scholarly journals Brain-age in midlife is associated with accelerated biological aging and cognitive decline in a longitudinal birth cohort

2019 ◽  
Author(s):  
Maxwell L. Elliott ◽  
Daniel W. Belsky ◽  
Annchen R. Knodt ◽  
David Ireland ◽  
Tracy R. Melzer ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Birth Cohort ◽  
Brain Aging ◽  
Chronological Age ◽  
Biological Aging ◽  
Imaging Data ◽  
Cross Sectional ◽  
Cohort Differences ◽  
Age Related ◽  
The Brain

AbstractAn individual’s brainAGE is the difference between chronological age and age predicted from machine-learning models of brain-imaging data. BrainAGE has been proposed as a biomarker of age-related deterioration of the brain. Having an older brainAGE has been linked to Alzheimer’s, dementia, and mortality. However, these findings are largely based on cross-sectional associations which can confuse age differences with cohort differences. To illuminate the validity of brainAGE as a biomarker of accelerated brain aging, a study is needed of a large cohort all born in the same year who nevertheless vary on brainAGE. In the Dunedin Study, a population-representative 1972–73 birth cohort, we measured brainAGE at age 45 years, as well as the pace of biological aging and cognitive decline in longitudinal data from childhood to midlife (N = 869). In this cohort, all chronological age 45 years, brainAGE was measured reliably (ICC = 0.81) and ranged from 24 to 72 years. Those with older midlife brainAGEs tended to have poorer cognitive function in both adulthood and childhood, as well as impaired brain health at age 3. Furthermore, those with older brainAGEs had an accelerated pace of biological aging, older facial appearance, and early signs of cognitive decline from childhood to midlife. These findings help to validate brainAGE as a potential surrogate biomarker for midlife intervention studies that seek to measure dementia-prevention efforts in midlife. However, the findings also caution against the assumption that brainAGE scores represent only age-related deterioration of the brain as they may also index central nervous system variation present since childhood.

scholarly journals Brain-age in midlife is associated with accelerated biological aging and cognitive decline in a longitudinal birth-cohort

2019 ◽  
Author(s):  
Maxwell L. Elliott ◽  
Daniel W. Belsky ◽  
Annchen R. Knodt ◽  
David Ireland ◽  
Tracy R. Melzer ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Birth Cohort ◽  
Brain Aging ◽  
Chronological Age ◽  
Biological Aging ◽  
Imaging Data ◽  
Cohort Differences ◽  
Age Related ◽  
Brain Age ◽  
The Brain

AbstractAn individual’s brain-age is the difference between chronological age and age predicted from machine-learning models of brain-imaging data. Brain-age has been proposed as a biomarker of age-related deterioration of the brain. Having an older brain-age has been linked to Alzheimer’s, dementia and mortality. However, these findings are largely based on cross-sectional associations which can confuse age differences with cohort differences. To illuminate the validity of brain-age a biomarker of accelerated brain aging, a study is needed of a large cohort all born the same year who nevertheless vary on brain-age. In a population-representative 1972-73 birth cohort we measured brain-age at age 45, as well as the pace of biological aging and cognitive decline in longitudinal data from childhood to midlife (N=869). In this cohort, all chronological age 45 years, brain-age was measured reliably (ICC=.81) and ranged from 24 to 72 years. Those with older midlife brain-ages tended to have poorer cognitive function in both adulthood and childhood, as well as impaired brain health at age 3. Furthermore, those with older brain-ages had an accelerated pace of biological aging, older facial appearance and early signs of cognitive decline from childhood to midlife. These findings help to validate brain-age as a potential surrogate biomarker for midlife intervention studies that seek to measure treatment response to dementia-prevention efforts in midlife. However, the findings also caution against the assumption that brain-age scores represent only age-related deterioration of the brain as they may also index central nervous system variation present since childhood.

