Article
Neurosciences
Jung-Min Pyun, Young Ho Park, Keon-Joo Lee, SangYun Kim, Andrew J. Saykin, Kwangsik Nho
Summary: The study found that polygenic risk scores (PRS) could predict the risk of MCI patients progressing to dementia, with a stronger association in APOE epsilon 4 non-carriers.
TRANSLATIONAL NEURODEGENERATION
(2021)
Article
Cell Biology
Moeen Riaz, Aamira Huq, Joanne Ryan, Suzanne G. Orchard, Jane Tiller, Jessica Lockery, Robyn L. Woods, Rory Wolfe, Alan E. Renton, Alison M. Goate, Robert Sebra, Eric Schadt, Amy Brodtmann, Raj C. Shah, Elsdon Storey, Anne M. Murray, John J. McNeil, Paul Lacaze
Summary: This study showed that the incidence of dementia is low among healthy older individuals, but APOE epsilon 4 genotype and high PRS increase the relative risk. APOE epsilon 4 is associated with cognitive decline while PRS is not.
Article
Geriatrics & Gerontology
D. A. Kashtanova, A. A. Mamchur, I. H. Dzhumaniyazova, M. V. Ivanov, V. V. Erema, E. A. Zelenova, A. Y. Yakovchik, M. S. Gusakova, A. M. Rumyantseva, M. V. Terekhov, L. R. Matkava, A. A. Akopyan, I. D. Strazhesko, V. S. Yudin, V. V. Makarov, S. A. Kraevoy, O. N. Tkacheva, S. M. Yudin
Summary: This study investigated possible causes of cognitive impairment and proposed preventive options. The rs429358 polymorphism in the APOE gene was found to cause changes in protein structure, potentially contributing to the development of cognitive impairment. However, cognitive impairment is determined by multiple factors, as confirmed by the polygenic risk score model. The findings can contribute to the development of early detection strategies for cognitive impairment in older adults.
FRONTIERS IN AGING NEUROSCIENCE
(2023)
Article
Geriatrics & Gerontology
Li Shang, Liling Dong, Xinying Huang, Tianyi Wang, Chenhui Mao, Jie Li, Jie Wang, Caiyan Liu, Jing Gao
Summary: This study aimed to investigate the associations of APOE epsilon 4/epsilon 4 with fluid biomarkers in dementia and biomarker-diagnosed AD. The results showed that APOE epsilon 4/epsilon 4 was associated with decreased CSF A beta 42 levels in AD patients, but not with tau protein. In non-AD patients, APOE epsilon 4 carriers had lower CSF A beta 42 levels and higher T-tau/A beta 42 and P-tau181/A beta 42 ratios.
FRONTIERS IN AGING NEUROSCIENCE
(2023)
Article
Clinical Neurology
Malan Johansen, Sofus Joensen, Marjun Restorff, Tormodur Stora, Darren Christy, Emil K. Gustavsson, Jiang Bian, Yi Guo, Matthew J. Farrer, Maria Skaalum Petersen
Summary: This study revealed the association of APOE and immunogenomic variability with AD and dementia risk in the Faroe Islands. The PRS+APOE based on SNP analysis showed excellent sensitivity and specificity for the diagnosis of AD. High PRSs were also associated with an earlier onset of late-onset AD.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Article
Cell Biology
Alexander M. Kulminski, Ethan Jain-Washburn, Elena Loiko, Yury Loika, Fan Feng, Irina Culminskaya, Alzheimer's Disease Neuroimaging Initiative Alzheimers Dis Neuroimaging Initiative
Summary: This study examined the associations of APOE alleles and polygenic profiles with cerebrospinal fluid and plasma biomarkers, revealing differential effects of specific alleles on different biomarkers.
Article
Neurosciences
Jagan A. Pillai, Lei Kou, James Bena, Lisa Penn, James B. Leverenz
Summary: In older individuals, hypercholesterolemia may be associated with a lower risk of dementia, while hypertension may be linked to a higher risk of dementia among non-carriers of APOE epsilon 4. Conversely, vascular risk factors have less impact on dementia risk among younger participants.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Clinical Neurology
Thomas J. Littlejohns, Jennifer A. Collister, Xiaonan Liu, Lei Clifton, Neo M. Tapela, David J. Hunter
Summary: Hypertension was associated with an increased risk of dementia regardless of genetic risk for dementia. The risk difference between those with and without hypertension was larger among those at higher genetic risk.
