scholarly journals An epigenetic predictor of death captures multi-modal measures of brain health

2019 ◽  
Author(s):  
Robert F. Hillary ◽  
Anna J. Stevenson ◽  
Simon R. Cox ◽  
Daniel L. McCartney ◽  
Sarah E. Harris ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Cognitive Ability ◽  
Vascular Lesions ◽  
Epigenetic Clock ◽  
General Cognitive Ability ◽  
Brain Health ◽  
Standard Deviation Increase ◽  
Brain White Matter ◽  
Age Related ◽  
Tentative Evidence

AbstractIndividuals of the same chronological age exhibit disparate rates of biological ageing. Consequently, a number of methodologies have been proposed to determine biological age and primarily exploit variation at the level of DNA methylation (DNAm). A novel epigenetic clock, termed ‘DNAm GrimAge’ has outperformed its predecessors in predicting the risk of mortality as well as many age-related morbidities. However, the association between DNAm GrimAge and cognitive or neuroimaging phenotypes remains unknown. We explore these associations in the Lothian Birth Cohort 1936 (n = 709, mean age 73 years). Higher DNAm GrimAge was strongly associated with all-cause mortality over the eighth decade (Hazard Ratio per standard deviation increase in GrimAge: 1.81, P < 2.0 × 10−16). Higher DNAm GrimAge was associated with lower age 11 IQ (β = −0.11), lower age 73 general cognitive ability (β = −0.18), decreased brain volume (β = −0.25) and increased brain white matter hyperintensities (β = 0.17). There was tentative evidence for a longitudinal association between DNAm GrimAge and cognitive decline from age 70 to 79. Sixty-nine of 137 health- and brain-related phenotypes tested were significantly associated with GrimAge. Adjusting all models for childhood intelligence attenuated to non-significance a small number of associations (12/69 associations; 6 of which were cognitive traits), but not the association with general cognitive ability (33.9% attenuation). Higher DNAm GrimAge associates with lower cognitive ability and brain vascular lesions in older age, independently of early-life cognitive ability. This epigenetic predictor of mortality associates with different measures of brain health and may aid in the prediction of age-related cognitive decline.

scholarly journals An epigenetic predictor of death captures multi-modal measures of brain health

2019 ◽  
Author(s):  
Robert F. Hillary ◽  
Anna J. Stevenson ◽  
Simon R. Cox ◽  
Daniel L. McCartney ◽  
Sarah E. Harris ◽  
...  
Keyword(s):  
Cognitive Ability ◽  
Epigenetic Mechanism ◽  
Vascular Lesions ◽  
Epigenetic Clock ◽  
General Cognitive Ability ◽  
Brain Health ◽  
Standard Deviation Increase ◽  
Brain White Matter ◽  
Age Related ◽  
Lothian Birth Cohort

AbstractIndividuals of the same chronological age exhibit disparate rates of biological ageing. Consequently, a number of methodologies have been proposed to determine biological age and primarily exploit variation at the level of DNA methylation (DNAm) – a commonly studied epigenetic mechanism. A novel epigenetic clock, termed ‘DNAm GrimAge’ has outperformed its predecessors in predicting the risk of mortality as well as a number of age-related morbidities. However, the association between DNAm GrimAge and cognitive or neuroimaging phenotypes remains unknown. We explore these associations in the Lothian Birth Cohort 1936 (n=709, mean age 73 years). Higher DNAm GrimAge was strongly associated with all-cause mortality over twelve years of follow-up (Hazard Ratio per standard deviation increase in GrimAge: 1.81, P < 2.0 × 10-16). Higher DNAm GrimAge was associated with lower age 11 IQ (β=-0.11), lower age 73 general cognitive ability (β=-0.18), decreased brain volume (β=-0.25) and increased brain white matter hyperintensities (β=0.17). Sixty-eight of 137 health- and brain-related phenotypes tested were significantly associated with DNAm GrimAge. Adjusting all models for childhood cognitive ability attenuated to non-significance a small number of associations (12/68 associations; 6 of which were cognitive traits), but not the association with general cognitive ability (33.9% attenuation). Higher DNAm GrimAge cross-sectionally associates with lower cognitive ability and brain vascular lesions in older age, independently of early life cognitive ability. Thus, this epigenetic predictor of mortality is also associated with multiple different measures of brain health and may aid in the prediction of age-related cognitive decline.

