scholarly journals Subject-specific multi-poroelastic model for exploring the risk factors associated with the early stages of Alzheimer's disease

2017 ◽  
Vol 8 (1) ◽  
pp. 20170019 ◽  
Author(s):  
Liwei Guo ◽  
John C. Vardakis ◽  
Toni Lassila ◽  
Micaela Mitolo ◽  
Nishant Ravikumar ◽  
...  

There is emerging evidence suggesting that Alzheimer's disease is a vascular disorder, caused by impaired cerebral perfusion, which may be promoted by cardiovascular risk factors that are strongly influenced by lifestyle. In order to develop an understanding of the exact nature of such a hypothesis, a biomechanical understanding of the influence of lifestyle factors is pursued. An extended poroelastic model of perfused parenchymal tissue coupled with separate workflows concerning subject-specific meshes, permeability tensor maps and cerebral blood flow variability is used. The subject-specific datasets used in the modelling of this paper were collected as part of prospective data collection. Two cases were simulated involving male, non-smokers (control and mild cognitive impairment (MCI) case) during two states of activity (high and low). Results showed a marginally reduced clearance of cerebrospinal fluid (CSF)/interstitial fluid (ISF), elevated parenchymal tissue displacement and CSF/ISF accumulation and drainage in the MCI case. The peak perfusion remained at 8 mm s −1 between the two cases.

1990 ◽  
Vol 157 (2) ◽  
pp. 273-275 ◽  
Author(s):  
Albert Hofman ◽  
Cornelia M. Van Duijn ◽  
Willem Schulte ◽  
Theunis A. Tanja ◽  
Robert Haaxma ◽  
...  

Advanced maternal and paternal age were investigated as putative risk factors for AD in 198 clinically diagnosed Alzheimer patients and in 198 randomly selected healthy controls. No significant differences in average age of fathers and of mothers at birth of the subject were observed. The risk of AD was not significantly different across categories of maternal and paternal age. The association with parental age was not different for sporadic and familial AD. These findings do not support the view of a maternal or paternal age effect on AD.


2020 ◽  
Vol 17 ◽  
Author(s):  
Hyung-Ji Kim ◽  
Jae-Hong Lee ◽  
E-nae Cheong ◽  
Sung-Eun Chung ◽  
Sungyang Jo ◽  
...  

Background: Amyloid PET allows for the assessment of amyloid β status in the brain, distinguishing true Alzheimer’s disease from Alzheimer’s disease-mimicking conditions. Around 15–20% of patients with clinically probable Alzheimer’s disease have been found to have no significant Alzheimer’s pathology on amyloid PET. However, a limited number of studies had been conducted this subpopulation in terms of clinical progression. Objective: We investigated the risk factors that could affect the progression to dementia in patients with amyloid-negative amnestic mild cognitive impairment (MCI). Methods: This study was a single-institutional, retrospective cohort study of patients over the age of 50 with amyloidnegative amnestic MCI who visited the memory clinic of Asan Medical Center with a follow-up period of more than 36 months. All participants underwent brain magnetic resonance imaging (MRI), detailed neuropsychological testing, and fluorine-18[F18]-florbetaben amyloid PET. Results: During the follow-up period, 39 of 107 patients progressed to dementia from amnestic MCI. In comparison with the stationary group, the progressed group had a more severe impairment in verbal and visual episodic memory function and hippocampal atrophy, which showed an Alzheimer’s disease-like pattern despite the lack of evidence for significant Alzheimer’s disease pathology. Voxel-based morphometric MRI analysis revealed that the progressed group had a reduced gray matter volume in the bilateral cerebellar cortices, right temporal cortex, and bilateral insular cortices. Conclusion: Considering the lack of evidence of amyloid pathology, clinical progression of these subpopulation may be caused by other neuropathologies such as TDP-43, abnormal tau or alpha synuclein that lead to neurodegeneration independent of amyloid-driven pathway. Further prospective studies incorporating biomarkers of Alzheimer’s diseasemimicking dementia are warranted.


2021 ◽  
Vol 8 (1) ◽  
pp. e000759
Author(s):  
Daniel Higbee ◽  
Raquel Granell ◽  
Esther Walton ◽  
Roxanna Korologou-Linden ◽  
George Davey Smith ◽  
...  

