Abnormal Saccadic Intrusions with Alzheimer's Disease in Darkness

Author(s): Kiyotaka Nakamagoe*, Shiori Yamada, Rio Kawakami, Tadachika Koganezawa, Akira Tamaoka.

Journal Name: Current Alzheimer Research

Volume 16 , Issue 4 , 2019

  Journal Home
Translate in Chinese
Become EABM
Become Reviewer

Abstract:

Background: Classified as saccadic intrusions, Square-Wave Jerks (SWJs) have been observed during Visual Fixation (VF) in Alzheimer’s Disease (AD). However, the pathological significance of this phenomenon remains unclear.

Objective: The present study analyzed the characteristics of SWJs in patients with AD with their eyes open in the dark without VF.

Methods: Fifteen patients with AD and 15 healthy age- and sex-matched controls were investigated and compared. Saccadic intrusions with and without VF were detected as SWJs and measured using an electronystagmogram.

Results: No significant difference in the frequency of SWJs was observed between control and AD groups with VF, but significantly more SWJs were observed in the AD group than in the control group in the absence of VF (p<0.01). In the control group, the frequency of SWJs was significantly higher with VF as compared to without VF. Conversely, the frequency in the AD group was significantly higher without VF. Furthermore, a directly proportional relationship was observed between the frequency of SWJs and higher-order function (R>0.55) in the AD group.

Conclusion: SWJs without VF may have pathological significance in AD. In healthy individuals, SWJs are generated by VF and suppressed without VF. Conversely, in AD, SWJs are generated rather than suppressed in the absence of VF. These pathognomonic SWJs without VF also appear to be correlated with higher-order dysfunction, reflecting AD-related cortical damage. These findings suggest that pathological SWJs without VF observed in AD derive from cortical damage and may constitute an important marker of a higher-order function.

Keywords: Alzheimer's disease, eye movements, saccadic intrusion, square-wave jerks, visual fixation, higher-order function, inferior parietal lobule, frontal eye field.

