Neural and Retinal Characteristics in Relation to Working Memory in Older Adults with Mild Cognitive Impairment

Author(s): Mabel N.K. Wong, Daniel W.L. Lai, Henry H.-L. Chan, Bess Y.-H. Lam*

Journal Name: Current Alzheimer Research

Volume 18 , Issue 3 , 2021

  Journal Home
Translate in Chinese
Become EABM
Become Reviewer
Call for Editor


Objective: This study investigated the relationship between neural activities and retinal structures associated with working memory (WM) in older adults with mild cognitive impairment (MCI).

Methods: Eleven older adults with MCI and 29 healthy controls (60 to 73 years old) were tested. All participants underwent an event-related potential (ERP) recording while performing the two-back memory task. The Optical coherence tomography angiography (OCT-A) was administered to examine the perfusion and vessel density in the retina.

Results: Results showed that WM performance in the MCI group was negatively associated with ERP latencies in central parietal regions (CP6 and CP8) (ps< 0.05). The left nasal vessel and perfusion densities were negatively correlated with the latencies in these two central parietal regions and positively related to WM performance only in the MCI group (ps< 0.05).

Conclusion: The findings on WM, central parietal brain activity, and left nasal vessel and perfusion densities in the retina help us gain a better understanding of the neural and retinal underpinnings of WM in relation to MCI.

Keywords: Mild cognitive impairment, retinal perfusion density, retinal vessel density, working memory, event-related potential, cognition.

