Hippocampal volumes in UK Biobank are associated with only in older adults.
paper
Primary
Public
- Authors
- Chaloemtoem, Ariya; Thornton, Vera; Chang, Yoonhoo; Anokhin, Andrey P; Belloy, Michaël E; Bijsterbosch, Janine; Gordon, Brian A; Hartz, Sarah M; Bierut, Laura J
- Year
- 2024
- Journal
- Alzheimer's & dementia (Amsterdam, Netherlands)
- PMID
- 39553251
- DOI
- 10.1002/dad2.70024
- PMCID
- PMC11567847
INTRODUCTION: The hippocampus atrophies with age and is implicated in neurodegenerative disorders including Alzheimer's disease (AD). We examined the interplay between age and apolipoprotein E () genotype on total hippocampal volume. METHODS: Using neuroimaging data from 37,463 UK Biobank participants, we applied linear regression to quantify the association of age and with hippocampal volume and identified the age when volumes of ε2/ε3, ε3/ε4, and ε4/ε4 carriers significantly deviated from ε3/ε3 using generalized additive modeling. RESULTS: Total hippocampal volume declined with age, with significant differences by genotype emerging after age 60. ε3/ε4 and ε4/ε4 carriers displayed reduced volumes from ages 69 and 61, respectively, while ε2/ε3 showed delayed decline starting at the age of 76. DISCUSSION: The association of and hippocampal volume is age-dependent, with differences in volumes of ε4/ε4 carriers detected as early as age 61. This work underscores the importance of genotype in determining when to begin screening for AD. HIGHLIGHTS: Apolipoprotein E () genotype shows an age-dependent association with total hippocampal volume.No association between and total hippocampal volume was detected before age 60.Accelerated decline was observed in ε4/ε4 carriers at age 61 and ε3/ε4 at age 69.Delayed decline was evident in ε2/ε3 carriers starting at age 76.
Five‐year centered moving average of (A) raw total hippocampal volume and (B) residual total hippocampal volume after adjusting for covariates and centering at the mean of ε3/ε3 age < 60. APOE, apolipoprotein E.
Sum of effect sizes for total hippocampal volume (mm3) relative to age < 60 and ε3/ε3 status based on results from the regression model with interactions. Error bars represent 95% CI and asterisks indicate significant interactions based on linear regression results. * P < 0.05, ** P < 0.01, *** P < 0.001. APOE, apolipoprotein E; CI, confidence interval.
Estimated differences in total hippocampal volume from ε3/ε3 by APOE genotype. APOE, apolipoprotein E.
← Prev
21–34 of 34
No entities extracted from this document yet.
No uploaded files.
Not in any collection.
| Citation | PMID | DOI | Status |
|---|---|---|---|
| 2023 Alzheimer's disease facts and figures. Alzheimers Dement. 2023;19(4):1598‐1695. doi:10.1002/alz.13016 36918389 | — | — | — |
| Alfaro‐Almagro F , Jenkinson M , Bangerter NK , et al. Image processing and quality control for the first 10,000 brain imaging datasets from UK Biobank. Neuroimage. 2018;166:400‐424. doi:10.1016/j.neuroimage.2017.10.034 29079522 PMC5770339 | — | — | — |
| Alfaro‐Almagro F , McCarthy P , Afyouni S , et al. Confound modelling in UK Biobank brain imaging. Neuroimage. 2021;224:117002. doi:10.1016/j.neuroimage.2020.117002 32502668 PMC7610719 | — | — | — |
| Ashton NJ , Brum WS , Di Molfetta G , et al. Diagnostic accuracy of a plasma phosphorylated tau 217 immunoassay for Alzheimer Disease Pathology. JAMA Neurol. 2024;81(3):255‐263. doi:10.1001/jamaneurol.2023.5319 38252443 PMC10804282 | — | — | — |
| Bateman RJ , Xiong C , Benzinger TL , et al. Clinical and biomarker changes in dominantly inherited Alzheimer's disease. N Engl J Med. 2012;367(9):795‐804. doi:10.1056/NEJMoa1202753 22784036 PMC3474597 | — | — | — |
| Burggren AC , Zeineh MM , Ekstrom AD , et al. Reduced cortical thickness in hippocampal subregions among cognitively normal apolipoprotein E e4 carriers. Neuroimage. 2008;41(4):1177‐1183. doi:10.1016/j.neuroimage.2008.03.039 18486492 PMC2601686 | — | — | — |
