Vestibular Loss Predicts Poorer Spatial Cognition in Patients with Alzheimer's Disease.

The vestibular system is an important contributor to balance control, spatial orientation, and falls risk. Recent evidence has shown that Alzheimer's disease (AD) patients have a higher prevalence of vestibular impairment relative to healthy controls. We sought to evaluate whether vestibular loss is specifically associated with poor spatial cognitive skills among patients with mild cognitive impairment (MCI) and AD. We enrolled 50 patients (22 MCI and 28 AD) from an interdisciplinary Memory Clinic and measured vestibular physiologic function in all patients. Spatial cognitive function was assessed using the Money Road Map Test (MRMT) and the Trail Making Test Part B (TMT-B). General cognitive function was assessed with the Mini-Mental Status Examination (MMSE). In multivariable linear regression analyses adjusted for age, gender, education level, and MMSE, MCI and AD patients with vestibular loss made significantly more errors on the MRMT relative to patients with normal vestibular function (β= 7.3, 95% CI 2.4, 12.1 for unilateral vestibular loss and β= 6.4, 95% CI 1.9, 10.9 for bilateral vestibular loss). We further stratified AD patients into "spatially normal" and "spatially impaired" groups based on MRMT performance, and found that the prevalence of vestibular loss was significantly higher in the spatially impaired AD group relative to the spatially normal AD group. These findings support the hypothesis that vestibular loss contributes specifically to a decline in spatial cognitive ability in MCI and AD patients, independently of general cognitive decline, and may predict a "spatially impaired" subtype of AD.

[1]  D. Bolton,et al.  Deficit in cognitive shifting ability in patients with obsessive-compulsive disorder , 1989, Biological Psychiatry.

[2]  T. Brandt,et al.  Vestibular loss causes hippocampal atrophy and impaired spatial memory in humans. , 2005, Brain : a journal of neurology.

[3]  Luigi Mansi,et al.  Cortical abnormalities in Alzheimer's disease , 1984, Annals of neurology.

[4]  J. Morris,et al.  The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer's disease , 2011, Alzheimer's & Dementia.

[5]  S. du Lac,et al.  Association Between Vestibular and Cognitive Function in U.S. Adults: Data From the National Health and Nutrition Examination Survey. , 2016, The journals of gerontology. Series A, Biological sciences and medical sciences.

[6]  Alan H Lockwood,et al.  Use of 64-channel electroencephalography to study neural otolith-evoked responses. , 2011, Journal of the American Academy of Audiology.

[7]  J. Carey,et al.  Test-Retest Reliability and Age-Related Characteristics of the Ocular and Cervical Vestibular Evoked Myogenic Potential Tests , 2010, Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology.

[8]  A. Berthoz,et al.  Activation of the hippocampal formation by vestibular stimulation: a functional magnetic resonance imaging study , 1996, Experimental Brain Research.

[9]  R. Tusa,et al.  Falls in patients with vestibular deficits. , 2000, The American journal of otology.

[10]  M. G. Zuniga,et al.  Head Impulse Test Abnormalities and Influence on Gait Speed and Falls in Older Individuals , 2013, Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology.

[11]  J. Morris,et al.  Longitudinal study of the transition from healthy aging to Alzheimer disease. , 2009, Archives of neurology.

[12]  Peter Graf,et al.  Increased Risk of Falling in Older Community-Dwelling Women With Mild Cognitive Impairment , 2008, Physical Therapy.

[13]  R. Reitan.  Trail Making Test: Manual for Administration and Scoring , 1992 .

[14]  S. Moffat,et al.  Navigation in a “Virtual” Maze: Sex Differences and Correlation With Psychometric Measures of Spatial Ability in Humans , 1998 .

[15]  B Horwitz,et al.  Longitudinal study of the early neuropsychological and cerebral metabolic changes in dementia of the Alzheimer type. , 1988, Journal of clinical and experimental neuropsychology.

