scholarly journals In-Vivo Staging of Regional Amyloid Progression In Healthy Middle Aged To Older People At Risk of Alzheimer’s Disease

Author(s):  
Fedor Levin ◽  
Irina Jelistratova ◽  
Tobey J. Betthauser ◽  
Ozioma Okonkwo ◽  
Sterling C. Johnson ◽  
...  

Abstract Background We investigated regional amyloid staging characteristics in 11C-PiB-PET data from middle-aged to older participants at elevated risk for AD enrolled in the Wisconsin Registry for Alzheimer’s Prevention. Methods We analyzed partial volume effect-corrected 11C-PiB-PET distribution volume ratio maps from 220 participants (mean age = 61.4y, range: 46.9-76.8y). Regional amyloid-positivity was established using region-specific thresholds. We used four stages from frequency-based staging of amyloid-positivity to characterize individual amyloid deposition. Longitudinal PET data was used to assess temporal progression of stages and to evaluate emergence of regional amyloid-positivity in participants who were amyloid-negative at baseline. We also assessed the effect of amyloid stage on longitudinal cognitive trajectories.Results The staging model suggested progressive accumulation of amyloid from associative to primary neocortex and gradually involving subcortical regions. Longitudinal PET measurements supported the cross-sectionally estimated amyloid progression. In mixed-effects longitudinal analysis of cognitive follow-up data obtained over an average period of 6.5 years following the baseline PET measurement, amyloid stage II showed a faster decline in executive function and advanced amyloid stages (III and IV) showed a faster decline across multiple cognitive domains compared to stage 0.Conclusions Overall, the 11C-PiB-PET-based staging model was generally consistent with previously derived models from 18F-labled amyloid PET scans and a longitudinal course of amyloid accumulation. Differences in longitudinal cognitive decline support the potential clinical utility of in-vivo amyloid staging for risk stratification of the preclinical phase of AD even in middle-aged to older individuals at risk for AD.

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Fedor Levin ◽  
Irina Jelistratova ◽  
Tobey J. Betthauser ◽  
Ozioma Okonkwo ◽  
Sterling C. Johnson ◽  
...  

Abstract Background We investigated regional amyloid staging characteristics in 11C-PiB-PET data from middle-aged to older participants at elevated risk for AD enrolled in the Wisconsin Registry for Alzheimer’s Prevention. Methods We analyzed partial volume effect-corrected 11C-PiB-PET distribution volume ratio maps from 220 participants (mean age = 61.4 years, range 46.9–76.8 years). Regional amyloid positivity was established using region-specific thresholds. We used four stages from the frequency-based staging of amyloid positivity to characterize individual amyloid deposition. Longitudinal PET data was used to assess the temporal progression of stages and to evaluate the emergence of regional amyloid positivity in participants who were amyloid-negative at baseline. We also assessed the effect of amyloid stage on longitudinal cognitive trajectories. Results The staging model suggested progressive accumulation of amyloid from associative to primary neocortex and gradually involving subcortical regions. Longitudinal PET measurements supported the cross-sectionally estimated amyloid progression. In mixed-effects longitudinal analysis of cognitive follow-up data obtained over an average period of 6.5 years following the baseline PET measurement, amyloid stage II showed a faster decline in executive function, and advanced amyloid stages (III and IV) showed a faster decline across multiple cognitive domains compared to stage 0. Conclusions Overall, the 11C-PiB-PET-based staging model was generally consistent with previously derived models from 18F-labeled amyloid PET scans and a longitudinal course of amyloid accumulation. Differences in longitudinal cognitive decline support the potential clinical utility of in vivo amyloid staging for risk stratification of the preclinical phase of AD even in middle-aged to older individuals at risk for AD.


2020 ◽  
Vol 16 (S2) ◽  
Author(s):  
Fedor Levin ◽  
Irina Jelistratova ◽  
Tobey J. Betthauser ◽  
Sterling C. Johnson ◽  
Stefan J. Teipel ◽  
...  

Author(s):  
L. Ruffini ◽  
F. Lauretani ◽  
M. Scarlattei ◽  
A. Ticinesi ◽  
T. Meschi ◽  
...  