RationaleLarge retrospective case-control studies have reported an association between chronic obstructive pulmonary disease (COPD), reduced lung function and an increased risk of Alzheimer’s disease. However, it remains unclear if these diseases are causally linked, or due to shared risk factors. Conventional observational epidemiology suffers from unmeasured confounding and reverse causation. Additional analyses addressing causality are required.ObjectivesTo examine a causal relationship between COPD, lung function and Alzheimer’s disease.MethodsUsing two-sample Mendelian randomisation, we used single nucleotide polymorphisms (SNPs) identified in a genome wide association study (GWAS) for lung function as instrumental variables (exposure). Additionally, we used SNPs discovered in a GWAS for COPD in those with moderate to very severe obstruction. The effect of these SNPs on Alzheimer’s disease (outcome) was taken from a GWAS based on a sample of 24 807 patients and 55 058 controls.ResultsWe found minimal evidence for an effect of either lung function (OR: 1.02 per SD; 95% CI 0.91 to 1.13; p value 0.68) or liability for COPD on Alzheimer’s disease (OR: 0.97 per SD; 95% CI 0.92 to 1.03; p value 0.40).ConclusionNeither reduced lung function nor liability COPD are likely to be causally associated with an increased risk of Alzheimer’s, any observed association is likely due to unmeasured confounding. Scientific attention and health prevention policy may be better focused on overlapping risk factors, rather than attempts to reduce risk of Alzheimer’s disease by targeting impaired lung function or COPD directly.


2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Carla VandeWeerd ◽  
Gregory J. Paveza ◽  
Margaret Walsh ◽  
Jaime Corvin

Physical mistreatment has been estimated to affect 2 million older persons each year and dramatically affects health outcomes. While researchers have attempted to examine risk factors for specific forms of abuse, many have been able to focus on only victim or perpetrator characteristics, or a limited number of psychosocial variables at any one time. Additionally, data on risk factors for subgroups such as persons with Alzheimer’s disease who may have heightened and/or unique risk profiles has also been limited. This paper examines risk for physical violence in caregiver/patient dyads who participated in the Aggression and Violence in Community-Based Alzheimer’s Families Grant. Data were collected via in-person interview and mailed survey and included demographics as well as measures of violence, physical and emotional health, and health behaviors. Logistic regression analysis indicated that caregivers providing care to elders with high levels of functional impairment or dementia symptoms, or who had alcohol problems, were more likely to use violence as a conflict resolution strategy, as were caregivers who were providing care to elders who used violence against them. By contrast, caregivers with high self-esteem were less likely to use violence as a conflict resolution strategy. Significant interaction effects were also noted.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tadeja Gracner ◽  
Patricia W. Stone ◽  
Mansi Agarwal ◽  
Mark Sorbero ◽  
Susan L Mitchell ◽  
...  

Abstract Background Though work has been done studying nursing home (NH) residents with either advanced Alzheimer’s disease (AD) or Alzheimer’s disease related dementia (ADRD), none have distinguished between them; even though their clinical features affecting survival are different. In this study, we compared mortality risk factors and survival between NH residents with advanced AD and those with advanced ADRD. Methods This is a retrospective observational study, in which we examined a sample of 34,493 U.S. NH residents aged 65 and over in the Minimum Data Set (2011–2013). Incident assessment of advanced disease was defined as the first MDS assessment with severe cognitive impairment (Cognitive Functional Score equals to 4) and diagnoses of AD or ADRD. Demographics, functional limitations, and comorbidities were evaluated as mortality risk factors using Cox models. Survival was characterized with Kaplan-Maier functions. Results Of those with advanced cognitive impairment, 35 % had AD and 65 % ADRD. At the incident assessment of advanced disease, those with AD had better health compared to those with ADRD. Mortality risk factors were similar between groups (shortness of breath, difficulties eating, substantial weight-loss, diabetes mellitus, heart failure, chronic obstructive pulmonary disease, and pneumonia; all p < 0.01). However, stroke and difficulty with transfer (for women) were significant mortality risk factors only for those with advanced AD. Urinary tract infection, and hypertension (for women) only were mortality risk factors for those with advanced ADRD. Median survival was significantly shorter for the advanced ADRD group (194 days) compared to the advanced AD group (300 days). Conclusions There were distinct mortality and survival patterns of NH residents with advanced AD and ADRD. This may help with care planning decisions regarding therapeutic and palliative care.


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