Association of tau pathology and vascular risk factor burden with longitudinal measures of plasma neurofilament light

ObjectiveGiven the potential therapeutic effect of vascular disease control timing to reduce dementia risk, we investigated the age-related influences of vascular risk factor burden on brain structure throughout the lifespan.MethodsWe studied participants from the community-based prospective Framingham Heart Study. Overall vascular risk factor burden was calculated according to the Framingham Stroke Risk Profile, a validated algorithm that predicts stroke risk. Brain volume was estimated by MRI. We used cross-sectional data to examine how the strength of association between vascular risk factor burden and brain volume changed across each age decade from age 45–54 years through to 85–94 years (N = 2,887). Second, we leveraged up to 40 years of longitudinal data to determine how the strength of association between vascular risk factor burden and brain volume changed when vascular risk factors were examined at progressively earlier ages (N = 7,868).ResultsIn both cross-sectional and longitudinal analyses, higher vascular risk factor burden was associated with lower brain volume across each age decade. In the cross-sectional analysis, the strength of this association decreased with each decade of advancing age (p for trend < 0.0001). In longitudinal analysis, the strength of association between vascular risk factor burden and brain volume was stronger when vascular risk factors were measured at younger ages. For example, vascular risk factor burden was most strongly associated with lower brain volume in later life when vascular risk factors were measured at age 45 years.ConclusionVascular risk factors at younger ages appear to have detrimental effects on current and future brain volume.

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Vascular risk factor burden and new-onset depression in the community

Preventive Medicine ◽

10.1016/j.ypmed.2017.11.022 ◽

2018 ◽

Vol 111 ◽

pp. 348-350 ◽

Cited By ~ 3

Author(s):

Shayna Adams ◽

Sarah Conner ◽

Jayandra J. Himali ◽

Alexa Beiser ◽

Ramachandran S. Vasan ◽

...

Keyword(s):

Risk Factor ◽

Vascular Risk Factor ◽

Vascular Risk ◽

Risk Factor Burden ◽

New Onset

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Mid‐life and late‐life vascular risk factor burden and neuropathology in old age

Annals of Clinical and Translational Neurology ◽

10.1002/acn3.50936 ◽

2019 ◽

Vol 6 (12) ◽

pp. 2403-2412 ◽

Cited By ~ 2

Author(s):

Sarah C. Conner ◽

Matthew P. Pase ◽

Herman Carneiro ◽

Mekala R. Raman ◽

Ann C. McKee ◽

...

Keyword(s):

Risk Factor ◽

Old Age ◽

Late Life ◽

Vascular Risk Factor ◽

Vascular Risk ◽

Risk Factor Burden

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The effect of vascular risk factor burden on the severity of COVID-19 illness, a retrospective cohort study

Respiratory Research ◽

10.1186/s12931-020-01510-0 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Houwei Du ◽

◽

Xiaobin Pan ◽

Nan Liu ◽

Junnian Chen ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Cox Regression ◽

Vascular Risk Factor ◽

Vascular Risk Factors ◽

Hospital Treatment ◽

Vascular Risk ◽

Laboratory Findings ◽

Increasing Risk ◽

Risk Factor Burden

Abstract Background Patients with cardiovascular comorbidities are at high risk of poor outcome from COVID-19. However, how the burden (number) of vascular risk factors influences the risk of severe COVID-19 disease remains unresolved. Our aim was to investigate the association of severe COVID-19 illness with vascular risk factor burden. Methods We included 164 (61.8 ± 13.6 years) patients with COVID-19 in this retrospective study. We compared the difference in clinical characteristics, laboratory findings and chest computed tomography (CT) findings between patients with severe and non-severe COVID-19 illness. We evaluated the association between the number of vascular risk factors and the development of severe COVID-19 disease, using a Cox regression model. Results Sixteen (9.8%) patients had no vascular risk factors; 38 (23.2%) had 1; 58 (35.4%) had 2; 34 (20.7%) had 3; and 18 (10.9%) had ≥4 risk factors. Twenty-nine patients (17.7%) experienced severe COVID-19 disease with a median (14 [7–27] days) duration between onset to developing severe COVID-19 disease, an event rate of 4.47 per 1000-patient days (95%CI 3.10–6.43). Kaplan-Meier curves showed a gradual increase in the risk of severe COVID-19 illness (log-rank P < 0.001) stratified by the number of vascular risk factors. After adjustment for age, sex, and comorbidities as potential confounders, vascular risk factor burden remained associated with an increasing risk of severe COVID-19 illness. Conclusions Patients with increasing vascular risk factor burden have an increasing risk of severe COVID-19 disease, and this population might benefit from specific COVID-19 prevention (e.g., self-isolation) and early hospital treatment measures.

