Hippocampal Volume Loss, Brain Amyloid Accumulation, and APOE Status in Cognitively Intact Elderly Subjects

2019 ◽  
Vol 19 (3-4) ◽  
pp. 139-147 ◽  
Author(s):  
Sven Haller ◽  
Marie-Louise Montandon ◽  
Cristelle Rodriguez ◽  
Valentina Garibotto ◽  
François R. Herrmann ◽  
...  
Keyword(s):  
Hippocampal Volume ◽  
Elderly Subjects ◽  
Neuropsychological Performance ◽  
Amyloid Pet ◽  
Volume Loss ◽  
Apoe Ε4 ◽  
Amyloid Accumulation ◽  
Ε4 Allele ◽  
The Impact

Background: Hippocampal volume loss (HVL), PET-documented brain amyloid accumulation, and APOE-ε4 status are predictive biomarkers of the transition from mild cognitive impairment to Alzheimer disease (AD). In asymptomatic cases, the role of these biomarkers remains ambiguous. In contrast to the idea that HVL occurs in late phases of neurodegeneration, recent contributions indicate that it might occur before abnormal amyloid PET occurrence in elderly subjects and that its severity could be only marginally related to APOE variants. Using a longitudinal design, we examined the determinants of HVL in our sample, i.e., brain amyloid burden and the presence of APOE-ε4, and made a longitudinal assessment of cognitive functions. Methods: We performed a 4.5-year longitudinal study on 81 elderly community dwellers (all right-handed;, 48 (59.3%) women; mean age 73.7 ± 3.7 years) including MRI at baseline and follow-up, PET amyloid during follow-up, neuropsychological assessment at 18 and 54 months, and APOE genotyping. All cases were assessed using a continuous cognitive score (CCS) that took into account the global evolution of neuropsychological performance. Linear regression models were used to identify predictors of HVL. Results: There was a negative association between the CCS and HVL bilaterally. In multivariate models adjusting for demographic variables, the presence of APOE-ε4 was related to increased HVL bilaterally. A trend of significance was observed with respect to the impact of amyloid positivity on HVL in the left hemisphere. No significant interaction was found between amyloid positivity and the APOE-ε4 allele. Conclusion: The progressive decrement of neuropsychological performance is associated with HVL long before the emergence of clinically overt symptoms. In this cohort of healthy individuals, the presence of the APOE-ε4 allele was shown to be an independent predictor of worst hippocampal integrity in asymptomatic cases independently of amyloid positivity.

scholarly journals SURVIVAL ADVANTAGE OF APOE2

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S621-S621
Author(s):  
Sudha Seshadri
Keyword(s):  
Lower Risk ◽  
Large Population ◽  
Population Based ◽  
European Ancestry ◽  
Aggregated Data ◽  
Risk Of Death ◽  
Apoe Ε4 ◽  
Increased Risk ◽  
Ε4 Allele

Abstract Apolipoprotein E is a glycoprotein mediator and regulator of lipid transport and uptake. The APOE-ε4 allele has been associated with higher risk of Alzheimer’s disease and of mortality, but the effect of the less prevalent APOE-ε2 on survival remains elusive. We aggregated data of 38,537 individuals of European ancestry (mean age 65.5 years; 55.6% women) from six large population-based cohorts to determine the association of APOE-ε2, with survival in the general population. During a mean follow-up of 11.7 years, 17,021 individuals died. Compared with homozygous APOE-ε3 carriers, APOE-ε2 carriers were at lower risk of death (hazard ratio,95% confidence interval: 0.94,0.90-0.99; P=1.1*10-2), whereas APOE-ε4 carriers were at increased risk (HR 1.17,1.12-1.21; P=2.8*10-16). Risk was lowest for homozygous APOE-ε2 (HR 0.89,0.74-1.08), and highest for homozygous APOE-ε4 (HR 1.52,1.37-1.70). Results did not differ by sex. The association was unaltered after adjustment for baseline LDL or cardiovascular disease. Larger, multiethnic collaborations are ongoing.

scholarly journals Age and sex impact plasma NFL and t-Tau trajectories in individuals with subjective memory complaints: a 3-year follow-up study

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Filippo Baldacci ◽  
◽  
Simone Lista ◽  
Maria Laura Manca ◽  
Patrizia A. Chiesa ◽  
...  
Keyword(s):  
Plasma Vitamin ◽  
Subjective Memory Complaints ◽  
Subjective Memory ◽  
Memory Complaints ◽  
Apoe Ε4 ◽  
Biological Variables ◽  
T Tau ◽  
The Impact ◽  
Over Time