A significant progress has been made in the understanding of the neurobiology of Alzheimer’s disease. The post-mortem studies are the gold standard for a correct histopathological diagnosis, contributing to clarify the correlation with cognitive, behavioral and extra-cognitive domains. However, the relationship between pathological staging and clinical involvement remains challenging. Neuroimaging, including positron emission tomography (PET) and magnetic resonance, could help to bridge the gap by providing in vivo information about disease staging. In the last decade, advances in the sensitivity of neuroimaging techniques have been described, in order to accurately distinguish AD from other causes of dementia. Fluorodeoxyglucose-traced PET (FDG-PET) is able to measure cerebral metabolic rates of glucose, a proxy for neuronal activity, theoretically allowing detection of AD. Many studies have shown that this technique could be used in early AD, where reduced metabolic activity correlates with disease progression and predicts histopathological diagnosis. More recently, molecular imaging has made possible to detect brain deposition of histopathology-confirmed neuritic β-amyloid plaques (Aβ) using PET. Although Aβ plaques are one of the defining pathological features of AD, elevated levels of Aβ can be detected with this technique also in older individuals without dementia. This raises doubts on the utility of Aβ PET to identify persons at high risk of developing AD. In the present case-series, we sought to combine metabolic information (from FDG-PET) and amyloid plaque load (from Aβ PET) in order to correctly distinguish AD from other forms of dementia. By selecting patients with Aβ PET + / FDG-PET + and Aβ PET – / FDG-PET +, we propose an integrated algorithm of clinical and molecular imaging information to better define type of dementia in older persons.


2018 ◽  
Vol 25 (10) ◽  
pp. 2599-2607 ◽  
Author(s):  
Bernard J. Hanseeuw ◽  
Victoria Jonas ◽  
Jonathan Jackson ◽  
Rebecca A. Betensky ◽  
Dorene M. Rentz ◽  
...  

Abstract Late-life anxiety has been associated with increased progression from normal cognition to amnestic MCI, suggesting that anxiety may be a neuropsychiatric symptom of Alzheimer’s disease (AD) pathological changes and a possible marker of anatomical progression in preclinical AD. This study examined whether cortical or subcortical amyloidosis, indicating earlier or later stages of preclinical AD, was associated with greater self-reported anxiety among 118 cognitively normal volunteers, aged 65–90 years, and whether this association was stronger in APOEε4 carriers. Participants underwent Pittsburgh Compound B Positron Emission Tomography (PiB-PET) to assess fibrillar amyloid-β burden in cortical and subcortical regions, and measurement of anxiety using the Hospital Anxiety and Depression Scale-anxiety subscale. Higher PiB-PET measures in the subcortex (striatum, amygdala, and thalamus), but not in the cortex, were associated with greater anxiety, adjusting for demographics, cognition, and depression. Findings were similar using a cortico-striatal staging system and continuous PET measurements. Anxiety was highest in APOEε4 carriers with subcortical amyloidosis. This work supports in vivo staging of amyloid-β deposition in both cortical and subcortical regions as a promising approach to the study of neuropsychiatric symptoms such as anxiety in cognitively normal older individuals. Elevated anxiety symptoms in combination with high-risk biological factors such as APOEε4 and subcortical amyloid-β may identify participants closest to MCI for secondary prevention trials.


2015 ◽  
Vol 85 (3-4) ◽  
pp. 129-144 ◽  
Author(s):  
Zahra Heidari ◽  
Awat Feizi ◽  
Leila Azadbakht ◽  
Nizal Sarrafzadegan

Abstract. Background: Minerals are required for the body’s normal function. Aim: The current study assessed the intake distribution of minerals and estimated the prevalence of inadequacy and excess among a representative sample of healthy middle aged and elderly Iranian people. Methods: In this cross-sectional study, the second follow up to the Isfahan Cohort Study (ICS), 1922 generally healthy people aged 40 and older were investigated. Dietary intakes were collected using 24 hour recalls and two or more consecutive food records. Distribution of minerals intake was estimated using traditional (averaging dietary intake days) and National Cancer Institute (NCI) methods, and the results obtained from the two methods, were compared. The prevalence of minerals intake inadequacy or excess was estimated using the estimated average requirement (EAR) cut-point method, the probability approach and the tolerable upper intake levels (UL). Results: There were remarkable differences between values obtained using traditional and NCI methods, particularly in the lower and upper percentiles of the estimated intake distributions. A high prevalence of inadequacy of magnesium (50 - 100 %), calcium (21 - 93 %) and zinc (30 - 55 % for males > 50 years) was observed. Significant gender differences were found regarding inadequate intakes of calcium (21 - 76 % for males vs. 45 - 93 % for females), magnesium (92 % vs. 100 %), iron (0 vs. 15 % for age group 40 - 50 years) and zinc (29 - 55 % vs. 0 %) (all; p < 0.05). Conclusion: Severely imbalanced intakes of magnesium, calcium and zinc were observed among the middle-aged and elderly Iranian population. Nutritional interventions and population-based education to improve healthy diets among the studied population at risk are needed.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lingxiao Wang ◽  
Zhenhua Gao ◽  
Yucheng Su ◽  
Qian Liu ◽  
Yi Ge ◽  
...  

