scholarly journals Eating a Weekly Serving of Walnuts Relates to Beneficial Brain Imaging Phenotypes in a Cohort at Increased Risk of Alzheimer's Disease

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1234-1234
Author(s):  
Aleix Sala-Vila ◽  
Marta Crous-Bou ◽  
Gonzalo Sánchez-Benavides ◽  
Eider M de Arenaza-Urquijo ◽  
Marc Suárez-Calvet ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mediterranean Diet ◽  
Successful Aging ◽  
Small Vessel Disease ◽  
Gray Matter Volume ◽  
Intracranial Volume ◽  
Cross Sectional ◽  
Apoe Ε4 ◽  
Increased Risk

Abstract Objectives There is increasing evidence on the brain benefits of nut consumption. Magnetic resonance imaging (MRI) enables the detection of brain changes associated with neurodegenerative and vascular diseases. In middle-aged cognitively unimpaired subjects at increased risk of Alzheimer's disease (AD), we searched for cross-sectional associations between nut consumption and MRI-assessed brain phenotypes, including white matter hyperintensities (WMH, a marker of cerebral small vessel disease that confers increased risk of AD and stroke) and topographic patterns of gray matter volume (GMv). Methods We performed high-resolution structural MRI in 382 participants from the ALFA study (ALzheimer and FAmilies) cohort, which is enriched by family history of sporadic AD and APOE-ε4 carriership, the most prevalent genetic risk factor for AD. We assessed nut consumption by a food-frequency questionnaire containing five items related to nuts. WMH volume was normalized by intracranial volume (TIV) and rank-transformed. For WMH, we conducted univariate models with two factors: nut consumption (<1 and ≥1 serving/week) and being APOE-ε4 homozygote (yes/no), and their interaction, adjusting for age, gender, hypertension, hypercholesterolemia, and adherence to Mediterranean Diet. We also explored whether nut consumption related to differences in GMv using a voxel-based morphometry analysis corrected by age, gender, number of APOE-ε4 alleles, hypertension, hypercholesterolemia, adherence to Mediterranean Diet, and TIV. Results 187 participants reported nut consumption of ≥1 serving/week, 148 of whom disclosed walnut consumption. Nut (or walnut) consumption of ≥1 serving/week related to a significantly lower WMH volume (P ≤ 0.035, both). We found no statistically significant nut × APOE-ε4 interactions. Participants reporting consumption of ≥1 walnut serving/week showed significantly greater GMv in areas including the anterior/middle cingulate cortex, which is relevant for cognition and has been associated with successful aging. Conclusions Nut (in particular walnut) consumption relates to beneficial phenotypes of both cerebral vasculature and regional GMv. Funding Sources Instituto de Salud Carlos III, Spain; “la Caixa” Foundation; California Walnut Commission.

MEDITERRANEAN DIET AND MAGNETIC RESONANCE IMAGING-ASSESSED BRAIN ATROPHY IN COGNITIVELY NORMAL INDIVIDUALS AT RISK FOR ALZHEIMER’S DISEASE

2014 ◽  
pp. 1-10
Author(s):  
L. Mosconi ◽  
J. Murray ◽  
W.H. Tsui ◽  
Y. Li ◽  
M. Davies ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mediterranean Diet ◽  
Brain Atrophy ◽  
Tissue Loss ◽  
Middle Temporal Gyrus ◽  
Intracranial Volume ◽  
Cross Sectional ◽  
Cognitively Normal ◽  
Lower Adherence