Aging

2019 ◽  
pp. 105-112
Author(s):  
Risto Näätänen ◽  
Teija Kujala ◽  
Gregory Light
Keyword(s):  
Hearing Loss ◽  
Speech Perception ◽  
Cognitive Decline ◽  
Temporal Processing ◽  
Brain Aging ◽  
Brain Plasticity ◽  
Part Of Speech ◽  
Memory Traces ◽  
Age Related ◽  
The Brain

This chapter shows that MMN and its magnetoencephalographic (MEG) equivalent MMNm are sensitive indices of aging-related perceptual and cognitive decline. Importantly, the age-related neural changes are associated with a decrease of general brain plasticity, i.e. that of the ability of the brain to form and maintain sensory-memory traces, a necessary basis for veridical perception and appropriate cognitive brain function. MMN/MMNm to change in stimulus duration is particularly affected by aging, suggesting the increased vulnerability of temporal processing to brain aging and accounting, for instance, for a large part of speech-perception difficulties of the aged beyond the age-related peripheral hearing loss.

scholarly journals Quantification of biological aging in young adults

2015 ◽  
Vol 112 (30) ◽  
pp. E4104-E4110 ◽  
Author(s):  
Daniel W. Belsky ◽  
Avshalom Caspi ◽  
Renate Houts ◽  
Harvey J. Cohen ◽  
David L. Corcoran ◽  
...  
Keyword(s):  
Young Adults ◽  
Brain Aging ◽  
Multiple Organ ◽  
Biological Aging ◽  
Research Translation ◽  
Human Aging ◽  
Aging Research ◽  
Cross Sectional ◽  
Age Related ◽  
Organ Systems

Antiaging therapies show promise in model organism research. Translation to humans is needed to address the challenges of an aging global population. Interventions to slow human aging will need to be applied to still-young individuals. However, most human aging research examines older adults, many with chronic disease. As a result, little is known about aging in young humans. We studied aging in 954 young humans, the Dunedin Study birth cohort, tracking multiple biomarkers across three time points spanning their third and fourth decades of life. We developed and validated two methods by which aging can be measured in young adults, one cross-sectional and one longitudinal. Our longitudinal measure allows quantification of the pace of coordinated physiological deterioration across multiple organ systems (e.g., pulmonary, periodontal, cardiovascular, renal, hepatic, and immune function). We applied these methods to assess biological aging in young humans who had not yet developed age-related diseases. Young individuals of the same chronological age varied in their “biological aging” (declining integrity of multiple organ systems). Already, before midlife, individuals who were aging more rapidly were less physically able, showed cognitive decline and brain aging, self-reported worse health, and looked older. Measured biological aging in young adults can be used to identify causes of aging and evaluate rejuvenation therapies.

Preserved cognition and reduced age-related cognitive decline during treatment with angiotensin II receptor blockers: A 20-year follow-up study

2017 ◽  
Vol 41 (S1) ◽  
pp. S372-S372 ◽  
Author(s):  
D. Wincewicz ◽  
T. Tolmunen ◽  
A.K. Brem ◽  
J. Kauhanen ◽  
S. Lehto
Keyword(s):  
Angiotensin Ii ◽  
Cognitive Decline ◽  
Population Based ◽  
Angiotensin Ii Receptor ◽  
Cross Sectional ◽  
Age Related ◽  
Receptor Blockers ◽  
Age Related Cognitive Decline ◽  
The Brain

IntroductionModulators of the brain renin-angiotensin system (RAS) have been shown to improve cognitive functioning in several animal models of neuropsychiatric disorders. Moreover, the brain RAS has been considered a new target for the treatment of Alzheimer's disease (AD). However, there are no population-based follow-up studies supporting this hypothesis.ObjectivesCross-sectional and prospective relationships between cognitive decline and ARB treatment were examined in the population-based Kuopio Ischemic Heart Disease Risk Factor Study.AimsTo evaluate procognitive/antidementia capacity of orally delivered angiotensin II receptor blockers (ARB).MethodsThe study was conducted on a sample of 1774 subjects (920 females, 854 males; age range at baseline: 42–61 years) from Eastern Finland. An established cutoff score of at least 2-point decrease in the Mini Mental State Examination over a 9-year follow-up was used to detect age-related cognitive decline in the cross-sectional setting. In the prospective setting, a hospital discharge diagnosis of dementia/AD was used as outcome variable. Cross-sectional relationships were determined with logistic regression and prospective analyses were conducted with the Cox proportional hazards model (both adjusted for relevant background variables).ResultsCross-sectional analysis displayed a decrease of the odds of cognitive decline (n = 87; 4.9% of participants) in those with ARB treatment; OR = 0.445, 95% CI: 0.22–0.90, P = 0.024. Furthermore, in the prospective setting, the risk of dementia/AD diagnosis (n = 149; 8.4% of participants) was significantly reduced in ARB treated participants; HR = 0.621, 95% CI: 0.40–0.98, P = 0.038.ConclusionsARB treatment is associated with a decreased risk for age-related cognitive decline and dementia/AD manifestation.Disclosure of interestThe authors have not supplied their declaration of competing interest.

