Disruptions in Brain Networks of Older Fallers Are Associated with Subsequent Cognitive Decline: A 12-Month Prospective Exploratory Study

Cognitive impairment and impaired mobility are major public health concerns. There is growing recognition that impaired mobility is an early biomarker of cognitive impairment and dementia. The neural basis for this association is currently unclear. We propose disrupted functional connectivity as a potential mechanism. In this 12-month prospective exploratory study, we compared functional connectivity of four brain networks– the default mode network (DMN), fronto-executive network (FEN), fronto-parietal network (FPN), and the primary motor sensory network (SMN) – between community-dwelling older adults with ≥ two falls in the last 12 months and their non-falling counterparts (≤ one fall in the last 12 months). Functional connectivity was examined both at rest and during a simple motor tapping task. Compared with non-fallers, fallers showed more connectivity between the DMN and FPN during right finger tapping (p = 0.04), and significantly less functional connectivity between the SMN and FPN during rest (p≤0.05). Less connectivity between the SMN and FPN during rest was significantly associated with greater decline in both cognitive function and mobility over the12-month period (r = −0.32 and 0.33 respectively; p≤0.04). Thus, a recent history of multiple falls among older adults without a diagnosis of dementia may indicate sub-clinical changes in brain function and increased risk for subsequent decline.

[1]  Jeffrey Kaye,et al.  The trajectory of gait speed preceding mild cognitive impairment. , 2010, Archives of neurology.

[2]  I. Deary,et al.  Brain white matter lesions detected by magnetic resonance [correction of resosnance] imaging are associated with balance and gait speed. , 2003, Journal of neurology, neurosurgery, and psychiatry.

[3]  W B Verwey,et al.  Concatenating familiar movement sequences: the versatile cognitive processor. , 2001, Acta psychologica.

[4]  L. Lipsitz,et al.  Cerebral white matter changes and geriatric syndromes: is there a link? , 2004, The journals of gerontology. Series A, Biological sciences and medical sciences.

[5]  Jonas Persson,et al.  Structure-function correlates of cognitive decline in aging. , 2006, Cerebral cortex.

[6]  W. O'Fallon,et al.  Dementia after ischemic stroke , 1996, Neurology.

[7]  Agnieszka Z. Burzynska,et al.  Diffusion tensor imaging of cerebral white matter integrity in cognitive aging. , 2012, Biochimica et biophysica acta.

[8]  Abraham Z. Snyder,et al.  Spurious but systematic correlations in functional connectivity MRI networks arise from subject motion , 2012, NeuroImage.

[9]  S. Cummings,et al.  Risk factors for recurrent nonsyncopal falls. A prospective study. , 1989, JAMA.

[10]  Sadanori Konishi,et al.  Normalizing transformations of some statistics in multivariate analysis , 1981 .

[11]  K. Onoda,et al.  Aging effects on functional connectivity within and between resting-state networks , 2012, 2012 ICME International Conference on Complex Medical Engineering (CME).

[12]  M. Albert,et al.  Self-efficacy beliefs and change in cognitive performance: MacArthur Studies of Successful Aging. , 1996, Psychology and aging.

[13]  R. Honea,et al.  Evidence of Altered Corticomotor System Connectivity in Early-Stage Alzheimer's Disease , 2012, Journal of neurologic physical therapy : JNPT.

[14]  Todd C. Handy,et al.  Mind wandering and motor control: off-task thinking disrupts the online adjustment of behavior , 2012, Front. Hum. Neurosci..

[15]  James G Wright,et al.  The development of a comorbidity index with physical function as the outcome. , 2005, Journal of clinical epidemiology.

[16]  V. Menon,et al.  A critical role for the right fronto-insular cortex in switching between central-executive and default-mode networks , 2008, Proceedings of the National Academy of Sciences.

[17]  D. Kahneman,et al.  Attention and Effort , 1973 .

[18]  P A Parmelee,et al.  Geriatric Depression Scale , 2002 .

