scholarly journals Predicting aging of brain metabolic topography using variational autoencoder

2017 ◽  
Author(s):  
Hongyoon Choi ◽  
Hyejin Kang ◽  
Dong Soo Lee ◽  

AbstractPredicting future brain topography can give insight into neural correlates of aging and neurodegeneration. Due to variability in aging process, it has been challenging to precisely estimate brain topographical change according to aging. Here, we predict age-related brain metabolic change by generating future brain 18F-Fluorodeoxyglucose PET. A cross-sectional PET dataset of cognitively normal subjects with different age was used to develop a generative model. The model generated PET images using age information and characteristic individual features. Predicted regional metabolic changes were correlated with the real changes obtained by follow-up data. This model was applied to produce a brain metabolism aging movie by generating PET at different ages. Normal population distribution of brain metabolic topography at each age was estimated as well. In addition, a generative model using APOE4 status as well as age as inputs revealed a significant effect of APOE4 status on age-related metabolic changes particularly in the calcarine, lingual cortex, hippocampus and amygdala. It suggested APOE4 could be a factor affecting individual variability in age-related metabolic degeneration in normal elderly. This predictive model may not only be extended to understanding cognitive aging process, but apply to development of a preclinical biomarker for various brain disorders.

GeroScience ◽  
2021 ◽  
Author(s):  
Monica Baciu ◽  
Sonja Banjac ◽  
Elise Roger ◽  
Célise Haldin ◽  
Marcela Perrone-Bertolotti ◽  
...  

AbstractIn the absence of any neuropsychiatric condition, older adults may show declining performance in several cognitive processes and among them, in retrieving and producing words, reflected in slower responses and even reduced accuracy compared to younger adults. To overcome this difficulty, healthy older adults implement compensatory strategies, which are the focus of this paper. We provide a review of mainstream findings on deficient mechanisms and possible neurocognitive strategies used by older adults to overcome the deleterious effects of age on lexical production. Moreover, we present findings on genetic and lifestyle factors that might either be protective or risk factors of cognitive impairment in advanced age. We propose that “aging-modulating factors” (AMF) can be modified, offering prevention opportunities against aging effects. Based on our review and this proposition, we introduce an integrative neurocognitive model of mechanisms and compensatory strategies for lexical production in older adults (entitled Lexical Access and Retrieval in Aging, LARA). The main hypothesis defended in LARA is that cognitive aging evolves heterogeneously and involves complementary domain-general and domain-specific mechanisms, with substantial inter-individual variability, reflected at behavioral, cognitive, and brain levels. Furthermore, we argue that the ability to compensate for the effect of cognitive aging depends on the amount of reserve specific to each individual which is, in turn, modulated by the AMF. Our conclusion is that a variety of mechanisms and compensatory strategies coexist in the same individual to oppose the effect of age. The role of reserve is pivotal for a successful coping with age-related changes and future research should continue to explore the modulating role of AMF.


Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1611
Author(s):  
Nur Fathiah Abdul Abdul Sani ◽  
Ahmad Imran Zaydi Amir Amir Hamzah ◽  
Zulzikry Hafiz Abu Abu Bakar ◽  
Yasmin Anum Mohd Mohd Yusof ◽  
Suzana Makpol ◽  
...  

The mechanism of cognitive aging at the molecular level is complex and not well understood. Growing evidence suggests that cognitive differences might also be caused by ethnicity. Thus, this study aims to determine the gene expression changes associated with age-related cognitive decline among Malay adults in Malaysia. A cross-sectional study was conducted on 160 healthy Malay subjects, aged between 28 and 79, and recruited around Selangor and Klang Valley, Malaysia. Gene expression analysis was performed using a HumanHT-12v4.0 Expression BeadChip microarray kit. The top 20 differentially expressed genes at p < 0.05 and fold change (FC) = 1.2 showed that PAFAH1B3, HIST1H1E, KCNA3, TM7SF2, RGS1, and TGFBRAP1 were regulated with increased age. The gene set analysis suggests that the Malay adult’s susceptibility to developing age-related cognitive decline might be due to the changes in gene expression patterns associated with inflammation, signal transduction, and metabolic pathway in the genetic network. It may, perhaps, have important implications for finding a biomarker for cognitive decline and offer molecular targets to achieve successful aging, mainly in the Malay population in Malaysia.


Author(s):  
Raphaele Tsao ◽  
Cecile Kindelberger ◽  
Benedicte Fréminville ◽  
Renaud Touraine ◽  
Gerald Bussy

Abstract The aim of this cross-sectional study was to analyze the typical aging process in adults with Down syndrome, focusing on its variability. The sample comprised 120 adults with Down syndrome who were free of dementia. Ages ranged from 20 to 69 years. Each participant was assessed on cognitive functioning and social adaptation, and was checked for the presence of psychopathological disorders. Results revealed an age-related deterioration in both cognitive and social adaptation skills, the extent of this decline depending on the dimension under scrutiny, and interindividual variability in aging profiles.