CLOCK genetic variations are associated with age-related changes in sleep duration and brain volume

2021 ◽  
Author(s):  
Song E Kim ◽  
Soriul Kim ◽  
Hyeon Jin Kim ◽  
Regina E Y Kim ◽  
Sol Ah Kim ◽  
...  
Keyword(s):  
Circadian Rhythm ◽  
Sleep Duration ◽  
Sleep Disturbances ◽  
Brain Volume ◽  
Brain Aging ◽  
Genetic Variations ◽  
Analysis Of Covariance ◽  
Imaging Data ◽  
Cross Sectional ◽  
Age Related

Abstract Background Although a connection between sleep disruption and brain aging has been documented, biological mechanisms need to be further clarified. Intriguingly, aging is associated with circadian rhythm and/or sleep dysfunction in a key gene regulating circadian rhythm, CLOCK, have been linked to both aging-related sleep disturbances and neurodegenerative diseases. This study aims to investigate how CLOCK genetic variation associates with sleep duration changes and/or volumetric brain alteration. Methods This population-based cross-sectional study used data from the Korean Genome Epidemiology Study (KoGES), and analyzed sleep characteristics and genetic and brain imaging data in 2,221 subjects (mean 58.8±6.8 years, 50.2% male). Eleven single-nucleotide polymorphisms (SNPs) in CLOCK were analyzed using PLINK software v1.09 to test for their association with sleep duration and brain volume. Haplotype analysis was performed by using pair-wise linkage disequilibrium (LD) of CLOCK polymorphisms, and multivariate analysis of covariance was for statistical analysis. Results Decreased sleep duration was associated with several SNPs in CLOCK intronic regions, with the highest significance for rs10002541 (P=1.58x10 -5). Five SNPs with the highest significance (rs10002541-rs6850524-rs4580704- rs3805151-rs3749474) revealed that CGTCT was the most prevalent. In the major CGTCT haplotype, decreased sleep duration over time was associated with lower cortical volumes predominantly in frontal and parietal regions. Less common haplotypes (GCCTC/CGTTC) had shorter sleep duration and more decreases in sleep duration over 8 years, which revealed smaller total and gray matter volumes, especially in frontal and temporal regions of the left hemisphere. Conclusion CLOCK genetic variations could be involved in age-related sleep and brain volume changes.

scholarly journals Gene Expression Profile in Different Age Groups and Its Association with Cognitive Function in Healthy Malay Adults in Malaysia

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 ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cognitive Decline ◽  
Cognitive Aging ◽  
Successful Aging ◽  
Expression Patterns ◽  
Age Groups ◽  
Genetic Network ◽  
Cross Sectional ◽  
Age Related ◽  
Age Related Cognitive Decline

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.

scholarly journals Aging-associated deficit in CCR7 is linked to worsened glymphatic function, cognition, neuroinflammation, and β-amyloid pathology

2021 ◽  
Vol 7 (21) ◽  
pp. eabe4601
Author(s):  
Sandro Da Mesquita ◽  
Jasmin Herz ◽  
Morgan Wall ◽  
Taitea Dykstra ◽  
Kalil Alves de Lima ◽  
...  
Keyword(s):  
T Cells ◽  
Cognitive Decline ◽  
Brain Aging ◽  
Therapeutic Potential ◽  
T Cell Response ◽  
Age Related ◽  
Lymphatic Vasculature ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Old Mice