Orru G, Sampietro S, Catanzaro S, et al. Serial position effect in a free recall task: Differences between probable dementia of Alzheimer type (PDAT), vascular (VaD) and mixed etiology dementia (MED). Arch Gerontol Geriatr 2009; 49(1): 207-10.
[ ] [PMID: 19836634]
Belleville S, Gilbert B, Fontaine F, Gagnon L, Ménard E, Gauthier S. Improvement of episodic memory in persons with mild cognitive impairment and healthy older adults: Evidence from a cognitive intervention program. Dement Geriatr Cogn Disord 2006; 22(5-6): 486-99.
[ ] [PMID: 17050952]
Desikan RS, Cabral HJ, Hess CP, et al. Automated MRI measures identify individuals with mild cognitive impairment and Alzheimer’s disease. Brain 2009; 132(Pt 8): 2048-57.
[ ] [PMID: 19460794]
Aurtenetxe S, García-Pacios J, Del Río D, et al. Maestú, F. Interference impacts working memory in mild cognitive impairment. Front Neurosci 2016; 10: 443.
[ ] [PMID: 27790082]
Gajewski PD, Falkenstein M. Age-related effects on ERP and oscillatory EEG dynamics in a 2-back task. J Psychophysiol 2014; 28: 162-77.
Li SC, Lindenberger U, Sikström S. Aging cognition: From neuromodulation to representation. Trends Cogn Sci 2001; 5(11): 479-86.
[ ] [PMID: 11684480]
Baddeley A. Working memory. Science 1992; 255(5044): 556-9.
[ ] [PMID: 1736359]
Missonnier P, Gold G, Leonards U, et al. Aging and working memory: Early deficits in EEG activation of posterior cortical areas. J Neural Transm (Vienna) 2004; 111(9): 1141-54.
[ ] [PMID: 15338330]
Nissim NR, O’Shea AM, Bryant V, Porges EC, Cohen R, Woods AJ. Frontal structural neural correlates of working memory performance in older adults. Front Aging Neurosci 2017; 8: 328.
[ ] [PMID: 28101053]
Hedden T, Gabrieli JD. Insights into the ageing mind: A view from cognitive neuroscience. Nat Rev Neurosci 2004; 5(2): 87-96.
[ ] [PMID: 14735112]
Schapkin SA, Gajewski PD, Freude G. Age differences in memory-based task switching with and without cues. J Psychophysiol 2014; 28: 187-201.
Kirchner WK. Age differences in short-term retention of rapidly changing information. J Exp Psychol 1958; 55(4): 352-8.
[ ] [PMID: 13539317]
Delorme A, Rousselet GA, Macé MJM, Fabre-Thorpe M. Interaction of top-down and bottom-up processing in the fast visual analysis of natural scenes. Brain Res Cogn Brain Res 2004; 19(2): 103-13.
[ ] [PMID: 15019707]
Fraga FJ, Ferreira LA, Falk TH, Johns E, Phillips ND. 2017 International Conference on Acoustics, Speech and Signal Processing (ICASSP). March 5-9, 2017; 2017; pp. 964-8.
Fraga FJ, Mamani GQ, Johns E, Tavares G, Falk TH, Phillips NA. Early diagnosis of mild cognitive impairment and Alzheimer’s with event-related potentials and event-related desynchronization in N-back working memory tasks. Comput Methods Programs Biomed 2018; 164: 1-13.
[ ] [PMID: 30195417]
Hou F, Liu C, Yu Z, et al. Yang, A. Age-related alterations in electroencephalography connectivity and network topology during n-back working memory task. Front Hum Neurosci 2018; 12: 484.
[ ] [PMID: 30574079]
Polich J. Meta-analysis of P300 normative aging studies. Psychophysiology 1996; 33(4): 334-53.
[ ] [PMID: 8753933]
Saliasi E, Geerligs L, Lorist MM, Maurits NM. The relationship between P3 amplitude and working memory performance differs in young and older adults. PLoS One 2013; 8(5)e63701
[ ] [PMID: 23667658]
Lubitz AF, Niedeggen M, Feser M. Aging and working memory performance: Electrophysiological correlates of high and low performing elderly. Neuropsychologia 2017; 106: 42-51.
[ ] [PMID: 28889995]
Missonnier P, Deiber MP, Gold G, et al. Working memory load-related electroencephalographic parameters can differentiate progressive from stable mild cognitive impairment. Neuroscience 2007; 150(2): 346-56.
[ ] [PMID: 17996378]
Mamani GQ, Fraga FJ, Tavares G, Johns E, Phillips ND. In 2017 Healthcare Innovations and Point of Care Technologies (HI-POCT Proceedings of the 2017 HI-POCT. Bethesda, Maryland, USA. 2017; pp. 237-40..
Deiber MP, Missonnier P, Bertrand O, et al. Distinction between perceptual and attentional processing in working memory tasks: A study of phase-locked and induced oscillatory brain dynamics. J Cogn Neurosci 2007; 19(1): 158-72.
[ ] [PMID: 17214572]
Cabrera DeBuc D, Gaca-Wysocka M, Grzybowski A, Kanclerz P. Identification of retinal biomarkers in Alzheimer’s disease using optical coherence tomography: Recent insights, challenges, and opportunities. J Clin Med 2019; 8(7): 996.
[ ] [PMID: 31323964]