2019 ◽  
Vol 34 (6) ◽  
pp. 1053-1053
Author(s):  
M Gonzalez Catalan ◽  
C Lindbergh ◽  
A Staffaroni ◽  
S Walters ◽  
K Casaletto ◽  
...  

Abstract Objective Cross-sectional studies have shown age-related differences in working memory (WM), but the trajectory is unclear due to the scarcity of longitudinal studies. Additional research is needed to better characterize the course of age-related changes in WM in older adults. The present study sought to address this gap in the literature by conducting serial assessments of WM in a longitudinally followed cohort of typically aging adults. We hypothesized a significant age × time interaction, such that WM would show pronounced declines with advancing age. Methods 640 functionally intact participants in an aging cohort (clinical dementia rating = 0; age range 52-99, mean age = 75) completed a computerized WM measure, Running Letter Memory (RLM), every ~15 months for up to 8.5 years (mean follow-up = 1.9 years). Longitudinal changes in RLM scores were analyzed using linear mixed effects models, allowing for random slopes and intercepts. All models were adjusted for sex and education. Results RLM performance did not significantly decline over time (b = -.14, p = .43). As hypothesized, there was a significant age × time interaction predicting RLM scores (b = -.08, p = .006). Specifically, RLM performance remained relatively stable (or slightly improved) until around age 75, beyond which increasingly precipitous declines were observed with advancing age. Conclusion The present results suggest that WM performance does not evidence declines until the mid-70s in typically aging adults, at which point increasingly steep decline trajectories are observed with advancing age. These findings highlight that cognitive aging does not occur at a constant rate in late life.


2010 ◽  
Vol 16 (5) ◽  
pp. 754-760 ◽  
Author(s):  
TIMOTHY A. SALTHOUSE

AbstractResearch concerned with relations between adult age and cognitive functioning is briefly reviewed. The coverage is necessarily selective, and is organized in terms of five major questions. These are what abilities are related to age, how many distinct influences are contributing to the relations between age and cognitive functioning, do the differences between people increase with advancing age, what is responsible for the discrepancies between cross-sectional and longitudinal age comparisons of cognitive functioning, and what methods can be used to identify causes of age-related influences on cognition. Although definitive answers are not yet possible, quite a bit of information relevant to the questions is now available. Moreover, the existing information has implications for the design, analysis, and interpretation of cognitive and neuropsychological research concerned with aging. (JINS, 2010, 16, 754–760.)


2014 ◽  
Vol 35 (5) ◽  
pp. 857-894 ◽  
Author(s):  
SHARI BAUM ◽  
DEBRA TITONE

ABSTRACTNormal aging is an inevitable race between increasing knowledge and decreasing cognitive capacity. Crucial to understanding and promoting successful aging is determining which of these factors dominates for particular neurocognitive functions. Here, we focus on the human capacity for language, for which healthy older adults are simultaneously advantaged and disadvantaged. In recent years, a more hopeful view of cognitive aging has emerged from work suggesting that age-related declines in executive control functions are buffered by life-long bilingualism. In this paper, we selectively review what is currently known and unknown about bilingualism, executive control, and aging. Our ultimate goal is to advance the views that these issues should be reframed as a specific instance of neuroplasticity more generally and, in particular, that researchers should embrace the individual variability among bilinguals by adopting experimental and statistical approaches that respect the complexity of the questions addressed. In what follows, we set out the theoretical assumptions and empirical support of the bilingual advantages perspective, review what we know about language, cognitive control, and aging generally, and then highlight several of the relatively few studies that have investigated bilingual language processing in older adults, either on their own or in comparison with monolingual older adults. We conclude with several recommendations for how the field ought to proceed to achieve a more multifactorial view of bilingualism that emphasizes the notion of neuroplasticity over that of simple bilingual versus monolingual group comparisons.


2019 ◽  
Author(s):  
Yunzhang Wang ◽  
Robert Karlsson ◽  
Juulia Jylhävä ◽  
Åsa K. Hedman ◽  
Catarina Almqvist ◽  
...  

