Combining Polygenic Hazard Score With Volumetric MRI and Cognitive Measures Improves Prediction of Progression From Mild Cognitive Impairment to Alzheimer's Disease
Open accessAbstract
Improved prediction of progression to Alzheimer’s Disease (AD) among older individuals with mild cognitive impairment (MCI) is of high clinical and societal importance. We recently developed a polygenic hazard score (PHS) that predicted age of AD onset above and beyond APOE. Here, we used data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) to further explore the potential clinical utility of PHS for predicting AD development in older adults with MCI. We examined the predictive value of PHS alone and in combination with baseline structural magnetic resonance imaging (MRI) data on performance on the Mini-Mental State Exam (MMSE). In survival analyses, PHS significantly predicted time to progression from MCI to AD over 120 months (p=1.07e-5), and PHS was significantly more predictive than APOE alone (p=0.015). Combining PHS with baseline brain atrophy score and/or MMSE score significantly improved prediction compared to models without PHS (three-factor model p=4.28e-17). Prediction model accuracies, sensitivities and area under the curve were also improved by including PHS in the model, compared to only using atrophy score and MMSE. Further, using linear mixed-effect modeling, PHS improved the prediction of change in the Clinical Dementia Rating – Sum of Boxes (CDR-SB) score and MMSE over 36 months in patients with MCI at baseline, beyond both APOE and baseline levels of brain atrophy. These results illustrate the potential clinical utility of PHS for assessment of risk for AD progression among individuals with MCI both alone, or in conjunction with clinical measures of prodromal disease including measures of cognitive function and regional brain atrophy.
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Kauppi et al. (2018) improved prediction of AD among MCI patients by uniting age-sensitive polygenic hazard score with structural neuroimaging relating to cognitive ability.
“Kauppi et al. (2018) recently improved the prediction of AD among MCI patients by uniting age-sensitive polygenic hazard score (PHS) with structural neuroimaging relating to cognitive ability.”
From Recent Advancements in Pathogenesis, Diagnostics and Treatment of Alzheimer’s Disease (2020) · cites this paper as [90]
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Self-citation
- Authors
- Kauppi, K., Fan, C. C., McEvoy, L. K., Holland, D., Tan, C. H., Chen, C.-H., Andreassen, O. A., Desikan, R. S., Dale, A. M., & Initiative, T. A. D. N.
- Affiliations
- University of California San Diego (US)
- University of California, San Francisco (US)
- Oslo University Hospital (NO)
- Corresponding author
- Kauppi, Karolina
- Dale, Anders M.
- ORCID
- Venue
- Frontiers in Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2018-04-30
- Volume
- 12
- Pages
- 260-260
- ISSN
- 1662-453X (ISSN-L)
- PMC
- PMC5937163
- OpenAlex
- W2802185677
- Cited by
- 60
- References
- 24
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 4 · 2023: 12 · 2022: 8 · 2021: 8 · 2020: 7 · 2019: 9 · 2018: 2
- FWCI
- 5.12
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Frontiers in Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- KTH Publication Database DiVA (KTH Royal Institute of Technology) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion)
- NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
- Funders
- National Institutes of Health (P30 AG010129, K01 AG030514)
- Vetenskapsrådet
- Norges Forskningsråd
- Stiftelsen Kristian Gerhard Jebsen
- National Institute on Alcohol Abuse and Alcoholism (R01AA021187)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- polygenic hazard score, mild cognitive impairment, Alzheimer's disease progression, apolipoprotein E, brain atrophy, volumetric MRI, Mini-Mental State Examination, Clinical Dementia Rating, genetic risk prediction, prodromal Alzheimer's disease, ADNI
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