AbstractThis study aimed to compare and verify the osseointegration performance of a novel implant (NI) in vivo, which could provide a useful scientific basis for the further development of NIs. Thirty-two NIs treated with hydrofluoric acid and anodization and sixteen control implants (CIs) were placed in the mandibles of 8 beagles. Micro-CT showed that the trabecular number (Tb.N) significantly increased and trabecular separation (Tb.Sp) significantly decreased in the NIs at 2 weeks. Significant differences were found in the trabecular thickness, Tb.N, Tb.Sp, bone surface/bone volume ratio, and bone volume/total volume ratio between the two groups from the 2nd–4th weeks. However, there were no significant differences between the two groups in the bone volume density at 2, 4, 8, or 12 weeks or bone-implant contact at 2 or 4 weeks, but the BIC in the CIs was higher than that in the NIs at the 8th and 12th weeks. Meanwhile, the histological staining showed a similar osseointegration process between the two groups over time. Overall, the NIs could be used as new potential implants after further improvement.


2020 ◽  
pp. 095646242094756
Author(s):  
Sabina O Nduaguba ◽  
Kentya H Ford ◽  
James P Wilson ◽  
Kenneth A Lawson ◽  
Robert L Cook

We aimed to identify subgroups within age, racial/ethnic, and transmission categories that drive increased risk for late HIV diagnosis (LHD). A 1996–2013 retrospective study of HIV-diagnosed individuals (N = 77,844) was conducted. The proportion of individuals with LHD (AIDS diagnosis within 365 days of HIV diagnosis) was determined, stratified by age, race/ethnicity, and transmission category. Logistic regression with interaction terms was used to identify groups/subgroups at risk for LHD during 1996–2001, 2002–2007, and 2008–2013. Respectively, 78%, 27%, 38%, and 31% were male, White, Black, and Hispanic. Overall, 39% had LHD with a 6.7% reduction for each year increase (OR = 0.93, 95% CI = 0.93–0.94, p < 0.01). Older age was significantly associated with increased odds of LHD (OR range = 1.90–4.55). Compared to their White counterparts, all Hispanic transmission categories (OR range = 1.31–2.58) and only Black female heterosexuals and men who have sex with men (MSM) (OR range = 1.14–1.33) had significantly higher odds of LHD during 1996–2001 and/or 2002–2007. Significance was limited to Hispanic MSM (all age categories), MSM/IDUs (30–59 years), and heterosexuals (18–29 years) and Black MSM (30–39 years) during 2008–2013. Older individuals and Hispanics (driven by MSM) are at increased risk for LHD. HIV testing interventions directed at seniors and Hispanic MSM can further reduce rates of LHD.


BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Olga E. Titova ◽  
John A. Baron ◽  
Karl Michaëlsson ◽  
Susanna C. Larsson

Abstract Background Cigarette smoking is a well-known risk factor for cardiovascular disease (CVD), but whether smokeless tobacco such as snuff is associated with the risk of CVD is still unclear. We investigated the association of the use of Swedish oral moist snuff (snus) with a broad range of CVDs and CVD mortality. Methods We used data from a population-based cohort of 41,162 Swedish adults with a mean baseline age of 70 (56–94) years who completed questionnaires regarding snus use and other lifestyle habits and health characteristics. Participants were followed up for incident cardiovascular outcomes and death over 8 years through linkage to the Swedish National Patient and Death Registers. Hazard ratios (HR) were estimated by Cox proportional hazards regression. We conducted analyses among all subjects as well as among never smokers to reduce residual confounding from smoking. Results After adjustment for smoking and other confounders, snus use was not associated with myocardial infarction, heart failure, atrial fibrillation, aortic valve stenosis, abdominal aortic aneurysm, stroke, or CVD mortality. However, in never smokers, snus use was associated with a statistically significant increased risk of total and ischemic stroke (HRs [95% confidence intervals] = 1.52 [1.01–2.30] and 1.63 [1.05–2.54], respectively) and non-significantly positively associated with some other CVDs. Conclusions In this middle-aged and elderly Swedish population, current Swedish snus use was not associated with the risk of major heart and valvular diseases, abdominal aortic aneurysm, or CVD mortality in the entire study population, but was linked to an increased risk of stroke in never smokers.


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