Although amnestic mild cognitive impairment (aMCI; often considered a prodromal phase of Alzheimer’s disease, AD) is most recognized by its implications for decline in memory function, research suggests that deficits in attention are present early in aMCI and may be predictive of progression to AD. The present study used functional magnetic resonance imaging to examine differences in the brain during the attention network test between 8 individuals with aMCI and 8 neurologically healthy, demographically matched controls. While there were no significant behavioral differences between groups for the alerting and orienting functions, patients with aMCI showed more activity in neural regions typically associated with the networks subserving these functions (e.g., temporoparietal junction and posterior parietal regions, respectively). More importantly, there were both behavioral (i.e., greater conflict effect) and corresponding neural deficits in executive control (e.g., less activation in the prefrontal and anterior cingulate cortices). Although based on a small number of patients, our findings suggest that deficits of attention, especially the executive control of attention, may significantly contribute to the behavioral and cognitive deficits of aMCI.
References
[1]
Geslani DM, Tierney MC, Herrmann N, Szalai JP (2005) Mild cognitive impairment: an operational definition and its conversion rate to Alzheimer’s disease. Dementia and Geriatric Cognitive Disorders 19: 383–389.
[2]
Gauthier S, Reisberg B, Zaudig M, Petersen RC, Ritchie K, et al. (2006) Mild cognitive impairment. The Lancet 367: 1262–1270.
[3]
Morris JC, Storandt M, Miller JP, McKeel DW, Price JL, et al. (2001) Mild cognitive impairment represents early-stage Alzheimer disease. Arch Neurol 58: 397–405.
[4]
Rafii MS, Aisen PS (2009) Recent developments in Alzheimer’s disease therapeutics. BMC medicine 7: 7.
[5]
Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM (2007) Forecasting the global burden of Alzheimer’s disease. Alzheimer’s and Dementia 3: 186–191.
[6]
Welsh KA, Butters N, Hughes JP, Mohs RC, Heyman A (1992) Detection and staging of dementia in Alzheimer’s disease. Use of the neuropsychological measures developed for the Consortium to Establish a Registry for Alzheimer’s Disease. Arch Neurol 49: 448–452.
[7]
Haxby JV, Grady CL, Koss E, Horwitz B, Heston L, et al. (1990) Longitudinal study of cerebral metabolic asymmetries and associated neuropsychological patterns in early dementia of the Alzheimer type. Arch Neurol 47: 753–760.
[8]
Perry RJ, Watson P, Hodges JR (2000) The nature and staging of attention dysfunction in early (minimal and mild) Alzheimer’s disease: relationship to episodic and semantic memory impairment. Neuropsychologia 38: 252–271.
[9]
Pignatti R, Rabuffetti M, Imbornone E, Mantovani F, Alberoni M, et al. (2005) Specific impairments of selective attention in mild Alzheimer’s disease. J Clin Exp Neuropsychol 27: 436–448.
[10]
Fernandez-Duque D, Black SE (2006) Attentional networks in normal aging and Alzheimer’s disease. Neuropsychology 20: 133–143.
[11]
Castel AD, Balota DA, Hutchison KA, Logan JM, Yap MJ (2007) Spatial attention and response control in healthy younger and older adults and individuals with Alzheimer’s disease: evidence for disproportionate selection impairments in the Simon task. Neuropsychology 21: 170–182.
[12]
Gorus E, De Raedt R, Lambert M, Lemper JC, Mets T (2006) Attentional processes discriminate between patients with mild Alzheimer’s disease and cognitively healthy elderly. Int Psychogeriatr 18: 539–549.
[13]
Marra C, Silveri MC, Gainotti G (2000) Predictors of cognitive decline in the early stage of probable Alzheimer’s disease. Dement Geriatr Cogn Disord 11: 212–218.
[14]
Fan J, Gu X, Guise KG, Liu X, Fossella J, et al. (2009) Testing the behavioral interaction and integration of attentional networks. Brain Cogn 70: 209–220.
[15]
Rizzo M, Anderson SW, Dawson J, Myers R, Ball K (2000) Visual attention impairments in Alzheimer’s disease. Neurology 54: 1954–1959.
[16]
Parasuraman R, Greenwood PM, Sunderland T (2002) The apolipoprotein E gene, attention, and brain function. Neuropsychology 16: 254–274.
[17]
Perry RJ, Hodges JR (1999) Attention and executive deficits in Alzheimer’s disease. A critical review. Brain 122 (Pt 3): 383–404.
[18]
Parasuraman R, Haxby JV (1993) Attention and brain function in Alzheimer’s disease: A review. Neuropsychology 7: 242–272.
