Cited by 2,572Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsCancer-related cognitive impairment studies

The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index; none of the 23 sources its claims cite is checked for support yet.

Alzheimer's Disease Neuroimaging Initiative (ADNI)

Open access

Abstract

BACKGROUND: Neuroimaging measures and chemical biomarkers may be important indices of clinical progression in normal aging and mild cognitive impairment (MCI) and need to be evaluated longitudinally. OBJECTIVE: To characterize cross-sectionally and longitudinally clinical measures in normal controls, subjects with MCI, and subjects with mild Alzheimer disease (AD) to enable the assessment of the utility of neuroimaging and chemical biomarker measures. METHODS: A total of 819 subjects (229 cognitively normal, 398 with MCI, and 192 with AD) were enrolled at baseline and followed for 12 months using standard cognitive and functional measures typical of clinical trials. RESULTS: The subjects with MCI were more memory impaired than the cognitively normal subjects but not as impaired as the subjects with AD. Nonmemory cognitive measures were only minimally impaired in the subjects with MCI. The subjects with MCI progressed to dementia in 12 months at a rate of 16.5% per year. Approximately 50% of the subjects with MCI were on antidementia therapies. There was minimal movement on the Alzheimer's Disease Assessment Scale-Cognitive Subscale for the normal control subjects, slight movement for the subjects with MCI of 1.1, and a modest change for the subjects with AD of 4.3. Baseline CSF measures of Abeta-42 separated the 3 groups as expected and successfully predicted the 12-month change in cognitive measures. CONCLUSION: The Alzheimer's Disease Neuroimaging Initiative has successfully recruited cohorts of cognitively normal subjects, subjects with mild cognitive impairment (MCI), and subjects with Alzheimer disease with anticipated baseline characteristics. The 12-month progression rate of MCI was as predicted, and the CSF measures heralded progression of clinical measures over 12 months.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

This ADNI clinical characterization paper reports baseline and 12-month clinical, cognitive, and CSF biomarker data for 819 participants: 229 cognitively normal, 398 with MCI, and 192 with mild AD. It shows expected group differences at baseline, a 16.5% 12-month MCI-to-AD progression rate, and baseline CSF Aβ-42 predicting 12-month cognitive change in normal and MCI groups.

Key findings

  • At baseline, ADAS-Cog total scores were 6.2 ± 2.9 in controls, 11.5 ± 4.4 in MCI, and 18.6 ± 6.3 in AD (p < 0.001); MCI subjects were most impaired on memory items and only mildly impaired in nonmemory domains.
  • Over 12 months, 64 of 398 MCI subjects progressed to AD, a rate of 16.5% (95% CI 11.9%–20.5%); normal controls progressed to MCI at an estimated 1.4% (95% CI 0%–3.2%).
  • ADAS-Cog 12-month change was −0.5 ± 3.0 in controls, 1.1 ± 4.4 in MCI, and 4.3 ± 6.6 in AD (p < 0.001).
  • Baseline CSF Aβ-42 decreased across groups (controls 206 ± 5, MCI 164 ± 4, AD 143 ± 4 pg/mL; p < 0.001), and higher baseline Aβ-42 was associated with better ADAS-Cog performance and smaller 12-month change in normal subjects and MCI.

Methods

  • Multicenter ADNI cohort of 819 subjects aged 55–90 enrolled at baseline and classified as cognitively normal, MCI, or mild AD using standard clinical, cognitive, and functional criteria; subjects were followed for 12 months with cognitive and functional measures, MRI/PET in subsets, and lumbar puncture in a minimum of 20% per site.
  • Baseline group comparisons used nonparametric tests (Kruskal-Wallis) with Hochberg multiple comparisons and exact tests for proportions; 12-month change was summarized as conversion proportion, baseline-to-12-month mean or percent difference, and rate per year from mixed-effects regression models.
  • Annual conversion rates were estimated using a hybrid interval-censored method; CSF Aβ-42 was related to diagnosis, ADAS-Cog performance, and 12-month ADAS-Cog change.

Limitations

  • The paper states that a 12-month change period is not sufficient to draw conclusions about the likelihood of clinical change, and that the ADNI cohort likely does not represent “typical” community subjects because participants were more highly educated, mostly white, and had a high proportion of APOE4 carriers in the MCI and AD groups.
  • The paper also states that the MCI criteria required a stringent degree of memory impairment, so these subjects were likely further along the clinical spectrum and more likely to progress than less-impaired MCI subjects.
  • Evident from the text: CSF analyses were limited to subsets (baseline n = 114 controls, 199 MCI, 102 AD), and some subjects lacked 12-month follow-up diagnoses (17 controls and 41 MCI subjects), which limits interpretation of conversion and biomarker results.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1212/wnl.0b013e3181cb3e25

Cites

28 of 28 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

53 Own result · 8 Sources not found · 8 Own interpretation · 5 No basis given · 3 Not checked yet · 3 Own method

Show all 49 claims

  • It may state two separate claims as one. 20
  • Probably not a substantial claim. 14
31 of 31
  • The paper relies on this without support.

    The expected 12-month progression rate for MCI was approximately 16.5% per year.

