Asymptomatic Elderly Individuals Research Articles

The Differences in Parameters in Ultrasound Imaging and Biomechanical Properties of the Quadriceps Femoris with Unilateral Knee Osteoarthritis in the Elderly: A Preliminary Observational Study.

Our study aims to evaluate differences in muscle parameters of the quadriceps muscles in patients with knee osteoarthritis (KOA) in older adults. The study included 40 patients diagnosed with unilateral knee osteoarthritis in the KOA group (KG) and 40 asymptomatic elderly individuals in the control group (CG). Muscle ultrasonic mean echo intensity and shear modulus, as well as tone and stiffness of the rectus femoris (RF), vastus medialis (VM), and vastus lateralis (VL) were analyzed. Additionally, clinical correlations were performed. In the KG group, there were significant differences in echo intensity, shear modulus, and tone between the affected and unaffected sides for RF (p=0.003, 0.019, 0.014), while VM showed significant differences in shear modulus and tone (p=0.006, 0.002). Additionally, VL exhibited significant differences in echo intensity, shear modulus, and stiffness (p=0.007, 0.006, 0.010). Compared to the CG group, the KG group showed significant differences in echo intensity of the affected side RF (p=0.001). VM exhibited statistically significant differences in echo intensity and shear modulus (p < 0.001, p=0.008), while VL showed statistically significant differences in echo intensity, tone, and stiffness (p < 0.001, p=0.028, p < 0.001). The correlation results showed that patients with unilateral KOA, VM, and VL echo intensity were correlated with K-L grade (r = 0.443, p=0.004; r = 0.469, p=0.002). The tone of VL was correlated with VAS and WOMAC (r = 0.327, p=0.039; r = 0.344, p=0.030). The parameters of the quadriceps femoris muscle exhibit asymmetry between the affected and unaffected sides in patients with unilateral KOA, as well as a difference between the dominant side of healthy older individuals and the affected side of KOA.

The association between microstructural MRI biomarkers and sequential amyloid and tau‐related cortical changes in asymptomatic elderly individuals

AbstractBackgroundIn Alzheimer’s disease, early amyloid‐β and tau deposition may have differential downstream effects on synaptic function and neuronal loss in a stage‐dependent manner. Amyloid‐related synaptic changes are thought to precede tau accumulation, which starts in the medial temporal lobe before propagating and leading to neurodegeneration. We explored whether microstructural MRI measures can detect these different sequential cortical changes.MethodSeventy‐nine healthy, asymptomatic individuals, recruited from the Insight 46 study of the British 1946 birth cohort underwent combined PET/MR with [18F]florbetapir Aβ‐PET at ∼73yrs, and [18F]MK‐6240 tau‐PET at ∼76yrs. Standard uptake value ratios were calculated using a whole cerebellar reference for florbetapir and an inferior cerebellar reference for MK‐6240. Multi‐shell diffusion MRI was acquired; neurite orientation dispersion and density imaging was used to quantify neurite density (NDI) and orientation dispersion (ODI, a proxy measure of dendritic morphology/complexity), with DTI measuring mean diffusivity (MD), a less specific measure of degenerative change. PET and microstructural MRI biomarkers were assessed in a neocortical composite ROI and across Braak stages.ResultThirty‐six participants were amyloid positive, 18 of whom were tau positive (eight Braak stage 1‐2, four Braak 3‐4, six Braak 5‐6). Across all participants, in the neocortical composite, significant differences between amyloid positive and amyloid negative individuals were found in both tau PET (p = 0.0092) and ODI (p = 0.030) but not for other measures. Within the amyloid positive group, in the cortical composite, significant differences in MD (p = 0.0093) but not ODI were seen when comparing those who were tau positive and negative. In the amyloid positive group, there was an association between tau PET and MD in the MTL (Braak 1‐2) (r = 0.34, p = 0.040) and Braak 3‐4 (r = 0.37, p = 0.025), with an association between tau and ODI (r = 0.48, p = 0.0031) in Braak 3‐4 only. After adjusting for volume, only the association between tau PET and ODI in Braak 3‐4 remained (p = 0.038).ConclusionOur results are consistent with amyloid deposition causing dendritic/changes (as assessed by ODI) with consequent synaptic dysfunction. Later tau propogation is then associated with frank neuronal breakdown (as measured by MD). dMRI cortical imaging biomarkers have the potential to provide proxy measures of underlying AD stage/pathology prior to symptom onset.

N-terminal natriuretic peptid does not relate to morfological and functional alterations in octagenarians without heart failure

Abstract Funding Acknowledgements Type of funding sources: None. Aims To investigate whether mild elevation of N-terminal natriuretic peptide (NT-proBNP) in asymptomatic elderly individuals is associated with alterations in structural/ functional cardiac abnormalities and assess its prognostic significance. Methods and results 201 individuals, 75 years of age, where randomly selected from a population-cohort study in Stockholm (STROKESTOP). Patients with permanent atrial fibrillation (AF), more than mild valvular disease or the heart failure (HF) diagnosis were excluded. NT-proBNP measurements, echocardiography, demographics and cardiovascular risk factors were accessed in all subjects. Thumb ECG was performed in all participants. Information regarding cardiovascular morbidity, HF and AF was obtained from the electronic medical record 5 years after inclusion [ median 5,01 years (interquartile range 4,8 – 5,5 years)]. The cohort was divided into three groups [group I: n=94, NT-proBNP 125–900 ng/L, no AF; group II: n= 77, NT-proBNP 125–900 ng/L, paroxysmal AF and group III: n=30; NT-proBNP &amp;lt; 125 ng/L, no AF. No association between NT-proBNP and echocardiographic or demographic variables was found in groups I and III. In group II, a weak correlation was found between NT-pro-BNP and body mass index (r=0.24, p = 0.038), left atrial volumes (r=0.28, p = 0.047) and E/é septal (r=0.30, p = 0.018). There was no association between individual risk factors and NT-proBNP levels in any group. Cox-regression analysis did not reveal any prognostic value of NT-proBNP for HF or AF development (p&amp;gt; 0.05). Conclusion Mild increase in NT-proBNP levels is not associated with morphologic, functional or prognostic information in octogenarians without HF diagnosis.