Aging leads to a progressive deterioration of meningeal lymphatics and peripheral immunity, which may accelerate cognitive decline. We hypothesized that an age-related reduction in C-C chemokine receptor type 7 (CCR7)–dependent egress of immune cells through the lymphatic vasculature mediates some aspects of brain aging and potentially exacerbates cognitive decline and Alzheimer’s disease–like brain β-amyloid (Aβ) pathology. We report a reduction in CCR7 expression by meningeal T cells in old mice that is linked to increased effector and regulatory T cells. Hematopoietic CCR7 deficiency mimicked the aging-associated changes in meningeal T cells and led to reduced glymphatic influx and cognitive impairment. Deletion of CCR7 in 5xFAD transgenic mice resulted in deleterious neurovascular and microglial activation, along with increased Aβ deposition in the brain. Treating old mice with anti-CD25 antibodies alleviated the exacerbated meningeal regulatory T cell response and improved cognitive function, highlighting the therapeutic potential of modulating meningeal immunity to fine-tune brain function in aging and in neurodegenerative diseases.

scholarly journals Multimodal measurement approach to identify individuals with mild cognitive impairment: study protocol for a cross-sectional trial

BMJ Open ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. e046879
Author(s):  
Bernhard Grässler ◽  
Fabian Herold ◽  
Milos Dordevic ◽  
Tariq Ali Gujar ◽  
Sabine Darius ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Statistical Analysis ◽  
Cognitive Decline ◽  
Cognitive Performance ◽  
Classification Accuracy ◽  
Multimodal Approach ◽  
Cross Sectional ◽  
Age Related ◽  
Age Related Cognitive Decline

IntroductionThe diagnosis of mild cognitive impairment (MCI), that is, the transitory phase between normal age-related cognitive decline and dementia, remains a challenging task. It was observed that a multimodal approach (simultaneous analysis of several complementary modalities) can improve the classification accuracy. We will combine three noninvasive measurement modalities: functional near-infrared spectroscopy (fNIRS), electroencephalography and heart rate variability via ECG. Our aim is to explore neurophysiological correlates of cognitive performance and whether our multimodal approach can aid in early identification of individuals with MCI.Methods and analysisThis study will be a cross-sectional with patients with MCI and healthy controls (HC). The neurophysiological signals will be measured during rest and while performing cognitive tasks: (1) Stroop, (2) N-back and (3) verbal fluency test (VFT). Main aims of statistical analysis are to (1) determine the differences in neurophysiological responses of HC and MCI, (2) investigate relationships between measures of cognitive performance and neurophysiological responses and (3) investigate whether the classification accuracy can be improved by using our multimodal approach. To meet these targets, statistical analysis will include machine learning approaches.This is, to the best of our knowledge, the first study that applies simultaneously these three modalities in MCI and HC. We hypothesise that the multimodal approach improves the classification accuracy between HC and MCI as compared with a unimodal approach. If our hypothesis is verified, this study paves the way for additional research on multimodal approaches for dementia research and fosters the exploration of new biomarkers for an early detection of nonphysiological age-related cognitive decline.Ethics and disseminationEthics approval was obtained from the local Ethics Committee (reference: 83/19). Data will be shared with the scientific community no more than 1 year following completion of study and data assembly.Trial registration numberClinicalTrials.gov, NCT04427436, registered on 10 June 2020, https://clinicaltrials.gov/ct2/show/study/NCT04427436.

scholarly journals Behavioral interventions to benefit cognition (Intervenciones cognitivas para beneficiar la cognición)

Retos ◽  
2015 ◽  
pp. 197-202
Author(s):  
Jennifer L. Etnier ◽  
Chia-Hao Shih ◽  
Aaron Piepmeier
Keyword(s):  
Cognitive Function ◽  
Cognitive Decline ◽  
Behavioral Interventions ◽  
Animal Studies ◽  
Exercise Intervention ◽  
Treatment Strategies ◽  
Future Research ◽  
Dietary Interventions ◽  
Cross Sectional ◽  
Age Related