| Button KS , Ioannidis JP , Mokrysz C , et al. Power failure: why small sample size undermines the reliability of neuroscience. Nat Rev Neurosci. 2013;14(5):365‐376. doi:10.1038/nrn3475 23571845 | — | — | — |
| Bycroft C , Freeman C , Petkova D , et al. The UK Biobank resource with deep phenotyping and genomic data. Nature. 2018;562(7726):203‐209. doi:10.1038/s41586-018-0579-z 30305743 PMC6786975 | — | — | — |
| Cardenas‐Iniguez C , Gonzalez MR . Recommendations for the responsible use and communication of race and ethnicity in neuroimaging research. Nat Neurosci. 2024;27(4):615‐628. doi:10.1038/s41593-024-01608-4 38519749 PMC11698468 | — | — | — |
| Chartier‐Harlin MC , Parfitt M , Legrain S , et al. Apolipoprotein E, epsilon 4 allele as a major risk factor for sporadic early and late‐onset forms of Alzheimer's disease: analysis of the 19q13.2 chromosomal region. Hum Mol Genet. 1994;3(4):569‐574. doi:10.1093/hmg/3.4.569 8069300 | — | — | — |
| Corder EH , Saunders AM , Risch NJ , et al. Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease. Nat Genet. 1994;7(2):180‐184. doi:10.1038/ng0694-180 7920638 | — | — | — |
| Corder EH , Saunders AM , Strittmatter WJ , et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science. 1993;261(5123):921‐923. doi:10.1126/science.8346443 8346443 | — | — | — |
| Farrer LA , Cupples LA , Haines JL , et al. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta‐analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA. 1997;278(16):1349‐1356.9343467 | — | — | — |
| Gong L , Xu R , Liu D , Lan L , Zhang B , Zhang C . The Specific impact of apolipoprotein E epsilon 2 on cognition and brain function in cognitively normal elders and mild cognitive impairment patients. Front Aging Neurosci. 2020;11:374. doi:10.3389/fnagi.2019.00374 32226373 PMC7081769 | — | — | — |
| Hostage CA , Roy Choudhury K , Doraiswamy PM , Petrella JR , Alzheimer's Disease Neuroimaging Initiative . Dissecting the gene dose‐effects of the APOE ε4 and ε2 alleles on hippocampal volumes in aging and Alzheimer's disease. PLoS One. 2013;8(2):e54483. doi:10.1371/journal.pone.0054483 23405083 PMC3566140 | — | — | — |
| Jack CR Jr , Holtzman DM . Biomarker modeling of Alzheimer's disease. Neuron. 2013;80(6):1347‐1358. doi:10.1016/j.neuron.2013.12.003 24360540 PMC3928967 | — | — | — |
| Jack CR Jr , Knopman DS , Jagust WJ , et al. Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers. Lancet Neurol. 2013;12(2):207‐216. doi:10.1016/S1474-4422(12)70291-0 23332364 PMC3622225 | — | — | — |
| Jack CR Jr , Petersen RC , Xu YC , et al. Hippocampal atrophy and apolipoprotein E genotype are independently associated with Alzheimer's disease. Ann Neurol. 1998;43(3):303‐310. doi:10.1002/ana.410430307 9506546 PMC2752747 | — | — | — |
| Khan W , Giampietro V , Banaschewski T , et al. A multi‐cohort study of ApoE ɛ4 and amyloid‐β effects on the hippocampus in Alzheimer's disease. J Alzheimers Dis. 2017;56(3):1159‐1174. doi:10.3233/JAD-161097 28157104 PMC5302035 | — | — | — |
| Lemaître H , Crivello F , Dufouil C , et al. No epsilon4 gene dose effect on hippocampal atrophy in a large MRI database of healthy elderly subjects. Neuroimage. 2005;24(4):1205‐1213. doi:10.1016/j.neuroimage.2004.10.016 15670698 | — | — | — |
| Littlejohns TJ , Holliday J , Gibson LM , et al. The UK Biobank imaging enhancement of 100,000 participants: rationale, data collection, management and future directions. Nat Commun. 2020;11(1):2624. doi:10.1038/s41467-020-15948-9 32457287 PMC7250878 | — | — | — |
| Manning EN , Barnes J , Cash DM , et al. APOE ε4 is associated with disproportionate progressive hippocampal atrophy in AD. PLoS One. 2014;9(5):e97608. doi:10.1371/journal.pone.0097608 24878738 PMC4039513 | — | — | — |
| Marek S , Tervo‐Clemmens B , Calabro FJ , et al. Reproducible brain‐wide association studies require thousands of individuals. Nature. 2022;603(7902):654‐660. doi:10.1038/s41586-022-04492-9 35296861 PMC8991999 | — | — | — |
