A Conceptual Framework for Research on Cognitive Impairment with no Dementia in Memory Clinic

Author(s): Lin Huang, Keliang Chen, Zhao Liu, Qihao Guo*

Journal Name: Current Alzheimer Research

Volume 17 , Issue 6 , 2020

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Background: Identifying and classifying individuals with Cognitive Impairment-No Dementia (CIND) has further challenged diagnostic methods, since varying the cutoffs for objective impairment as well as the neuropsychological tests considered can significantly affect diagnosis. Therefore, we investigated the applicability of an actuarial neuropsychological approach for clinical subdivision of CIND and quantified the variability in diagnostic outcomes that results from diverse neuropsychologically derived definition of objective cognitive impairment.

Methods: 1459 non-demented, clinic-based individuals were recruited from a monocentric memory clinic from 1/1/2016/ to 1/1/2018 and classified as Cognitively Normal (NC), Slight Cognitive Symptom (SCS), SSubtle Cognitive Decline (SCD) or Mild Cognitive Impairment (MCI) via different diagnostic strategies, which varied the composition of objective cognitive assessments involved in the diagnostic process.

Results: We compared two methods of criteria proposed by Jak/Bondi and Petersen/Winblad to classify individuals with CIND. A substantial range of differences in the percentages recognized as NC, SCS, SCD, and MCI was presented, depending on the classification criteria adopted. Our data revealed that the application of a set of six neuropsychological scores dividing CIND into 4 subgroups (NC, SCS, SCD, and MCI) was able to classify all non-demented individuals without overlap or omission.

Conclusion: Our study provided clinical support for an operational framework of the CIND classification system and underlined the value of applying comprehensive neuropsychological assessments for definition. The concept of SCS, considered appropriate for a preclinical stage, was proposed as the symptomatic definition for early intervention.

Keywords: Slight cognitive symptom (SCS), subtle cognitive decline (SCD), mild cognitive impairment (MCI), Alzheimer's disease (AD), cognitive impairment with no dementia (CIND), neurodegeneration.