[19]  J. Mulder,et al.  Evaluation of the feasibility, reliability and diagnostic value of shortened versions of the geriatric depression scale. , 1995, The British journal of general practice : the journal of the Royal College of General Practitioners.

[20]  C. Becker,et al.  Systematic review of definitions and methods of measuring falls in randomised controlled fall prevention trials. , 2006, Age and ageing.

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

[22]  Rainer Goebel,et al.  Independent component model of the default-mode brain function: combining individual-level and population-level analyses in resting-state fMRI. , 2008, Magnetic resonance imaging.

[23]  Roberto Cabeza,et al.  Assessing the effects of age on long white matter tracts using diffusion tensor tractography , 2009, NeuroImage.

[24]  K. Boone,et al.  SENSITIVITY AND SPECIFICITY OF FINGER TAPPING TEST SCORES FOR THE DETECTION OF SUSPECT EFFORT , 2005, The Clinical neuropsychologist.

[25]  D. Schacter,et al.  The Brain's Default Network , 2008, Annals of the New York Academy of Sciences.

[26]  J. Morris,et al.  Functional deactivations: Change with age and dementia of the Alzheimer type , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[27]  M. Greicius,et al.  Default-mode network activity distinguishes Alzheimer's disease from healthy aging: Evidence from functional MRI , 2004, Proc. Natl. Acad. Sci. USA.

[28]  T. Handy,et al.  Mind-wandering and falls risk in older adults. , 2013, Psychology and aging.

[29]  Kristina M. Visscher,et al.  A Core System for the Implementation of Task Sets , 2006, Neuron.

[30]  Leonardo Fogassi,et al.  Motor functions of the parietal lobe , 2005, Current Opinion in Neurobiology.

[31]  M. Greicius Resting-state functional connectivity in neuropsychiatric disorders , 2008, Current opinion in neurology.

[32]  S. Rubin,et al.  Cognitive function, gait speed decline, and comorbidities: the health, aging and body composition study. , 2007, The journals of gerontology. Series A, Biological sciences and medical sciences.

[33]  Karl J. Friston,et al.  Functional Connectivity: The Principal-Component Analysis of Large (PET) Data Sets , 1993, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[34]  Maurizio Corbetta,et al.  The human brain is intrinsically organized into dynamic, anticorrelated functional networks. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[35]  Linda Geerligs,et al.  Reduced specificity of functional connectivity in the aging brain during task performance , 2014, Human brain mapping.

[36]  Jeffrey S. Spence,et al.  Deficits in functional connectivity of hippocampal and frontal lobe circuits after traumatic axonal injury. , 2011, Archives of neurology.

[37]  C. Kelly,et al.  The extrinsic and intrinsic functional architectures of the human brain are not equivalent. , 2013, Cerebral cortex.

[38]  Li Yao,et al.  Impairment and compensation coexist in amnestic MCI default mode network , 2010, NeuroImage.

[39]  Richard B. Buxton,et al.  Resting-state BOLD networks versus task-associated functional MRI for distinguishing Alzheimer's disease risk groups , 2009, NeuroImage.

[40]  Anne B. Newman,et al.  Gait Speed Predicts Decline in Attention and Psychomotor Speed in Older Adults: The Health Aging and Body Composition Study , 2007, Neuroepidemiology.

[41]  A. Shumway-cook,et al.  Predicting the probability for falls in community-dwelling older adults. , 1997, Physical therapy.

[42]  J. Morris,et al.  Loss of Intranetwork and Internetwork Resting State Functional Connections with Alzheimer's Disease Progression , 2012, The Journal of Neuroscience.

[43]  A. Luft,et al.  Consequences of Stroke in Community-Dwelling Elderly: The Health and Retirement Study 1998-2008 , 2011 .

[44]  B. L. Beattie,et al.  Self-efficacy is independently associated with brain volume in older women. , 2012, Age and ageing.

[45]  James K. Nelson,et al.  Age Differences in Deactivation: A Link to Cognitive Control? , 2007, Journal of Cognitive Neuroscience.