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Vascular risk burden is a key player in the early progression of Alzheimer's disease

10.1101/2021.12.18.21267994 ◽

2021 ◽

Author(s):

João Pedro Ferrari-Souza ◽

Wagner S. Brum ◽

Lucas A. Hauschild ◽

Lucas U. Da Ros ◽

Pâmela C. L. Ferreira ◽

...

Keyword(s):

Risk Factors ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Risk Factor ◽

Cognitive Decline ◽

Vascular Risk Factor ◽

Vascular Risk Factors ◽

Vascular Risk ◽

Preclinical Alzheimer’S Disease ◽

Risk Factor Burden

Understanding whether vascular risk factors synergistically potentiate Alzheimer's disease progression is important in the context of emerging treatments for preclinical Alzheimer's disease. The existence of a synergistic relationship could suggest that the combination of therapies targeting Alzheimer's disease pathophysiology and vascular risk factors might potentiate treatment outcomes. In the present retrospective cohort study, we tested whether vascular risk factor burden interacts with Alzheimer's disease pathophysiology to accelerate neurodegeneration and cognitive decline in cognitively unimpaired subjects. We evaluated 503 cognitively unimpaired participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. Baseline vascular risk factor burden was calculated considering the history of cardiovascular disease, hypertension, diabetes mellitus, hyperlipidemia, stroke or transient ischemic attack, smoking, atrial fibrillation, and left ventricular hypertrophy. Alzheimer's disease pathophysiology was evaluated using cerebrospinal fluid (CSF) amyloid-β1-42 (Aβ1-42) reflecting brain amyloidosis (A) and tau phosphorylated at threonine 181 (p-tau181) reflecting brain tau pathology (T). Individuals were dichotomized as having an elevated vascular risk factor burden (V+ if having two or more vascular risk factors) and as presenting preclinical Alzheimer's disease [(AT)+ if having abnormal CSF p-tau181 and Aβ1-42 levels]. Neurodegeneration was assessed with plasma neurofilament light (NfL) and global cognition with the modified version of the Preclinical Alzheimer's Cognitive Composite. Linear mixed-effects models revealed that an elevated vascular risk factor burden synergistically interacted with Alzheimer's disease pathophysiology to drive longitudinal increases in plasma NfL levels (β = 5.08, P = 0.016) and cognitive decline (β = -0.43, P = 0.020). Additionally, we observed that vascular risk factor burden was not associated with CSF Aβ1-42 or p-tau181 changes over time. Survival analysis demonstrated that individuals with preclinical Alzheimer's disease and elevated vascular risk factor burden [(AT)+V+] had a significantly greater risk of clinical progression to cognitive impairment (adjusted Hazard Ratio = 3.5, P < 0.001). Our results support the notion that vascular risk factor burden and Alzheimer's disease pathophysiology are independent processes; however, they synergistically lead to neurodegeneration and cognitive decline. These findings can help in providing the blueprints for the combination of vascular risk factor management and Alzheimer's disease pathophysiology treatment in preclinical stages. Moreover, we observed plasma NfL as a robust marker of disease progression that may be used to track therapeutic response in future trials.

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The Age-Dependent Association Between Vascular Risk Factors and Depressed Mood

10.31219/osf.io/u2j8h ◽

2019 ◽

Author(s):

Maria Blöchl ◽

H. Lina Schaare ◽

Ute Kunzmann ◽

Steffen Nestler

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Depressed Mood ◽

Growth Models ◽

Later Life ◽

Vascular Risk Factor ◽

Vascular Risk Factors ◽

Vascular Risk ◽

Latent Growth ◽

Risk Factor Burden

Objectives: Cumulative burden from multiple vascular risk factors has been linked to depressed mood but whether this association becomes stronger or weaker from mid- to later life is still unclear. This study investigated whether vascular risk factor burden is associated with levels and longitudinal changes in depressed mood and whether these associations are dependent on age. Method: Our sample included 6,835 individuals (52–89 years) from the English Longitudinal Study of Ageing (ELSA), who were free of vascular disease at baseline and underwent up to five bi-yearly follow-up assessments of depressed mood. A composite score incorporated the presence of five vascular risk factors: hypertension, diabetes, smoking, obesity, and hypercholesterolemia. We used second-order latent growth models to test whether levels and changes of depressed mood differed as a function of baseline vascular risk factor burden, and how these associations were moderated by age. Results: Baseline vascular risk factor burden was associated with higher levels of depressed mood, and this association varied with age, such that it was stronger in midlife compared to later life. Vascular risk factor burden was not associated with changes in depressed mood. Discussion: Our findings suggest that vascular risk factor burden in midlife, but less so in later life, predicts individual differences in depressed mood. These findings are consistent with reports on the importance of midlife vascular risk and support the idea that prevention of vascular risk in this age period may be critical to maintain mental health.

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