Neuropsychological Criteria for Mild Cognitive Impairment Improves Diagnostic Precision, Biomarker Associations, and Progression Rates

The percentage of older adults classified as MCI ranges greatly from 11% to 74% depending on the number of tests considered in the diagnosis and the cutoffs used to define objective cognitive impairment.

“Jak and Bondi and colleagues [24, 25] have found that the percentage of older adults classified as MCI ranges greatly from 11% to 74% depending on the number of tests considered in the diagnosis and the cutoffs used to define objective cognitive impairment (see also [26]).”

• cites [24] Bondi MW Jak AJ Delano-Wood L Jacobson MW Delis DC Salmon DP 2008 Neuropsychological contributions to the early identification of Alzheimer’s disease Neuropsychol Rev 18 73 90 18347989 PMC2882236 sourceNot checked — no full text of the source
• cites [25] Jak AJ Bondi MW Delano-Wood L Wierenga C Corey-Bloom J Salmon DP Delis DC 2009 Quantification of five neuropsychological approaches to defining mild cognitive impairment Am J Geriatr Psychiatry 17 368 375 19390294 PMC2743175 sourcePartly supported

  The Results report that 10–74% of participants were classified as MCI depending on the diagnostic strategy, not 11–74%. The Methods describe those strategies as differing in the number of impaired tests required and the cutoff used to define impairment. Thus the explanation and upper bound are supported, but the stated lower bound differs from our copy. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [26] Ward A Arrighi HM Michels S Cedarbaum JM 2012 Mild cognitive impairment: Disparity of incidence and prevalence estimates Alzheimers Dement 8 14 21 22265588 sourceNot checked — no full text of the source

The lack of objective tests of other cognitive domains reduces the ability to detect cognitive impairment profiles that might identify distinct subtypes of MCI that vary in clinical and biological characteristics.

“Finally, the lack of objective tests of other cognitive domains reduces the ability to detect cognitive impairment profiles that might identify distinct subtypes of MCI that vary in clinical and biological characteristics [19–21].”

• cites [19] Ferman TJ Smith GE Kantarci K Boeve BF Pankratz VS Dickson DW Graff-Radford NR Wszolek Z Van Gerpen J Uitti R Pedraza O Murray ME Aakre J Parisi J Knopman DS Petersen RC 2013 Nonamnestic mild cognitive impairment progesses to dementia with Lewy bodies Neurology 81 2032 2038 24212390 PMC3854825 sourceNot checked — no full text of the source
• cites [20] Jak AJ Urban S McCauley A Bangen KJ Delano-Wood L Corey-Bloom J Bondi MW 2009 Profile of hippocampal volumes and stroke risk varies by neuropsychological definition of mild cognitive impairment J Int Neuropsychol Soc 15 890 897 19570306 PMC2864786 sourceSupported
• cites [21] Loewenstein DA Acevedo A Small BJ Agron J Crocco E Duara R 2009 Stability of different subtypes of mild cognitive impairment among the elderly over a 2- to 3-year follow-up period Dement Geriatr Cogn Disord 27 418 423 19365121 PMC2814021 sourceNot checked — no full text of the source

Story recall may be less sensitive to MCI or an evolving dementia than tests of verbal list learning or visual memory.

“Second, story recall may be less sensitive to MCI or an evolving dementia than tests of verbal list learning [11–16] or perhaps visual memory [17].”

• cites [11] Bondi MW Monsch AU Galasko D Butters N Salmon DP Delis DC 1994 Preclinical cognitive markers of dementia of the Alzheimer type Neuropsychology 8 374 384Not checked yet

  Not checked in the free run.