ALZHEIMERS & DEMENTIA
(2023)
Article
Neurosciences
Nicholas J. Schork, Jeremy A. Elman
Summary: By studying specific pathways associated with Alzheimer's disease, we can gain a better understanding of the disease's progression and risk factors. Pathway-specific polygenic risk scores may not have significant predictive power, but they can be useful in studying other complex diseases.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Neurosciences
Daniel J. Panyard, Yuetiva K. Deming, Burcu F. Darst, Carol A. Van Hulle, Henrik Zetterberg, Kaj Blennow, Gwendlyn Kollmorgen, Ivonne Suridjan, Cynthia M. Carlsson, Sterling C. Johnson, Sanjay Asthana, Corinne D. Engelman, Qiongshi Lu
Summary: Functional annotation of genomic data can be used to build tissue-specific polygenic risk score (PRS) models for Alzheimer's disease (AD), which are associated with AD diagnosis and cerebrospinal fluid biomarkers. The liver AD PRS model was particularly predictive of AD diagnosis and showed significant associations with amyloid-beta and phosphorylated tau levels.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Neurosciences
Smita Patel, Jun Wei, Zhuqing Shi, Andrew S. Rifkin, S. Lilly Zheng, Elizabeth Gelfman, David Duggan, Brian T. Helfand, Peter J. Hulick, Jianfeng Xu
Summary: In a large population-based cohort, not all heterozygous APOE epsilon 4 carriers are at increased risk for Alzheimer's disease (AD). Only epsilon 3/epsilon 4 carriers showed a significantly higher proportion of AD, not epsilon 2/epsilon 4 carriers. Among epsilon 3/epsilon 4 carriers (24% in the cohort), the AD proportion differed significantly based on polygenic risk score (PRS). Particularly, subjects in the bottom 20-percentile PRS had a lower AD proportion compared to the entire cohort, while subjects at the top 5th-percentile PRS had a higher AD proportion than homozygous epsilon 4 carriers. Family history was no longer a significant predictor of AD risk after adjusting APOE and PRS.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Geriatrics & Gerontology
Olesya Ajnakina, Diana Shamsutdinova, Daniel Stahl, Andrew Steptoe
Summary: By investigating the influence of genetic predisposition to longevity and APOE-e4 on mortality risk, we found that genetic predisposition to longevity and APOE-e4 are associated with all-cause mortality and specific causes of mortality. Dementia was identified as a potential mediator in these relationships. Increasing the polygenic score for longevity was associated with a decreased risk of all-cause mortality and mortality due to other causes, while APOE-e4 status was associated with a reduced risk of all-cause mortality and cancer-related mortality in women.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2023)
Article
Rheumatology
Chien-Yu Lin, Ya-Sian Chang, Ting-Yuan Liu, Chung-Ming Huang, Chin-Chun Chung, Yu-Chia Chen, Fuu-Jen Tsai, Jan-Gowth Chang, Shun-Jen Chang
Summary: This study identified genetic variants and polygenic risk scores related to female gout and asymptomatic hyperuricaemia (AH) through a genome-wide association study (GWAS). The variants in the SLC2A9 gene were found to be the major genetic factors associated with gout in females aged >= 50, while variants in the SLC2A9, ZNF518B, PKD2, and ABCG2 genes were significantly related to AH in both age groups. The polygenic risk score provided a more accurate prediction of gout and AH.
Article
Neurosciences
Sarang Kang, Jungsoo Gim, Jiwoon Lee, Tamil Iniyan Gunasekaran, Kyu Yeong Choi, Jang Jae Lee, Eun Hyun Seo, Pan-Woo Ko, Ji Yeon Chung, Seong-Min Choi, Young Min Lee, Jee Hyang Jeong, Kyung Won Park, Min Kyung Song, Ho-Won Lee, Ki Woong Kim, Seong Hye Choi, Dong Young Lee, Sang Yun Kim, Hoowon Kim, Byeong C. Kim, Takeshi Ikeuchi, Kun Ho Lee
Summary: This study identified two novel genome-wide significant loci for late-onset Alzheimer's disease (LOAD) in East Asian APOE epsilon 4 non-carrier subjects, located in the PRIG1 and CACNA1A genes. The findings suggest that the discovery of AD-associated variants is possible in non-European ethnic groups, even with fewer subjects and a more homogeneous genetic background.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Endocrinology & Metabolism
Enrique Soto-Pedre, Paul J. Newey, Sundararajan Srinivasan, Moneeza K. Siddiqui, Colin N. A. Palmer, Graham P. Leese
Summary: This study investigates the genetic associations with primary hyperparathyroidism (PHPT) using both a genome-wide association study (GWAS) and candidate gene approaches. The results suggest that genetic variants at SOX9, SLITRK5, LPAR3, and BCDIN3D-AS1 are associated with an increased risk of PHPT. Furthermore, carriers of more PHPT-risk alleles, both male and female, have a significantly higher risk of developing PHPT.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Psychiatry
Emma Ruby Francis, Dorina Cadar, Andrew Steptoe, Olesya Ajnakina
Summary: A diet rich in fruit and vegetables is important in reducing the risk of dementia, especially for individuals with a polygenic predisposition to AD, schizophrenia, and general cognition. Consuming less than 5 portions of fruit and vegetables a day is associated with a higher risk of dementia, and the risk is increased by higher polygenic scores for AD and SZ. The interaction between polygenic scores for general cognition and low fruit and vegetable intake is also significantly associated with AD diagnosis.