[1]
Zaccara G, Gangemi PF, Muscas GC, Paganini M, Pallanti S, Parigi A, et al. Smooth-pursuit eye movements: alterations in Alzheimer’s disease. J Neurol Sci 112: 81-9. (1992).
[2]
Fletcher WA, Sharpe JA. Saccadic eye movement dysfunction in Alzheimer’s disease. Ann Neurol 20: 464-71. (1986).
[3]
Shakespeare TJ, Kaski D, Yong KX, Paterson RW, Slattery CF, Ryan NS, et al. Abnormalities of fixation, saccade and pursuit in posterior cortical atrophy. Brain 138: 1976-91. (2015).
[4]
Moschos MM, Markopoulos I, Chatziralli I, Rouvas A, Papageorgiou SG, Ladas I, et al. Structural and functional impairment of the retina and optic nerve in Alzheimer’s disease. Curr Alzheimer Res 9: 782-8. (2012).
[5]
Frost S, Kanagasingam Y, Sohrabi H, Bourgeat P, Villemagne V, Rowe CC, et al. Pupil response biomarkers for early detection and monitoring of Alzheimer’s disease. Curr Alzheimer Res 10: 931-9. (2013).
[6]
Shen Y, Liu L, Cheng Y, Feng W, Shi Z, Zhu Y, et al. Retinal nerve fiber layer thickness is associated with episodic memory deficit in mild cognitive impairment patients. Curr Alzheimer Res 11: 259-66. (2014).
[7]
Frost S, Guymer R, Aung KZ, Macaulay SL, Sohrabi HR, Bourgeat P, et al. Alzheimer’s disease and the early signs of age-related macular degeneration. Curr Alzheimer Res 13: 1259-66. (2016).
[8]
Reed BT, Behar-Cohen F, Krantic S. Seeing early signs of Alzheimer’s disease through the lens of the eye. Curr Alzheimer Res 14: 6-17. (2017).
[9]
Shariflou S, Georgevsky D, Mansour H, Rezaeian M, Hosseini N, Gani F, et al. Diagnostic and prognostic potential of retinal biomarkers in early on-set Alzheimer’s disease. Curr Alzheimer Res 14: 1000-7. (2017).
[10]
Ukalovic K, Cao S, Lee S, Tang Q, Beg MF, Sarunic MV, et al. Drusen in the peripheral retina of the Alzheimer’s eye. Curr Alzheimer Res 15: 743-50. (2018).
[11]
Lee CS, Larson EB, Gibbons LE, Lee AY, McCurry SM, Bowen JD, et al. Associations between recent and established ophthalmic conditions and risk of Alzheimer’s disease. Alzheimers Dement 15: 34-41. (2019).
[12]
Hirao K, Ohnishi T, Hirata Y, Yamashita F, Mori T, Moriguchi Y, et al. The prediction of rapid conversion to Alzheimer’s disease in mild cognitive impairment using regional cerebral blood flow SPECT. Neuroimage 28: 1014-21. (2005).
[13]
Matsuda H. Role of neuroimaging in Alzheimer’s disease, with emphasis on brain perfusion SPECT. J Nucl Med 48: 1289-300. (2007).
[14]
Matsuda H, Imabayashi E. Molecular neuroimaging in Alzheimer’s disease. Neuroimaging Clin N Am 22: 57-65. (2012).
[15]
Schiller PH, True SD, Conway JL. Deficits in eye movements following frontal eye-field and superior colliculus ablations. J Neurophysiol 44: 1175-89. (1980).
[16]
Schiller PH, Sandell JH, Maunsell JH. The effect of frontal eye field and superior colliculus lesions on saccadic latencies in the rhesus monkey. J Neurophysiol 57: 1033-49. (1987).
[17]
Faugier-Grimaud S, Ventre J. Anatomic connections of inferior parietal cortex (area 7) with subcortical structures related to vestibulo-ocular function in a monkey (Macaca fascicularis). J Comp Neurol 280: 1-14. (1989).
[18]
Grüsser OJ, Pause M, Schreiter U. Localization and responses of neurones in the parieto-insular vestibular cortex of awake monkeys (Macaca fascicularis). J Physiol 430: 537-57. (1990).
[19]
Grüsser OJ, Pause M, Schreiter U. Vestibular neurones in the parieto-insular cortex of monkeys (Macaca fascicularis): visual and neck receptor responses. J Physiol 430: 559-83. (1990).
[20]
Nakamagoe K, Fujimiya S, Koganezawa T, Kadono K, Shimizu K, Fujizuka N, et al. Vestibular function impairment in Alzheimer’s disease. J Alzheimers Dis 47: 185-96. (2015).
[21]
Schiller PH. The effect of superior colliculus ablation on saccades elicted by cortical stimulation. Brain Res 122: 154-6. (1977).
[22]
Sharpe JA, Herishanu YO, White OB. Cerebral square wave jerks. Neurology 32: 57-62. (1982).
[23]
Rascol O, Sabatini U, Simonetta-Moreau M, Montastruc JL, Rascol A, Clanet M. Square wave jerks in parkinsonian syndromes. J Neurol Neurosurg Psychiatry 54: 599-602. (1991).
[24]
Nakamagoe K, Fujizuka N, Koganezawa T, Shimizu K, Takiguchi S, Horaguchi T, et al. Residual central nervous system damage due to organoarsenic poisoning. Neurotoxicol Teratol 37: 33-8. (2013).
[25]
Leigh RJ, Zee DS. Diagnosis of nystagmus and saccadic intrusion. Chapter 11; Saccadic intrusions and oscillations. The Neurology of Eye Movements. 5th ed. Oxford University Press, Oxford, UK. pp 716-726 (2015).
