Progression of white matter hyperintensities of presumed vascular origin increases the risk of falls in older people.

BACKGROUND Greater volume of cerebral white matter hyperintensities (WMH) of presumed vascular origin may affect postural control and gait. WMH measured at one time point predicts an increased risk of incident multiple falls. However, it is unknown whether WMH progression increases falls risk. We hypothesized that the progression of WMH would be associated with a greater risk of multiple falls. METHODS A population-based sample aged more than 60 years was randomly selected from the electoral roll and followed up 2.5 years apart with two phases of measurement. Magnetic resonance imaging scans from both time points were subjected to automated segmentation to derive WMH volumes. Falls were recorded prospectively over 12 months after the second magnetic resonance imaging measurement. A generalized linear model was used to estimate the relative risk of multiple falls associated with WMH progression adjusted for confounders. RESULTS There were 187 people (mean age 70.4, SD 6.5) with a mean follow-up of 2.5 (SD 0.4) years. Over 12 months, 35 (18.7%) participants reported multiple falls. A greater progression of WMH was associated with an increased risk of multiple falls (adjusted relative risk 1.30, 95% confidence interval 1.00-1.70, p = .05) independent of baseline WMH volume, duration of follow-up, age, sex, and total intracranial volume. This association was unchanged when adjusted for medical history, peripheral sensorimotor factors, gait speed, cognition, medications, mood, and magnetic resonance imaging infarcts. CONCLUSION Greater WMH progression independently increased the risk of multiple falls. Interventions to slow the progression of WMH may be successful in reducing this risk.

[1]  D. Harvey,et al.  Anatomical Mapping of White Matter Hyperintensities (WMH): Exploring the Relationships Between Periventricular WMH, Deep WMH, and Total WMH Burden , 2005, Stroke.

[2]  V. Srikanth,et al.  Gait, gait variability and the risk of multiple incident falls in older people: a population-based study. , 2011, Age and ageing.

[3]  A. Hofman,et al.  Cerebral white matter lesions and cognitive function: The Rotterdam scan study , 2000, Annals of neurology.

[4]  L. Ferrucci,et al.  White matter lesions and the risk of incident hip fracture in older persons: results from the progetto veneto anziani study. , 2007, Archives of internal medicine.

[5]  Richard Beare,et al.  Cerebral White Matter Lesions, Gait, and the Risk of Incident Falls: A Prospective Population-Based Study , 2009, Stroke.

[6]  S. Lord,et al.  Impact of White Matter Lesions on Physical Functioning and Fall Risk in Older People: A Systematic Review , 2011, Stroke.

[7]  M. Lezak Neuropsychological assessment, 3rd ed. , 1995 .

[8]  O. Spreen,et al.  A Compendium of Neuropsychological Tests: Administration, Norms, and Commentary , 1991 .

[9]  S. Lord,et al.  Physiological Factors Associated with Falls in Older Community‐Dwelling Women , 1994, Journal of the American Geriatrics Society.

[10]  P. Box Small vessel disease and general cognitive function in nondisabled elderly: The LADIS study , 2006 .

[11]  E Auffray,et al.  Longitudinal study of blood pressure and white matter hyperintensities , 2001, Neurology.

[12]  Frederik Barkhof,et al.  Changes in white matter as determinant of global functional decline in older independent outpatients: three year follow-up of LADIS (leukoaraiosis and disability) study cohort , 2009, BMJ : British Medical Journal.

[13]  Henry Brodaty,et al.  Brain white matter hyperintensities, executive dysfunction, instability, and falls in older people: a prospective cohort study. , 2012, The journals of gerontology. Series A, Biological sciences and medical sciences.

[14]  T. Taoka,et al.  Comparison between Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers on the Risk of Stroke Recurrence and Longitudinal Progression of White Matter Lesions and Silent Brain Infarcts on MRI (CEREBRAL Study): Rationale, Design, and Methodology , 2015, International journal of stroke : official journal of the International Stroke Society.

[15]  R W Baloh,et al.  White matter lesions and disequilibrium in older people. I. Case-control comparison. , 1995, Archives of neurology.

[16]  G. Zou,et al.  A modified poisson regression approach to prospective studies with binary data. , 2004, American journal of epidemiology.

[17]  F Fazekas,et al.  Deep frontal and periventricular age related white matter changes but not basal ganglia and infratentorial hyperintensities are associated with falls: cross sectional results from the LADIS study , 2009, Journal of Neurology, Neurosurgery, and Psychiatry.

[18]  H. Menz,et al.  A physiological profile approach to falls risk assessment and prevention. , 2003, Physical therapy.

[19]  I. White,et al.  Review of inverse probability weighting for dealing with missing data , 2013, Statistical methods in medical research.

[20]  Richard Beare,et al.  Silent Infarcts and Cerebral Microbleeds Modify the Associations of White Matter Lesions With Gait and Postural Stability: Population-Based Study , 2012, Stroke.

[21]  Christian Enzinger,et al.  Progression of cerebral white matter lesions: 6-year results of the Austrian Stroke Prevention Study , 2003, The Lancet.

[22]  V. Leirer,et al.  Development and validation of a geriatric depression screening scale: a preliminary report. , 1982, Journal of psychiatric research.

[23]  C. Becker,et al.  Development of a Common Outcome Data Set for Fall Injury Prevention Trials: The Prevention of Falls Network Europe Consensus , 2005, Journal of the American Geriatrics Society.

[24]  P. Scheltens,et al.  Association of gait and balance disorders with age-related white matter changes , 2008, Neurology.

[25]  G Lantos,et al.  Brain white-matter changes in the elderly prone to falling. , 1989, Archives of neurology.

[26]  M. Woodward,et al.  Effects of blood pressure lowering on cerebral white matter hyperintensities in patients with stroke. The PROGRESS MRI Substudy , 2005 .

[27]  Benjamin S Aribisala,et al.  Close Correlation between Quantitative and Qualitative Assessments of White Matter Lesions , 2012, Neuroepidemiology.

[28]  Henry Brodaty,et al.  White Matter Hyperintensities Are an Independent Predictor of Physical Decline in Community-Dwelling Older People , 2012, Gerontology.

[29]  Nick C Fox,et al.  Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration , 2013, The Lancet Neurology.

[30]  A. Hofman,et al.  Periventricular cerebral white matter lesions predict rate of cognitive decline , 2002, Annals of neurology.

[31]  Richard Beare,et al.  Brain Structural Change and Gait Decline: A Longitudinal Population‐Based Study , 2013, Journal of the American Geriatrics Society.

[32]  Wiro J Niessen,et al.  High Blood Pressure and Cerebral White Matter Lesion Progression in the General Population , 2013, Hypertension.

[33]  O. Spreen,et al.  Comprar A Compendium of Neuropsychological Tests - Administration, Norms, and Commentary | Esther Strauss | 9780195159578 | Oxford University Press , 2009 .

[34]  Jian Chen,et al.  Development and validation of morphological segmentation of age-related cerebral white matter hyperintensities , 2009, NeuroImage.

[35]  L. Rubenstein Falls in older people: epidemiology, risk factors and strategies for prevention. , 2006, Age and ageing.

[36]  Richard Beare,et al.  The location of white matter lesions and gait—A voxel‐based study , 2010, Annals of neurology.

[37]  M. Woodward,et al.  Effects of Blood Pressure Lowering on Cerebral White Matter Hyperintensities in Patients With Stroke: The PROGRESS (Perindopril Protection Against Recurrent Stroke Study) Magnetic Resonance Imaging Substudy , 2005, Circulation.