• cites [12] Bondi MW Salmon DP Galasko D Thomas RG Thal J 1999 Neuropsychological function and apolipoprotein E genotype in the preclinical detection of Alzheimer’s disease Psychol Aging 14 295 303 10403716 sourceNot checked — no full text of the source
• cites [13] De Jager CA Hogervorst E Combrinck M Budge MM 2003 Sensitivity and specificity of neuropsychological tests for mild cognitive impairment, vascular cognitive impairment and Alzheimer’s disease Psychol Med 33 1039 1050 12946088 sourceNot checked — no full text of the source
• cites [14] Lange KL Bondi MW Salmon DP Galasko D Delis DC Thomas RG Thal LJ 2002 Decline in verbal memory during preclinical Alzheimer’s disease: Examination of the effect of APOE genotype J Int Neuropsychol Soc 8 943 955 12405546 PMC1621042 sourceNot checked — no full text of the source
• cites [15] Rabin LA Paré N Saykin AJ Brown MJ Wishart HA Flashman LA Santulli RB 2009 Differential memory test sensitivity for diagnosing amnestic mild cognitive impairment and predicting conversion to Alzheimer’s disease Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 16 57 76 PMC3114447 19353345 sourceCould not verify

  Citation [17] is attached to the suggestion that visual memory tests may be more sensitive than story recall. The Discussion (page unavailable) says visual-memory measures were excluded from the comparison and calls for future research on their relative value. Our copy therefore does not establish the attributed comparison. (LLM, conf=0.76)

  Experimental — accuracy not yet measured
• cites [16] Tierney MC Yao C Kiss A McDowell I 2005 Neuropsychological tests accurately predict incident Alzheimer disease after 5 and 10 years Neurology 64 1853 1859 15955933 sourceNot checked — no full text of the source
• cites [17] Kawas CH Corrada MM Brookmeyer R Morrison A Resnick SM Zonderman AB Arenberg D 2003 Visual memory predicts Alzheimer’s disease more than a decade before diagnosis Neurology 60 1089 1093 12682311 sourcePartly supported

  The Results report that errors on a visual-memory test predicted Alzheimer’s disease years before diagnosis, and the Discussion describes that test as sensitive to mild-to-moderate dementia. The paper does not compare visual memory with story recall or assess MCI, so it does not establish the cited comparison. (LLM, conf=0.82)

  Experimental — accuracy not yet measured

Clark et al. observed amnestic and mixed MCI subtypes and a third cluster-derived normal subtype when MCI was determined using conventional 'one test' criteria.

“In contrast, when MCI had been determined using the conventional “one test” MCI criteria, Clark et al. [31] observed amnestic and mixed MCI subtypes, and a third cluster-derived normal subtype that performed within normal limits across all neuropsychological measures.”

• cites [31] Clark LR Delano-Wood L Libon DJ McDonald CR Nation DA Bangen KJ Jak AJ Au R Salmon DP Bondi MW 2013 Are empirically derived subtypes of mild cognitive impairment diagnoses consistent with conventional subtypes? J Int Neuropsychol Soc 19 635 645 23552486 PMC3742806 sourceSupported

Clark et al. found that conventional 'one test' MCI criteria identified more participants as having MCI (n=134) than actuarial neuropsychological criteria (n=80).

“The conventional “one test” MCI criteria identified more participants as having MCI (n = 134) than did the actuarial neuropsychological criteria (n = 80).”

• cites [31] Clark LR Delano-Wood L Libon DJ McDonald CR Nation DA Bangen KJ Jak AJ Au R Salmon DP Bondi MW 2013 Are empirically derived subtypes of mild cognitive impairment diagnoses consistent with conventional subtypes? J Int Neuropsychol Soc 19 635 645 23552486 PMC3742806 sourceSupported

Delano-Wood et al. and Libon et al. independently identified three clusters representing amnestic, dysexecutive, and mixed MCI subtypes.

“Applying these methods to different samples of individuals with clinically-diagnosed MCI, Delano-Wood et al. [27] and Libon et al. [28] independently identified three clusters that represented amnestic, dysexecutive, and mixed (i.e., memory and language deficits) MCI subtypes.”