Associating emotions with Wagner’s music: A developmental perspective

2016 ◽  
Vol 45 (5) ◽  
pp. 752-760 ◽  
Author(s):  
Paulo E. Andrade ◽  
Patrícia Vanzella ◽  
Olga V. C. A. Andrade ◽  
E. Glenn Schellenberg
Keyword(s):  
Academic Achievement ◽  
Young Children ◽  
University Students ◽  
Cognitive Ability ◽  
Dimensional Space ◽  
Two Dimensional ◽  
General Cognitive Ability ◽  
Music Training ◽  
Age Related ◽  
Musical Excerpts

Brazilian listeners ( N = 303) were asked to identify emotions conveyed in 1-min instrumental excerpts from Wagner’s operas. Participants included musically untrained 7- to 10-year-olds and university students in music (musicians) or science (nonmusicians). After hearing each of eight different excerpts, listeners made a forced-choice judgment about which of eight emotions best matched the excerpt. The excerpts and emotions were chosen so that two were in each of four quadrants in two-dimensional space as defined by arousal and valence. Listeners of all ages performed at above-chance levels, which means that complex, unfamiliar musical materials from a different century and culture are nevertheless meaningful for young children. In fact, children performed similarly to adult nonmusicians. There was age-related improvement among children, however, and adult musicians performed best of all. As in previous research that used simpler musical excerpts, effects due to age and music training were due primarily to improvements in selecting the appropriate valence. That is, even 10-year-olds with no music training were as likely as adult musicians to match a high- or low-arousal excerpt with a high- or low-arousal emotion, respectively. Performance was independent of general cognitive ability as measured by academic achievement but correlated positively with basic pitch-perception skills.

scholarly journals Transcriptional profiling predicts running promotes cerebrovascular remodeling in young but not midlife mice

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Kate E. Foley ◽  
Hongtian Stanley Yang ◽  
Leah C. Graham ◽  
Gareth R. Howell
Keyword(s):  
Cognitive Decline ◽  
Transcriptional Profiling ◽  
Cell Types ◽  
Brain Health ◽  
New Approach ◽  
Age Related ◽  
Voluntary Running ◽  
Differential Gene ◽  
Age Related Cognitive Decline ◽  
Potential Therapeutic Intervention

Abstract Background The incidence of dementia and cognitive decline is increasing with no therapy or cure. One of the reasons treatment remains elusive is because there are various pathologies that contribute to age-related cognitive decline. Specifically, with Alzheimer’s disease, targeting to reduce amyloid beta plaques and phosphorylated tau aggregates in clinical trials has not yielded results to slow symptomology, suggesting a new approach is needed. Interestingly, exercise has been proposed as a potential therapeutic intervention to improve brain health and reduce the risk for dementia, however the benefits throughout aging are not well understood. Results To better understand the effects of exercise, we preformed transcriptional profiling on young (1–2 months) and midlife (12 months) C57BL/6 J (B6) male mice after 12 weeks of voluntary running. Data was compared to age-matched sedentary controls. Interestingly, the midlife running group naturally broke into two cohorts based on distance ran - either running a lot and more intensely (high runners) or running less and less intensely (low runners). Midlife high runners had lower LDL cholesterol as well as lower adiposity (%fat) compared to sedentary, than midlife low runners compared to sedentary suggesting more intense running lowered systemic markers of risk for age-related diseases including dementias. Differential gene analysis of transcriptional profiles generated from the cortex and hippocampus showed thousands of differentially expressed (DE) genes when comparing young runners to sedentary controls. However, only a few hundred genes were DE comparing either midlife high runners or midlife low runners to midlife sedentary controls. This indicates that, in our study, the effects of running are reduced through aging. Gene set enrichment analyses identified enrichment of genes involved in extracellular matrix (ECM), vascular remodeling and angiogenesis in young runners but not midlife runners. These genes are known to be expressed in multiple vascular-related cell types including astrocytes, endothelial cells, pericytes and smooth muscle cells. Conclusions Taken together these results suggest running may best serve as a preventative measure to reduce risk for cerebrovascular decline. Ultimately, this work shows that exercise may be more effective to prevent dementia if introduced at younger ages.

scholarly journals Cerebral small vessel disease burden and longitudinal cognitive decline from age 73 to 82: the Lothian Birth Cohort 1936

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
O. K. L. Hamilton ◽  
S. R. Cox ◽  
J. A. Okely ◽  
F. Conte ◽  
L. Ballerini ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Cognitive Ability ◽  
Birth Cohort ◽  
Processing Speed ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
General Cognitive Ability ◽  
Vessel Disease ◽  
Lothian Birth Cohort

