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Cognitive composite score association with Alzheimer's disease plaque and tangle pathology.
Alzheimers Res Ther 2018; 10(1):90AR

Abstract

BACKGROUND

Cognitive composite scores are used as the primary outcome measures for Alzheimer's disease (AD) prevention trials; however, the extent to which these composite measures correlate with AD pathology has not been fully investigated. Since many on-going AD prevention studies are testing therapies that target either amyloid or tau, we sought to establish an association between a cognitive composite score and the underlying pathology of AD.

METHODS

Data from 192 older deceased and autopsied persons from the Rush Religious Order Study were used in this study. All participants were classified at their initial evaluations with a clinical diagnosis of no cognitive impairment (NCI). Of these individuals, 105 remained NCI at the time of their death while the remaining 87 progressed to mild cognitive impairment (MCI) or AD. A cognitive composite score composed of eight cognitive tests was used as the outcome measure. Individuals were classified into groups based on Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropathological diagnosis and Braak stage.

RESULTS

The rate of annualized composite score decline was significantly greater for the high CERAD (p < 0.001, d = 0.56) and Braak (p < 0.001, d = 0.55) groups compared with the low CERAD and Braak groups, respectively. Mixed-model repeated measure (MMRM) analyses revealed a significantly greater difference in composite score change from baseline for the high CERAD group relative to the low CERAD group after 5 years (Δ = -2.74, 95% confidence interval (CI) -5.01 to -0.47; p = 0.02). A similar analysis between low and high Braak stage groups found no significant difference in change from baseline (Δ = -0.69, 95% CI -3.03 to 1.66; p = 0.56).

CONCLUSIONS

These data provide evidence that decreased cognitive composite scores were significantly associated with increased AD pathology and provide support for the use of cognitive composite scores in AD prevention trials.

Authors+Show Affiliations

Banner Alzheimer's Institute, 901 E. Willetta St, Phoenix, AZ, USA.Banner Alzheimer's Institute, 901 E. Willetta St, Phoenix, AZ, USA.Department of Neurobiology and Neurology, Barrow Neurological Institute, 350 W. Thomas Rd, Phoenix, AZ, 85013, USA.Banner Alzheimer's Institute, 901 E. Willetta St, Phoenix, AZ, USA.Department of Neurobiology and Neurology, Barrow Neurological Institute, 350 W. Thomas Rd, Phoenix, AZ, 85013, USA. elliott.mufson@dignityhealth.com.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30205840

Citation

Malek-Ahmadi, Michael, et al. "Cognitive Composite Score Association With Alzheimer's Disease Plaque and Tangle Pathology." Alzheimer's Research & Therapy, vol. 10, no. 1, 2018, p. 90.
Malek-Ahmadi M, Chen K, Perez SE, et al. Cognitive composite score association with Alzheimer's disease plaque and tangle pathology. Alzheimers Res Ther. 2018;10(1):90.
Malek-Ahmadi, M., Chen, K., Perez, S. E., He, A., & Mufson, E. J. (2018). Cognitive composite score association with Alzheimer's disease plaque and tangle pathology. Alzheimer's Research & Therapy, 10(1), p. 90. doi:10.1186/s13195-018-0401-z.
Malek-Ahmadi M, et al. Cognitive Composite Score Association With Alzheimer's Disease Plaque and Tangle Pathology. Alzheimers Res Ther. 2018 09 11;10(1):90. PubMed PMID: 30205840.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cognitive composite score association with Alzheimer's disease plaque and tangle pathology. AU - Malek-Ahmadi,Michael, AU - Chen,Kewei, AU - Perez,Sylvia E, AU - He,Anna, AU - Mufson,Elliott J, Y1 - 2018/09/11/ PY - 2017/12/19/received PY - 2018/07/02/accepted PY - 2018/9/13/entrez PY - 2018/9/13/pubmed PY - 2019/9/10/medline KW - Amyloid KW - Cognition KW - Neuropathology KW - Pre-clinical KW - Prevention KW - Tau SP - 90 EP - 90 JF - Alzheimer's research & therapy JO - Alzheimers Res Ther VL - 10 IS - 1 N2 - BACKGROUND: Cognitive composite scores are used as the primary outcome measures for Alzheimer's disease (AD) prevention trials; however, the extent to which these composite measures correlate with AD pathology has not been fully investigated. Since many on-going AD prevention studies are testing therapies that target either amyloid or tau, we sought to establish an association between a cognitive composite score and the underlying pathology of AD. METHODS: Data from 192 older deceased and autopsied persons from the Rush Religious Order Study were used in this study. All participants were classified at their initial evaluations with a clinical diagnosis of no cognitive impairment (NCI). Of these individuals, 105 remained NCI at the time of their death while the remaining 87 progressed to mild cognitive impairment (MCI) or AD. A cognitive composite score composed of eight cognitive tests was used as the outcome measure. Individuals were classified into groups based on Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropathological diagnosis and Braak stage. RESULTS: The rate of annualized composite score decline was significantly greater for the high CERAD (p < 0.001, d = 0.56) and Braak (p < 0.001, d = 0.55) groups compared with the low CERAD and Braak groups, respectively. Mixed-model repeated measure (MMRM) analyses revealed a significantly greater difference in composite score change from baseline for the high CERAD group relative to the low CERAD group after 5 years (Δ = -2.74, 95% confidence interval (CI) -5.01 to -0.47; p = 0.02). A similar analysis between low and high Braak stage groups found no significant difference in change from baseline (Δ = -0.69, 95% CI -3.03 to 1.66; p = 0.56). CONCLUSIONS: These data provide evidence that decreased cognitive composite scores were significantly associated with increased AD pathology and provide support for the use of cognitive composite scores in AD prevention trials. SN - 1758-9193 UR - https://www.unboundmedicine.com/medline/citation/30205840/Cognitive_composite_score_association_with_Alzheimer's_disease_plaque_and_tangle_pathology_ L2 - https://alzres.biomedcentral.com/articles/10.1186/s13195-018-0401-z DB - PRIME DP - Unbound Medicine ER -