[46]  T. Seeman,et al.  Self-efficacy beliefs and perceived declines in functional ability: MacArthur studies of successful aging. , 1999, The journals of gerontology. Series B, Psychological sciences and social sciences.

[47]  David G Norris,et al.  Loss of white matter integrity is associated with gait disorders in cerebral small vessel disease. , 2011, Brain : a journal of neurology.

[48]  R A Boileau,et al.  The physical activity scale for the elderly (PASE): evidence for validity. , 1999, Journal of clinical epidemiology.

[49]  M. Ashe,et al.  Dual-task gait performance among community-dwelling senior women: the role of balance confidence and executive functions. , 2009, The journals of gerontology. Series A, Biological sciences and medical sciences.

[50]  Cindy Lustig,et al.  Brain aging: reorganizing discoveries about the aging mind , 2005, Current Opinion in Neurobiology.

[51]  Donatella Spinelli,et al.  Prefrontal hyperactivity in older people during motor planning , 2012, NeuroImage.

[52]  Jeffrey M. Hausdorff,et al.  High‐Level Gait Disorder: Associations with Specific White Matter Changes Observed on Advanced Diffusion Imaging , 2013, Journal of neuroimaging : official journal of the American Society of Neuroimaging.

[53]  Mark W. Woolrich,et al.  Advances in functional and structural MR image analysis and implementation as FSL , 2004, NeuroImage.

[54]  A. Grabowska,et al.  Switching handedness: fMRI study of hand motor control in right-handers, left-handers and converted left-handers. , 2012, Acta neurobiologiae experimentalis.

[55]  Henry Brodaty,et al.  A Multifactorial Approach to Understanding Fall Risk in Older People , 2010, Journal of the American Geriatrics Society.

[56]  M. D’Esposito Working memory. , 2008, Handbook of clinical neurology.

[57]  R. Della Nave,et al.  Whole-Brain Histogram and Voxel-Based Analyses of Diffusion Tensor Imaging in Patients with Leukoaraiosis: Correlation with Motor and Cognitive Impairment , 2007, American Journal of Neuroradiology.

[58]  S. Rombouts,et al.  Altered resting state networks in mild cognitive impairment and mild Alzheimer's disease: An fMRI study , 2005, Human brain mapping.

[59]  Denise C. Park,et al.  The adaptive brain: aging and neurocognitive scaffolding. , 2009, Annual review of psychology.

[60]  L. Nyberg,et al.  Altered deactivation in individuals with genetic risk for Alzheimer's disease , 2008, Neuropsychologia.

[61]  V. Weerdesteyn,et al.  Falls in individuals with stroke. , 2008, Journal of rehabilitation research and development.

[62]  Henry Brodaty,et al.  Determinants of disparities between perceived and physiological risk of falling among elderly people: cohort study , 2010, BMJ : British Medical Journal.

[63]  E. McAuley,et al.  Frontiers in Aging Neuroscience Aging Neuroscience , 2022 .

[64]  Herman Buschke,et al.  Abnormality of gait as a predictor of non-Alzheimer's dementia. , 2002, The New England journal of medicine.

[65]  S. Cummings,et al.  Forgetting Falls , 1988, Journal of the American Geriatrics Society.

[66]  Ahmed,et al.  Changing the structure of complex visuo-motor sequences selectively activates the fronto-parietal network , 2012, NeuroImage.

[67]  Mert R. Sabuncu,et al.  The influence of head motion on intrinsic functional connectivity MRI , 2012, NeuroImage.

[68]  L. Kurlowicz,et al.  The Mini Mental State Examination (MMSE). , 1999, Director.

[69]  J. Eng,et al.  Falls-related self-efficacy is independently associated with balance and mobility in older women with low bone mass. , 2006, The journals of gerontology. Series A, Biological sciences and medical sciences.

[70]  I. Deary,et al.  Brain white matter lesions detected by magnetic resosnance imaging are associated with balance and gait speed , 2003 .

[71]  S. Lord,et al.  Physiological Factors Associated with Falls in an Elderly Population , 1991, Journal of the American Geriatrics Society.