[19]
Sano M (2006) Neuropsychological testing in the diagnosis of dementia. J Geriatr Psychiatry Neurol 19: 155–159.
[20]
Fan J, McCandliss BD, Sommer T, Raz A, Posner MI (2002) Testing the efficiency and independence of attentional networks. J Cogn Neurosci 14: 340–347.
[21]
Fan J, Raz A, Posner MI (2003) Attentional Mechanisms. In: Aminoff MJ, Daroff RB, editors. Encyclopedia of Neurological Sciences. San Diego: Academic Press. pp. 292–299.
[22]
Posner MI, Petersen SE (1990) The attention system of the human brain. Annu Rev Neurosci 13: 25–42.
[23]
Fan J, McCandliss BD, Fossella J, Flombaum JI, Posner MI (2005) The activation of attentional networks. Neuroimage 26: 471–479.
[24]
Corbetta M, Shulman GL (2002) Control of goal-directed and stimulus-driven attention in the brain. Nat Rev Neurosci 3: 201–215.
[25]
Corbetta M, Patel G, Shulman GL (2008) The reorienting system of the human brain: from environment to theory of mind. Neuron 58: 306–324.
[26]
Nebes RD, Brady CB (1989) Focused and divided attention in Alzheimer’s disease. Cortex 25: 305–315.
[27]
Parasuraman R, Greenwood PM, Haxby JV, Grady CL (1992) Visuospatial attention in dementia of the Alzheimer type. Brain 115: 711–733.
[28]
Oken BS, Kishiyama SS, Kaye JA, Howieson DB (1994) Attention deficit in Alzheimer’s disease is not simulated by an anticholinergic/antihistaminergic drug and is distinct from deficits in healthy aging. Neurology 44: 657–662.
[29]
Faust ME, Balota DA (1997) Inhibition of return and visuospatial attention in healthy older adults and individuals with dementia of the Alzheimer type. Neuropsychology 11: 13–29.
[30]
Ballard C, O’Brien J, Gray A, Cormack F, Ayre G, et al. (2001) Attention and fluctuating attention in patients with dementia with Lewy bodies and Alzheimer disease. Arch Neurol 58: 977–982.
[31]
Tales A, Muir JL, Bayer A, Jones R, Snowden RJ (2002) Phasic visual alertness in Alzheimer’s disease and ageing. Neuroreport 13: 2557–2560.
[32]
Festa-Martino E, Ott BR, Heindel WC (2004) Interactions between phasic alerting and spatial orienting: effects of normal aging and Alzheimer’s disease. Neuropsychology 18: 258–268.
[33]
Berardi AM, Parasuraman R, Haxby JV (2005) Sustained attention in mild Alzheimer’s disease. Dev Neuropsychol 28: 507–537.
[34]
Tales A, Snowden RJ, Brown M, Wilcock G (2006) Alerting and orienting in Alzheimer’s disease. Neuropsychology 20: 752–756.
[35]
Festa EK, Ott BR, Heindel WC (2006) Considering phasic alerting in Alzheimer’s disease: comment on Tales et al. (2006). Neuropsychology 20: 757–760; discussion 761–752.
[36]
Baddeley AD, Baddeley HA, Bucks RS, Wilcock GK (2001) Attentional control in Alzheimer’s disease. Brain 124: 1492–1508.
[37]
Sebastian MV, Menor J, Elosua MR (2006) Attentional dysfunction of the central executive in AD: evidence from dual task and perseveration errors. Cortex 42: 1015–1020.
[38]
Rapp MA, Reischies FM (2005) Attention and executive control predict Alzheimer disease in late life: results from the Berlin Aging Study (BASE). Am J Geriatr Psychiatry 13: 134–141.
[39]
Backman L, Jones S, Berger AK, Laukka EJ, Small BJ (2005) Cognitive impairment in preclinical Alzheimer’s disease: a meta-analysis. Neuropsychology 19: 520–531.
[40]
Foster JK (2001) Selective attention in Alzheimer’s disease. Front Biosci 6: D135–153.
[41]
Foster JK, Behrmann M, Stuss DT (1999) Visual attention deficits in Alzheimer’s disease: simple versus conjoined feature search. Neuropsychology 13: 223–245.
[42]
Levinoff EJ, Li KZ, Murtha S, Chertkow H (2004) Selective attention impairments in Alzheimer’s disease: evidence for dissociable components. Neuropsychology 18: 580–588.
[43]
Grady CL, Haxby JV, Horwitz B, Sundaram M, Berg G, et al. (1988) Longitudinal study of the early neuropsychological and cerebral metabolic changes in dementia of the Alzheimer type. J Clin Exp Neuropsychol 10: 576–596.