[16]  M. L. Lambon Ralph,et al.  Homogeneity and heterogeneity in mild cognitive impairment and Alzheimer's disease: a cross-sectional and longitudinal study of 55 cases. , 2003, Brain : a journal of neurology.

[17]  Stephanie Studenski,et al.  Vestibular Impairment in Dementia , 2016, Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology.

[18]  Andrew J. Layman,et al.  Epidemiology of vestibular evoked myogenic potentials: Data from the Baltimore Longitudinal Study of Aging , 2015, Clinical Neurophysiology.

[19]  C. Zhong,et al.  Iron Deposition Leads to Neuronal α-Synuclein Pathology by Inducing Autophagy Dysfunction , 2017, Front. Neurol..

[20]  Charles J Duffy,et al.  A visuospatial variant of mild cognitive impairment , 2003, Neurology.

[21]  S. Lord,et al.  Neuropsychological, physical, and functional mobility measures associated with falls in cognitively impaired older adults. , 2014, The journals of gerontology. Series A, Biological sciences and medical sciences.

[22]  V. Henderson,et al.  Spatial disorientation in Alzheimer's disease. , 1989, Archives of neurology.

[23]  F. Previc.  Vestibular loss as a contributor to Alzheimer's disease. , 2013, Medical hypotheses.

[24]  M. Lobo,et al.  Shining light on motivation, emotion, and memory processes , 2015, Front. Behav. Neurosci..

[25]  D. Buchner,et al.  Falls and fractures in patients with Alzheimer-type dementia. , 1987, JAMA.

[26]  F. Lacquaniti,et al.  Role of the Insula and Vestibular System in Patients with Chronic Subjective Dizziness: An fMRI Study Using Sound-Evoked Vestibular Stimulation , 2015, Front. Behav. Neurosci..

[27]  S. Muir,et al.  The role of cognitive impairment in fall risk among older adults: a systematic review and meta-analysis. , 2012, Age and ageing.

[28]  H. Welch,et al.  Survival of outpatients with Alzheimer-type dementia. , 1990, Annals of internal medicine.

[29]  M. Hitier,et al.  Integrative Neuroscience Review Article Vestibular Pathways Involved in Cognition , 2022 .

[30]  K. Sugawara,et al.  Time Course of Corticospinal Excitability and Intracortical Inhibition Just before Muscle Relaxation , 2016, Front. Hum. Neurosci..

[31]  L. Ferrucci,et al.  Association Between Visuospatial Ability and Vestibular Function in the Baltimore Longitudinal Study of Aging , 2015, Journal of the American Geriatrics Society.

[32]  R. Passini,et al.  Performances of patients with a dementia of the Alzheimer type in the Standardized Road-Map test of Direction Sense , 2002, Neuropsychologia.

[33]  Scott D. Moffat,et al.  Vestibular Loss in Older Adults Is Associated with Impaired Spatial Navigation: Data from the Triangle Completion Task , 2017, Front. Neurol..

[34]  T. Brandt,et al.  Beyond Dizziness: Virtual Navigation, Spatial Anxiety and Hippocampal Volume in Bilateral Vestibulopathy , 2016, Front. Hum. Neurosci..

[35]  M. G. Zuniga,et al.  How to interpret latencies of cervical and ocular vestibular‐evoked myogenic potentials: Our experience in fifty‐three participants , 2014, Clinical otolaryngology : official journal of ENT-UK ; official journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery.

[36]  G. Jacobson,et al.  Effects of Age on the Tuning of the cVEMP and oVEMP , 2013, Ear and hearing.

[37]  Jinna Kim,et al.  The change of hippocampal volume and its relevance with inner ear function in Meniere's disease patients. , 2016, Auris, nasus, larynx.

[38]  Jean-Ha Baek,et al.  Evidence that spatial memory deficits following bilateral vestibular deafferentation in rats are probably permanent , 2010, Neurobiology of Learning and Memory.