Ikram MK, Cheung CY, Wong TY, Chen CP. Retinal pathology as biomarker for cognitive impairment and Alzheimer’s disease. J Neurol Neurosurg Psychiatry 2012; 83(9): 917-22.
[ ] [PMID: 22733082]
Lim JK, Li QX, He Z, et al. Nguyen, C.T. The eye as a biomarker for Alzheimer’s disease. Front Neurosci 2016; 10: 536.
[ ] [PMID: 27909396]
Maalikjy Akkawi N, Borroni B, Agosti C, et al. Volume cerebral blood flow reduction in pre-clinical stage of Alzheimer disease: Evidence from an ultrasonographic study. J Neurol 2005; 252(5): 559-63.
[ ] [PMID: 15726249]
Berisha F, Feke GT, Trempe CL, McMeel JW, Schepens CL. Retinal abnormalities in early Alzheimer’s disease. Invest Ophthalmol Vis Sci 2007; 48(5): 2285-9.
[ ] [PMID: 17460292]
Feke GT, Hyman BT, Stern RA, Pasquale LR. Retinal blood flow in mild cognitive impairment and Alzheimer’s disease. Alzheimers Dement (Amst) 2015; 1(2): 144-51.
[ ] [PMID: 27239502]
Snyder PJ, Johnson LN, Lim YY, et al. Nonvascular retinal imaging markers of preclinical Alzheimer’s disease. Alzheimers Dement (Amst) 2016; 4: 169-78.
[ ] [PMID: 27830174]
Yeo JM, Waddell B, Khan Z, Pal S. A systematic review and meta-analysis of (18)F-labeled amyloid imaging in Alzheimer’s disease. Alzheimers Dement (Amst) 2015; 1(1): 5-13.
[ ] [PMID: 27239488]
Danesh-Meyer HV, Birch H, Ku JY, Carroll S, Gamble G. Reduction of optic nerve fibers in patients with Alzheimer disease identified by laser imaging. Neurology 2006; 67(10): 1852-4.
[ ] [PMID: 17130422]
Cheng DL, Thompson L, Snyder PJ. A potential association between retinal changes, subjective memory impairment, and anxiety in older adults at risk for Alzheimer’s disease: A 27-Month Pilot Study. Front Aging Neurosci 2019; 11: 288.
[ ] [PMID: 31736739]
Guo L, Duggan J, Cordeiro MF. Alzheimer’s disease and retinal neurodegeneration. Curr Alzheimer Res 2010; 7(1): 3-14.
[ ] [PMID: 20205667]
Zhang L, Xu Y, Zhu Y. Relationships between optic nerve damage and the severity of cognitive impairment in patients with mild cognitive impairment and Alzheimer’s disease. Biomed Res (Aligarh) 2017; •••: 28.
Pehlivanoglu D, Jain S, Ariel R, Verhaeghen P. The ties to unbind: Age-related differences in feature (un)binding in working memory for emotional faces. Front Psychol 2014; 5: 253.
[ ] [PMID: 24795660]
Braak H, Thal DR, Ghebremedhin E, Del Tredici K. Stages of the pathologic process in Alzheimer disease: Age categories from 1 to 100 years. J Neuropathol Exp Neurol 2011; 70(11): 960-9.
[ ] [PMID: 22002422]
Benarroch EE. The locus ceruleus norepinephrine system: Functional organization and potential clinical significance. Neurology 2009; 73(20): 1699-704.
[ ] [PMID: 19917994]
Granholm EL, Panizzon MS, Elman JA, et al. Kremen, W.S. Pupillary responses as a biomarker of early risk for Alzheimer’s disease. J Alzheimers Dis 2017; 56(4): 1419-28.
[ ] [PMID: 28157098]
van der Meer E, Beyer R, Horn J, et al. Resource allocation and fluid intelligence: Insights from pupillometry. Psychophysiology 2010; 47(1): 158-69.
[ ] [PMID: 19761522]
Frost S, Kanagasingam Y, Sohrabi H, et al. Pupil response biomarkers for early detection and monitoring of Alzheimer’s disease. Curr Alzheimer Res 2013; 10(9): 931-9.
[ ] [PMID: 24117119]
Granholm EL, Panizzon MS, Elman JA, et al. Pupillary responses as a biomarker of early risk for Alzheimer’s disease. J Alzheimers Dis 2017; 56(4): 1419-28.
[ ] [PMID: 28157098]
Brown L, Sherbenou RJ, Johnsen SK. Test of Nonverbal Intelligence. Third Edition Examiner’s Manual. Austin, TX: Pro-Ed. 1997.
Lu J, Li D, Li F, et al. Montreal cognitive assessment in detecting cognitive impairment in Chinese elderly individuals: A population-based study. J Geriatr Psychiatry Neurol 2011; 24(4): 184-90.
[ ] [PMID: 22228824]
Petersen RC, Morris JC. Mild cognitive impairment as a clinical entity and treatment target. Arch Neurol 2005; 62(7): 1160-3.
[ ] [PMID: 16009779]
Lee LP, Har AWY, Ngai CH, Lai DWL, Lam BYH, Chan CCH. Audiovisual integrative training for augmenting cognitive- motor functions in older adults with mild cognitive impairment. BMC Geriatr 2020; 20(1): 64.
[ ] [PMID: 32066384]
Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E. Mild cognitive impairment: Clinical characterization and outcome. Arch Neurol 1999; 56(3): 303-8.
[ ] [PMID: 10190820]
Yeung PY, Wong LL, Chan CC, Leung JL, Yung CY. A validation study of the Hong Kong version of Montreal Cognitive Assessment (HK-MoCA) in Chinese older adults in Hong Kong. Hong Kong Med J 2014; 20(6): 504-10.