[44]
Lafleche G, Albert M (1995) Executive function deficits in mild Alzheimer’s disease. Neuropsychology 9: 313–320.
[45]
Binetti G, Magni E, Padovani A, Cappa SF, Bianchetti A, et al. (1996) Executive dysfunction in early Alzheimer’s disease. J Neurol Neurosurg Psychiatry 60: 91–93.
[46]
Collette F, Van der Linden M, Salmon E (1999) Executive dysfunction in Alzheimer’s disease. Cortex 35: 57–72.
[47]
Royall DR, Lauterbach EC, Cummings JL, Reeve A, Rummans TA, et al. (2002) Executive control function: a review of its promise and challenges for clinical research. A report from the Committee on Research of the American Neuropsychiatric Association. J Neuropsychiatry Clin Neurosci 14: 377–405.
[48]
Baudic S, Barba GD, Thibaudet MC, Smagghe A, Remy P, et al. (2006) Executive function deficits in early Alzheimer’s disease and their relations with episodic memory. Arch Clin Neuropsychol 21: 15–21.
[49]
Woo BK, Harwood DG, Melrose RJ, Mandelkern MA, Campa OM, et al. (2010) Executive deficits and regional brain metabolism in Alzheimer’s disease. International Journal of Geriatric Psychiatry 25: 1150–1158.
[50]
Bush G, Luu P, Posner MI (2000) Cognitive and emotional influences in anterior cingulate cortex. Trends in Cognitive Science 4: 215–222.
[51]
Shackman AJ, Salomons TV, Slagter HA, Fox AS, Winter JJ, et al. (2011) The integration of negative affect, pain and cognitive control in the cingulate cortex. Nat Rev Neurosci 12: 154–167.
[52]
Johnson KA, Jones K, Holman BL, Becker JA, Spiers PA, et al. (1998) Preclinical prediction of Alzheimer’s disease using SPECT. Neurology 50: 1563–1571.
[53]
El Fakhri G, Kijewski MF, Johnson KA, Syrkin G, Killiany RJ, et al. (2003) MRI-guided SPECT perfusion measures and volumetric MRI in prodromal Alzheimer disease. Arch Neurol 60: 1066–1072.
[54]
Mosconi L, Perani D, Sorbi S, Herholz K, Nacmias B, et al. (2004) MCI conversion to dementia and the APOE genotype: a prediction study with FDG-PET. Neurology 63: 2332–2340.
[55]
Salmon E, Lekeu F, Garraux G, Guillaume B, Magis D, et al.. (2007) Metabolic correlates of clinical heterogeneity in questionable Alzheimer’s disease. Neurobiol Aging.
[56]
Johannsen P, Jakobsen J, Bruhn P, Gjedde A (1999) Cortical responses to sustained and divided attention in Alzheimer’s disease. Neuroimage 10: 269–281.
[57]
Hao J, Li K, Li K, Zhang D, Wang W, et al. (2005) Visual attention deficits in Alzheimer’s disease: an fMRI study. Neurosci Lett 385: 18–23.
[58]
Dannhauser TM, Walker Z, Stevens T, Lee L, Seal M, et al. (2005) The functional anatomy of divided attention in amnestic mild cognitive impairment. Brain 128: 1418–1427.
[59]
Bozzali M, Giulietti G, Basile B, Serra L, Spanò B, et al. (2012) Damage to the cingulum contributes to alzheimer’s disease pathophysiology by deafferentation mechanism. Human Brain Mapping 33: 1295–1308.
[60]
Fan J, Posner M (2004) Human attentional networks. Psychiatr Prax 31 Suppl 2210–214.
[61]
Wang K, Fan J, Dong Y, Wang CQ, Lee TM, et al. (2005) Selective impairment of attentional networks of orienting and executive control in schizophrenia. Schizophr Res 78: 235–241.
[62]
Petersen RC, Thomas RG, Grundman M, Bennett D, Doody R, et al. (2005) Vitamin E and donepezil for the treatment of mild cognitive impairment. New England Journal of Medicine 352: 2379–2388.
[63]
Sano M, Raman R, Emond J, Thomas RG, Petersen R, et al. (2011) Adding delayed recall to the Alzheimer Disease Assessment Scale is useful in studies of mild cognitive impairment but not Alzheimer disease. Alzheimer Disease and Associated Disorders 25: 122–127.
[64]
Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research 12: 189–198.
[65]
Wechsler D (1997) Wechsler Memory Scale - 3rd Edition (WMS-III). Sant Antonio, TX: Harcourt Assessment.
[66]
Morris JC (1993) The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology 43: 2412–2414.