Dubois B, Feldman HH, Jacova C, et al. Advancing research diagnostic criteria for Alzheimer’s disease: The IWG-2 criteria. Lancet Neurol 2014; 13(6): 614-29.
[http://dx.doi.org/10.1016/S1474-4422(14)70090-0] [PMID: 24849862]
Reiman EM. Alzheimer’s disease and other dementias: Advances in 2013. Lancet Neurol 2014; 13(1): 3-5.
[http://dx.doi.org/10.1016/S1474-4422(13)70257-6] [PMID: 24331781]
Petersen RC. Alzheimer’s disease: Progress in prediction. Lancet Neurol 2010; 9(1): 4-5.
[http://dx.doi.org/10.1016/S1474-4422(09)70330-8] [PMID: 20083022]
Jack CR Jr, Bennett DA, Blennow K, et al. Contributors. NIA-AA research framework: Toward a biological definition of Alzheimer’s disease. Alzheimers Dement 2018; 14(4): 535-62.
[http://dx.doi.org/10.1016/j.jalz.2018.02.018] [PMID: 29653606]
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.
[http://dx.doi.org/10.1001/archneur.56.3.303] [PMID: 10190820]
Winblad B, Palmer K, Kivipelto M, et al. Mild cognitive impairment--beyond controversies, towards a consensus: Report of the International Working Group on Mild Cognitive Impairment. J Intern Med 2004; 256(3): 240-6.
[http://dx.doi.org/10.1111/j.1365-2796.2004.01380.x] [PMID: 15324367]
Petersen RC, Morris JC. Mild cognitive impairment as a clinical entity and treatment target. Arch Neurol 2005; 62(7): 1160-3.
[http://dx.doi.org/10.1001/archneur.62.7.1160] [PMID: 16009779]
Villemagne VL, Chételat G. Neuroimaging biomarkers in Alzheimer’s disease and other dementias. Ageing Res Rev 2016; 30: 4-16.
[http://dx.doi.org/10.1016/j.arr.2016.01.004] [PMID: 26827785]
Langa KM, Levine DA. The diagnosis and management of mild cognitive impairment: a clinical review. JAMA 2014; 312(23): 2551-61.
[http://dx.doi.org/10.1001/jama.2014.13806] [PMID: 25514304]
Khan W, Westman E, Jones N, et al. AddNeuroMed consortium and for the Alzheimer’s Disease Neuroimaging Initiative. Automated hippocampal subfield measures as predictors of conversion from mild cognitive impairment to Alzheimer’s disease in two independent cohorts. Brain Topogr 2015; 28(5): 746-59.
[http://dx.doi.org/10.1007/s10548-014-0415-1] [PMID: 25370484]
De Marco M, Meneghello F, Pilosio C, Rigon J, Venneri A. Up-regulation of DMN connectivity in mild cognitive impairment via network-based cognitive training. Curr Alzheimer Res 2018; 15(6): 578-89.
[http://dx.doi.org/10.2174/1567205015666171212103323] [PMID: 29231140]
Petersen RC, Caracciolo B, Brayne C, Gauthier S, Jelic V, Fratiglioni L. Mild cognitive impairment: a concept in evolution. J Intern Med 2014; 275(3): 214-28.
[http://dx.doi.org/10.1111/joim.12190] [PMID: 24605806]
Thomas KR, Edmonds EC, Eppig J, Salmon DP, Bondi MW. Alzheimer’s Disease Neuroimaging Initiative. Using neuropsychological process scores to identify subtle cognitive decline and predict progression to mild cognitive impairment. J Alzheimers Dis 2018; 64(1): 195-204.
[http://dx.doi.org/10.3233/JAD-180229] [PMID: 29865077]
Edmonds EC, Delano-Wood L, Galasko DR, Salmon DP, Bondi MW. Alzheimer’s disease neuroimaging initiative. subtle cognitive decline and biomarker staging in preclinical Alzheimer’s disease. J Alzheimers Dis 2015; 47(1): 231-42.
[http://dx.doi.org/10.3233/JAD-150128] [PMID: 26402771]
Thomas KR, Bangen KJ, Weigand AJ, et al. Objective subtle cognitive difficulties predict future amyloid accumulation and neurodegeneration. Neurology 2020; 94(4): e397-406.
Thomas KR, Eppig J, Edmonds EC, et al. Alzheimer’s Disease Neuroimaging Initiative. Word-list intrusion errors predict progression to mild cognitive impairment. Neuropsychology 2018; 32(2): 235-45.
[http://dx.doi.org/10.1037/neu0000413] [PMID: 29528684]