[39]  J. Morris,et al.  Senile dementia of the Alzheimer's type: an important risk factor for serious falls. , 1987, Journal of gerontology.

[40]  V. Phillips,et al.  The Incremental Effect of Dementia‐Related Problem Behaviors on the Time to Nursing Home Placement in Poor, Frail, Demented Older People , 2003, Journal of the American Geriatrics Society.

[41]  T. Münte,et al.  Hippocampal gray matter volume in bilateral vestibular failure , 2016, Human brain mapping.

[42]  P. Schlindwein,et al.  Cortical representation of saccular vestibular stimulation: VEMPs in fMRI , 2008, NeuroImage.

[43]  L. Nadel,et al.  The Hippocampus as a Cognitive Map , 1978 .

[44]  Jeffrey L. Cummings,et al.  Cognitive and behavioral heterogeneity in Alzheimer’s disease: seeking the neurobiological basis , 2000, Neurobiology of Aging.

[45]  S. Kammermeier,et al.  Intermediate latency evoked potentials of cortical multimodal vestibular areas: Acoustic stimulation , 2015, Clinical Neurophysiology.

[46]  C. Armstrong,et al.  The emergence of spatial rotation deficits in dementia and normal aging. , 1998, Neuropsychology.

[47]  Philip D. Harvey,et al.  Administration and interpretation of the Trail Making Test , 2006, Nature Protocols.

[48]  C. Ballard,et al.  Incidence and Prediction of Falls in Dementia: A Prospective Study in Older People , 2009, PloS one.

[49]  S. Whitney,et al.  The dynamic gait index relates to self-reported fall history in individuals with vestibular dysfunction. , 2000, Journal of vestibular research : equilibrium & orientation.

[50]  J. Taube,et al.  Hippocampal spatial representations require vestibular input , 2002, Hippocampus.

[51]  S. Lord,et al.  Reaction Time and Postural Sway Modify the Effect of Executive Function on Risk of Falls in Older People with Mild to Moderate Cognitive Impairment. , 2017, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[52]  Frederik Barkhof,et al.  The identification of cognitive subtypes in Alzheimer's disease dementia using latent class analysis , 2015, Journal of Neurology, Neurosurgery & Psychiatry.

[53]  J. Money,et al.  A standardized road-map test of direction sense , 1965 .

[54]  Nick C. Fox,et al.  The diagnosis of mild cognitive impairment due to Alzheimer's disease: Recommendations from the National Institute on Aging and Alzheimer's Association workgroup , 2011 .

[55]  L. Mansi,et al.  CORTICAL ABNORMALITIES IN ALZHEIMER'S DISEASE , 1984, Annals of neurology.

[56]  T. Brandt,et al.  Cognitive deficits in patients with a chronic vestibular failure , 2017, Journal of Neurology.

[57]  C. Lucetti,et al.  Wandering and dementia , 2014, Psychogeriatrics : the official journal of the Japanese Psychogeriatric Society.

[58]  Hikari Yamashita.  Self-rated right–left confusability and performance on the Money Road-Map Test , 2013, Psychological research.

[59]  R. Keren,et al.  An exploration of cognitive subgroups in Alzheimer’s disease , 2009, Journal of the International Neuropsychological Society.

[60]  K. Fukushima,et al.  Saccular Projections in the Human Cerebral Cortex , 2005, Annals of the New York Academy of Sciences.

[61]  N. Foster,et al.  Wechsler Adult Intelligence Scale performance. Cortical localization by fluorodeoxyglucose F 18-positron emission tomography. , 1984, Archives of neurology.

[62]  R. Gürkov,et al.  Utilisation of multi-frequency VEMPs improves diagnostic accuracy for Meniere’s disease , 2016, European Archives of Oto-Rhino-Laryngology.

[63]  Michael C Schubert,et al.  Disorders of balance and vestibular function in US adults: data from the National Health and Nutrition Examination Survey, 2001-2004. , 2009, Archives of internal medicine.