• cites [27] Delano-Wood L Bondi MW Sacco J Abeles N Jak AJ Libon DJ Bozoki A 2009 Heterogeneity in mild cognitive impairment: Differences in neuropsychological profile and associated white matter lesion pathology J Int Neuropsychol Soc 15 906 914 19891820 PMC3034688 sourceSupported
• cites [28] Libon DJ Xie SX Eppig J Wicas G Lamar M Lippa C Bettcher BM Price CC Giovannetti T Swenson R Wambach DM 2010 The heterogeneity of mild cognitive impairment: A neuropsychological analysis J Int Neuropsychol Soc 16 84 93 19887015 sourceNot checked — no full text of the source

The susceptibility of the conventional criteria for MCI to diagnostic error is likely to be amplified if used to characterize and stage preclinical AD.

“The susceptibility of the conventional criteria for MCI to diagnostic error is likely to be amplified if used to characterize and stage preclinical AD—a pre-MCI categorization based on subtle cognitive decline [8].”

• cites [8] Sperling RA Aisen PS Beckett LA Bennett DA Craft S Fagan AM Iwatsubo T Jack CR Jr Kaye J Montine TJ Park DC Reiman EM Rowe CC Siemers E Stern Y Yaffe K Carrillo MC Thies B Morrison-Bogorad M Wagster MV Phelps CH 2011 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 Alzheimers Dement 7 280 292 21514248 PMC3220946 sourcePartly supported

  Section 3 describes people with very subtle decline who do not yet meet MCI criteria as part of preclinical AD. Section 9.3 adds that they may still score within the normal range on standard cognitive measures. These passages support the pre-MCI characterization, but do not say that conventional MCI criteria are susceptible to diagnostic error or that such error would be amplified when staging preclinical AD. Page numbers were not available in our copy. (LLM, conf=0.78)

  Experimental — accuracy not yet measured

Several studies suggest that a cut-point for impairment of -1 SD below normative means provides an optimal balance of sensitivity and specificity.

“and several studies suggest that a cut-point for impairment of -1 SD below normative means provides an optimal balance of sensitivity and specificity [25, 44, 45].”

• cites [25] Jak AJ Bondi MW Delano-Wood L Wierenga C Corey-Bloom J Salmon DP Delis DC 2009 Quantification of five neuropsychological approaches to defining mild cognitive impairment Am J Geriatr Psychiatry 17 368 375 19390294 PMC2743175 sourcePartly supported

  The Methods (§2.3; page unavailable) say the authors adopted a −1 SD cutoff as part of comprehensive criteria requiring impairment on at least two tests within a cognitive domain. The Comment (§4; page unavailable) says those combined criteria may offer a better balance of sensitivity and specificity, but does not establish that the −1 SD cut-point alone provides an optimal balance. (LLM, conf=0.85)

  Experimental — accuracy not yet measured
• cites [44] Busse A Hensel A Guhne U Angermeyer MC Riedel-Heller SG 2006 Mild cognitive impairment: Long-term course of four clinical subtypes Neurology 67 2176 2185 17190940 sourceNot checked — no full text of the source
• cites [45] Taylor MJ Heaton RK 2001 Sensitivity and specificity of WAIS-III/WMS-III demographically corrected factor scores in neuropsychological assessment J Int Neuropsychol Soc 7 867 874 11771630 sourceNot checked — no full text of the source

CSF biomarker values for the ADNI Amnestic and Dysexecutive/Mixed MCI subgroups were significantly different from those of the Cluster-Derived Normal subgroup.

“For MCI participants identified using the ADNI diagnostic criteria, analyses of covariance showed that CSF biomarker values for the Amnestic and Dysexecutive/Mixed MCI subgroups were significantly different from those of the Cluster-Derived Normal subgroup, but did not differ from one another (see Table 2).”

The ADNI Amnestic and Dysexecutive/Mixed MCI subgroups did not differ from one another on CSF biomarker values.

“For MCI participants identified using the ADNI diagnostic criteria, analyses of covariance showed that CSF biomarker values for the Amnestic and Dysexecutive/Mixed MCI subgroups were significantly different from those of the Cluster-Derived Normal subgroup, but did not differ from one another (see Table 2).”

All CSF biomarker levels of the ADNI Amnestic and Dysexecutive/Mixed MCI subgroups were significantly different from those of ADNI CN participants.