Abstract Background Plasma neurofilament light (NFL) and total Tau (t-Tau) proteins are candidate biomarkers for early stages of Alzheimer’s disease (AD). The impact of biological factors on their plasma concentrations in individuals with subjective memory complaints (SMC) has been poorly explored. We longitudinally investigate the effect of sex, age, APOE ε4 allele, comorbidities, brain amyloid-β (Aβ) burden, and cognitive scores on plasma NFL and t-Tau concentrations in cognitively healthy individuals with SMC, a condition associated with AD development. Methods Three hundred sixteen and 79 individuals, respectively, have baseline and three-time point assessments (at baseline, 1-year, and 3-year follow-up) of the two biomarkers. Plasma biomarkers were measured with an ultrasensitive assay in a mono-center cohort (INSIGHT-preAD study). Results We show an effect of age on plasma NFL, with women having a higher increase of plasma t-Tau concentrations compared to men, over time. The APOE ε4 allele does not affect the biomarker concentrations while plasma vitamin B12 deficiency is associated with higher plasma t-Tau concentrations. Both biomarkers are correlated and increase over time. Baseline NFL is related to the rate of Aβ deposition at 2-year follow-up in the left-posterior cingulate and the inferior parietal gyri. Baseline plasma NFL and the rate of change of plasma t-Tau are inversely associated with cognitive score. Conclusion We find that plasma NFL and t-Tau longitudinal trajectories are affected by age and female sex, respectively, in SMC individuals. Exploring the influence of biological variables on AD biomarkers is crucial for their clinical validation in blood.

Cognitive impairment and the role of the ApoE ε4-allele after stroke-a 13 months follow-up study

2009 ◽  
Vol 25 (8) ◽  
pp. 833-842 ◽  
Author(s):  
Jørgen Wagle ◽  
Lasse Farner ◽  
Kjell Flekkøy ◽  
Torgeir B. Wyller ◽  
Leiv Sandvik ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Follow Up Study ◽  
Apoe Ε4 ◽  
Ε4 Allele

Apolipoprotein E ε4/4 genotype limits response to dietary induction of hyperhomocysteinemia and resulting inflammatory signaling

2022 ◽  
pp. 0271678X2110690
Author(s):  
Charles E Seaks ◽  
Erica M Weekman ◽  
Tiffany L Sudduth ◽  
Kevin Xie ◽  
Brandi Wasek ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Risk Factor ◽  
Apolipoprotein E ◽  
Late Onset ◽  
Apoe Ε4 ◽  
Perivascular Inflammation ◽  
Ε4 Allele ◽  
Barrier Breakdown ◽  
The Impact

Vascular contributions to cognitive impairment and dementia (VCID) are the second leading cause of dementia behind Alzheimer’s disease. Apolipoprotein E (ApoE) is a lipid transporting lipoprotein found within the brain and periphery. The APOE ε4 allele is the strongest genetic risk factor for late onset Alzheimer’s disease and is a risk factor for VCID. Our lab has previously utilized a dietary model of hyperhomocysteinemia (HHcy) to induce VCID pathology and cognitive deficits in mice. This diet induces perivascular inflammation through cumulative oxidative damage leading to glial mediated inflammation and blood brain barrier breakdown. Here, we examine the impact of ApoE ε4 compared to ε3 alleles on the progression of VCID pathology and inflammation in our dietary model of HHcy. We report a significant resistance to HHcy induction in ε4 mice, accompanied by a number of related differences related to homocysteine (Hcy) metabolism and methylation cycle, or 1-C, metabolites. There were also significant differences in inflammatory profiles between ε3 and ε4 mice, as well as significant reduction in Serpina3n, a serine protease inhibitor associated with ApoE ε4, expression in ε4 HHcy mice relative to ε4 controls. Finally, we find evidence of pervasive sex differences within both genotypes in response to HHcy induction.

scholarly journals Evaluation of PiB visual interpretation with CSF Aβ and longitudinal SUVR in J-ADNI study

2019 ◽  
Vol 34 (2) ◽  
pp. 108-118 ◽  
Author(s):  
Yusuke Okada ◽  
◽  
Takashi Kato ◽  
Kaori Iwata ◽  
Yasuyuki Kimura ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Amyloid Pet ◽  
Negative Group ◽  
Visual Interpretation ◽  
Positive Group ◽  
Amyloid Accumulation ◽  
Over Time