AbstractSlowed processing speed is considered a hallmark feature of cognitive decline in cerebral small vessel disease (SVD); however, it is unclear whether SVD’s association with slowed processing might be due to its association with overall declining general cognitive ability. We quantified the total MRI-visible SVD burden of 540 members of the Lothian Birth Cohort 1936 (age: 72.6 ± 0.7 years; 47% female). Using latent growth curve modelling, we tested associations between total SVD burden at mean age 73 and changes in general cognitive ability, processing speed, verbal memory and visuospatial ability, measured at age 73, 76, 79 and 82. Covariates included age, sex, vascular risk and childhood cognitive ability. In the fully adjusted models, greater SVD burden was associated with greater declines in general cognitive ability (standardised β: −0.201; 95% CI: [−0.36, −0.04]; pFDR = 0.022) and processing speed (−0.222; [−0.40, −0.04]; pFDR = 0.022). SVD burden accounted for between 4 and 5% of variance in declines of general cognitive ability and processing speed. After accounting for the covariance between tests of processing speed and general cognitive ability, only SVD’s association with greater decline in general cognitive ability remained significant, prior to FDR correction (−0.222; [−0.39, −0.06]; p = 0.008; pFDR = 0.085). Our findings do not support the notion that SVD has a specific association with declining processing speed, independent of decline in general cognitive ability (which captures the variance shared across domains of cognitive ability). The association between SVD burden and declining general cognitive ability supports the notion of SVD as a diffuse, whole-brain disease and suggests that trials monitoring SVD-related cognitive changes should consider domain-specific changes in the context of overall, general cognitive decline.

scholarly journals Transcriptional profiling reveals running promotes cerebrovascular remodeling in young but not aged mice

2019 ◽  
Author(s):  
Kate E. Foley ◽  
Stanley Yang ◽  
Leah C. Graham ◽  
Gareth R. Howell
Keyword(s):  
Cognitive Decline ◽  
Transcriptional Profiling ◽  
Cell Types ◽  
Brain Health ◽  
New Approach ◽  
Age Related ◽  
Voluntary Running ◽  
Differential Gene ◽  
Age Related Cognitive Decline ◽  
Potential Therapeutic Intervention

AbstractBackgroundThe incidence of dementia and cognitive decline is increasing with no therapy or cure. One of the reasons treatment remains elusive is because there are various pathologies that contribute to age-related cognitive decline. Specifically, with Alzheimer’s disease, targeting to reduce amyloid beta plaques and phosphorylated tau aggregates in clinical trials has not yielded results to slow symptomology, suggesting a new approach is needed. Interestingly, exercise has been proposed as a potential therapeutic intervention to improve brain health and reduce the risk for dementia, however the benefits throughout aging are not well understood.ResultsTo better understand the effects of exercise, we preformed transcriptional profiling on young (1-2 months) and midlife (12 months) C57BL/6J (B6) male mice after 12 weeks of voluntary running. Data was compared to age-matched sedentary controls. Interestingly, the midlife running group naturally broke into two cohorts based on distance ran - either running a lot and more intensely (high runners) or running less and less intensely (low runners). Midlife high runners had lower LDL cholesterol as well as lower adiposity (%fat) compared to sedentary, than midlife low runners compared to sedentary suggesting more intense running lowered systemic markers of risk for age-related diseases including dementias. Differential gene analysis of transcriptional profiles generated from the cortex and hippocampus showed thousands of differentially expressed (DE) genes when comparing young runners to sedentary controls. However, only a few hundred genes were DE comparing either midlife high runners or midlife low runners to midlife sedentary controls. This indicates that, in our study, the effects of running are reduced through aging. Gene set enrichment analyses identified enrichment of genes involved in extracellular matrix (ECM), vascular remodeling and angiogenesis in young runners but not midlife runners. These genes are known to be expressed in multiple vascular-related cell types including astrocytes, endothelial cells, pericytes and smooth muscle cells.ConclusionsTaken together these results suggest running may best serve as a preventative measure to reduce risk for cerebrovascular decline. Ultimately, this work shows that exercise may be more effective to prevent dementia if introduced at younger ages.

scholarly journals Impact of Cardiovascular Hemodynamics on Cognitive Aging

2021 ◽  
Author(s):  
Elizabeth E. Moore ◽  
Angela L. Jefferson
Keyword(s):  
Cardiovascular Disease ◽  
Cognitive Decline ◽  
Cognitive Aging ◽  
Brain Aging ◽  
The Body ◽  
Brain Health ◽  
Age Related ◽  
Brain Structure And Function ◽  
Aging Adults ◽  
Abnormal Brain

It is well known that cardiovascular disease and related vascular risk factors are associated with cognitive decline and worse brain health outcomes among aging adults. Recently, subtle age-related changes in cardiac hemodynamics have been proposed as an emerging risk factor for abnormal brain aging, even in the absence of cardiovascular disease. Changes in cardiac function, vital for determining the total amount of blood available for perfusing the body, and arterial stiffness, important for regulating blood flow delivery, have been associated with compromised brain structure and function among older adults. Such alterations in cardiac output and arterial stiffening may directly affect brain health through blood-brain barrier breakdown or oligemia or may interact with Alzheimer disease and concomitant pathologies common in aging adults to accelerate cognitive decline. This review examines how age-related alterations in cardiovascular integrity contribute to abnormal brain aging, emphasizing that changes in systemic hemodynamics may compromise brain health before or concurrently with the development of neurodegenerative processes that are common in aging.

