Cerebrovascular risk factors impact frontoparietal network integrity and executive function in healthy ageing

Veldsman, Michele; Tai, Xin-You; Nichols, Thomas E.; Smith, Steve; Peixoto, João Pedro Fernandes; Manohar, Sanjay; Husain, Masud

doi:10.1038/s41467-020-18201-5

Cited by 76 publications

(74 citation statements)

References 60 publications

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“… 36 , 37 , 39 , 40 , 106 Moreover, recent findings show that DWI metrics can be more sensitive than visible markers of SVD alone in detecting white matter disruption. 45 , 107 , 108 …”

Section: Discussionmentioning

confidence: 99%

Apathy in small vessel cerebrovascular disease is associated with deficits in effort-based decision making

Saleh

Heron

Petitet

et al. 2021

Brain

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Patients with small vessel cerebrovascular disease frequently suffer from apathy, a debilitating neuropsychiatric syndrome, the underlying mechanisms of which remain to be established. Here we investigated the hypothesis that apathy is associated with disrupted decision making in effort-based decision making, and that these alterations are associated with abnormalities in the white matter network connecting brain regions that underpin such decisions. Eighty-two patients with MRI evidence of small vessel disease were assessed using a behavioural paradigm as well as diffusion weighted MRI. The decision-making task involved accepting or rejecting monetary rewards in return for performing different levels of physical effort (hand grip force). Choice data and reaction times were integrated into a drift diffusion model that framed decisions to accept or reject offers as stochastic processes approaching a decision boundary with a particular drift rate. Tract-based spatial statistics were used to assess the relationship between white matter tract integrity and apathy, while accounting for depression. Overall, patients with apathy accepted significantly fewer offers on this decision-making task. Notably, while apathetic patients were less responsive to low rewards, they were also significantly averse to investing in high effort. Significant reductions in white matter integrity were observed to be specifically related to apathy, but not to depression. These included pathways connecting brain regions previously implicated in effort-based decision making in healthy people. The drift rate to decision parameter was significantly associated with both apathy and altered white matter tracts, suggesting that both brain and behavioural changes in apathy are associated with this single parameter. On the other hand, depression was associated with an increase in the decision boundary, consistent with an increase in the amount of evidence required prior to making a decision. These findings demonstrate altered effort-based decision making for reward in apathy, and also highlight dissociable mechanisms underlying apathy and depression in small vessel disease. They provide clear potential brain and behavioural targets for future therapeutic interventions, as well as modelling parameters that can be used to measure the effects of treatment at the behavioural level.

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“… 36 , 37 , 39 , 40 , 106 Moreover, recent findings show that DWI metrics can be more sensitive than visible markers of SVD alone in detecting white matter disruption. 45 , 107 , 108 …”

Section: Discussionmentioning

confidence: 99%

Apathy in small vessel cerebrovascular disease is associated with deficits in effort-based decision making

Saleh

Heron

Petitet

et al. 2021

Brain

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“…With the present dataset, the authors predicted that protective factors (higher cognitive reserve and female sex) would be related to better performance in domain-specific cognition, whereas adverse factors (worse allostatic load, older age, APOE ε4 carrier status, higher Aβ, and tau/neuroinflammation burden) would be related to worse performance. We further anticipated that the influence of protective and adverse factors should be visible only for episodic memory and executive function (Hohman et al, 2017;McFall et al, 2019;Veldsman et al, 2020). As tau and APOE status were available only in a subsample of participants, analyses including these factors will be presented as exploratory.…”

Section: Introductionmentioning

confidence: 99%

Positive Effect of Cognitive Reserve on Episodic Memory, Executive and Attentional Functions Taking Into Account Amyloid-Beta, Tau, and Apolipoprotein E Status

Narbutas

Chylinski

Egroo

et al. 2021

Front. Aging Neurosci.

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Studies exploring the simultaneous influence of several physiological and environmental factors on domain-specific cognition in late middle-age remain scarce. Therefore, our objective was to determine the respective contribution of modifiable risk/protective factors (cognitive reserve and allostatic load) on specific cognitive domains (episodic memory, executive functions, and attention), taking into account non-modifiable factors [sex, age, and genetic risk for Alzheimer’s disease (AD)] and AD-related biomarker amount (amyloid-beta and tau/neuroinflammation) in a healthy late-middle-aged population. One hundred and one healthy participants (59.4 ± 5 years; 68 women) were evaluated for episodic memory, executive and attentional functioning via neuropsychological test battery. Cognitive reserve was determined by the National Adult Reading Test. The allostatic load consisted of measures of lipid metabolism and sympathetic nervous system functioning. The amyloid-beta level was assessed using positron emission tomography in all participants, whereas tau/neuroinflammation positron emission tomography scans and apolipoprotein E genotype were available for 58 participants. Higher cognitive reserve was the main correlate of better cognitive performance across all domains. Moreover, age was negatively associated with attentional functioning, whereas sex was a significant predictor for episodic memory, with women having better performance than men. Finally, our results did not show clear significant associations between performance over any cognitive domain and apolipoprotein E genotype and AD biomarkers. This suggests that domain-specific cognition in late healthy midlife is mainly determined by a combination of modifiable (cognitive reserve) and non-modifiable factors (sex and age) rather than by AD biomarkers and genetic risk for AD.

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“…More recently, studies based on the UK Biobank have supported these findings. In (Veldsman et al, 2020) cerebrovascular risk factors were associated with reduced cerebral grey matter and white matter integrity, and in (Cox et al, 2019) hypertension was independently associated with generalised atrophy of the brain (reduced brain volume and thinner cortex) and a higher burden of WMHs, while increased pulse pressure was related to poorer white matter measures.…”

Section: Methodological Contextmentioning

confidence: 94%

Biophysics-based statistical learning: Application to heart and brain interactions

Banus

Lorenzi

Cámara

et al. 2021

Medical Image Analysis

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Initiatives such as the UK Biobank provide joint cardiac and brain imaging information for thousands of individuals, representing a unique opportunity to study the relationship between heart and brain. Most of research on large multimodal databases has been focusing on studying the associations among the available measurements by means of univariate and multivariate association models. However, these approaches do not provide insights about the underlying mechanisms and are often hampered by the lack of prior knowledge on the physiological relationships between measurements. For instance, important indices of the cardiovascular function, such as cardiac contractility, cannot be measured in-vivo. While these non-observable parameters can be estimated by means of biophysical models, their personalisation is generally an ill-posed problem, often lacking critical data and only applied to small datasets. Therefore, to jointly study brain and heart, we propose an approach in which the parameter personalisation of a lumped cardiovascular model is constrained by the statistical relationships observed between model parameters and brain-volumetric indices extracted from imaging, i.e. ventricles or white matter hyperintensities volumes, and clinical information such as age or body surface area. We explored the plausibility of the learnt relationships by inferring the model parameters conditioned on the absence of part of the target clinical features, applying this framework in a cohort of more than 3 000 subjects and in a pathological subgroup of 59 subjects diagnosed with atrial fibrillation. Our

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Cerebrovascular risk factors impact frontoparietal network integrity and executive function in healthy ageing

Cited by 76 publications

References 60 publications

Apathy in small vessel cerebrovascular disease is associated with deficits in effort-based decision making

Apathy in small vessel cerebrovascular disease is associated with deficits in effort-based decision making

Positive Effect of Cognitive Reserve on Episodic Memory, Executive and Attentional Functions Taking Into Account Amyloid-Beta, Tau, and Apolipoprotein E Status

Biophysics-based statistical learning: Application to heart and brain interactions

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