“Follow-up analyses showed that all CSF biomarker levels of the Amnestic and Dysexecutive/Mixed MCI subgroups were significantly different from those of a group of ADNI’s CN participants (n = 168; all p-values bold>0.001; see Fig. 3).”

The Impaired Language MCI subtype was uniquely identified by the Jak/Bondi actuarial criteria and not by the conventional ADNI criteria.

“The neuropsychological Jak/Bondi criteria uniquely yielded a third Impaired Language subtype, whereas conventional Petersen/Winblad ADNI criteria produced a third subtype comprising nearly one-third of the sample that performed within normal limits across the cognitive measures, suggesting this method’s susceptibility to false positive diagnoses.”

The actuarial neuropsychological method did not produce a cluster-derived normal subgroup.

“In contrast to the results obtained with ADNI criteria, there was no evidence for a cluster derived normal group in any of the cluster solutions based on the neuropsychological method.”

• Also stated in: § Abstract · plain

  “Importantly, the actuarial neuropsychological method did not produce a subtype that performed within normal limits on the cognitive testing, unlike the conventional diagnostic method.”

CSF biomarker levels in the ADNI Cluster-Derived Normal subgroup and CN participants did not differ.

“In contrast, CSF biomarker levels in the Cluster-Derived Normal subgroup and the CN participants did not differ (all p-values >0.05).”

Conventional MCI participants in the two impaired phenotypes rarely revert to CN status.

“While the MCI participants in the two impaired phenotypes tended to remain as MCI or progress to dementia, rarely revert to a CN status, have a higher than normal APOE ε4 allelic frequency, and abnormal CSF Aβ1–42 and tau biomarkers, those in the “cognitively normal” phenotype had a very low rate of progression (approximately four to five times less than the impaired phenotypes), were as likely to”

Cross-validation of the actuarial MCI cluster solution fell minimally to 90.3%.

“Classification accuracy fell minimally to 90.3% when using the leave-one-out cross-validation procedure.”

Regardless of cognitive phenotype, actuarial MCI participants had higher than normal APOE-ε4 allelic frequencies.

“Regardless of cognitive phenotype, the participants with MCI diagnosed in this way tended to remain as MCI or progress to dementia, rarely reverted to a cognitively normal status, had higher than normal APOE-ε4 allelic frequencies, and had abnormal CSF levels of Aβ1–42, total tau, and p-tau181 biomarkers associated with AD.”

The ADNI Amnestic and Dysexecutive/Mixed MCI subgroups had significantly higher APOE ε4 frequencies than the Cluster-Derived Normal subgroup.

“The Amnestic and Dysexecutive/Mixed MCI subgroups demonstrated significantly higher ε4 frequencies than the Cluster-Derived Normal subgroup.”

Conventional MCI participants in the 'cognitively normal' phenotype had only a slightly higher than normal APOE ε4 allelic frequency.

“While the MCI participants in the two impaired phenotypes tended to remain as MCI or progress to dementia, rarely revert to a CN status, have a higher than normal APOE ε4 allelic frequency, and abnormal CSF Aβ1–42 and tau biomarkers, those in the “cognitively normal” phenotype had a very low rate of progression (approximately four to five times less than the impaired phenotypes), were as likely to”

The Impaired Language subgroup had different levels of Aβ1-42, total tau, and p-tau181/Aβ1-42 compared to the CN participants.

“The Impaired Language subgroup had different levels of Aβ1–42, total tau, and p-tau181/Aβ1–42 compared to the CN participants.”

The six neuropsychological measures accurately classified 91.8% of actuarial MCI cases into the three subgroups.

“The six neuropsychological measures accurately classified 91.8% of the cases into the three subgroups.”

Conventional ADNI MCI included a third 'cognitively normal' phenotype that comprised nearly one-third of their MCI sample.

“In contrast, when participants with MCI were identified through the conventional criteria used by ADNI, they could be dissociated into two cognitive phenotypes that varied in the salience of impairment in memory and executive functions, and a third “cognitively normal” phenotype (i.e., they performed within normal limits on the six neuropsychological tests) that comprised nearly one-third of their”

Conventional MCI participants in the 'cognitively normal' phenotype had a very low rate of progression (approximately four to five times less than the impaired phenotypes).