Thomas KR, Bangen KJ, Weigand AJ, et al. Alzheimer’s disease neuroimaging initiative. type 2 diabetes interacts with alzheimer disease risk factors to predict functional decline. Alzheimer Dis Assoc Disord 2020; 34(1): 10-7.
[http://dx.doi.org/10.1097/WAD.0000000000000332] [PMID: 31305320]
Bondi MW, Edmonds EC, Jak AJ, et al. Neuropsychological criteria for mild cognitive impairment improves diagnostic precision, biomarker associations, and progression rates. J Alzheimers Dis 2014; 42(1): 275-89.
[http://dx.doi.org/10.3233/JAD-140276] [PMID: 24844687]
Zhao Q, Guo Q, Li F, Zhou Y, Wang B, Hong Z. The shape trail test: Application of a new variant of the trail making test. PLoS One 2013; 8(2) e57333
[http://dx.doi.org/10.1371/journal.pone.0057333] [PMID: 23437370]
Jessen F, Amariglio RE, van Boxtel M, et al. Subjective Cognitive Decline Initiative (SCD-I) Working Group. A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer’s disease. Alzheimers Dement 2014; 10(6): 844-52.
[http://dx.doi.org/10.1016/j.jalz.2014.01.001] [PMID: 24798886]
Jessen F, Wolfsgruber S, Wiese B, et al. German study on aging, cognition and dementia in primary care patients. AD dementia risk in late MCI, in early MCI, and in subjective memory impairment. Alzheimers Dement 2014; 10(1): 76-83.
[http://dx.doi.org/10.1016/j.jalz.2012.09.017] [PMID: 23375567]
Rabin LA, Smart CM, Amariglio RE. Subjective cognitive decline in preclinical Alzheimer’s disease. Annu Rev Clin Psychol 2017; 13(13): 369-96.
[http://dx.doi.org/10.1146/annurev-clinpsy-032816-045136] [PMID: 28482688]
Perrotin A, La Joie R, de La Sayette V, et al. Subjective cognitive decline in cognitively normal elders from the community or from a memory clinic: Differential affective and imaging correlates. Alzheimers Dement 2017; 13(5): 550-60.
[http://dx.doi.org/10.1016/j.jalz.2016.08.011] [PMID: 27693187]
Eliassen CF, Reinvang I, Selnes P, Grambaite R, Fladby T, Hessen E. Biomarkers in subtypes of mild cognitive impairment and subjective cognitive decline. Brain Behav 2017; 7(9) e00776
[http://dx.doi.org/10.1002/brb3.776] [PMID: 28948074]
Fernández-Blázquez MA, Ávila-Villanueva M, Maestú F, Medina M. specific features of subjective cognitive decline predict faster conversion to mild cognitive impairment. J Alzheimers Dis 2016; 52(1): 271-81.
Ossenkoppele R, Jagust WJ. The complexity of subjective cognitive decline. JAMA Neurol 2017; 74(12): 1400-2.
Edmonds EC, Weigand AJ, Thomas KR, et al. Increasing inaccuracy of self-reported subjective cognitive complaints over 24 months in empirically derived subtypes of mild cognitive impairment. J Int Neuropsychol Soc 2018; 24(8): 842-53.
[http://dx.doi.org/10.1017/S1355617718000486] [PMID: 30278855]
Edmonds EC, Delano-Wood L, Galasko DR, Salmon DP, Bondi MW. Alzheimer’s Disease Neuroimaging Initiative. Subjective cognitive complaints contribute to misdiagnosis of mild cognitive impairment. J Int Neuropsychol Soc 2014; 20(8): 836-47.
[http://dx.doi.org/10.1017/S135561771400068X] [PMID: 25156329]
Jak AJ, Bondi MW, Delano-Wood L, et al. Quantification of five neuropsychological approaches to defining mild cognitive impairment. Am J Geriatr Psychiatry 2009; 17(5): 368-75.
[http://dx.doi.org/10.1097/JGP.0b013e31819431d5] [PMID: 19390294]
Staff PH. ADL-assessment. Scand J Rehabil Med Suppl 1980; 7: 153-7.
[PMID: 6932724]
Morris JC. The Clinical Dementia Rating (CDR): Current version and scoring rules. Neurology 1993; 43(11): 2412-4.
[http://dx.doi.org/10.1212/WNL.43.11.2412-a] [PMID: 8232972]
Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960; 23: 56-62.
[http://dx.doi.org/10.1136/jnnp.23.1.56] [PMID: 14399272]