[67]
Friston KJ, Holmes AP, Poline JB, Grasby PJ, Williams SC, et al. (1995) Analysis of fMRI time-series revisited. Neuroimage 2: 45–53.
[68]
Friston KJ, Fletcher P, Josephs O, Holmes A, Rugg MD, et al. (1998) Event-Related fMRI: Characterizing Differential Responses. Neuroimage 7: 30–40.
[69]
Slotnick SD, Moo LR, Segal JB, Hart Jr J (2003) Distinct prefrontal cortex activity associated with item memory and source memory for visual shapes. Cognitive Brain Research 17: 75–82.
[70]
Miller J (1988) A warning about median reaction time. Journal of Experimental Psychology: Human Perception and Performance 14: 539–543.
Dosenbach NU, Fair DA, Cohen AL, Schlaggar BL, Petersen SE (2008) A dual-networks architecture of top-down control. Trends Cogn Sci 12: 99–105.
[73]
Jeyakumar SLE, Warriner EM, Raval VV, Ahmad SA (2004) Balancing the Need for Reliability and Time Efficiency: Short Forms of the Wechsler Adult Intelligence Scale-III. Educational and Psychological Measurement 64: 71–87.
[74]
Fan J, Guise KG, Liu X, Wang HB (2008) Searching for the Majority: Algorithms of Voluntary Control. PLoS One 3: e3522.
[75]
Stern Y, Moeller JR, Anderson KE, Luber B, Zubin NR, et al. (2000) Different brain networks mediate task performance in normal aging and AD: defining compensation. Neurology 55: 1291–1297.
[76]
Rombouts SA, Barkhof F, Goekoop R, Stam CJ, Scheltens P (2005) Altered resting state networks in mild cognitive impairment and mild Alzheimer’s disease: an fMRI study. Hum Brain Mapp 26: 231–239.
[77]
Fouquet M, Desgranges B, Landeau B, Duchesnay E, Mezenge F, et al. (2009) Longitudinal brain metabolic changes from amnestic mild cognitive impairment to Alzheimer’s disease. Brain : a journal of neurology 132: 2058–2067.
[78]
Han Y, Wang J, Zhao Z, Min B, Lu J, et al. (2011) Frequency-dependent changes in the amplitude of low-frequency fluctuations in amnestic mild cognitive impairment: a resting-state fMRI study. Neuroimage 55: 287–295.
[79]
Grady CL, Furey ML, Pietrini P, Horwitz B, Rapoport SI (2001) Altered brain functional connectivity and impaired short-term memory in Alzheimer’s disease. Brain 124: 739–756.
[80]
Greicius MD, Srivastava G, Reiss AL, Menon V (2004) Default-mode network activity distinguishes Alzheimer’s disease from healthy aging: evidence from functional MRI. Proc Natl Acad Sci U S A 101: 4637–4642.
[81]
Bokde AL, Lopez-Bayo P, Meindl T, Pechler S, Born C, et al. (2006) Functional connectivity of the fusiform gyrus during a face-matching task in subjects with mild cognitive impairment. Brain 129: 1113–1124.
[82]
Celone KA, Calhoun VD, Dickerson BC, Atri A, Chua EF, et al. (2006) Alterations in memory networks in mild cognitive impairment and Alzheimer’s disease: an independent component analysis. J Neurosci 26: 10222–10231.
[83]
Wang L, Zang Y, He Y, Liang M, Zhang X, et al. (2006) Changes in hippocampal connectivity in the early stages of Alzheimer’s disease: evidence from resting state fMRI. Neuroimage 31: 496–504.
[84]
Zhou J, Greicius MD, Gennatas ED, Growdon ME, Jang JY, et al. (2010) Divergent network connectivity changes in behavioural variant frontotemporal dementia and Alzheimer’s disease. Brain 133: 1352–1367.
[85]
Buckner RL, Snyder AZ, Shannon BJ, LaRossa G, Sachs R, et al. (2005) Molecular, structural, and functional characterization of Alzheimer’s Disease: Evidence for a relationship between default activity, amyloid, and memory. The Journal of Neuroscience 25: 7709–7717.
[86]
Castel AD, Balota DA, McCabe DP (2009) Memory efficiency and the strategic control of attention at encoding: impairments of value-directed remembering in Alzheimer’s disease. Neuropsychology 23: 297–306.
[87]
Cowan N (1988) Evolving conceptions of memory storage, selective attention, and their mutual constraints within the human information-processing system. Psychological Bulletin 104: 163–191.
[88]
Simon SS, Yokomizo JE, Bottino CM (2012) Cognitive intervention in amnestic Mild Cognitive Impairment: A systematic review. Neuroscience and Biobehavioral Reviews 36: 1163–1178.
