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Validating the role of the Australian National University Alzheimer's Disease Risk Index (ANU-ADRI) and a genetic risk score in progression to cognitive impairment in a population-based cohort of older adults followed for 12 years.
Alzheimers Res Ther. 2017 Mar 04; 9(1):16.AR

Abstract

BACKGROUND

The number of people living with dementia is expected to exceed 130 million by 2050, which will have serious personal, social and economic implications. Employing successful intervention and treatment strategies focused on disease prevention is currently the only available approach that can have an impact on the projected rates of dementia, with risk assessment being a key component of population-based risk reduction for identification of at-risk individuals. We evaluated a risk index comprising lifestyle, medical and demographic factors (the Australian National University Alzheimer's Disease Risk Index [ANU-ADRI]), as well as a genetic risk score (GRS), for assessment of the risk of progression to mild cognitive impairment (MCI).

METHODS

The ANU-ADRI was computed for the baseline assessment of 2078 participants in the Personality and Total Health (PATH) Through Life project. GRSs were constructed on the basis of 25 single-nucleotide polymorphisms previously associated with Alzheimer's disease (AD). Participants were assessed for clinically diagnosed MCI and dementia as well as psychometric test-based MCI (MCI-TB) at 12 years of follow-up. Multi-state models were used to estimate the odds of transitioning from cognitively normal (CN) to MCI, dementia and MCI-TB over 12 years according to baseline ANU-ADRI and GRS.

RESULTS

A higher ANU-ADRI score was associated with increased risk of progressing from CN to both MCI and MCI-TB (HR 1.07 [95% CI 1.04-1.11]; 1.07 [1.04-1.09]). The GRS was associated with transitions from CN to dementia (HR 4.19 [95% CI 1.72-10.20), but not to MCI or MCI-TB (HR 1.05 [95% CI 0.86-1.29]; 1.03 [0.87-1.21]). Limitations of our study include that the ethnicity of participants in the PATH project is predominately Caucasian, potentially limiting the generalisability of the results of this study to people of other ethnicities. Biomarkers of AD were not available to define MCI attributable to AD. Not all the predictive variables for the ANU-ADRI were available in the PATH project.

CONCLUSIONS

In the general population, the ANU-ADRI, comprising lifestyle, medical and demographic factors, is associated with the risk of progression from CN to MCI, whereas a GRS comprising the main AD risk genes was not associated with this risk. The ANU-ADRI may be used for population-level risk assessment and screening.

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Authors+Show Affiliations

Andrews SJ
John Curtin School of Medical Research, Australian National University, Canberra, Australia. shea.andrews@anu.edu.au. Centre for Research on Ageing, Health and Wellbeing, Research School of Population Health Australian National University, The Australian National University Florey, Building 54, Mills Road, Acton ACT 2601, Canberra, Australia. shea.andrews@anu.edu.au.
Eramudugolla R
Centre for Research on Ageing, Health and Wellbeing, Research School of Population Health Australian National University, The Australian National University Florey, Building 54, Mills Road, Acton ACT 2601, Canberra, Australia.
Velez JI
John Curtin School of Medical Research, Australian National University, Canberra, Australia. Universidad del Norte, Barranquilla, Colombia. Neuroscience Research Group, University of Antioquia, Medellin, Colombia.
Cherbuin N
Centre for Research on Ageing, Health and Wellbeing, Research School of Population Health Australian National University, The Australian National University Florey, Building 54, Mills Road, Acton ACT 2601, Canberra, Australia.
Easteal S
John Curtin School of Medical Research, Australian National University, Canberra, Australia.
Anstey KJ
Centre for Research on Ageing, Health and Wellbeing, Research School of Population Health Australian National University, The Australian National University Florey, Building 54, Mills Road, Acton ACT 2601, Canberra, Australia.

MeSH

AgedAlzheimer DiseaseAustraliaAustralian Capital TerritoryCognitive DysfunctionComorbidityDisease ProgressionFemaleGenetic MarkersGenetic Predisposition to DiseaseGenetic TestingHumansIncidenceLongitudinal StudiesMaleMiddle AgedPolymorphism, Single NucleotidePrognosisProportional Hazards ModelsReproducibility of ResultsRisk AssessmentSensitivity and Specificity

Pub Type(s)