“While the MCI participants in the two impaired phenotypes tended to remain as MCI or progress to dementia, rarely revert to a CN status, have a higher than normal APOE ε4 allelic frequency, and abnormal CSF Aβ1–42 and tau biomarkers, those in the “cognitively normal” phenotype had a very low rate of progression (approximately four to five times less than the impaired phenotypes), were as likely to”

When participants with MCI were identified through actuarial neuropsychological method, they dissociated into three distinct cognitive phenotypes that varied in salience of impairment in memory, language, and/or executive functions.

“When participants with MCI were identified through our actuarial neuropsychological method, they dissociated into three distinct cognitive phenotypes that varied in the salience of impairment in memory, language, and/or executive functions.”

Conventional MCI participants in the two impaired phenotypes have abnormal CSF Aβ1-42 and tau biomarkers.

“While the MCI participants in the two impaired phenotypes tended to remain as MCI or progress to dementia, rarely revert to a CN status, have a higher than normal APOE ε4 allelic frequency, and abnormal CSF Aβ1–42 and tau biomarkers, those in the “cognitively normal” phenotype had a very low rate of progression (approximately four to five times less than the impaired phenotypes), were as likely to”

Conventional MCI participants in the two impaired phenotypes have a higher than normal APOE ε4 allelic frequency.

“While the MCI participants in the two impaired phenotypes tended to remain as MCI or progress to dementia, rarely revert to a CN status, have a higher than normal APOE ε4 allelic frequency, and abnormal CSF Aβ1–42 and tau biomarkers, those in the “cognitively normal” phenotype had a very low rate of progression (approximately four to five times less than the impaired phenotypes), were as likely to”

For ADNI-diagnosed MCI, APOE ε4 allelic frequencies differed significantly across the three subgroups.

“For MCI participants identified by ADNI criteria, a Genotype (APOE ε4 versus non-ε4) × Subgroup (Amnestic MCI, Dysexecutive/Mixed MCI, Cluster-Derived Normal) chi-square analysis showed significant differences in APOE ε4 allelic frequencies across the three subgroups (see Table 2).”

The Dysexecutive/Mixed subgroup had different levels of Aβ1-42, p-tau, and p-tau181/Aβ1-42 compared to the CN participants.

“The Dysexecutive/Mixed subgroup had different levels of Aβ1–42, p-tau, and p-tau181/Aβ1–42 compared to the CN participants.”

For MCI participants identified using conventional ADNI diagnostic criteria, a chi-square analysis revealed significant differences in prevalence of various types of change across the three subgroups (p < 0.001).

“For MCI participants identified using the conventional ADNI diagnostic criteria, a Type-of-Change (MCI to AD [progression], MCI to CN [reversion], or no change) ×Subgroup (Amnestic, Dysexecutive/Mixed, Cluster-Derived Normal) chi-square analysis revealed significant differences in prevalence of various types of change across the three subgroups (p < 0.001) (see Table 3).”

For MCI participants identified using actuarial neuropsychological criteria, a chi-square analysis showed no significant differences in clinical outcomes for the three subgroups (p = 0.10).

“For MCI participants identified using the actuarial neuropsychological criteria, a Type-of-Change ×Subgroup (Amnestic, Impaired Language, Dysexecutive/Mixed) chi-square analysis showed no significant differences in clinical outcomes for the three subgroups (p = 0.10) (see Table 3).”

For actuarial neuropsychological MCI, there was no significant difference in APOE ε4 allelic frequencies across the three subgroups.

“In contrast, a Genotype × Subgroup (Amnestic, Impaired Language, Dysexecutive/Mixed) chi-square analysis with MCI defined using actuarial neuropsychological criteria showed no significant difference in APOE ε4 allelic frequencies across the three subgroups (see Table 2).”

Conventional MCI participants in the two impaired phenotypes tended to remain as MCI or progress to dementia.