| McKay GJ , Silvestri G , Chakravarthy U , et al. Variations in apolipoprotein E frequency with age in a pooled analysis of a large group of older people. Am J Epidemiol. 2011;173(12):1357‐1364. doi:10.1093/aje/kwr015 21498624 PMC3145394 | — | — | — |
| Miller KL , Alfaro‐Almagro F , Bangerter NK , et al. Multimodal population brain imaging in the UK Biobank prospective epidemiological study. Nat Neurosci. 2016;19(11):1523‐1536. doi:10.1038/nn.4393 27643430 PMC5086094 | — | — | — |
| Mishra S , Blazey TM , Holtzman DM , et al. Longitudinal brain imaging in preclinical Alzheimer disease: impact of APOE ε4 genotype. Brain. 2018;141(6):1828‐1839. doi:10.1093/brain/awy103 29672664 PMC5972633 | — | — | — |
| Moffat SD , Szekely CA , Zonderman AB , Kabani NJ , Resnick SM . Longitudinal change in hippocampal volume as a function of apolipoprotein E genotype. Neurology. 2000;55(1):134‐136. doi:10.1212/wnl.55.1.134 10891924 | — | — | — |
| National Academies of Sciences, Engineering, and Medicine . Using Population Descriptors in Genetics and Genomics Research: A New Framework for an Evolving Field. The National Academies Press; 2023. doi:10.17226/26902 36989389 | — | — | — |
| O'Dwyer L , Lamberton F , Matura S , et al. Reduced hippocampal volume in healthy young ApoE4 carriers: an MRI study. PLoS One. 2012;7(11):e48895. doi:10.1371/journal.pone.0048895 23152815 PMC3494711 | — | — | — |
| Reiman EM , Uecker A , Caselli RJ , et al. Hippocampal volumes in cognitively normal persons at genetic risk for Alzheimer's disease. Ann Neurol. 1998;44(2):288‐291. doi:10.1002/ana.410440226 9708558 | — | — | — |
| Riedel BC , Thompson PM , Brinton RD . Age, APOE and sex: triad of risk of Alzheimer's disease. J Steroid Biochem Mol Biol. 2016;160:134‐147. doi:10.1016/j.jsbmb.2016.03.012 26969397 PMC4905558 | — | — | — |
| Sudlow C , Gallacher J , Allen N , et al. UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med. 2015;12(3):e1001779. doi:10.1371/journal.pmed.1001779 25826379 PMC4380465 | — | — | — |
| Szucs D , Ioannidis JP . Sample size evolution in neuroimaging research: an evaluation of highly‐cited studies (1990‐2012) and of latest practices (2017‐2018) in high‐impact journals. Neuroimage. 2020;221:117164. doi:10.1016/j.neuroimage.2020.117164 32679253 | — | — | — |
| van Buuren S , Groothuis‐Oudshoorn K . mice: multivariate Imputation by Chained Equations in R. J Stat Softw. 2011;45(3):1‐67. doi:10.18637/jss.v045.i03 | — | — | — |
| Veldsman M , Nobis L , Alfaro‐Almagro F , Manohar S , Husain M . The human hippocampus and its subfield volumes across age, sex and APOE e4 status. Brain Commun. 2020;3(1):fcaa219. doi:10.1093/braincomms/fcaa219 33615215 PMC7884607 | — | — | — |
| Walhovd KB , Fjell AM , Sørensen Ø , et al. Genetic risk for Alzheimer disease predicts hippocampal volume through the human lifespan. Neurol Genet. 2020;6(5):e506. doi:10.1212/NXG.0000000000000506 33134508 PMC7577559 | — | — | — |
| Wang X , Zhou W , Ye T , Lin X , Zhang J ; Alzheimer's Disease Neuroimaging Initiative . The relationship between hippocampal volumes and delayed recall is modified by APOE ε4 in mild cognitive impairment. Front Aging Neurosci. 2019;11:36. doi:10.3389/fnagi.2019.00036 30863302 PMC6399520 | — | — | — |
| Wood SN . Fast stable restricted maximum likelihood and marginal likelihood estimation of semiparametric generalized linear models. J R Stat Soc Series B Stat Methodol. 2011;73(1):3‐36. doi:10.1111/j.1467-9868.2010.00749.x | — | — | — |
| Ziegler G , Dahnke R , Jäncke L , Yotter RA , May A , Gaser C . Brain structural trajectories over the adult lifespan. Hum Brain Mapp. 2012;33(10):2377‐2389. doi:10.1002/hbm.21374 21898677 PMC6870331 | — | — | — |
No papers in this knowledge base cite this source.
No citations found for this source.