Association Between Polygenic Risk Score and the Progression from Mild Cognitive Impairment to Alzheimer’s Disease

2021 ◽  
pp. 1-13
Author(s):  
Hongliang Liu ◽  
Michael Lutz ◽  
Sheng Luo ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Risk Scores ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Increased Risk ◽  
Risk Of Progression ◽  
Clinical Changes

Background: Mild cognitive impairment (MCI) is a heterogeneous condition and MCI patients are at increased risk of progression to dementia due to Alzheimer’s disease (AD). Objective: In this study, we aim to evaluate the associations between polygenic risk scores (PRSs) and 1) time to AD progression from MCI, 2) changes in longitudinal cognitive impairment, and 3) biomarkers from cerebrospinal fluid and imaging. Methods: We constructed PRS by using 40 independent non-APOE SNPs from well-replicated AD GWASs and tested its association with the progression time from MCI to AD by using 767 MCI patients from the ADNI study and 1373 patients from the NACC study. PRSs calculated with other methods were also computed. Results: We found that the PRS constructed with SNPs that reached genome-wide significance predicted the progression from MCI to AD (beta = 0.182, se = 0.061, p = 0.003) after adjusting for the demographic and clinical variables. This association was replicated in the NACC dataset (beta = 0.094, se = 0.037, p = 0.009). Further analyses revealed that PRS was associated with the increased ADAS-Cog11/ADAS-Cog13/ADASQ4 scores, tau/ptau levels, and cortical amyloid burdens (PIB and AV45), but decreased hippocampus and entorhinal cortex volumes (p <  0.05). Mediation analysis showed that the effect of PRS on the increased risk of AD may be mediated by Aβ 42 (beta = 0.056, SE = 0.026, p = 0.036). Conclusion: Our findings suggest that PRS can be useful for the prediction of time to AD and other clinical changes after the diagnosis of MCI.

scholarly journals Predictability of polygenic risk score for progression to dementia and its interaction with APOE ε4 in mild cognitive impairment

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Jung-Min Pyun ◽  
Young Ho Park ◽  
Keon-Joo Lee ◽  
SangYun Kim ◽  
Andrew J. Saykin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Disease Progression ◽  
Risk Score ◽  
Polygenic Risk Score ◽  
Carrier Status ◽  
Polygenic Risk ◽  
Increased Risk

Abstract Background The combinatorial effect of multiple genetic factors calculated as a polygenic risk score (PRS) has been studied to predict disease progression to Alzheimer’s disease (AD) from mild cognitive impairment (MCI). Previous studies have investigated the performance of PRS in the prediction of disease progression to AD by including and excluding single nucleotide polymorphisms within the region surrounding the APOE gene. These studies may have missed the APOE genotype-specific predictability of PRS for disease progression to AD. Methods We analyzed 732 MCI from the Alzheimer’s Disease Neuroimaging Initiative cohort, including those who progressed to AD within 5 years post-baseline (n = 270) and remained stable as MCI (n = 462). The predictability of PRS including and excluding the APOE region (PRS+APOE and PRS−APOE) on the conversion to AD and its interaction with the APOE ε4 carrier status were assessed using Cox regression analyses. Results PRS+APOE (hazard ratio [HR] 1.468, 95% CI 1.335–1.615) and PRS−APOE (HR 1.293, 95% CI 1.157–1.445) were both associated with a significantly increased risk of MCI progression to dementia. The interaction between PRS+APOE and APOE ε4 carrier status was significant with a P-value of 0.0378. The association of PRSs with the progression risk was stronger in APOE ε4 non-carriers (PRS+APOE: HR 1.710, 95% CI 1.244–2.351; PRS−APOE: HR 1.429, 95% CI 1.182–1.728) than in APOE ε4 carriers (PRS+APOE: HR 1.167, 95% CI 1.005–1.355; PRS−APOE: HR 1.172, 95% CI 1.020–1.346). Conclusions PRS could predict the conversion of MCI to dementia with a stronger association in APOE ε4 non-carriers than APOE ε4 carriers. This indicates PRS as a potential genetic predictor particularly for MCI with no APOE ε4 alleles.

P3-077: ALZHEIMER'S DISEASE (AD) POLYGENIC RISK SCORE (PRS) AS A PREDICTOR OF CONVERSION FROM MILD COGNITIVE IMPAIRMENT (MCI)

2006 ◽  
Vol 14 (7S_Part_20) ◽  
pp. P1094-P1094
Author(s):  
Sultan Raja Chaudhury ◽  
Tulsi Patel ◽  
Abigail Fallows ◽  
Keeley J. Brookes ◽  
Tamar Guetta-Baranes ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Risk Score ◽  
Polygenic Risk Score ◽  
Polygenic Risk

scholarly journals Use of an Alzheimer’s disease polygenic risk score to identify mild cognitive impairment in adults in their 50s

2018 ◽  
Vol 24 (3) ◽  
pp. 421-430 ◽  
Author(s):  
Mark W. Logue ◽  
Matthew S. Panizzon ◽  
Jeremy A. Elman ◽  
Nathan A. Gillespie ◽  
Sean N. Hatton ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Risk Score ◽  
Polygenic Risk Score ◽  
Polygenic Risk

scholarly journals Alzheimer’s disease polygenic risk score as a predictor of conversion from mild-cognitive impairment

