Genetic Prοpensity for Different Aspects of Dementia Pathology and Cognitive Decline in a Community Elderly Population
Abstract
1. Introduction
2. Results
2.1. Baseline Clinical and Socio-Demographic Characteristics
2.2. PRSs and Cognitive Decline
3. Discussion
4. Materials and Methods
4.1. Participants and Procedures
4.2. Neuropsychological Assessment
4.3. Genotyping and Imputation
4.4. Polygenic Risk Score Estimation
4.5. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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All Participants | PRS 1 Aβ42 | PRS WMH | |||||
---|---|---|---|---|---|---|---|
Low | High | Low | High | ||||
N = 512 | N = 256 | N = 256 | p-Value | N = 256 | N = 256 | p-Value | |
Age (years), mean ± SD 2 | 73.4 ± 4.9 | 72.8 ± 4.5 | 74.0 ± 5.3 | 0.030 | 73.7 ± 5.1 | 73.2 ± 4.7 | 0.238 |
Sex, females (%) | 290 (56.6) | 148 (57.8) | 142 (55.5) | 0.467 | 135 (52.7) | 155 (60.5) | 0.084 |
Education years, mean ± SD | 7.1 ± 4.5 | 7.0 ± 4.6 | 7.2 ± 4.4 | 0.662 | 7.2 ± 4.4 | 7.0 ± 4.5 | 0.623 |
Follow-up duration, mean ± SD | 2.9 ± 0.8 | 3.0 ± 0.9 | 2.9 ± 0.8 | 0.156 | 2.9 ± 0.8 | 3.0 ± 0.8 | 0.167 |
APOE ε4 carriers, yes (%) | 86 (16.8) | 38 (14.8) | 48 (18.8) | 0.188 | 42 (16.4) | 44 (17.2) | 0.804 |
Global score, mean ± SD | −0.39 ± 0.79 | −0.47 ± 0.86 | −0.32 ± 0.71 | 0.042 | −0.41 ± 0.85 | −0.37 ± 0.74 | 0.530 |
Memory score, mean ± SD | −0.32 ± 0.90 | −0.38 ± 0.93 | −0.26 ± 0.87 | 0.124 | −0.28 ± 0.94 | −0.36 ± 0.86 | 0.325 |
Attention score, mean ± SD | −0.40 ± 1.21 | −0.50 ± 1.37 | −0.30 ± 1.02 | 0.082 | −0.43 ± 1.26 | −0.36 ± 1.17 | 0.459 |
Visuospatial score, mean ± SD | −0.42 ± 0.94 | −0.47 ± 1.01 | −0.36 ± 0.86 | 0.222 | −0.45 ± 1.03 | −0.38 ± 0.84 | 0.509 |
Executive score, mean ± SD | −0.34 ± 0.78 | −0.30 ± 0.72 | −0.38 ± 0.85 | 0.303 | −0.36 ± 0.78 | −0.32 ± 0.78 | 0.525 |
Language score, mean ± SD | −0.37 ± 0.89 | −0.44 ± 0.92 | −0.31 ± 0.85 | 0.105 | −0.39 ± 0.93 | −0.35 ± 0.85 | 0.550 |
All Participants | Low GC 1 Group | High GC 1 Group | ||
---|---|---|---|---|
N = 512 | N = 256 | N = 256 | p-Value | |
Age (years), mean ± SD 2 | 73.4 ± 4.9 | 75.1 ± 4.7 | 71.8 ± 4.5 | <0.001 |
Sex, females (%) | 290 (56.6) | 141 (55.1) | 149 (58.2) | 0.585 |
Education years, mean ± SD | 7.1 ± 4.5 | 4.9 ± 3.1 | 9.4 ± 4.5 | <0.001 |
Follow-up duration, mean ± SD | 2.9 ± 0.8 | 3.0 ± 0.9 | 2.8 ± 0.8 | 0.146 |
APOE ε4 carriers, yes (%) | 86 (16.8) | 47 (18.4) | 39 (15.2) | 0.397 |
PRS Aβ42, high (%) | 256 (50.0) | 133 (52.0) | 123 (48.0) | 0.416 |
PRS WMH, high (%) | 256 (50.0) | 131 (51.2) | 125 (48.8) | 0.641 |
Global | Memory | Executive | Visuospatial | Language | Attention | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
N = 512 | Β 1 | p | β | p | β | p | β | p | β | p | β | p |
PRS 2 Aβ42 | −0.042 | 0.002 | −0.025 | 0.198 | −0.028 | 0.161 | −0.005 | 0.464 | −0.024 | 0.273 | −0.020 | 0.375 |
PRS WMH | −0.029 | 0.037 | −0.016 | 0.325 | −0.017 | 0.146 | −0.005 | 0.439 | −0.013 | 0.468 | −0.012 | 0.348 |
Males | Global | Memory | Executive | Visuospatial | Language | Attention | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
N = 222 | β 1 | p | β | p | β | p | β | p | β | p | β | p |
PRS 2 Aβ42 | −0.029 | 0.019 | −0.012 | 0.337 | −0.025 | 0.306 | −0.008 | 0.309 | −0.014 | 0.329 | −0.022 | 0.278 |
PRS WMH | −0.028 | 0.039 | −0.003 | 0.341 | −0.010 | 0.351 | −0.010 | 0.309 | 0.003 | 0.324 | −0.020 | 0.180 |
Females | Global | Memory | Executive | Visuospatial | Language | Attention | ||||||