“While the MCI participants in the two impaired phenotypes tended to remain as MCI or progress to dementia, rarely revert to a CN status, have a higher than normal APOE ε4 allelic frequency, and abnormal CSF Aβ1–42 and tau biomarkers, those in the “cognitively normal” phenotype had a very low rate of progression (approximately four to five times less than the impaired phenotypes), were as likely to”

The Amnestic subgroup was significantly different from the CN participants (n = 405) for all CSF biomarker levels (all p-values <0.001).

“Follow-up analyses showed that the Amnestic subgroup was significantly different from the CN participants (n = 405) for all CSF biomarker levels (all p-values <0.001).”

Regardless of cognitive phenotype, participants with MCI diagnosed by actuarial method tended to remain as MCI or progress to dementia.

“Regardless of cognitive phenotype, the participants with MCI diagnosed in this way tended to remain as MCI or progress to dementia, rarely reverted to a cognitively normal status, had higher than normal APOE-ε4 allelic frequencies, and had abnormal CSF levels of Aβ1–42, total tau, and p-tau181 biomarkers associated with AD.”

For the 239 participants who progressed to AD under conventional MCI criteria, the mean time point at which a dementia diagnosis was made was 22.5 months post-screening.

“For the 239 participants who progressed to AD, the mean time point at which a dementia diagnosis was made was 22.5 months post-screening.”

When participants with MCI were identified through conventional ADNI criteria, they could be dissociated into two cognitive phenotypes that varied in salience of impairment in memory and executive functions.

“In contrast, when participants with MCI were identified through the conventional criteria used by ADNI, they could be dissociated into two cognitive phenotypes that varied in the salience of impairment in memory and executive functions, and a third “cognitively normal” phenotype (i.e., they performed within normal limits on the six neuropsychological tests) that comprised nearly one-third of their”

Conventional MCI participants in the 'cognitively normal' phenotype demonstrated normal levels of CSF Aβ1-42 and tau biomarkers.

“While the MCI participants in the two impaired phenotypes tended to remain as MCI or progress to dementia, rarely revert to a CN status, have a higher than normal APOE ε4 allelic frequency, and abnormal CSF Aβ1–42 and tau biomarkers, those in the “cognitively normal” phenotype had a very low rate of progression (approximately four to five times less than the impaired phenotypes), were as likely to”

Cross-validation of the ADNI MCI cluster solution fell minimally to 89.5%.

“Overall, classification fell minimally to 89.5% upon cross-validation.”

For MCI participants identified using actuarial neuropsychological criteria, analyses of covariance showed no significant differences among the subgroups for all CSF biomarkers.

“For MCI participants identified using the actuarial neuropsychological criteria, analyses of covariance showed no significant differences among the subgroups for all CSF biomarkers.”

For the 179 participants who progressed to AD under actuarial MCI criteria, the mean time point at which a dementia diagnosis was made was 19.6 months post-screening.

“For the 179 participants who progressed to AD, the mean time point at which a dementia diagnosis was made was 19.6 months post-screening.”

Conventional MCI participants in the 'cognitively normal' phenotype were as likely to revert as to progress.

“While the MCI participants in the two impaired phenotypes tended to remain as MCI or progress to dementia, rarely revert to a CN status, have a higher than normal APOE ε4 allelic frequency, and abnormal CSF Aβ1–42 and tau biomarkers, those in the “cognitively normal” phenotype had a very low rate of progression (approximately four to five times less than the impaired phenotypes), were as likely to”

Regardless of cognitive phenotype, actuarial MCI participants rarely reverted to cognitively normal status.

“Regardless of cognitive phenotype, the participants with MCI diagnosed in this way tended to remain as MCI or progress to dementia, rarely reverted to a cognitively normal status, had higher than normal APOE-ε4 allelic frequencies, and had abnormal CSF levels of Aβ1–42, total tau, and p-tau181 biomarkers associated with AD.”

The six neuropsychological measures accurately classified 90.0% of ADNI MCI cases into the three subgroups.

“Overall, the six neuropsychological measures accurately classified 90.0% of the cases into the three subgroups.”

