Advertisement

Analysis of the Relationship of Cognitive Impairment and Functional Impairment in Mild Alzheimer’s Disease in EXPEDITION 3

  • Hong Liu-Seifert
  • E. Siemers
  • K. Sundell
  • M. Mynderse
  • J. Cummings
  • R. Mohs
  • P. Aisen
Original Research

Abstract

Background

Clinical progression of Alzheimer’s disease is characterized by impairment in cognition and function.

Objective

To assess the relationship between cognitive and functional impairment in mild Alzheimer’s disease.

Design

Spearman’s rank correlations between cognitive and functional measures were calculated. Autoregressive cross-lagged panel analyses were used to determine the temporal relationship between cognitive and functional decline.

Setting

Post-hoc analysis of clinical trial data.

Participants

Placebo-treated patients with mild Alzheimer’s disease from the Phase 3 solanezumab study EXPEDITION 3.

Intervention

Placebo.

Measurements

Cognitive and functional measures were assessed at baseline and at six post-baseline time points through Week 80.

Results

Correlation between cognitive and functional measures was 0.41 at baseline and 0.65 at Week 80. Autoregressive cross-lagged panel analysis demonstrated that cognitive impairment preceded and predicted subsequent functional decline, but functional scores did not predict cognitive outcomes.

Conclusions

This study supports the hypothesis that functional impairment predictably follows cognitive decline in mild Alzheimer’s disease dementia.

Key words

Cognition function Alzheimer’s disease correlation 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Montine TJ, Phelps CH, Beach TG, et al. National Institute on Aging-Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease: a practical approach. Acta Neuropathol 2012;123:1–11.CrossRefPubMedGoogle Scholar
  2. 2.
    Albert MS, DeKosky ST, Dickson D, et al. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011;7:270–279.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Dubois B, Hampel H, Feldman HH, et al. Preclinical Alzheimer’s disease: Definition, natural history, and diagnostic criteria. Alzheimers Dement 2016;12:292–323.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011;7:263–269.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Liu-Seifert H, Siemers E, Price K, et al. Cognitive impairment precedes and predicts functional impairment in mild Alzheimer’s disease. J Alzheimers Dis 2015;47:205–214.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Liu-Seifert H, Siemers E, Sundell K, et al. Cognitive and functional decline and their relationship in patients with mild Alzheimer’s dementia. J Alzheimers Dis 2015;43:949–955.CrossRefPubMedGoogle Scholar
  7. 7.
    Liu-Seifert H, Siemers E, Selzler K, et al. Correlation between Cognition and function across the spectrum of Alzheimer’s disease. J Prev Alzheimers Dis 2016;3:138–144.PubMedGoogle Scholar
  8. 8.
    Zahodne LB, Manly JJ, MacKay-Brandt A, et al. Cognitive declines precede and predict functional declines in aging and Alzheimer’s disease. PLoS One 2013;8:e73645.CrossRefGoogle Scholar
  9. 9.
    Honig LS, Vellas B, Woodward M, et al. Trial of solanezumab for mild dementia due to Alzheimer’s disease. N Engl J Med [In press].Google Scholar
  10. 10.
    Doody RS, Thomas RG, Farlow M, et al. Phase 3 trials of solanezumab for mild-to-moderate Alzheimer’s disease. N Engl J Med 2014;370:311–321.CrossRefPubMedGoogle Scholar
  11. 11.
    Mohs RC, Knopman D, Petersen RC, et al. Development of cognitive instruments for use in clinical trials of antidementia drugs: additions to the Alzheimer’s Disease Assessment Scale that broaden its scope. The Alzheimer’s Disease Cooperative Study. Alzheimer Dis Assoc Disord 1997;11(Suppl 2):S13–S21.CrossRefPubMedGoogle Scholar
  12. 12.
    Galasko D, Bennett D, Sano M, et al. An inventory to assess activities of daily living for clinical trials in Alzheimer’s disease. The Alzheimer’s Disease Cooperative Study. Alzheimer Dis Assoc Disord 1997;11(Suppl 2):S33–S39.CrossRefPubMedGoogle Scholar
  13. 13.
    Aisen PS, Cummings J, Jack CR Jr, et al. On the path to 2025: understanding the Alzheimer’s disease continuum. Alzheimers Res Ther 2017;9:60.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Serdi and Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Hong Liu-Seifert
    • 1
    • 6
  • E. Siemers
    • 1
  • K. Sundell
    • 1
  • M. Mynderse
    • 2
  • J. Cummings
    • 3
  • R. Mohs
    • 4
  • P. Aisen
    • 5
  1. 1.Lilly Research Laboratories, Lilly Corporate CenterIndianapolisUSA
  2. 2.Syneos HealthRaleighUSA
  3. 3.Cleveland Clinic Lou Ruvo Center for Brain HealthLas VegasUSA
  4. 4.formerly of Lilly Research Laboratories, Lilly Corporate CenterIndianapolisUSA
  5. 5.Alzheimer’s Therapeutic Research InstituteUniversity of Southern CaliforniaSan DiegoUSA
  6. 6.Eli Lilly and Company, Lilly Corporate CenterIndianapolisUSA

Personalised recommendations