Genetic and Lifestyle Risks for Coronary Artery Disease and Long-Term Risk of Incident Dementia Subtypes DOI

Arisa Sittichokkananon,

Victoria Garfield, Scott T. Chiesa

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 18, 2024

ABSTRACT Background Shared genetic and lifestyle risk factors may underlie the development of both coronary artery disease (CAD) dementia. This study aimed to examine if an increased for CAD is associated with long-term developing all-cause, Alzheimer’s, or vascular dementia, investigate whether presence healthy behaviours in mid-to-late life period attenuate this risk. Methods A prospective cohort 365,782 participants free from dementia at least 5 years post-baseline assessment was conducted within UK Biobank study. Genetic assessed using a genome-wide polygenic score (PRS) CAD, modified version American Heart Association’s Life’s Essential 8 Lifestyle Risk Score (LRS). Primary outcomes were incident diagnoses obtained linked electronic health records. Secondary neuroimaging phenotypes well-established links future measured 32,592 recalled MRI imaging. Results 8,870 cases all-cause observed over median 13.9-year follow-up. Higher elevated all subtypes (HRs = 1.08-1.16; p<0.001 all). higher LRS modestly (HR 1.06 [1.04-1.08]; p < 0.001), likely arising through rates 1.22 [1.17-1.28]) as no evidence found any associations Alzheimer’s 0.99 [0.95-1.02]; 0.535). Individuals combination high scores more than twice develop during follow-up compared those low levels both. substantially attenuated following baseline, however, regardless underlying (e.g. HR vs 1.43 [1.12-1.81] vs. 2.16 [1.73-2.69] respectively individuals risk). In subset assessments, demonstrated 30% greater volume white matter hyperintensities risk, while showing little difference grey hippocampal volumes. Conclusions who are genetically predisposed also face old age. reduced adopting earlier lifespan, particularly caused by pathology.

Language: Английский

Genetic and Lifestyle Risks for Coronary Artery Disease and Long-Term Risk of Incident Dementia Subtypes DOI

Arisa Sittichokkananon,

Victoria Garfield, Scott T. Chiesa

et al.

Circulation, Journal Year: 2025, Volume and Issue: unknown

Published: April 4, 2025

BACKGROUND: Shared genetic and lifestyle risk factors may underlie the development of both coronary artery disease (CAD) dementia. We examined whether an increased for CAD is associated with long-term developing all-cause, Alzheimer’s, or vascular dementia, investigated differences in potentially modifiable mid- to late-life period attenuate this risk. METHODS: A prospective cohort study 365 782 participants free from dementia at least 5 years after baseline assessment was conducted within UK Biobank cohort. Genetic assessed using a genomewide polygenic score (PRS) modified version American Heart Association’s Life’s Essential 8 Lifestyle Risk Score (LRS). Higher values scores were deemed represent Primary outcomes incident diagnoses obtained electronic health records. Secondary neuroimaging phenotypes measured 32 028 recalled magnetic resonance imaging. Sensitivity analyses test extent by which biological behavioral contributed observed associations. RESULTS: total 8870 cases all-cause over median 13.9-year follow-up. Both (LRS) modestly elevated (subhazard ratio per SD increase, 1.10 [1.08, 1.12], P <0.001, PRS 1.04 [1.02, 1.06], =0.006, LRS). This appeared largely attributable underlying ratio, 1.16 [1.11, 1.21], <0.001 1.15 [1.09, 1.22], LRS), because Alzheimer’s found demonstrate moderate associations alone 1.09 [1.06, 1.13]; <0.001). LRS have additive rather than interactive effect PRS, individuals highest tertiles ≈70% more likely develop during follow-up compared those lowest 1.71 [1.39, 2.11]; substantially attenuated low baseline, however, regardless (40% 50% reduction versus high tertile tertile; all). In subset assessments, demonstrated ≈25% greater volume white matter hyperintensities tertiles, but showed little difference gray hippocampal volumes. identified between hyperintensity burden whereas some seemingly paradoxical relationships. CONCLUSIONS: Individuals who are genetically predisposed also face old age. reduced demonstrating healthy profiles earlier lifespan, particularly be caused pathology.

Language: Английский

Citations

0
Fronto-motor circuits linked to subclinical apathy DOI Creative Commons
Gérard Derosière, Pierre Vassiliadis, Laurence Dricot

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 11, 2024

SUMMARY Apathy is a syndrome characterized by disruption in effort-reward decision-making, accompanied structural and functional changes related fronto-basal ganglia (BG) network. While activity the primary motor cortex (M1) during effort reward valuation have been repeatedly observed, previous work on apathy has largely overlooked connections between fronto-BG network M1, potentially missing key circuits This study addresses this gap investigating effective connectivity fronto-M1, fronto-BG-M1, intra-M1 relation to subclinical 45 healthy subjects. Behavior was assessed using battery of apathy-related questionnaires computational modeling decision-making task. Fronto-motor were examined through combination MRI-derived tractography paired-pulse transcranial magnetic stimulation, which probed connectivity, respectively. The data reveal that scores are associated with both fronto-M1 fronto-BG-M1 circuits. Circuits originating from supplementary area primarily index valuation, while GABAergic correlates exclusively valuation. These findings suggest distinct fronto-motor linked different dimensions motivated behavior may constitute specific neuromodulation targets for patients suffering apathy.

Language: Английский

Citations

2
Association of early life cardiovascular risk factors with grey matter structure in young adults in the United Kingdom: the ALSPAC study DOI Creative Commons
Helen Haines, Sana Suri, Raihaan Patel

et al.

EBioMedicine, Journal Year: 2024, Volume and Issue: 110, P. 105490 - 105490

Published: Dec. 1, 2024

Language: Английский

Citations

0
Genetic and Lifestyle Risks for Coronary Artery Disease and Long-Term Risk of Incident Dementia Subtypes DOI

Arisa Sittichokkananon,

Victoria Garfield, Scott T. Chiesa

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 18, 2024

ABSTRACT Background Shared genetic and lifestyle risk factors may underlie the development of both coronary artery disease (CAD) dementia. This study aimed to examine if an increased for CAD is associated with long-term developing all-cause, Alzheimer’s, or vascular dementia, investigate whether presence healthy behaviours in mid-to-late life period attenuate this risk. Methods A prospective cohort 365,782 participants free from dementia at least 5 years post-baseline assessment was conducted within UK Biobank study. Genetic assessed using a genome-wide polygenic score (PRS) CAD, modified version American Heart Association’s Life’s Essential 8 Lifestyle Risk Score (LRS). Primary outcomes were incident diagnoses obtained linked electronic health records. Secondary neuroimaging phenotypes well-established links future measured 32,592 recalled MRI imaging. Results 8,870 cases all-cause observed over median 13.9-year follow-up. Higher elevated all subtypes (HRs = 1.08-1.16; p<0.001 all). higher LRS modestly (HR 1.06 [1.04-1.08]; p < 0.001), likely arising through rates 1.22 [1.17-1.28]) as no evidence found any associations Alzheimer’s 0.99 [0.95-1.02]; 0.535). Individuals combination high scores more than twice develop during follow-up compared those low levels both. substantially attenuated following baseline, however, regardless underlying (e.g. HR vs 1.43 [1.12-1.81] vs. 2.16 [1.73-2.69] respectively individuals risk). In subset assessments, demonstrated 30% greater volume white matter hyperintensities risk, while showing little difference grey hippocampal volumes. Conclusions who are genetically predisposed also face old age. reduced adopting earlier lifespan, particularly caused by pathology.

Language: Английский

Citations

0