AbstractBackgroundThe role of DNA methylation in aging has been widely studied. However, epigenetic mutations, here defined as aberrant methylation levels compared to the distribution in a population, are less understood. Hence, we investigated longitudinal accumulation of epigenetic mutations, using 994 blood samples collected at up to five time points from 375 individuals in old ages.ResultsWe verified earlier cross-sectional evidence on the increase of epigenetic mutations with age, and identified important contributing factors including sex, CD19+ B cells, genetic background, cancer diagnosis and technical artifacts. We further classified epigenetic mutations into High/Low Methylation Outliers (HMO/LMO) according to their changes in methylation, and specifically studied methylation sites (CpGs) that were prone to mutate (frequently mutated CpGs). We validated four epigenetically mutated CpGs using pyrosequencing in 93 samples. Furthermore, by using twins, we concluded that the age-related accumulation of epigenetic mutations was not related to genetic factors, hence driven by stochastic or environmental effects.ConclusionsHere we conducted a comprehensive study of epigenetic mutation and highlighted its important role in aging process and cancer development.


2017 ◽  
Author(s):  
Qin Wang ◽  
Diana L Santos Ferreira ◽  
Scott M Nelson ◽  
Naveed Sattar ◽  
Mika Ala-Korpela ◽  
...  

AbstractBackgroundIt remains elusive whether the changes in cardiometabolic biomarkers during the menopausal transition are due to ovarian aging or chronological aging. Well-conducted longitudinal studies are required to determine this. The aim of this study was to explore the cross-sectional and longitudinal associations of reproductive status defined according to the 2012 Stages of Reproductive Aging Workshop criteria with 74 metabolic biomarkers, and establish whether any associations are independent of age related changes.MethodsWe determined cross-sectional associations of reproductive status with metabolic profiling in 3,312 UK midlife women. In a subgroup of 1,492 women who had repeat assessments after 2.5 years, we assessed how change in reproductive status was associated with the changes in metabolic biomarkers. Metabolic profiles were measured by high-throughput quantitative serum NMR metabolomics. In longitudinal analyses, we compared the change in metabolic biomarkers for each reproductive status category change to that in the reference of being pre-menopausal at both time points. As all women aged by a similar amount during follow-up, these analyses contribute to distinguish age related changes from those related to change in reproductive status.ResultsConsistent cross-sectional and longitudinal associations of menopause with a wide range of metabolic biomarkers were observed, suggesting transition to menopause induces multiple metabolic changes independent of chronological aging. The metabolic changes included increased concentrations of very small VLDL, IDL and LDL subclasses, remnant and LDL cholesterol, and reduced LDL particle size, all towards an atherogenic lipoprotein profile. Increased inflammation was suggested via an inflammatory biomarker, glycoprotein acetyls, but not via C-reactive protein. Also, levels of glutamine and albumin were increased during the transition. Most of these metabolic changes seen at the time of becoming post-menopausal remained or became slightly stronger during the post-menopausal years.ConclusionsTransition to post-menopause has effects on multiple circulating metabolic biomarkers, over and above the underlying age trajectory. The adverse changes in multiple apolipoprotein-B containing lipoprotein subclasses and increased inflammation may underlie women’s increased cardiometabolic risk in post-menopausal years.AbbreviationsALSPACAvon Longitudinal Study of Parents and ChildrenBMIbody mass indexCRPhigh sensitive C-reactive proteinCVDcardiovascular diseasesHDLhigh-density lipoproteinHRThormone replacement therapyIDLintermediate-density lipoproteinLDLlow-density lipoproteinSDstandard deviationSTRAWStages of Reproductive Aging WorkshopSWANThe Study of Women’s health Across the NationVLDLvery low-density lipoprotein


2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Yunzhang Wang ◽  
Robert Karlsson ◽  
Juulia Jylhävä ◽  
Åsa K. Hedman ◽  
Catarina Almqvist ◽  
...  

Abstract Background The role of DNA methylation in aging has been widely studied. However, epigenetic mutations, here defined as aberrant methylation levels compared to the distribution in a population, are less understood. Hence, we investigated longitudinal accumulation of epigenetic mutations, using 994 blood samples collected at up to five time points from 375 individuals in old ages. Results We verified earlier cross-sectional evidence on the increase of epigenetic mutations with age, and identified important contributing factors including sex, CD19+ B cells, genetic background, cancer diagnosis, and technical artifacts. We further classified epigenetic mutations into High/Low Methylation Outliers (HMO/LMO) according to their changes in methylation, and specifically studied methylation sites (CpGs) that were prone to mutate (frequently mutated CpGs). We validated four epigenetically mutated CpGs using pyrosequencing in 93 samples. Furthermore, by using twins, we concluded that the age-related accumulation of epigenetic mutations was not related to genetic factors, hence driven by stochastic or environmental effects. Conclusions Here we conducted a comprehensive study of epigenetic mutation and highlighted its important role in aging process and cancer development.


Sign in / Sign up

Export Citation Format

Share Document