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Sultan Chaudhury ◽  
Keeley J. Brookes ◽  
Tulsi Patel ◽  
Abigail Fallows ◽  
Tamar Guetta-Baranes ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Risk Score ◽  
Polygenic Risk Score ◽  
Polygenic Risk

scholarly journals Polygenic Risk Scoring is an Effective Approach to Predict Those Individuals Most Likely to Decline Cognitively Due to Alzheimer’s Disease

2020 ◽  
pp. 1-6
Author(s):  
P. Daunt ◽  
C.G. Ballard ◽  
B. Creese ◽  
G. Davidson ◽  
J. Hardy ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Risk Scores ◽  
Cognitively Normal ◽  
Polygenic Risk ◽  
Csf Biomarker ◽  
Risk Scoring

BACKGROUND: There is a clear need for simple and effective tests to identify individuals who are most likely to develop Alzheimer’s Disease (AD) both for the purposes of clinical trial recruitment but also for improved management of patients who may be experiencing early pre-clinical symptoms or who have clinical concerns. OBJECTIVES: To predict individuals at greatest risk of progression of cognitive impairment due to Alzheimer’s Disease in individuals from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) using a polygenic risk scoring algorithm. To compare the performance of a PRS algorithm in predicting cognitive decline against that of using the pTau/Aß1-42 ratio CSF biomarker profile. DESIGN: A longitudinal analysis of data from the Alzheimer’s Disease Neuroimaging Initiative study conducted across over 50 sites in the US and Canada. SETTING: Multi-center genetics study. PARTICPANTS: 515 subjects who upon entry to the study were diagnosed as cognitively normal or with mild cognitive impairment. MEASUREMENTS: Use of genotyping and/or whole genome sequencing data to calculate polygenic risk scores and assess ability to predict subsequent cognitive decline as measured by CDR-SB and ADAS-Cog13 over 4 years. RESULTS: The overall performance for predicting those individuals who would decline by at least 15 ADAS-Cog13 points from a baseline mild cognitive impairment in 4 years was 72.8% (CI:67.9-77.7) AUC increasing to 79.1% (CI: 75.6-82.6) when also including cognitively normal participants. Assessing mild cognitive impaired subjects only and using a threshold of greater than 0.6, the high genetic risk participant group declined, on average, by 1.4 points (CDR-SB) more than the low risk group over 4 years. The performance of the PRS algorithm tested was similar to that of the pTau/Aß1-42 ratio CSF biomarker profile in predicting cognitive decline. CONCLUSION: Calculating polygenic risk scores offers a simple and effective way, using DNA extracted from a simple mouth swab, to select mild cognitively impaired patients who are most likely to decline cognitively over the next four years.

scholarly journals Correction: Alzheimer’s disease polygenic risk score as a predictor of conversion from mild-cognitive impairment

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Sultan Chaudhury ◽  
Keeley J. Brookes ◽  
Tulsi Patel ◽  
Abigail Fallows ◽  
Tamar Guetta-Baranes ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Risk Score ◽  
Polygenic Risk Score ◽  
Polygenic Risk

[P3-114]: ALZHEIMER'S DISEASE POLYGENIC RISK SCORE PREDICTS MILD COGNITIVE IMPAIRMENT (MCI) IN MIDDLE AGE

2017 ◽  
Vol 13 (7S_Part_20) ◽  
pp. P978-P978
Author(s):  
William S. Kremen ◽  
Mark W. Logue ◽  
Matthew Panizzon ◽  
Jeremy A. Elman ◽  
Nathan Gillespie ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Risk Score ◽  
Middle Age ◽  
Polygenic Risk Score ◽  
Polygenic Risk

Association Between the APOE ɛ2/ɛ4 Genotype and Alzheimer’s Disease and Mild Cognitive Impairment Among African Americans

2021 ◽  
pp. 1-6
Author(s):  
Dianxu Ren ◽  
Oscar L. Lopez ◽  
Jennifer H. Lingler ◽  
Yvette Conley
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
African Americans ◽  
Hazard Ratio ◽  
Adjusted Hazard Ratio ◽  
Increased Risk ◽  
Similar Risk

We examined the association between APOE ɛ2/ɛ4 with incident Alzheimer’s disease (AD) and mild cognitive impairment (MCI) among African Americans using the national dataset from the National Alzheimer’s Coordinating Center (NACC) from 2005 to September 2019. Compared to ɛ3/ɛ3 carriers, ɛ2/ɛ4 carriers exhibited a similar risk of incident AD (adjusted hazard ratio [aHR] = 0.85, 95% CI [0.39, 1.84]) among the AD cohort and similar risk of incident MCI (aHR = 0.88, 95% CI [0.51, 1.50]) among the MCI cohort. Our findings suggest that, unlike the increased risk of AD and MCI in non-Latino whites, APOE ɛ2/ɛ4 genotype is not associated with the incidence of AD and MCI among African Americans.

Sign in / Sign up

Export Citation Format

Share Document