OBJECTIVES: Epidemiological evidence linking diet, one of the most important modifiable environmental factors, and risk of Alzheimer’s disease (AD) is rapidly increasing. Several studies have shown that higher adherence to a Mediterranean diet (MeDi) is associated with reduced risk of AD. This study examines the associations between high vs. lower adherence to a MeDi and structural MRI-based brain atrophy in key regions for AD in cognitively normal (NL) individuals with and without risk factors for AD. DESIGN: Cross-sectional study. SETTING: Manhattan (broader area). PARTICIPANTS: Fifty-two NL individuals (age 54+12 y, 70% women) with complete dietary information and cross-sectional, 3D T1-weighted MRI scans were examined. MEASUREMENTS: Subjects were dichotomized into those showing higher vs. lower adherences to the MeDi using published protocols. Estimates of cortical thickness for entorhinal cortex (EC), inferior parietal lobe, middle temporal gyrus, orbitofrontal cortex (OFC) and posterior cingulate cortex (PCC) were obtained by use of automated segmentation tools (FreeSurfer). Multivariate general linear models and linear regressions assessed the associations of MeDi with MRI measures. RESULTS: Of the 52 participants, 20 (39%) showed higher MeDi adherence (MeDi+) and 32 (61%) showed lower adherence (MeDi-). Groups were comparable for clinical, neuropsychological measures, presence of a family history of AD (FH), and frequency of Apolipoprotein E (APOE) ε4 genotype. With and without controlling for age and total intracranial volume, MeDi+ subjects showed greater thickness of AD-vulnerable ROIs as compared to MeDi- subjects (Wilk’s Lambda p=0.026). Group differences were most pronounced in OFC (p=0.001), EC (p=0.03) and PCC (p=0.04) of the left hemisphere. Adjusting for gender, education, FH, APOE status, BMI, insulin resistance scores and presence of hypertension did not attenuate the relationship. CONCLUSION: NL individuals showing lower adherence to the MeDi had cortical thinning in the same brain regions as clinical AD patients compared to those showing higher adherence. These data indicate that the MeDi may have a protective effect against tissue loss, and suggest that dietary interventions may play a role in the prevention of AD

Influence of White Matter Hyperintensities on Baseline and Longitudinal Amyloid-β in Cognitively Normal Individuals

2021 ◽  
pp. 1-11
Author(s):  
Fennie Choy Chin Wong ◽  
Seyed Ehsan Saffari ◽  
Chathuri Yatawara ◽  
Kok Pin Ng ◽  
Nagaendran Kandiah ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Executive Function ◽  
White Matter ◽  
White Matter Hyperintensities ◽  
Small Vessel Disease ◽  
Amyloid Β ◽  
Intracranial Volume ◽  
Linear Regression Models ◽  
Cognitively Normal

Background: The associations between small vessel disease (SVD) and cerebrospinal amyloid-β1-42 (Aβ1-42) pathology have not been well-elucidated. Objective: Baseline (BL) white matter hyperintensities (WMH) were examined for associations with month-24 (M24) and longitudinal Aβ1-42 change in cognitively normal (CN) subjects. The interaction of WMH and Aβ1-42 on memory and executive function were also examined. Methods: This study included 72 subjects from the Alzheimer’s Disease Neuroimaging Initiative. Multivariable linear regression models evaluated associations between baseline WMH/intracranial volume ratio, M24 and change in Aβ1-42 over two years. Linear mixed effects models evaluated interactions between BL WMH/ICV and Aβ1-42 on memory and executive function. Results: Mean age of the subjects (Nmales = 36) = 73.80 years, SD = 6.73; mean education years = 17.1, SD = 2.4. BL WMH was significantly associated with M24 Aβ1-42 (p = 0.008) and two-year change in Aβ1-42 (p = 0.006). Interaction between higher WMH and lower Aβ1-42 at baseline was significantly associated with worse memory at baseline and M24 (p = 0.003). Conclusion: BL WMH was associated with M24 and longitudinal Aβ1-42 change in CN. The interaction between higher WMH and lower Aβ1-42 was associated with poorer memory. Since SVD is associated with longitudinal Aβ1-42 pathology, and the interaction of both factors is linked to poorer cognitive outcomes, the mitigation of SVD may be correlated with reduced amyloid pathology and milder cognitive deterioration in Alzheimer’s disease.

scholarly journals THE APOE-ε4 ALLELE AND AGE SYNERGISTICALLY DRIVE DISEASE PROGRESSION IN ALZHEIMER’S DISEASE

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S943-S943
Author(s):  
Luca Kleineidam ◽  
Andrea R Zammit ◽  
Alyssa DeVito ◽  
Richard B Lipton ◽  
Oliver Peters ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Progression ◽  
Underlying Mechanism ◽  
Additive Models ◽  
Tau Pathology ◽  
Case Control Studies ◽  
Cross Sectional ◽  
Apoe Ε4 ◽  
Ε4 Allele