Article
Psychology, Clinical
Olesya Ajnakina, Robin Murray, Andrew Steptoe, Dorina Cadar
Summary: This study examines the relationship between polygenic predisposition to general cognition and the rate of cognitive decline during a 10-year follow-up period. The results show that an increase in polygenic scores for general cognition is associated with higher baseline verbal memory and semantic fluency scores. However, there is no association between polygenic predisposition and age-related cognitive decline.
PSYCHOLOGICAL MEDICINE
(2023)
Article
Medicine, General & Internal
Olesya Ajnakina, Diana Shamsutdinova, Theresa Wimberley, Soren Dalsgaard, Andrew Steptoe
Summary: The study investigates whether a high polygenetic predisposition to ADHD exacerbates the risk of all-cause mortality in older adults from the general population in the UK. The results show that a high polygenetic predisposition to ADHD is a risk factor for all-cause mortality in older adults, and this risk is better captured when incorporating genetic information from correlated traits.
Article
Clinical Neurology
Pamela Almeida-Meza, Marcus Richards, Dorina Cadar
Summary: This study examined the impact of genetic and life course factors on cognitive state at age 69. The results showed that childhood cognition, cognitive reserve index (CRI), and reading ability were positively associated with cognitive state. The CRI and reading ability were found to moderate the association between childhood cognition and cognitive state.
Article
Health Care Sciences & Services
Barbara Angel, Olesya Ajnakina, Cecilia Albala, Lydia Lera, Carlos Marquez, Leona Leipold, Avri Bilovich, Richard Dobson, Rebecca Bendayan
Summary: Growing evidence suggests that early changes in physical functioning can serve as a potential biomarker for cognitive impairment. Our study provides robust evidence of the association between grip strength and cognitive performance, and explores how socioeconomic factors can impact this association and its variability across countries.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Geriatrics & Gerontology
Paramita Khairan, Kokoro Shirai, Yugo Shobugawa, Dorina Cadar, Tami Saito, Katsunori Kondo, Tomotaka Sobue, Hiroyasu Iso
Summary: A prior history of frailty and pre-frailty, with or without pneumonia, was associated with an increased risk of dementia. However, there was no association between a previous history of pneumonia alone and dementia risk.
INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY
(2022)
Article
Immunology
Keqin Chu, Dorina Cadar, Eleonora Iob, Philipp Frank
Summary: This study aimed to investigate whether systemic low-grade inflammation mediated the association between excess body weight and different symptom domains of depression. The results showed that systemic low-grade inflammation partially mediated the association between excess body weight and somatic depressive symptoms, but not cognitive-affective or overall depressive symptoms.
BRAIN BEHAVIOR AND IMMUNITY
(2023)
Article
Geriatrics & Gerontology
Charlotte L. Campbell, Dorina Cadar, Anne McMunn, Paola Zaninotto
Summary: This study operationalized intrinsic capacity (IC) in older people using item response theory and tested its predictive value for functional ability, mortality, and hospital admission. The results showed that higher IC scores were associated with reduced risk of subsequent difficulties, hospital admission, and mortality.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2023)
Article
Geriatrics & Gerontology
Dorina Cadar, Laura Brocklebank, Li Yan, Yaohui Zhao, Andrew Steptoe
Summary: This study aimed to examine the impact of sociocultural differentials between the western and eastern parts of the world on cognitive functioning. The findings showed that education and wealth were associated with memory performance in both England and China, but the effect of urbanicity differed between the two countries. Additionally, memory decline was socioeconomically patterned in China but not in England.
JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES
(2023)
Meeting Abstract
Public, Environmental & Occupational Health
Olesya Ajnakina, Robin Murray, Andrew Steptoe, Dorina Cadar
JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH
(2022)
Meeting Abstract
Public, Environmental & Occupational Health
Dorina Cadar, Laura Brocklebank, Shabina Hayat, Li Yan, Yaohui Zhao, Andrew Steptoe
JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH
(2022)
Meeting Abstract
Public, Environmental & Occupational Health
Anne McMunn, Paola Zaninotto, Charlotte Campbell, Dorina Cadar
JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH
(2022)
Correction
Psychiatry
L. A. Duffner, K. Deckers, D. Cadar, A. Steptoe, M. de Vugt, S. Kohler
EPIDEMIOLOGY AND PSYCHIATRIC SCIENCES
(2022)