    “The 12-month progression rate of MCI was as predicted”
    “The subjects with MCI progressed to dementia in 12 months at a rate of 16.5% per year.”
  • The paper relies on this without support.

    The baseline characteristics observed in the recruited cohorts matched the characteristics anticipated for normal, MCI, and AD cohorts.

    “The Alzheimer's DiseaseNeuroimaging Initiative has successfully recruited cohorts of cognitively normal subjects, subjects with mild cognitive impairment (MCI), and subjects with Alzheimer disease with anticipated baseline characteristics.”
  • The paper relies on this without support.

    The MCI subjects have an underlying Alzheimer's disease process that drives clinical progression.

    “As such, these subjects were likely further down the clinical spectrum with respect to the underlying AD process such that they would be more likely to progress than subjects with less impairment in the MCI spectrum.”
  • The paper relies on this without support.

    CSF Aβ-42 level is a valid biomarker of Alzheimer's disease pathology and progression.

    “The CSF A␤-42 data correlated with the diagnostic groups in the expected fashion with levels being lower in the subjects with MCI than in the normal subjects.”
4 of 4

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Citations

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Metadata

Authors
Petersen, R. C., Aisen, P. S., Beckett, L. A., Donohue, M. C., Gamst, A. C., Harvey, D. J., Jack, C. R., Jagust, W. J., Shaw, L. M., Toga, A. W., Trojanowski, J. Q., & Weiner, M. W.
Affiliations
Mayo Clinic (US)
Venue
Neurology
Published
2010-01-19
Volume
74
Issue
3
Pages
201-209
ISSN
  • 0028-3878 (ISSN-L)
  • 1526-632X
OpenAlex
W2122328291
Cited by
2,572
References
27
Citations by year
2026: 312 · 2025: 391 · 2024: 327 · 2023: 254 · 2022: 233 · 2021: 209 · 2020: 182 · 2019: 121 · 2018: 85 · 2017: 67 · 2016: 71 · 2015: 66 · 2014: 45 · 2013: 63 · 2012: 59
FWCI
26.56
Type
journal article
Language
en
Open access
Locations
  • Neurology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (submittedVersion)
  • PubMed Central (submittedVersion)
Funders
  • Alzheimer's Disease Neuroimaging Initiative (AG024904)
  • National Institutes of Health (5r01ag027984-03, 5r01ag030048-05, n01mh22005-16-0-1, 5r01dk075128-05, 5u01ag006786-38, 5r01mh083552-05, 5r01ca104573-05, 5p30ag010124-30, 5p01ag009215-20, 5r01ag011378-25, 5p41rr023953-04, 5u01ag024904-10, 5u01ag029213-05, 5r01ag016381-08, 5r01eb006266-04, 5r01ag010897-27, AG024904, 5p01ag019724-23, 5p30ca093373-23, 5p50ag016574-20)
  • National Institute on Aging (AG027984, U01-AG-024904, R01AG11378, P30AG010129, U19 AG010483, U01‐AG10483, R01-AG030048, P50‐AG16574, P01 & AG019724, U01AG06786, P50-AG23501, RC1AG035427, AG 010483, R01AG031224, AG031224, P01 AG 17586-10, 1 U01 AG024904, AG 024904, UO1AG029213-01, P30AG036468, 2 P50 AG016570, 1 U01 AG 024904-05, P30 AG 10124-18, R01 AG031252, P01AG017586, U01AG010483, 1 U01 AG24904, 1P01 AG-19724-07, R01AG027859, P50AG023501, AG027859, P01 AG012435, AG-11378, 2P50AG005133, RC2AG036535, P01-AG19724, P01 AG 09215-20, R01-AG 10897, 2P30AG10129, R01 AG029672, R01 AG16381)
  • National Heart, Lung, and Blood Institute (HL-095089, R01HL095089)
  • National Institute of Mental Health (U01MH083506, MH 22005, MH062512, MH083506, R01MH079752, R01MH069433, MH083552, MH079752, R01 MH069259, 5 R01 MH071940, MH069433, R01MH072641, P30MH062512)
  • National Institute on Drug Abuse (1 R01 DA017830)
  • National Cancer Institute (2 P30 CA93373, CA104573)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK075128)
  • National Institute of Neurological Disorders and Stroke (1 R01 NS050792, RL1NS062412, P50NS053488, 1 R01 NS049194, RC2NS069368, R01NS031966)
  • National Institute of Biomedical Imaging and Bioengineering (1 U54 EB05149, 1 R01 EB 006266-01, U54EB005149, P01EB001955, 5R01EB002138-07)
  • U.S. National Library of Medicine (2 R01LM005639)
  • National Center for Research Resources (5 P41 RR013642, P41 RR-023953, U24RR021760, U54RR021813, R24 RR021382, R24 RR021992, KL2RR024144)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD050735, 1R01 HD053893-01)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Oncology › Cancer-related cognitive impairment studies
Keywords
Alzheimer's disease, mild cognitive impairment, neuroimaging biomarkers, cerebrospinal fluid biomarkers, amyloid-beta 42, longitudinal cognitive change, normal aging, memory impairment, ADAS-Cog
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Cross-Sectional Studies, Diagnostic Imaging, Female, Follow-Up Studies, Humans, Longitudinal Studies, Male, Middle Aged, Biomarkers

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