Shortening of Saccades as a Possible Easy-to-Use Biomarker to Detect Risk of Alzheimer’s Disease

Background: Wide-ranging functional defects in eye movements have been reported in Alzheimer’s disease (AD) dementia. The detection of abnormal eye movements and reading problems may identify persons at risk of AD when clear clinical symptoms are lacking. Objective: To examine whether computer-based eye-tracking (ET) analysis of King-Devick (KD) test results differentiates cognitively healthy persons from persons with minor problems in cognitive testing or diagnosed mild AD. Methods: We recruited 78 participants (57 non-demented, 21 with mild AD) who underwent neurological examination, the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological test battery (CERAD-NB), and a Clinical Dementia Rating (CDR) interview. The non-demented participants were further divided into control (normal CERAD subtests, mean MMSE = 28) and objective mild cognitive impairment (MCI; decline in at least one CERAD memory score, mean MMSE = 27) groups. The KD reading test was performed using computer-based ET. The total time used for the reading test, errors made, fixation and saccade durations, and saccade amplitudes were analyzed. Results: We found significant differences between the control, objective MCI, and AD groups in regard to the mean saccade amplitude (3.58, 3.33, and 3.21 ms, respectively, p < 0.03) and duration (27.1, 25.3, and 24.8 ms, respectively, p < 0.05). The KD error scores in the AD group differed significantly (p < 0.01) from the other groups. Conclusion: Computed ET analysis of the KD test may help detect persons with objective MCI early when clear clinical symptoms are lacking. The portable device for ET is easy to use in primary health care memory clinics.

[1]  J. Trojanowski,et al.  Diagnostic performance and prediction of clinical progression of plasma phospho-tau181 in the Alzheimer’s Disease Neuroimaging Initiative , 2020, Molecular Psychiatry.

[2]  V. Julkunen,et al.  Cerebrospinal Fluid and MRI Biomarkers in Neurodegenerative Diseases: A Retrospective Memory Clinic-Based Study , 2020, Journal of Alzheimer's disease : JAD.

[3]  Fátima L. S. Nunes,et al.  Visual Search Efficiency in Mild Cognitive Impairment and Alzheimer's Disease: An Eye Movement Study. , 2020, Journal of Alzheimer's disease : JAD.

[4]  Jing Wang,et al.  Eye tracking metrics to screen and assess cognitive impairment in patients with neurological disorders , 2020, Neurological Sciences.

[5]  R. Morishita,et al.  Novel Method for Rapid Assessment of Cognitive Impairment Using High-Performance Eye-Tracking Technology , 2019, Scientific Reports.

[6]  H. Gellersen,et al.  Abnormalities of saccadic eye movements in dementia due to Alzheimer’s disease and mild cognitive impairment , 2019, Aging.

[7]  K. Blennow,et al.  Fluid and PET biomarkers for amyloid pathology in Alzheimer's disease , 2019, Molecular and Cellular Neuroscience.

[8]  V. Nejati,et al.  Behavioral and cognitive markers of mild cognitive impairment: diagnostic value of saccadic eye movements and Simon task , 2019, Aging Clinical and Experimental Research.

[9]  Magali Seassau,et al.  Prodromal Alzheimer's Disease Demonstrates Increased Errors at a Simple and Automated Anti-Saccade Task. , 2018, Journal of Alzheimer's disease : JAD.

[10]  B. Garner,et al.  Understanding the Role of ApoE Fragments in Alzheimer’s Disease , 2018, Neurochemical Research.

[11]  Yorghos Tripodis,et al.  Screening Utility of the King-Devick Test in Mild Cognitive Impairment and Alzheimer Disease Dementia , 2017, Alzheimer disease and associated disorders.

[12]  Liliana R. Castro,et al.  Patients with Mild Alzheimer's Disease Fail When Using Their Working Memory: Evidence from the Eye Tracking Technique. , 2016, Journal of Alzheimer's disease : JAD.

[13]  A. Koivisto,et al.  Self-Rated and Caregiver-Rated Quality of Life in Alzheimer Disease with a Focus on Evolving Patient Ability to Respond to Questionnaires: 5-Year Prospective ALSOVA Cohort Study. , 2015, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[14]  C. Gissane,et al.  Use of the King–Devick test for sideline concussion screening in junior rugby league , 2015, Journal of the Neurological Sciences.

[15]  Osvaldo Agamennoni,et al.  Lack of contextual-word predictability during reading in patients with mild Alzheimer disease , 2014, Neuropsychologia.

[16]  H. Soininen,et al.  CERAD neuropsychological compound scores are accurate in detecting prodromal alzheimer's disease: a prospective AddNeuroMed study. , 2014, Journal of Alzheimer's disease : JAD.

[17]  G. Fernández,et al.  Eye movement alterations during reading in patients with early Alzheimer disease. , 2013, Investigative ophthalmology & visual science.

[18]  H. Soininen,et al.  CSF biomarkers for Alzheimer disease correlate with cortical brain biopsy findings , 2012, Neurology.

[19]  Ricardo Matos,et al.  Identifying parameter values for an I-VT fixation filter suitable for handling data sampled with various sampling frequencies , 2012, ETRA.

[20]  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.

[21]  Denise C. Park,et al.  Toward defining the preclinical stages of 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.

[22]  D. Munoz,et al.  Age-related trends in saccade characteristics among the elderly , 2011, Neurobiology of Aging.

[23]  D. Selkoe Alzheimer's disease. , 2011, Cold Spring Harbor perspectives in biology.

[24]  H. Soininen,et al.  CERAD neuropsychological battery total score in multinational mild cognitive impairment and control populations: the AddNeuroMed study. , 2011, Journal of Alzheimer's disease : JAD.

[25]  M. Rhodes,et al.  Assessment of two flexible and compatible SNP genotyping platforms: TaqMan SNP Genotyping Assays and the SNPlex Genotyping System. , 2005, Mutation research.

[26]  S. Barth,et al.  Neuropsychologische Profile in der Demenzdiagnostik: Eine Untersuchung mit der CERAD-NP-Testbatterie , 2005 .

[27]  P. Bertolucci,et al.  Applicability of the CERAD neuropsychological battery to Brazilian elderly. , 2001, Arquivos de neuro-psiquiatria.

[28]  K. Perryman,et al.  Eye movement abnormalities during reading in patients with Alzheimer disease. , 2000, Neuropsychiatry, neuropsychology, and behavioral neurology.

[29]  R. Corbo,et al.  Apolipoprotein E (APOE) allele distribution in the world. Is APOE*4 a ‘thrifty’ allele? , 1999, Annals of human genetics.

[30]  C. Clark,et al.  The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) , 1994, Neurology.

[31]  N. Butters,et al.  The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part V. A normative study of the neuropsychological battery , 1994, Neurology.

[32]  J. Haines,et al.  Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. , 1993, Science.

[33]  N Butters,et al.  Detection of abnormal memory decline in mild cases of Alzheimer's disease using CERAD neuropsychological measures. , 1991, Archives of neurology.

[34]  M. Mendez,et al.  Disorders of the visual system in Alzheimer's disease. , 1990, Journal of clinical neuro-ophthalmology.

[35]  M. Borchert,et al.  Assessment of visual impairment in patients with Alzheimer's disease. , 1987, American journal of ophthalmology.

[36]  J. Cummings,et al.  The pattern of reading deterioration in dementia of the Alzheimer type: Observations and implications , 1986, Brain and Language.