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

[73]  G. Glover,et al.  Dissociable Intrinsic Connectivity Networks for Salience Processing and Executive Control , 2007, The Journal of Neuroscience.

[74]  S. Rombouts,et al.  Reduced resting-state brain activity in the "default network" in normal aging. , 2008, Cerebral cortex.

[75]  M. Greicius,et al.  Default-Mode Activity during a Passive Sensory Task: Uncoupled from Deactivation but Impacting Activation , 2004, Journal of Cognitive Neuroscience.

[76]  Roberto Cabeza,et al.  Cerebral White Matter Integrity Mediates Adult Age Differences in Cognitive Performance , 2009, Journal of Cognitive Neuroscience.

[77]  C. Rosano,et al.  Subclinical Brain Magnetic Resonance Imaging Abnormalities Predict Physical Functional Decline in High‐Functioning Older Adults , 2005, Journal of the American Geriatrics Society.

[78]  Kuncheng Li,et al.  Changes of functional connectivity of the motor network in the resting state in Parkinson's disease , 2009, Neuroscience Letters.

[79]  M. Woollacott,et al.  Predicting the probability for falls in community-dwelling older adults using the Timed Up & Go Test. , 2000, Physical therapy.

[80]  R. C. Oldfield The assessment and analysis of handedness: the Edinburgh inventory. , 1971, Neuropsychologia.

[81]  Rieko Osu,et al.  Resource-demanding versus cost-effective bimanual interaction in the brain , 2010, Experimental Brain Research.

[82]  Scott T. Grafton,et al.  Differential Recruitment of the Sensorimotor Putamen and Frontoparietal Cortex during Motor Chunking in Humans , 2012, Neuron.

[83]  Ack,et al.  LOWER-EXTREMITY FUNCTION IN PERSONS OVER THE AGE OF 70 YEARS AS A PREDICTOR OF SUBSEQUENT DISABILITY , 2001 .

[84]  Paige E. Scalf,et al.  The implications of cortical recruitment and brain morphology for individual differences in inhibitory function in aging humans. , 2005, Psychology and aging.

[85]  Lewis H Kuller,et al.  Association Between Lower Digit Symbol Substitution Test Score and Slower Gait and Greater Risk of Mortality and of Developing Incident Disability in Well‐Functioning Older Adults , 2008, Journal of the American Geriatrics Society.

[86]  P. Graf,et al.  Color- and picture-word Stroop tests: performance changes in old age. , 1995, Journal of clinical and experimental neuropsychology.

[87]  Justin L. Vincent,et al.  Disruption of Large-Scale Brain Systems in Advanced Aging , 2007, Neuron.

[88]  J. Cummings,et al.  The Montreal Cognitive Assessment, MoCA: A Brief Screening Tool For Mild Cognitive Impairment , 2005, Journal of the American Geriatrics Society.

[89]  Willem B. Verwey,et al.  Diminished motor skill development in elderly: indications for limited motor chunk use. , 2010, Acta psychologica.

[90]  R. N. Spreng,et al.  Default network modulation and large-scale network interactivity in healthy young and old adults. , 2012, Cerebral cortex.

[91]  Giuseppe Pagnoni,et al.  Altered resting-state effective connectivity of fronto-parietal motor control systems on the primary motor network following stroke , 2012, NeuroImage.

[92]  S. Swinnen,et al.  White matter fractional anisotropy predicts balance performance in older adults , 2012, Neurobiology of Aging.

[93]  N. Volkow,et al.  Aging and Functional Brain Networks , 2011, Molecular Psychiatry.

[94]  Abraham Z. Snyder,et al.  A method for using blocked and event-related fMRI data to study “resting state” functional connectivity , 2007, NeuroImage.

[95]  Paul B. Johnson,et al.  Premotor and parietal cortex: corticocortical connectivity and combinatorial computations. , 1997, Annual review of neuroscience.

[96]  C. Jack,et al.  Diffusion tensor imaging and cognitive function in older adults with no dementia , 2011, Neurology.