N = 290 | β | p | β | p | β | p | β | p | β | p | β | p |
PRS Aβ42 | −0.057 | <0.001 | −0.038 | 0.012 | −0.029 | 0.252 | −0.003 | 0.335 | −0.031 | 0.091 | −0.018 | 0.103 |
PRS WMH | −0.031 | 0.023 | −0.030 | 0.031 | −0.025 | 0.260 | −0.003 | 0.342 | −0.029 | 0.095 | −0.004 | 0.347 |
Younger Group | Global | Memory | Executive | Visuospatial | Language | Attention | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
N = 256 | β 1 | p | β | p | β | p | β | p | β | p | β | p |
PRS 2 Aβ42 | −0.036 | 0.013 | −0.011 | 0.299 | −0.026 | 0.305 | −0.011 | 0.302 | −0.025 | 0.112 | −0.019 | 0.298 |
PRS WMH | −0.027 | 0.040 | −0.007 | 0.302 | −0.010 | 0.304 | −0.010 | 0.301 | −0.024 | 0.097 | −0.011 | 0.314 |
Older Group | Global | Memory | Executive | Visuospatial | Language | Attention | ||||||
N = 256 | β | p | β | p | β | p | β | p | β | p | β | p |
PRS Aβ42 | −0.048 | 0.002 | −0.039 | 0.002 | −0.029 | 0.214 | −0.002 | 0.425 | −0.023 | 0.152 | −0.021 | 0.276 |
PRS WMH | −0.030 | 0.021 | −0.027 | 0.005 | −0.023 | 0.219 | −0.002 | 0.473 | −0.003 | 0.356 | −0.014 | 0.340 |
Low CR 1 | Global | Memory | Executive | Visuospatial | Language | Attention | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
N = 340 | β 2 | p | β | p | β | p | β | p | β | p | β | p |
PRS 3 Aβ42 | −0.047 | <0.001 | −0.006 | 0.301 | −0.032 | 0.145 | −0.008 | 0.366 | −0.030 | 0.073 | −0.023 | 0.125 |
PRS WMH | −0.029 | 0.031 | −0.008 | 0.300 | −0.016 | 0.302 | −0.010 | 0.345 | −0.007 | 0.386 | −0.013 | 0.314 |
High CR | Global | Memory | Executive | Visuospatial | Language | Attention | ||||||
N = 172 | β | p | β | p | β | p | β | p | β | p | β | p |
PRS Aβ42 | −0.039 | 0.004 | −0.046 | <0.001 | −0.023 | 0.247 | −0.003 | 0.472 | −0.022 | 0.123 | −0.015 | 0.237 |
PRS WMH | −0.030 | 0.021 | −0.032 | 0.020 | −0.019 | 0.272 | −0.003 | 0.415 | −0.004 | 0.401 | −0.010 | 0.407 |
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Sampatakakis, S.N.; Mourtzi, N.; Hatzimanolis, A.; Koutsis, G.; Charisis, S.; Gkelmpesi, I.; Mamalaki, E.; Ntanasi, E.; Ramirez, A.; Yannakoulia, M.; et al. Genetic Prοpensity for Different Aspects of Dementia Pathology and Cognitive Decline in a Community Elderly Population. Int. J. Mol. Sci. 2025, 26, 910. https://doi.org/10.3390/ijms26030910
Sampatakakis SN, Mourtzi N, Hatzimanolis A, Koutsis G, Charisis S, Gkelmpesi I, Mamalaki E, Ntanasi E, Ramirez A, Yannakoulia M, et al. Genetic Prοpensity for Different Aspects of Dementia Pathology and Cognitive Decline in a Community Elderly Population. International Journal of Molecular Sciences. 2025; 26(3):910. https://doi.org/10.3390/ijms26030910
Chicago/Turabian StyleSampatakakis, Stefanos N., Niki Mourtzi, Alex Hatzimanolis, Georgios Koutsis, Sokratis Charisis, Iliana Gkelmpesi, Eirini Mamalaki, Eva Ntanasi, Alfredo Ramirez, Mary Yannakoulia, and et al. 2025. "Genetic Prοpensity for Different Aspects of Dementia Pathology and Cognitive Decline in a Community Elderly Population" International Journal of Molecular Sciences 26, no. 3: 910. https://doi.org/10.3390/ijms26030910
APA StyleSampatakakis, S. N., Mourtzi, N., Hatzimanolis, A., Koutsis, G., Charisis, S., Gkelmpesi, I., Mamalaki, E., Ntanasi, E., Ramirez, A., Yannakoulia, M., Kosmidis, M. H., Dardiotis, E., Hadjigeorgiou, G., Sakka, P., & Scarmeas, N. (2025). Genetic Prοpensity for Different Aspects of Dementia Pathology and Cognitive Decline in a Community Elderly Population. International Journal of Molecular Sciences, 26(3), 910. https://doi.org/10.3390/ijms26030910