Evaluation Study
Journal Article
Validation Study

Language

eng

PubMed ID

28259165

Citation

Andrews, Shea J., et al. "Validating the Role of the Australian National University Alzheimer's Disease Risk Index (ANU-ADRI) and a Genetic Risk Score in Progression to Cognitive Impairment in a Population-based Cohort of Older Adults Followed for 12 Years." Alzheimer's Research & Therapy, vol. 9, no. 1, 2017, p. 16.
Andrews SJ, Eramudugolla R, Velez JI, et al. Validating the role of the Australian National University Alzheimer's Disease Risk Index (ANU-ADRI) and a genetic risk score in progression to cognitive impairment in a population-based cohort of older adults followed for 12 years. Alzheimers Res Ther. 2017;9(1):16.
Andrews, S. J., Eramudugolla, R., Velez, J. I., Cherbuin, N., Easteal, S., & Anstey, K. J. (2017). Validating the role of the Australian National University Alzheimer's Disease Risk Index (ANU-ADRI) and a genetic risk score in progression to cognitive impairment in a population-based cohort of older adults followed for 12 years. Alzheimer's Research & Therapy, 9(1), 16. https://doi.org/10.1186/s13195-017-0240-3
Andrews SJ, et al. Validating the Role of the Australian National University Alzheimer's Disease Risk Index (ANU-ADRI) and a Genetic Risk Score in Progression to Cognitive Impairment in a Population-based Cohort of Older Adults Followed for 12 Years. Alzheimers Res Ther. 2017 Mar 4;9(1):16. PubMed PMID: 28259165.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Validating the role of the Australian National University Alzheimer's Disease Risk Index (ANU-ADRI) and a genetic risk score in progression to cognitive impairment in a population-based cohort of older adults followed for 12 years. AU - Andrews,Shea J, AU - Eramudugolla,Ranmalee, AU - Velez,Jorge I, AU - Cherbuin,Nicolas, AU - Easteal,Simon, AU - Anstey,Kaarin J, Y1 - 2017/03/04/ PY - 2016/10/10/received PY - 2017/02/01/accepted PY - 2017/3/6/entrez PY - 2017/3/6/pubmed PY - 2018/1/30/medline KW - Alzheimer’s disease KW - Cognitive aging KW - Cohort studies KW - Mild cognitive impairment (MCI) KW - Multi-state models KW - Risk factors in epidemiology SP - 16 EP - 16 JF - Alzheimer's research & therapy JO - Alzheimers Res Ther VL - 9 IS - 1 N2 - BACKGROUND: The number of people living with dementia is expected to exceed 130 million by 2050, which will have serious personal, social and economic implications. Employing successful intervention and treatment strategies focused on disease prevention is currently the only available approach that can have an impact on the projected rates of dementia, with risk assessment being a key component of population-based risk reduction for identification of at-risk individuals. We evaluated a risk index comprising lifestyle, medical and demographic factors (the Australian National University Alzheimer's Disease Risk Index [ANU-ADRI]), as well as a genetic risk score (GRS), for assessment of the risk of progression to mild cognitive impairment (MCI). METHODS: The ANU-ADRI was computed for the baseline assessment of 2078 participants in the Personality and Total Health (PATH) Through Life project. GRSs were constructed on the basis of 25 single-nucleotide polymorphisms previously associated with Alzheimer's disease (AD). Participants were assessed for clinically diagnosed MCI and dementia as well as psychometric test-based MCI (MCI-TB) at 12 years of follow-up. Multi-state models were used to estimate the odds of transitioning from cognitively normal (CN) to MCI, dementia and MCI-TB over 12 years according to baseline ANU-ADRI and GRS. RESULTS: A higher ANU-ADRI score was associated with increased risk of progressing from CN to both MCI and MCI-TB (HR 1.07 [95% CI 1.04-1.11]; 1.07 [1.04-1.09]). The GRS was associated with transitions from CN to dementia (HR 4.19 [95% CI 1.72-10.20), but not to MCI or MCI-TB (HR 1.05 [95% CI 0.86-1.29]; 1.03 [0.87-1.21]). Limitations of our study include that the ethnicity of participants in the PATH project is predominately Caucasian, potentially limiting the generalisability of the results of this study to people of other ethnicities. Biomarkers of AD were not available to define MCI attributable to AD. Not all the predictive variables for the ANU-ADRI were available in the PATH project. CONCLUSIONS: In the general population, the ANU-ADRI, comprising lifestyle, medical and demographic factors, is associated with the risk of progression from CN to MCI, whereas a GRS comprising the main AD risk genes was not associated with this risk. The ANU-ADRI may be used for population-level risk assessment and screening. SN - 1758-9193 UR - https://www.unboundmedicine.com/medline/citation/28259165/Validating_the_role_of_the_Australian_National_University_Alzheimer's_Disease_Risk_Index__ANU_ADRI__and_a_genetic_risk_score_in_progression_to_cognitive_impairment_in_a_population_based_cohort_of_older_adults_followed_for_12_years_ L2 - https://alzres.biomedcentral.com/articles/10.1186/s13195-017-0240-3 DB - PRIME DP - Unbound Medicine ER -