Association of Midlife Cardiovascular Risk Profiles With Cerebral Perfusion at Older Ages

Suri, Sana; Topiwala, Anya; Chappell, Michael A.; Okell, Thomas W.; Zsoldos, Enikő; Singh‐Manoux, Archana; Kivimäki, Mika; Mackay, Clare E.; Ebmeier, Klaus P.

doi:10.1001/jamanetworkopen.2019.5776

Cited by 41 publications

(37 citation statements)

References 63 publications

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“…This did not remove all the effects of FSRS, so FSRS makes a unique contribution to lower GM density, presumably based on vascular pathology beyond a simple function of time ( Uiterwijk et al , 2018 ). In a recent study of a subset ( N = 116) of the Whitehall II imaging sub-study, we found that cardiovascular risk in midlife was significantly associated with lower GM perfusion at older ages, whereas this association was not significant for cardiovascular risk in later life, which lends further support to these results ( Suri et al , 2019 ). FSRS is a composite score and is incremental with age, which makes it difficult to estimate when it starts to affect GM, and when its effects become evident.…”

Section: Discussionsupporting

confidence: 65%

Association of midlife stroke risk with structural brain integrity and memory performance at older ages: a longitudinal cohort study

Zsoldos

Mahmood

Filippini

et al. 2020

Brain Communications

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Cardiovascular health in midlife is an established risk factor for cognitive function later in life. Knowing mechanisms of this association may allow preventative steps to be taken to preserve brain health and cognitive performance in older age. In this study, we investigated the association of the Framingham stroke-risk score, a validated multifactorial predictor of 10-year risk of stroke, with brain measures and cognitive performance in stroke-free individuals. We used a large (N = 800) longitudinal cohort of community-dwelling adults of the Whitehall II imaging sub-study with no obvious structural brain abnormalities, who had Framingham stroke risk measured five times between 1991 and 2013 and MRI measures of structural integrity, and cognitive function performed between 2012 and 2016 [baseline mean age 47.9 (5.2) years, range 39.7–62.7 years; MRI mean age 69.81 (5.2) years, range 60.3–84.6 years; 80.6% men]. Unadjusted linear associations were assessed between the Framingham stroke-risk score in each wave and voxelwise grey matter density, fractional anisotropy and mean diffusivity at follow-up. These analyses were repeated including socio-demographic confounders as well as stroke risk in previous waves to examine the effect of residual risk acquired between waves. Finally, we used structural equation modelling to assess whether stroke risk negatively affects cognitive performance via specific brain measures. Higher unadjusted stroke risk measured at each of the five waves over 20 years prior to the MRI scan was associated with lower voxelwise grey and white matter measures. After adjusting for socio-demographic variables, higher stroke risk from 1991 to 2009 was associated with lower grey matter volume in the medial temporal lobe. Higher stroke risk from 1997 to 2013 was associated with lower fractional anisotropy along the corpus callosum. In addition, higher stroke risk from 2012 to 2013, sequentially adjusted for risk measured in 1991–94, 1997–98 and 2002–04 (i.e. ‘residual risks’ acquired from the time of these examinations onwards), was associated with widespread lower fractional anisotropy, and lower grey matter volume in sub-neocortical structures. Structural equation modelling suggested that such reductions in brain integrity were associated with cognitive impairment. These findings highlight the importance of considering cerebrovascular health in midlife as important for brain integrity and cognitive function later in life (ClinicalTrials.gov Identifier: NCT03335696).

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Section: Discussionsupporting

confidence: 65%

Association of midlife stroke risk with structural brain integrity and memory performance at older ages: a longitudinal cohort study

Zsoldos

Mahmood

Filippini

et al. 2020

Brain Communications

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“…The relationship between late-life BP and cognition may be determine by the presence and chronicity of past hypertension. In very recently published data from the ARIC study, a prospective cohort study that included 4,761 participants with 24-year followup and BP measurements at midlife and at late life, those with midlife and late-life hypertension (hazard ratio, 1.49) and those with midlife hypertension and late-life hypotension (hazard ratio, 1.62) had higher risk for incident dementia compared with those who remained normotensive (35).…”

Section: Hypotension and Risk Of Cognitive Impairment/dementiamentioning

confidence: 99%

Hypertension and the Risk of Dementia

Sierra

2020

Front. Cardiovasc. Med.

115

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Hypertension, particularly midlife high blood pressure, has been related to a higher risk of cognitive decline and dementia, including Alzheimer disease. However, these associations are complex and not fully elucidated. Cerebral small vessel disease emerges as one of the most important causes. Several observational studies have shown the potential beneficial role of antihypertensive treatment in preventing cognitive decline. However, randomized clinical trials (RCTs) have shown controversial results without proving nor disproving the association. On the other hand, in very elderly or frail people some studies have observed a relationship between low blood pressure and worse cognitive function. The optimal systolic and diastolic blood pressure values for protecting cognitive function, especially in elderly people, are not known.

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“…In summary, imaging studies in AD have shown that dysregulation for CBF and rCBV are critically involved in the pathogenesis of the disease. Changes in rCBF occur earlier than rCBV during the disease course [98], where metabolic and vascular risk factors have been implicated as a driver of hemodynamic disturbances [102,103]. Consistent, experimental studies have shown that these risk factors compromises cerebral perfusion, contribute to cognitive impairment and enhances AD pathology [104,105].…”

Section: Dysregulation Regional Rcbf and Volumementioning

confidence: 99%

An Integrated View on Vascular Dysfunction in Alzheimer’s Disease

Klohs

2019

Neurodegener Dis

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Background: Cerebrovascular disease is a common comorbidity in patients with Alzheimer's disease (AD). It is believed to contribute additively to the cognitive impairment and to lower the threshold for the development of dementia. However, accumulating evidence suggests that dysfunction of the cerebral vasculature and AD neuropathology interact in multiple ways. Vascular processes even proceed AD neuropathology, implicating a causal role in the etiology of AD. Thus, the review aims to provide an integrated view on vascular dysfunction in AD. Summary: In AD, the cerebral vasculature undergoes pronounced cellular, morphological and structural changes, which alters regulation of blood flow, vascular fluid dynamics and vessel integrity. Stiffening of central blood vessels lead to transmission of excessive pulsatile energy to the brain microvasculature, causing endorgan damage. Moreover, a dysregulated hemostasis and chronic vascular inflammation further impede vascular function, where its mediators interact synergistically. Changes of the cerebral vasculature are triggered and driven by systemic vascular abnormalities that are part of aging, and which can be accelerated and aggravated by cardiovascular diseas-es. Key Messages: In AD, the cerebral vasculature is the locus where multiple pathogenic processes converge and contribute to cognitive impairment. Understanding the molecular mechanism and pathophysiology of vascular dysfunction in AD and use of vascular blood-based and imaging biomarker in clinical studies may hold promise for future prevention and therapy of the disease.

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Association of Midlife Cardiovascular Risk Profiles With Cerebral Perfusion at Older Ages

Cited by 41 publications

References 63 publications

Association of midlife stroke risk with structural brain integrity and memory performance at older ages: a longitudinal cohort study

Association of midlife stroke risk with structural brain integrity and memory performance at older ages: a longitudinal cohort study

Hypertension and the Risk of Dementia

An Integrated View on Vascular Dysfunction in Alzheimer’s Disease

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