The revised criteria for MCI still largely rely on simple cognitive screening measures, clinical judgment, and limited neuropsychological assessment utilizing a 'one test equals one domain' methodology.

“The revised criteria for MCI still largely rely on simple cognitive screening measures, clinical judgment, and limited neuropsychological assessment utilizing a ‘one test equals one domain’ methodology.”

• cites [7] Albert MS DeKosky ST Dickson D Dubois B Feldman HH Fox NC Gamst A Holtzman DM Jagust WJ Petersen RC Snyder PJ Carrillo MC Thies B Phelps CH 2011 The diagnosis of mild cognitive impairment due to Alzheimer’s disease: Recommendations from the National Institute on Aging and Alzheimer’s Association workgroup Alzheimers Dement 7 270 279 21514249 PMC3312027Not checked yet

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In these studies the median number of impaired scores in a neurologically normal sample was 10%.

“In these studies the median number of impaired scores in a neurologically normal sample was 10%.”

• cites [39] Heaton RK Avitable N Grant I Matthews CG 1999 Further cross validation of regression-based neuropsychological norms with an update for the Boston Naming Test J Clin Exp Neuropsychol 21 562 582 10550815 sourceNot checked — no full text of the source
• cites [40] Heaton RK Miller SW Taylor MJ Grant I 2004 Revised comprehensive norms for an expanded Halstead-Reitan Battery: Demographically adjusted neuropsychological norms for African-American and Caucasian adults Psychological Assessment Resources, Inc Lutz, FLNot checked yet

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ADNI largely identifies the amnestic form of MCI based on impaired performance on delayed recall of a single prose passage.

“the Alzheimer’s Disease Neuroimaging Initiative (ADNI; http://www.adni-info.org), which largely identify the amnestic form of MCI based on impaired performance on delayed recall of a single prose passage [10].”

• cites [10] Wechsler D 1987 Wechsler Memory Scale-Revised The Psychological Corporation New YorkNot checked yet

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The application of a neuropsychological method of actuarial diagnostic decision-making based on a minimal set of six neuropsychological variables and one functional measure provided a more accurate and better characterization of MCI than did conventional criteria.

“The application of a neuropsychological method of actuarial diagnostic decision-making based on a minimal set of six neuropsychological variables and one functional measure provided a more accurate and better characterization of MCI than did conventional criteria based on subjective memory complaints, clinical interviews, cognitive screening and rating scales, and impairment on a single objective”

• AssumptionRests on an assumption: The conventional criteria for MCI used in ADNI are based in part on a cutoff from one test of memory, together with other cognitive and informant-derived tests and clinical consensus.

These findings suggest that the conventional criteria for MCI used in ADNI produce a relatively high rate of 'false positive' diagnostic errors.

“These findings suggest that the conventional criteria for MCI used in ADNI, based in part on a cutoff from one test of memory, together with other cognitive and informant-derived tests and clinical consensus, produce a relatively high rate of “false positive” diagnostic errors.”

• AssumptionRests on an assumption: Many MCI studies diagnose participants on the basis of a single impaired test score, the most prevalent of which is an impaired memory score.
• AssumptionRests on an assumption: The conventional criteria for MCI used in ADNI are based in part on a cutoff from one test of memory, together with other cognitive and informant-derived tests and clinical consensus.

The use of a single memory measure violates the statistical maxim that multiple measures provide a more reliable estimate of a cognitive construct than any single measure.

“Third, the use of a single memory measure violates the statistical maxim that multiple measures provide a more reliable estimate of a cognitive construct than any single measure [18].”

• cites [18] Anastasi A Urbina S 1997 Psychological Testing 7 Prentice Hall Upper Saddle River, NJNot checked yet

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When MCI was defined by actuarial neuropsychological criteria, all three MCI subgroups had abnormal levels of almost all the CSF AD biomarkers.

“Thus, when MCI was defined by actuarial neuropsychological criteria, all three MCI subgroups had abnormal levels of almost all the CSF AD biomarkers (see Fig. 3).”