Abstract Objective The objectives of the present study were to investigate (1) whether trinary visual interpretation of amyloid positron emission tomography (PET) imaging (negative/equivocal/positive) reflects quantitative amyloid measurements and the time course of 11C-Pittsburgh compound B (PiB) amyloid accumulation, and (2) whether visually equivocal scans represent an early stage of the Alzheimer’s disease (AD) continuum in terms of an intermediate state of quantitative amyloid measurements and the changes in amyloid accumulation over time. Methods From the National Bioscience Database Center Human Database of the Japanese Alzheimer’s Disease Neuroimaging Initiative, we selected 133 individuals for this study including 33 with Alzheimer’s disease dementia (ADD), 52 with late mild cognitive impairment (LMCI), and 48 cognitively normal (CN) subjects who underwent clinical assessment, PiB PET, and structural magnetic resonance imaging (MRI) with 2 or 3-years of follow-up. Sixty-eight of the 133 individuals underwent cerebrospinal fluid amyloid-β1-42 (CSF-Ab42) analysis at baseline. The standard uptake value ratio (SUVR) of PiB PET was calculated with a method using MRI at each visit. The cross-sectional values, longitudinal changes in SUVR, and baseline CSF-Ab42 were compared among groups, which were categorized based on trinary visual reads of amyloid PET (negative/equivocal/positive). Results From the trinary visual interpretation of the PiB PET images, 55 subjects were negative, 8 were equivocal, and 70 were positive. Negative interpretation was most frequent in the CN group (70.8/10.4/18.8%: negative/equivocal/positive), and positive was most frequent in the LMCI group (34.6/1.9/63.5%) and in the ADD group (9.1/6.1/84.8%). The baseline SUVRs were 1.08 ± 0.06 in the negative group, 1.23 ± 0.15 in the equivocal group, and 1.86 ± 0.31 in the positive group (F = 174.9, p < 0.001). The baseline CSF-Ab42 level was 463 ± 112 pg/mL in the negative group, 383 ± 125 pg/mL in the equivocal group, and 264 ± 69 pg/mL in the positive group (F = 37, p < 0.001). Over the 3-year follow-up, annual changes in SUVR were − 0.00 ± 0.02 in the negative group, 0.02 ± 0.02 in the equivocal group, and 0.04 ± 0.07 in the positive group (F = 8.4, p < 0.001). Conclusions Trinary visual interpretation (negative/equivocal/positive) of amyloid PET imaging reflects quantitative amyloid measurements evaluated with PET and the CSF amyloid test as well as the amyloid accumulation over time evaluated with PET over 3 years. Subjects in the early stage of the AD continuum could be identified with an equivocal scan, because they showed intermediate quantitative amyloid PET, CSF measurements, and the amyloid accumulation over time.

The Effect of the APOE-ε4 Allele and ACE-I/D Polymorphism on Cognition during a Two-Year Follow-Up in First-Ever Stroke Patients

2010 ◽  
Vol 29 (6) ◽  
pp. 534-542 ◽  
Author(s):  
A.M.J.J. Bour ◽  
S.M.C. Rasquin ◽  
L. Baars ◽  
M.P.J. van Boxtel ◽  
P.J. Visser ◽  
...  
Keyword(s):  
Stroke Patients ◽  
Apoe Ε4 ◽  
Ε4 Allele

scholarly journals COPD detected with screening: impact on patient management and prognosis

2014 ◽  
Vol 44 (6) ◽  
pp. 1571-1578 ◽  
Author(s):  
Loes C.M. Bertens ◽  
Johannes B. Reitsma ◽  
Yvonne van Mourik ◽  
Jan-Willem J. Lammers ◽  
Karel G.M. Moons ◽  
...  
Keyword(s):  
Frail Elderly ◽  
Patient Management ◽  
Drug Prescription ◽  
Screening Strategy ◽  
Community Dwelling ◽  
Elderly Subjects ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
The Impact

It is uncertain whether screening of older persons for chronic obstructive pulmonary disease (COPD) is worthwhile because the effects on patient management and prognosis are unknown.We aimed to assess the short-term consequences of detecting COPD in frail elderly subjects with dyspnoea, considering pulmonary drug use, hospitalisations and all-cause mortality.Community-dwelling frail elderly subjects, aged 65 years and older, with dyspnoea, participating in a screening study on COPD and heart failure were included. Final diagnoses were assigned by an expert panel based on all data from the screening strategy, including spirometry. Follow-up data were collected from the general practitioners.Of the 386 patients, 84 (21.8%) were received a new diagnosis of COPD. Overall, changes in pulmonary drug prescription during 6 months of follow-up were infrequent (n = 53, 13.7%; among new cases of COPD, 15 (17.9%) out of 84). Of all participants, 25.9% were hospitalised in the first year of follow-up, with the highest rate in patients with newly detected COPD (32.1%).Many new cases of COPD could be detected by screening frail elderly subjects with dyspnoea, but the impact on patient management seems limited. Our study underlines the importance of obtaining follow-up data to assess the true impact of a (screen-detected) diagnosis of COPD on patient management and outcome.

scholarly journals Falls Associate with Neurodegenerative Changes in ATN Framework of Alzheimer’s Disease