Abstract The Apolipoprotein E (APOE)-ε4 allele is the strongest genetic risk factor for Alzheimer’s disease (AD) and other neurodegenerative dementias. Cross-sectional case-control studies suggest that the effect of APOE-ε4 decreases in old age. However, since APOE- ε4 is associated with mortality, these studies might be prone to bias due to selective survival. Therefore, we used multi-state-modeling in longitudinal cohort studies to examine the effect of APOE-ε4 on the transition through cognitive states (i.e. cognitively normal, mild cognitive impairment (MCI) and dementia) while taking death as a competing risk into account. Results from the German AgeCoDe study (n=3000, aged 75-101 years) showed that APOE-ε4 increases the risk for cognitive deterioration in all disease stages. Contrary to results from cross-sectional studies, the effect of APOE-ε4 on the transition from MCI to dementia increased with increasing age (HR=1.044, 95%-CI=1.001-1090). The direction of this effect was confirmed in a smaller sample from the Einstein Aging Study (n=744, HR=1.032, 95%-CI=0.949-1.122). To examine the pathophysiological basis of these results, generalized additive models were used to study AD biomarkers in the liquor of 1045 patients with MCI or AD-dementia. Here, increased amyloid (Abeta1-42) pathology was associated with increased tau pathology (pTau181), consistent with the amyloid-cascade-hypothesis. Interestingly, higher age and presence of the APOE-ε4 synergistically lowered the amount of amyloid required to exacerbate tau pathology (interaction p=0.012). Taken together, our results suggest that the effect of APOE-ε4 on disease progression increases with advancing age. An altered neuroinflammatory response to neurodegeneration should be further explored as potential underlying mechanism.

scholarly journals Evolution of Konglish Based on the Current Prevalence and South Korean Public Attitude Towards Konglish

2020 ◽  
Vol 3 ◽  
Author(s):  
Jennifer Tse
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Olive Oil ◽  
Mediterranean Diet ◽  
Cognitive Abilities ◽  
Brain Disorder ◽  
Preventative Measures ◽  
Increased Risk ◽  
The Future ◽  
The Mediterranean

Alzheimer’s disease is a brain disorder that negatively affects memory and other cognitive abilities, including language and maintaining one’s orientation. Eventually, one’s ability to function cognitively or physically ceases altogether. The Mediterranean diet is characterized by large amounts of fruits, vegetables, olive oil, and a lack of red meat. Such a diet is most often consumed near areas surrounding the Mediterranean Sea and has been linked to a reduced risk of Alzheimer’s disease. This correlation is crucial to study as there is no current effective treatment for Alzheimer’s disease. Understanding what can prevent this disease is important for public health, as well as helping us identify the causes of the disease, which aid in creating effective treatments in the future. In this paper, research on the link between the Mediterranean diet and the risk of developing Alzheimer’s disease as one ages will be examined. Evidence shows that people who follow the Mediterranean diet have a lower risk of Alzheimer’s as they grow older. Research indicates that this is due to the polyphenols in olive oil—a staple in the Mediterranean diet—and the general heart and body health that the diet promotes. This healthy diet also reduces obesity, which is linked to an increased risk of Alzheimer’s disease. In the future, more effort should be put into impeding the development of Alzheimer’s disease, which could potentially be done using knowledge of which populations are at risk, critical biomarkers of the disease, and preventative measures like the Mediterranean diet.

scholarly journals Investigating the role of APOE: limitations of human pluripotent stem cell-derived cerebral organoids

2020 ◽  
Author(s):  
Damián Hernández ◽  
Louise A. Rooney ◽  
Maciej Daniszewski ◽  
Lerna Gulluyan ◽  
Helena H. Liang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Line ◽  
Human Fibroblasts ◽  
Susceptibility Gene ◽  
Tau Phosphorylation ◽  
Isogenic Lines ◽  
Apoe Ε4 ◽  
Increased Risk ◽  
Β Amyloid