[26]
Jones A, Friedland RP, Koss B, Stark L, Thompkins-Ober BA. Saccadic intrusions in Alzheimer-type dementia. J Neurol 229: 189-94. (1983).
[27]
Schewe HJ, Uebelhack R, Vohs K. Abnormality in saccadic eye movement in dementia. Eur Psychiatry 14: 52-3. (1999).
[28]
Tokuda S, Obinata G, Palmer E, Chaparro A. Estimation of mental workload using saccadic eye movements in a free-viewing task. Conf Proc IEEE Eng Med Biol Soc 2011: 4523-9. (2011).
[29]
Biswas P, Prabhakar G. Detecting drivers’ cognitive load from saccadic intrusion. Transp Res, Part F Traffic Psychol Behav 54: 63-78. (2018).
[30]
Cockrell JR, Folstein MF. Mini-Mental State Examination (MMSE). Psychopharmacol Bull 24: 689-92. (1988).
[31]
Dubois B, Slachevsky A, Litvan I, Pillon B. The FAB: a frontal assessment battery at bedside. Neurology 55: 1621-6. (2000).
[32]
McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, 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. Alzheimers Dement 7: 263-9. (2011).
[33]
Abadi RV, Gowen E. Characteristics of saccadic intrusions. Vision Res 44: 2675-90. (2004).
[34]
Kapoula Z, Yang Q, Otero-Millan J, Xiao S, Macknik SL, Lang A, et al. Distinctive features of microsaccades in Alzheimer’s disease and in mild cognitive impairment. Age (Dordr) 36: 535-43. (2014).
[35]
Herishanu YO, Sharpe JA. Normal square wave jerks. Invest Ophthalmol Vis Sci 20: 268-72. (1981).
[36]
Salman MS, Sharpe JA, Eizenman M, Lillakas L, To T, Westall C, et al. Saccadic adaptation in children. J Child Neurol 21: 1025-31. (2006).
[37]
Komatsu H, Suzuki H. Projections from the functional subdivisions of the frontal eye field to the superior colliculus in the monkey. Brain Res 327: 324-7. (1985).
[38]
Lee JH, Byun MS, Sohn BK, Choe YM, Yi D, Han JY, et al. Functional neuroanatomical correlates of the frontal assessment battery performance in Alzheimer disease: a FDG-PET study. J Geriatr Psychiatry Neurol 28: 184-92. (2015).
[39]
Suzuki H, Azuma M. Prefrontal neuronal activity during gazing at a light spot in the monkey. Brain Res 126: 497-508. (1977).
[40]
Suzuki H, Azuma M, Yumiya H. Stimulus and behavioral factors contributing to the activation of monkey prefrontal neurons during gazing. Jpn J Physiol 29: 471-89. (1979).
[41]
Barbas H, Mesulam MM. Organization of afferent input to subdivisions of area 8 in the rhesus monkey. J Comp Neurol 200: 407-31. (1981).
[42]
Ungerleider LG, Desimone R. Cortical connections of visual area MT in the macaque. J Comp Neurol 248: 190-222. (1986).
[43]
Nagahama Y, Nabatame H, Okina T, Yamauchi H, Narita M, Fujimoto N, et al. Cerebral correlates of the progression rate of the cognitive decline in probable Alzheimer’s disease. Eur Neurol 50: 1-9. (2003).
[44]
Highstein SM, Baker R. Excitatory termination of abducens internuclear neurons on medial rectus motoneurons: relationship to syndrome of internuclear ophthalmoplegia. J Neurophysiol 41: 1647-61. (1978).
[45]
Hikosaka O, Igusa Y, Nakao S, Shimazu H. Direct inhibitory synaptic linkage of pontomedullary reticular burst neurons with abducens motoneurons in the cat. Exp Brain Res 33: 337-52. (1978).
[46]
Igusa Y, Sasaki S, Shimazu H. Excitatory premotor burst neurons in the cat pontine reticular formation related to the quick phase of vestibular nystagmus. Brain Res 182: 451-6. (1980).
[47]
Sasaki S, Shimazu H. Reticulovestibular organization participating in generation of horizontal fast eye movement. Ann N Y Acad Sci 374: 130-43. (1981).
[48]
Scudder CA, Kaneko CS, Fuchs AF. The brainstem burst generator for saccadic eye movements: a modern synthesis. Exp Brain Res 142: 439-62. (2002).
[49]
Yoshida K, McCrea R, Berthoz A, Vidal PP. Morphological and physiological characteristics of inhibitory burst neurons controlling horizontal rapid eye movements in the alert cat. J Neurophysiol 48: 761-84. (1982).
[50]
Yoshida K, Iwamoto Y, Chimoto S, Shimazu H. Saccade-related inhibitory input to pontine omnipause neurons: an intracellular study in alert cats. J Neurophysiol 82: 1198-208. (1999).
[51]
Yoshida K, Iwamoto Y, Chimoto S, Shimazu H. Disynaptic inhibition of omnipause neurons following electrical stimulation of the superior colliculus in alert cats. J Neurophysiol 85: 2639-42. (2001).


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 16
ISSUE: 4
Year: 2019
Page: [293 - 301]
Pages: 9
DOI: 10.2174/1567205016666190311102130
Price: $58

Article Metrics

PDF: 31
HTML: 2
EPUB: 1
PRC: 2