With the growing population of older adults, the identification of treatment strategies to prevent or ameliorate age-related cognitive decline has been an important topic in recent years. After reviewing cross-sectional, longitudinal, and experimentally designed studies, as well as evidence from narrative and meta-analytic reviews, the authors concluded that behavioral approaches such as physical activity, cognitive training, and dietary interventions show promising results. In addition, given the likelihood that multiple underlying mechanisms support cognitive function, research is currently focusing on how to combine lifestyle factors into multi-component interventions to generate greater and more meaningful effects. Though evidence for these enhanced benefits exists from animal studies, few multi-component studies have been performed with humans. However, the findings from these studies are promising and a continued pursuit of multi-component behavioral interventions to benefit cognitive performance is warranted. Given the world’s aging population and accompanying age-related health issues such as cognitive decline and dementia, future research should focus on understanding the biological mechanisms responsible for these effects in order to allow for the development of behavioral lifestyle prescriptions to benefit cognitive performance.Keywords. aging, cognitive function, exercise intervention, oxidative stress, cognitive engagement.Resumen. Con la creciente población de adultos mayores, la identificación de las estrategias de tratamiento para prevenir o mejorar el deterioro cognitivo relacionado con la edad ha sido un tema importante en los últimos años. Después de revisar estudios con diseños transversales, longitudinales y experimentales, así como la evidencia de revisiones de literatura narrativa y meta-analítica, los autores concluyen que los enfoques conductuales como la actividad física, el entrenamiento cognitivo y las intervenciones dietéticas muestran resultados prometedores. Además, dada la probabilidad de que múltiples mecanismos subyacentes apoyan la función cognitiva, las investigaciones se enfocan actualmente en la manera de cómo combinar factores del estilo de vida en las intervenciones con múltiples componentes para generar efectos mayores y más significativos. Aunque existe evidencia de estos beneficios a partir de estudios en animales, se han realizado pocos estudios de componentes múltiples en humanos. Sin embargo, los resultados de estos estudios son prometedores y se garantiza un seguimiento continuo de las intervenciones conductuales de componentes múltiples para beneficiar el rendimiento cognitivo. Teniendo en cuenta el envejecimiento de la población mundial y los problemas de salud relacionados con la edad que la acompañan, tales como el deterioro cognitivo y la demencia, la investigación futura debería centrarse en la comprensión de los mecanismos biológicos responsables de estos efectos con el fin de permitir el desarrollo de las prescripciones de comportamiento de estilo de vida para beneficiar el rendimiento cognitivo.Palabras claves. envejecimiento, funcionamiento cognitivo, intervención con ejercicio, estrés oxidativo, participación cognitiva.

scholarly journals Impairments in Brain Bioenergetics in Aging and Tau Pathology: A Chicken and Egg Situation?

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2531
Author(s):  
Amandine Grimm
Keyword(s):  
Brain Metabolism ◽  
Brain Aging ◽  
Cognitive Impairments ◽  
Tau Phosphorylation ◽  
The Body ◽  
Tau Pathology ◽  
Age Related ◽  
Energy Consuming ◽  
Effects Of Aging ◽  
The Brain

The brain is the most energy-consuming organ of the body and impairments in brain energy metabolism will affect neuronal functionality and viability. Brain aging is marked by defects in energetic metabolism. Abnormal tau protein is a hallmark of tauopathies, including Alzheimer’s disease (AD). Pathological tau was shown to induce bioenergetic impairments by affecting mitochondrial function. Although it is now clear that mutations in the tau-coding gene lead to tau pathology, the causes of abnormal tau phosphorylation and aggregation in non-familial tauopathies, such as sporadic AD, remain elusive. Strikingly, both tau pathology and brain hypometabolism correlate with cognitive impairments in AD. The aim of this review is to discuss the link between age-related decrease in brain metabolism and tau pathology. In particular, the following points will be discussed: (i) the common bioenergetic features observed during brain aging and tauopathies; (ii) how age-related bioenergetic defects affect tau pathology; (iii) the influence of lifestyle factors known to modulate brain bioenergetics on tau pathology. The findings compiled here suggest that age-related bioenergetic defects may trigger abnormal tau phosphorylation/aggregation and cognitive impairments after passing a pathological threshold. Understanding the effects of aging on brain metabolism may therefore help to identify disease-modifying strategies against tau-induced neurodegeneration.

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