scholarly journals Intellectual engagement and cognitive ability in later life (the “use it or lose it” conjecture): longitudinal, prospective study

BMJ ◽  
2018 ◽  
pp. k4925 ◽  
Author(s):  
Roger T Staff ◽  
Michael J Hogan ◽  
Daniel S Williams ◽  
L J Whalley
Keyword(s):  
Life Course ◽  
Cognitive Decline ◽  
Cognitive Ability ◽  
Cognitive Performance ◽  
Processing Speed ◽  
Verbal Memory ◽  
Later Life ◽  
Cognitive Test ◽  
Intellectual Engagement ◽  
Age Related

Abstract Objectives To examine the association between intellectual engagement and cognitive ability in later life, and determine whether the maintenance of intellectual engagement will offset age related cognitive decline. Design Longitudinal, prospective, observational study. Setting Non-clinical volunteers in late middle age (all born in 1936) living independently in northeast Scotland. Participants Sample of 498 volunteers who had taken part in the Scottish Mental Health Survey of 1947, from one birth year (1936). Main outcome measures Cognitive ability and trajectory of cognitive decline in later life. Typical intellectual engagement was measured by a questionnaire, and repeated cognitive measurements of information processing speed and verbal memory were obtained over a 15 year period (recording more than 1200 longitudinal data points for each cognitive test). Results Intellectual engagement was significantly associated with level of cognitive performance in later life, with each point on a 24 point scale accounting for 0.97 standardised cognitive performance (IQ-like) score, for processing speed and 0.71 points for memory (both P<0.05). Engagement in problem solving activities had the largest association with life course cognitive gains, with each point accounting for 0.43 standardised cognitive performance score, for processing speed and 0.36 points for memory (both P<0.05). However, engagement did not influence the trajectory of age related decline in cognitive performance. Engagement in intellectual stimulating activities was associated with early life ability, with correlations between engagement and childhood ability and education being 0.35 and 0.22, respectively (both P<0.01). Conclusion These results show that self reported engagement is not associated with the trajectory of cognitive decline in late life, but is associated with the acquisition of ability during the life course. Overall, findings suggest that high performing adults engage and those that engage more being protected from relative decline.

scholarly journals Cerebral Small Vessel Disease Burden and Longitudinal Cognitive Decline from age 73 to 82: the Lothian Birth Cohort 1936

2021 ◽  
Author(s):  
Olivia KL Hamilton ◽  
Simon R Cox ◽  
Judy A Okely ◽  
Federica Conte ◽  
Lucia Ballerini ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Cognitive Ability ◽  
Birth Cohort ◽  
Processing Speed ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
General Cognitive Ability ◽  
Vessel Disease ◽  
Lothian Birth Cohort

Slowed processing speed is considered a hallmark feature of cognitive decline in cerebral small vessel disease (SVD), however, it is unclear whether SVDs association with slowed processing might be due to its association with overall declining general cognitive ability. We quantified the total MRI-visible SVD burden of 540 members of the Lothian Birth Cohort 1936 (age:72.6±0.7 years; 47% female). Using latent growth curve modelling, we tested associations between total SVD burden at mean age 73 and changes in general cognitive ability, processing speed, verbal memory, and visuospatial ability, measured at age 73, 76, 79 and 82. Covariates included age, sex, vascular risk, and childhood cognitive ability. In the fully-adjusted models, greater SVD burden was associated with greater declines in general cognitive ability (standardised β: -0.201; 95%CI: [-0.36, -0.04]; pFDR=0.022) and processing speed (-0.222; [-0.40, -0.04]; pFDR=0.022). SVD burden accounted for between 4 and 5% of variance in declines of general cognitive ability and processing speed. After accounting for the covariance between tests of processing speed and general cognitive ability, only SVDs association with greater decline in general cognitive ability remained significant, prior to FDR correction (-0.222; [-0.39, -0.06]; p=0.008; pFDR=0.085). Our findings do not support the notion that SVD has a specific association with declining processing speed, independent of decline in general cognitive ability (which captures the variance shared across domains of cognitive ability). The association between SVD burden and declining general cognitive ability supports the notion of SVD as a diffuse, whole-brain disease and suggests that trials monitoring SVD-related cognitive changes should consider domain-specific changes in the context of overall, general cognitive decline.

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