SummaryApolipoprotein E (APOE) is the most important susceptibility gene for late onset of Alzheimer’s disease, with the presence of APOE-ε4 associated with increased risk of developing Alzheimer’s disease. Here, we reprogrammed human fibroblasts from individuals with different APOE-ε genotypes into induced pluripotent stem cells, and generated isogenic lines with different APOE profiles. We then differentiated these into cerebral organoids for six months and assessed the suitability of this in vitro system to measure APOE, β amyloid, and Tau phosphorylation levels. We identified intra- and inter-variabilities in the organoids’ cell composition. Using the CRISPR-edited APOE isogenic lines, we observed more homogenous cerebral organoids, and similar levels of APOE, β amyloid, and Tau between the isogenic lines, with the exception of one site of Tau phosphorylation which was higher in the APOE-ε4/ε4 organoids. These data describe that pathological hallmarks of AD are observed in cerebral organoids, and that their variation is mainly independent of the APOE-ε status of the cells, but associated with the high variability of cerebral organoid differentiation. It demonstrates that the batch-to-batch and cell-line-to-cell-line variabilities need to be considered when using cerebral organoids.

scholarly journals A comprehensive analysis of methods for assessing polygenic burden on Alzheimer’s disease pathology and risk beyond APOE

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Andre Altmann ◽  
Marzia A Scelsi ◽  
Maryam Shoai ◽  
Eric de Silva ◽  
Leon M Aksman ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Diagnosis ◽  
Risk Scores ◽  
Imaging Biomarkers ◽  
Cross Sectional ◽  
Polygenic Risk ◽  
Apoe Ε4 ◽  
Polygenic Scores ◽  
Apoe Locus

Abstract Genome-wide association studies have identified dozens of loci that alter the risk to develop Alzheimer’s disease. However, with the exception of the APOE-ε4 allele, most variants bear only little individual effect and have, therefore, limited diagnostic and prognostic value. Polygenic risk scores aim to collate the disease risk distributed across the genome in a single score. Recent works have demonstrated that polygenic risk scores designed for Alzheimer’s disease are predictive of clinical diagnosis, pathology confirmed diagnosis and changes in imaging biomarkers. Methodological innovations in polygenic risk modelling include the polygenic hazard score, which derives effect estimates for individual single nucleotide polymorphisms from survival analysis, and methods that account for linkage disequilibrium between genomic loci. In this work, using data from the Alzheimer’s disease neuroimaging initiative, we compared different approaches to quantify polygenic disease burden for Alzheimer’s disease and their association (beyond the APOE locus) with a broad range of Alzheimer’s disease-related traits: cross-sectional CSF biomarker levels, cross-sectional cortical amyloid burden, clinical diagnosis, clinical progression, longitudinal loss of grey matter and longitudinal decline in cognitive function. We found that polygenic scores were associated beyond APOE with clinical diagnosis, CSF-tau levels and, to a minor degree, with progressive atrophy. However, for many other tested traits such as clinical disease progression, CSF amyloid, cognitive decline and cortical amyloid load, the additional effects of polygenic burden beyond APOE were of minor nature. Overall, polygenic risk scores and the polygenic hazard score performed equally and given the ease with which polygenic risk scores can be derived; they constitute the more practical choice in comparison with polygenic hazard scores. Furthermore, our results demonstrate that incomplete adjustment for the APOE locus, i.e. only adjusting for APOE-ε4 carrier status, can lead to overestimated effects of polygenic scores due to APOE-ε4 homozygous participants. Lastly, on many of the tested traits, the major driving factor remained the APOE locus, with the exception of quantitative CSF-tau and p-tau measures.

IC-P-106: Cross-Sectional Modeling of Regional Perfusion and Gray Matter Volume in Alzheimer's Disease

2016 ◽  
Vol 12 ◽  
pp. P80-P81
Author(s):  
Esther E. Bron ◽  
Alexandra L. Young ◽  
Neil P. Oxtoby ◽  
Marion Smits ◽  
John C. van Swieten ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Gray Matter ◽  
Gray Matter Volume ◽  
Regional Perfusion ◽  
Cross Sectional ◽  
Matter Volume

scholarly journals Environmental factors influencing the link between APOE ε4 and Alzheimer's disease (AD) risk