• AssumptionRests on an assumption: CSF Aβ1–42, total tau, and p-tau181 are biomarkers associated with AD.

The high rate of false positive diagnostic errors may arise from an over-reliance on a single impaired test score.

“This may arise from an over-reliance on a single impaired test score.”

• AssumptionRests on an assumption: Many MCI studies diagnose participants on the basis of a single impaired test score, the most prevalent of which is an impaired memory score.

None of the six neuropsychological measures used for actuarial reclassification were used in making the initial ADNI diagnostic classification.

“None of these cognitive measures were used in making the initial ADNI diagnostic classification.”

Several studies have shown that a majority of neurologically normal adults score in the impaired range on at least one measure when tested with an extensive battery of cognitive tests.

“Several studies have shown that a majority of neurologically normal adults score in the impaired range on at least one measure when tested with an extensive battery of cognitive tests [39, 40].”

• cites [39] Heaton RK Avitable N Grant I Matthews CG 1999 Further cross validation of regression-based neuropsychological norms with an update for the Boston Naming Test J Clin Exp Neuropsychol 21 562 582 10550815 sourceNot checked — no full text of the source
• cites [40] Heaton RK Miller SW Taylor MJ Grant I 2004 Revised comprehensive norms for an expanded Halstead-Reitan Battery: Demographically adjusted neuropsychological norms for African-American and Caucasian adults Psychological Assessment Resources, Inc Lutz, FLNot checked yet

  Not checked in the free run.

Participants misclassified as CN but found to have cognitive impairment on more extensive testing or who subsequently declined were not included in the CN sample.

“In other words, participants misclassified as CN but found to have cognitive impairment on more extensive testing or who subsequently declined were not included in the CN sample.”

Brooks et al. showed that 26% of the older adults in the standardization sample for the WMS-III obtained one or more age-adjusted standard score that was more than 1.5 SDs below the mean.

“Brooks et al. [42] showed that 26% of the older adults in the standardization sample for the WMS-III [43] obtained one or more age-adjusted standard score that was more than 1.5 SDs below the mean.”

• cites [42] Brooks BL Iverson GL White T 2007 Substantial risk of ‘accidental MCI’ in healthy older adults: Base rates of low memory scores in neuropsychological assessment J Int Neuropsychol Soc 13 490 500 17445298 sourceNot checked — no full text of the source

If a high number of cognitively normal individuals without significant amyloidosis or neurodegeneration are incorrectly identified as MCI in studies of potential genetic, imaging, or other biomarkers, the perceived accuracy of these biomarkers could be greatly reduced.

“If a high number of cognitively normal individuals without significant amyloidosis or neurodegeneration are incorrectly identified as MCI in studies of potential genetic, imaging, or other biomarkers, the perceived accuracy of these biomarkers could be greatly reduced.”

More strict cut-points on cognitive tests of -1.5 or -2 SDs below normative means generally trade modest gains in specificity for larger losses in sensitivity.

“More strict cut-points on cognitive tests of -1.5 or -2 SDs below normative means generally trade modest gains in specificity for larger losses in sensitivity [44, 45]”

• cites [44] Busse A Hensel A Guhne U Angermeyer MC Riedel-Heller SG 2006 Mild cognitive impairment: Long-term course of four clinical subtypes Neurology 67 2176 2185 17190940 sourceNot checked — no full text of the source
• cites [45] Taylor MJ Heaton RK 2001 Sensitivity and specificity of WAIS-III/WMS-III demographically corrected factor scores in neuropsychological assessment J Int Neuropsychol Soc 7 867 874 11771630 sourceNot checked — no full text of the source

Including inaccurately identified 'false-positive' MCI cases in clinical trials of drug therapies that target the underlying biology of AD could dilute their results.

“This possibility is also true for clinical trials of drug therapies that target the underlying biology of AD, such that including inaccurately identified “false-positive” MCI cases in the cohort could dilute their results.”

The susceptibility of the conventional criteria for MCI to false positive errors could have unfortunate downstream consequences.

“The susceptibility of the conventional criteria for MCI to false positive errors could have unfortunate ‘downstream’ consequences.”