel disease: The RUN DMC study. Journal of Alzheimer's Disease, 49(3), 863–873. https://doi.org/10.3233/jad-150573.CrossRefGoogle Scholar
- Zheng, J. J., Lord, S. R., Close, J. C., Sachdev, P. S., Wen, W., Brodaty, H., et al. (2012). Brain white matter hyperintensities, executive dysfunction, instability, and falls in older people: A prospective cohort study. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 67(10), 1085–1091. https://doi.org/10.1093/gerona/gls063.CrossRefGoogle Scholar