2018 ◽  
Vol 31 (2) ◽  
pp. 305-306 ◽  
Author(s):  
Keith Fluegge
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Genetic Risk ◽  
Temporal Relationship ◽  
Disease Risk ◽  
Apoe Ε4 ◽  
Factors Influencing ◽  
Increased Risk ◽  
Ε4 Allele

While APOE ε4 allele is considered a genetic risk factor for Alzheimer's disease (AD), no relation existed between APOE ε4 and AD in the Yoruba in Nigeria among cohorts included in early prevalence waves. The authors’ explanation that other disease susceptibilities may provoke earlier mortality is inconsistent with the Yoruba having a lower incidence of disease risk factors. Cohort enrichment in 2001 has altered the authors’ conclusions; Yorba participants homozygous, and not heterozygous, for the ε4 allele had significantly increased risk for AD (HR = 2.95, p = 0.0002) (Hendrie et al., 2014). This is a critical revelation, yet it is not clear why such a temporal relationship exists between risk genotypes and AD among the Yoruba. This letter proposes an explanation.

scholarly journals Open Access Series of Imaging Studies (OASIS): Cross-sectional MRI Data in Young, Middle Aged, Nondemented, and Demented Older Adults

2007 ◽  
Vol 19 (9) ◽  
pp. 1498-1507 ◽  
Author(s):  
Daniel S. Marcus ◽  
Tracy H. Wang ◽  
Jamie Parker ◽  
John G. Csernansky ◽  
John C. Morris ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Magnetic Resonance ◽  
Open Access ◽  
Intracranial Volume ◽  
Resonance Imaging ◽  
Imaging Studies ◽  
Cross Sectional ◽  
Data Set

The Open Access Series of Imaging Studies is a series of magnetic resonance imaging data sets that is publicly available for study and analysis. The initial data set consists of a cross-sectional collection of 416 subjects aged 18 to 96 years. One hundred of the included subjects older than 60 years have been clinically diagnosed with very mild to moderate Alzheimer's disease. The subjects are all right-handed and include both men and women. For each subject, three or four individual T1-weighted magnetic resonance imaging scans obtained in single imaging sessions are included. Multiple within-session acquisitions provide extremely high contrast-to-noise ratio, making the data amenable to a wide range of analytic approaches including automated computational analysis. Additionally, a reliability data set is included containing 20 subjects without dementia imaged on a subsequent visit within 90 days of their initial session. Automated calculation of whole-brain volume and estimated total intracranial volume are presented to demonstrate use of the data for measuring differences associated with normal aging and Alzheimer's disease.

scholarly journals Plasma cholesterol in Alzheimer’s disease and frontotemporal dementia

2020 ◽  
Vol 11 (1) ◽  
pp. 116-123
Author(s):  
Pan Wang ◽  
Huihong Zhang ◽  
Yan Wang ◽  
Miao Zhang ◽  
Yuying Zhou
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Frontotemporal Dementia ◽  
Cholesterol Level ◽  
Plasma Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Apoe Ε4 ◽  
Cholesterol Levels ◽  
Increased Risk

AbstractBackgroundThe relationship between the apolipoprotein E (APOE)-ε4 allele, triglyceride (TG) level, and cholesterol level and an increased risk of developing Alzheimer’s disease (AD) has been well established, but their relationship with behavioral-variant frontotemporal dementia (bvFTD) is not well-known.MethodologyThe levels of TGs, total cholesterol (TC), low-density lipoprotein (LDL), and high-density lipoprotein were measured in bvFTD and AD patients and in normal controls (NCs). DNA was extracted, and APOE was genotyped.ResultsThe APOE-ε4 allele frequency was higher in the AD group than in the NC group, but no difference was found between the AD and the bvFTD groups. The bvFTD group had higher LDL than the AD group, and significant differences were also found for the cholesterol level in the dementia groups compared with the NC group. Elevated LDL level was positively correlated with appetite and eating score in the bvFTD group. Compared with the AD patients and NCs without the APOE-ε4 allele, those with the APOE-ε4 allele had higher TC, but its correlation with the bvFTD group was absent.ConclusionsThe bvFTD and the AD groups had higher cholesterol levels. The APOE-ε4 allele and eating behavior might modify lipid metabolism in dementia. TG and cholesterol analyses may offer a new opportunity for targeted treatments.

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