[ ] [PMID: 25125421]
Gevins A, Smith ME, Le J, et al. High resolution evoked potential imaging of the cortical dynamics of human working memory. Electroencephalogr Clin Neurophysiol 1996; 98(4): 327-48.
[ ] [PMID: 8641154]
Deiber MP, Ibañez V, Missonnier P, et al. Abnormal-induced theta activity supports early directed-attention network deficits in progressive MCI. Neurobiol Aging 2009; 30(9): 1444-52.
[ ] [PMID: 18179844]
de Carlo TE, Romano A, Waheed NK, Duker JS. A review of optical coherence tomography angiography (OCTA). Int J Retina Vitreous 2015; 1: 5.
[ ] [PMID: 27847598]
Suwan Y, Geyman LS, Fard MA, et al. Peripapillary perfused capillary density in exfoliation syndrome and exfoliation glaucoma versus POAG and healthy controls: An OCTA study. Asia Pac J Ophthalmol (Phila) 2018; 7(2): 84-9.
[PMID: 29165935]
Bulut M, Kurtuluş F, Gözkaya O, et al. Evaluation of optical coherence tomography angiographic findings in Alzheimer’s type dementia. Br J Ophthalmol 2018; 102(2): 233-7.
[ ] [PMID: 28600299]
Kirova AM, Bays RB, Lagalwar S. Working memory and executive function decline across normal aging, mild cognitive impairment, and Alzheimer’s disease Biomed Res Int 2015; 2015.
Braver TS, Cohen JD, Nystrom LE, Jonides J, Smith EE, Noll DC. A parametric study of prefrontal cortex involvement in human working memory. Neuroimage 1997; 5(1): 49-62.
[ ] [PMID: 9038284]
Berryhill ME. Insights from neuropsychology: Pinpointing the role of the posterior parietal cortex in episodic and working memory. Front Integr Nuerosci 2012; 6: 31.
[ ] [PMID: 22701406]
Fiez JA, Raife EA, Balota DA, Schwarz JP, Raichle ME, Petersen SE. A positron emission tomography study of the short-term maintenance of verbal information. J Neurosci 1996; 16(2): 808-22.
[ ] [PMID: 8551361]
Moretti VD. Atrophy and lower regional perfusion of temporo-parietal brain areas are correlated with impairment in memory performances and increase of EEG upper alpha power in prodromal Alzheimer’s disease. Am J Neurodegener Dis 2015; 4(1): 13-27.
[PMID: 26389016]
Jiang ZY. Study on EEG power and coherence in patients with mild cognitive impairment during working memory task. J Zhejiang Univ Sci B 2005; 6(12): 1213-9.
[ ] [PMID: 16358382]
Querques G, Borrelli E, Sacconi R, De Vitis L, Leocani L, Santangelo R, et al. Bandello, F. 2019. Functional and morphological changes of the retinal vessels in Alzheimer’s disease and mild cognitive impairment. Sci Rep 2019; 9: 1-10.
Pham TQ, Kifley A, Mitchell P, Wang JJ. Relation of age-related macular degeneration and cognitive impairment in an older population. Gerontology 2006; 52(6): 353-8.
[ ] [PMID: 16902306]
Appaji A, Nagendra B, Chako DM, et al. Relation between retinal vascular abnormalities and working memory impairment in patients with schizophrenia and bipolar disorder. Asian J Psychiatr 2020; 49101942
[ ] [PMID: 32070935]
Patton N, Pattie A, MacGillivray T, et al. The association between retinal vascular network geometry and cognitive ability in an elderly population. Invest Ophthalmol Vis Sci 2007; 48(5): 1995-2000.
[ ] [PMID: 17460252]
Williams MA, McGowan AJ, Cardwell CR, et al. Retinal microvascular network attenuation in Alzheimer’s disease. Alzheimers Dement (Amst) 2015; 1(2): 229-35.
[ ] [PMID: 26634224]
Patton N, Aslam T, Macgillivray T, Pattie A, Deary IJ, Dhillon B. Retinal vascular image analysis as a potential screening tool for cerebrovascular disease: A rationale based on homology between cerebral and retinal microvasculatures. J Anat 2005; 206(4): 319-48.
[ ] [PMID: 15817102]
Jorge L, Canário N, Quental H, Bernardes R, Castelo-Branco M. Is the retina a mirror of the aging brain? Aging of neural retina layers and primary visual cortex across the lifespan. Front Aging Neurosci 2020; 11: 360.
[ ] [PMID: 31998115]
den Haan J, Janssen SF, van de Kreeke JA, Scheltens P, Verbraak FD, Bouwman FH. Retinal thickness correlates with parietal cortical atrophy in early-onset Alzheimer’s disease and controls. Alzheimers Dement (Amst) 2017; 10: 49-55.
[ ] [PMID: 29201990]
Hill AC, Laird AR, Robinson JL. Gender differences in working memory networks: A BrainMap meta-analysis. Biol Psychol 2014; 102: 18-29.
[ ] [PMID: 25042764]

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2021
Published on: 23 September, 2021
Page: [185 - 195]
Pages: 11
DOI: 10.2174/1567205018666210608114044
Price: $65

Article Metrics

PDF: 97