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

Author(s):  
João Pedro Ferrari-Souza ◽  
Wagner S. Brum ◽  
Lucas A. Hauschild ◽  
Lucas U. Da Ros ◽  
Pâmela C. L. Ferreira ◽  
...  

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.

Neurology ◽  
2018 ◽  
Vol 91 (16) ◽  
pp. e1479-e1486 ◽  
Author(s):  
Matthew P. Pase ◽  
Kendra Davis-Plourde ◽  
Jayandra J. Himali ◽  
Claudia L. Satizabal ◽  
Hugo Aparicio ◽  
...  

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.


Aging ◽  
2020 ◽  
Vol 12 (14) ◽  
pp. 15058-15076
Author(s):  
Qing Wang ◽  
Cancan He ◽  
Yao Zhu ◽  
Qianqian Zhang ◽  
Zhijun Zhang ◽  
...  

Maturitas ◽  
2014 ◽  
Vol 79 (1) ◽  
pp. 96-99 ◽  
Author(s):  
Kim Blom ◽  
Ilonca Vaartjes ◽  
Sanne A.E. Peters ◽  
Huiberdina L. Koek

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Houwei Du ◽  
◽  
Xiaobin Pan ◽  
Nan Liu ◽  
Junnian Chen ◽  
...  

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.


2016 ◽  
Vol 12 ◽  
pp. P1059-P1061
Author(s):  
Isabelle Bos ◽  
Stephanie J.B. Vos ◽  
Lutz Frölich ◽  
Johannes Kornhuber ◽  
Jens Wiltfang ◽  
...  

2019 ◽  
Author(s):  
Maria Blöchl ◽  
H. Lina Schaare ◽  
Ute Kunzmann ◽  
Steffen Nestler

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.


2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
Márcia L. Chaves ◽  
Ana L. Camozzato ◽  
Cristiano Köhler ◽  
Jeffrey Kaye

Introduction. This study evaluates the progression of dementia and identifies prognostic risk factors for dementia.Methods. A group of 80 Brazilian community residents with dementia (34 with Alzheimer's disease and 46 with vascular dementia) was assessed over the course of 2 years. Data were analyzed with Cox regression survival analysis.Results. The data showed that education predicted cognitive decline (HR=1.2;P<.05) when analyzed without controlling for vascular risk factors. After the inclusion of vascular risk factors, education (HR=1.32;P<.05) and hypertension were predictive for cognitive decline (HR=38;P<.05), and Alzheimer's disease diagnosis was borderline predictive (P=.055).Conclusion.Vascular risk factors interacted with the diagnosis of vascular dementia. Education was a strong predictor of decline.


US Neurology ◽  
2010 ◽  
Vol 05 (02) ◽  
pp. 18 ◽  
Author(s):  
Simon Forstmeier ◽  
Andreas Maercker ◽  
◽  

This article summarises empirical findings on major potentially modifiable risk factors in the development of Alzheimer’s disease (AD), drawing on data from longitudinal epidemiological studies on the incidence of AD or any-cause dementia. Risk factors investigated to date include cognitive ability, motivational ability, emotional health, physical activity, social activity and social network, vascular risk factors and nutrition. The authors find most empirical support for two main clusters of risk factors that also represent potential targets for prevention. First, an active and stimulating lifestyle including cognitive, social, and physical activities reduces the risk of AD. Second, the absence of vascular risk factors such as diabetes, hypertension, hypercholesterol and obesity reduces the risk of AD. More prevention trials are warranted to investigate the preventative effects of an active and stimulating lifestyle on the one hand, and vascular health on the other, in delaying the onset of AD or slowing its progression.


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