Katzman R, Zhang MY. Ouang-Ya-Qu , et al A Chinese version of the Mini-Mental State Examination; impact of illiteracy in a Shanghai dementia survey. J Clin Epidemiol 1988; 41(10): 971-8.
[http://dx.doi.org/10.1016/0895-4356(88)90034-0] [PMID: 3193141]
Hamilton M. The assessment of anxiety states by rating. Br J Med Psychol 1959; 32(1): 50-5.
[http://dx.doi.org/10.1111/j.2044-8341.1959.tb00467.x] [PMID: 13638508]
Zhao Q, Guo Q, Liang X, et al. Auditory verbal learning test is superior to rey-osterrieth complex figure memory for predicting mild cognitive impairment to Azheimer’s disease. Curr Alzheimer Res 2015; 12(6): 520-6.
[http://dx.doi.org/10.2174/1567205012666150530202729] [PMID: 26027810]
Guo Q, Zhao Q, Chen M, Ding D, Hong Z. A comparison study of mild cognitive impairment with 3 memory tests among Chinese individuals. Alzheimer Dis Assoc Disord 2009; 23(3): 253-9.
[http://dx.doi.org/10.1097/WAD.0b013e3181999e92] [PMID: 19812468]
Zhao Q, Guo Q, Hong Z. Clustering and switching during a semantic verbal fluency test contribute to differential diagnosis of cognitive impairment. Neurosci Bull 2013; 29(1): 75-82.
[http://dx.doi.org/10.1007/s12264-013-1301-7] [PMID: 23322003]
Guo Q, Hong Z, Shi W, Et A. Boston naming test in chinese elderly, patient with mild cognitive impairment and Alzheimer’s dementia. Chin Ment Health J 1991.
Zhao Q, Lv Y, Zhou Y, Hong Z, Guo Q. Short-term delayed recall of auditory verbal learning test is equivalent to long-term delayed recall for identifying amnestic mild cognitive impairment. PLoS One 2012; 7(12) e51157
[http://dx.doi.org/10.1371/journal.pone.0051157] [PMID: 23236445]
Gorno-Tempini ML, Hillis AE, Weintraub S, et al. Classification of primary progressive aphasia and its variants. Neurology 2011; 76(11): 1006-14.
[http://dx.doi.org/10.1212/WNL.0b013e31821103e6] [PMID: 21325651]
Galton CJ, Patterson K, Graham K, et al. Differing patterns of temporal atrophy in Alzheimer’s disease and semantic dementia. Neurology 2001; 57(2): 216-25.
[http://dx.doi.org/10.1212/WNL.57.2.216] [PMID: 11468305]
Busse A, Hensel A, Gühne U, Angermeyer MC, Riedel-Heller SG. Mild cognitive impairment: Long-term course of four clinical subtypes. Neurology 2006; 67(12): 2176-85.
[http://dx.doi.org/10.1212/01.wnl.0000249117.23318.e1] [PMID: 17190940]
Aisen PS, Petersen RC, Donohue MC, et al. Alzheimer’s Disease Neuroimaging Initiative. Clinical core of the Alzheimer’s disease neuroimaging initiative: Progress and plans. Alzheimers Dement 2010; 6(3): 239-46.
[http://dx.doi.org/10.1016/j.jalz.2010.03.006] [PMID: 20451872]
Thomas KR, Edmonds EC, Eppig JS, et al. Alzheimer’s Disease Neuroimaging Initiative. MCI-to-normal reversion using neuropsychological criteria in the Alzheimer’s Disease Neuroimaging Initiative. Alzheimers Dement 2019; 15(10): 1322-32.
[http://dx.doi.org/10.1016/j.jalz.2019.06.4948] [PMID: 31495605]
Papp KV, Buckley R, Mormino E, et al. Clinical meaningfulness of subtle cognitive decline on longitudinal testing in preclinical AD. Alzheimers Dement 2019; 19: S1552-5260.
[PMID: 31759879]
Crutch SJ, Lehmann M, Schott JM, Rabinovici GD, Rossor MN, Fox NC. Posterior cortical atrophy. Lancet Neurol 2012; 11(2): 170-8.
[http://dx.doi.org/10.1016/S1474-4422(11)70289-7] [PMID: 22265212]
Neary D, Snowden JS, Gustafson L, et al. Frontotemporal lobar degeneration: A consensus on clinical diagnostic criteria. Neurology 1998; 51(6): 1546-54.
[http://dx.doi.org/10.1212/WNL.51.6.1546] [PMID: 9855500]

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Year: 2020
Page: [517 - 525]
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DOI: 10.2174/1567205017666200807193253
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