2020 ◽  
Vol 77 (2) ◽  
pp. 745-752
Author(s):  
Audrey Keleman ◽  
Julie K. Wisch ◽  
Rebecca M. Bollinger ◽  
Elizabeth A. Grant ◽  
Tammie L. Benzinger ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Connectivity ◽  
Hippocampal Volume ◽  
Cross Sectional Study ◽  
Amyloid Pet ◽  
Resting State Functional Connectivity ◽  
Cross Sectional ◽  
Preclinical Ad ◽  
Amyloid Accumulation

Background: Behavioral markers for Alzheimer’s disease (AD) are not included within the widely used amyloid-tau-neurodegeneration framework. Objective: To determine when falls occur among cognitively normal (CN) individuals with and without preclinical AD. Methods: This cross-sectional study recorded falls among CN participants (n = 83) over a 1-year period. Tailored calendar journals recorded falls. Biomarkers including amyloid positron emission tomography (PET) and structural and functional magnetic resonance imaging were acquired within 2 years of fall evaluations. CN participants were dichotomized by amyloid PET (using standard cutoffs). Differences in amyloid accumulation, global resting state functional connectivity (rs-fc) intra-network signature, and hippocampal volume were compared between individuals who did and did not fall using Wilcoxon rank sum tests. Among preclinical AD participants (amyloid-positive), the partial correlation between amyloid accumulation and global rs-fc intra-network signature was compared for those who did and did not fall. Results: Participants who fell had smaller hippocampal volumes (p = 0.04). Among preclinical AD participants, those who fell had a negative correlation between amyloid uptake and global rs-fc intra-network signature (R = –0.75, p = 0.012). A trend level positive correlation was observed between amyloid uptake and global rs-fc intra-network signature (R = 0.70, p = 0.081) for preclinical AD participants who did not fall. Conclusion: Falls in CN older adults correlate with neurodegeneration biomarkers. Participants without falls had lower amyloid deposition and preserved global rs-fc intra-network signature. Falls most strongly correlated with presence of amyloid and loss of brain connectivity and occurred in later stages of preclinical AD.

006 Effect of apolipoprotein e ε4 allele on medial temporal lobe atrophy in ischaemic stroke patients

2018 ◽  
Vol 89 (6) ◽  
pp. A4.1-A4
Author(s):  
Mohamed Salah Khlif ◽  
Emilio Werden ◽  
Natalia Egorova ◽  
Wasim Khan ◽  
Amy Brodtmann
Keyword(s):  
Cognitive Impairment ◽  
Ischaemic Stroke ◽  
Temporal Lobe ◽  
Medial Temporal Lobe ◽  
Hippocampal Volume ◽  
Stroke Survivors ◽  
Apoe Ε4 ◽  
Ε4 Allele ◽  
The Right ◽  
Time Point

IntroductionApolipoprotein E (APOE) ε4 allele is a known risk factor for the development of cognitive impairment. APOE ε4 carriers have been reported as having lower hippocampal volume in Alzheimer’s disease, mild cognitive impairment, and in healthy cohorts,1 but this is not well investigated in stroke. Here, we compared the regional volume in the medial temporal lobe in ischaemic stroke survivors, with and without the ε4 allele, three (time point 1, t1) and twelve (t2) months after stroke.Methods21 APOE ε4 carriers and 21 non-carriers, matched for lesion size and location and for neurological impairment as measured by NIHSS, were sampled from the CANVAS study, a longitudinal imaging study in stroke survivors.2 A mixed-effect linear model was used to analyse the effect of the ε4 allele on hippocampal, entorhinal, and para-hippocampal volumes, adjusting for age, sex, years of education, and total intracranial volume. Volumes were estimated using the longitudinal stream in FreeSurfer 5.3.ResultsThe left hippocampal (pt1=0.038, pt2=0.040) and entorhinal (pt1=0.044, pt2=0.038) volumes were significantly lower in the ε4-carrier group at each time point. The right entorhinal (pt1=pt2=0.002) and para-hippocampal (pt1=0.018, pt2=0.020) volumes were also significantly lower in the ε4-carrier group, but there was no difference in the right hippocampal volume (pt1=pt2=0.055) between the two groups. The group-time interaction was significant for the left para-hippocampal cortex (p=0.019): ε4 non-carriers showed a significant volume increase (p=0.018) between t1 and t2.ConclusionThese findings suggest that stroke survivors who carry the APOE-ε4 allele will experience greater atrophy in the medial temporal lobe in the twelve months following their stroke.References1. Manning EN, et al. e4 Is Associated with Disproportionate Progressive Hippocampal Atrophy in AD. PLoS ONE2014;9(5):e97608.2. Brodtmann A, et al. Charting cognitive and volumetric trajectories after stroke: Protocol for the Cognition And Neocortical Volume After Stroke (CANVAS) study. Int J Stroke2014;9(6):824–828.

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