Medial Temporal Tau Predicts Memory Decline in Cognitively Unimpaired Elderly (P5-6.011)

<h3>Objective:</h3> Here, we assess the prognostic accuracy of baseline [18F]-MK-6420 tau PET for predicting longitudinal memory decline in asymptomatic elderly individuals. <h3>Background:</h3> Alzheimer’s disease (AD) can be detected in living people using in vivo biomarkers of amyloid-β (Aβ) and tau, even in the absence of cognitive impairment during the preclinical phase. [18F]-MK-6420 is a high affinity positron emission tomography (PET) tracer that quantifies tau neurofibrillary tangles, but its ability to predict cognitive changes associated with early AD symptoms, such as memory decline, is unclear. <h3>Design/Methods:</h3> In a longitudinal observational study, we evaluated a cohort of cognitively normal elderly participants from the Translational Biomarkers in Aging and Dementia (TRIAD) study (October 2017-July 2020, follow-up period of 12 months). All participants underwent tau PET with [18F]-MK-6420 and Aβ PET with [18F]-AZD-4694. <h3>Results:</h3> There were 111 eligible participants who were chosen based on the availability of Aβ PET, tau PET, magnetic resonance imaging (MRI), and APOEɛ4 genotyping. Among these participants, the mean (SD) age was 70.1 (8.6) years; 20 (18%) were tau PET positive and 71 of 111 (63.9%) were women. A significant association between baseline Braak I-II [18F]-MK-6240 SUVR positivity and change in composite memory score was observed at the 12 month follow-up, after correcting for age, sex, and years of education (Logical Memory and RAVLT, standardized beta = −0.52 (−0.82−0.21), p &lt; 0.001, for dichotomized tau PET and −1.22 (−1.84−(−0.61)), p &lt; 0.0001, for continuous tau PET). Moderate cognitive decline was observed for A+T+ over the follow-up period, whereas no significant change was observed for A-T+, A+T- and A-T−, though it should be noted that the A-T+ group was small. Our results indicate that baseline tau neurofibrillary tangle pathology is associated with longitudinal changes in memory function. <h3>Conclusions:</h3> [18F]-MK-6420 PET is a promising tool for predicting memory decline in older adults without cognitive impairment at baseline. <b>Disclosure:</b> Miss Kwan has nothing to disclose. Mr. Arfaie has nothing to disclose. Mr. Therriault has nothing to disclose. Dr. Azizi has nothing to disclose. Miss Lussier has nothing to disclose. Mrs. Tissot has nothing to disclose. Dr. Chamoun has nothing to disclose. Dr. Bezgin has nothing to disclose. Dr. Servaes has nothing to disclose. Miss Stevenson has nothing to disclose. Ms. Rahmouni has nothing to disclose. Miss Pallen has nothing to disclose. The institution of Dr. Rosa Neto has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novo Nordisk.

Increased plasma DYRK1A with aging may protect against neurodegenerative diseases

Early markers are needed for more effective prevention of Alzheimer’s disease. We previously showed that individuals with Alzheimer’s disease have decreased plasma DYRK1A levels compared to controls. We assessed DYRK1A in the plasma of cognitively healthy elderly volunteers, individuals with either Alzheimer’s disease (AD), tauopathies or Down syndrome (DS), and in lymphoblastoids from individuals with DS. DYRK1A levels were inversely correlated with brain amyloid β burden in asymptomatic elderly individuals and AD patients. Low DYRK1A levels were also detected in patients with tauopathies. Individuals with DS had higher DYRK1A levels than controls, although levels were lower in individuals with DS and with dementia. These data suggest that plasma DYRK1A levels could be used for early detection of at risk individuals of AD and for early detection of AD. We hypothesize that lack of increase of DYRK1A at middle age (40–50 years) could be a warning before the cognitive decline, reflecting increased risk for AD.

Medial temporal tau predicts memory decline in cognitively unimpaired elderly.

Alzheimer's disease can be detected in living people using in vivo biomarkers of amyloid-β and tau, even in the absence of cognitive impairment during the preclinical phase. [18F]-MK-6420 is a high-affinity PET tracer that quantifies tau neurofibrillary tangles, but its ability to predict cognitive changes associated with early Alzheimer's disease symptoms, such as memory decline, is unclear. Here, we assess the prognostic accuracy of baseline [18F]-MK-6420 tau-PET for predicting longitudinal memory decline in asymptomatic elderly individuals. In a longitudinal observational study, we evaluated a cohort of cognitively normal elderly participants (n = 111) from the translational biomarkers in ageing and dementia study (data collected between October 2017 and July 2020, with a follow-up period of 12 months). All participants underwent tau-PET with [18F]-MK-6420 and amyloid-β PET with [18F]-AZD-4694. The exclusion criteria included the presence of head trauma, stroke or other neurological disorders. There were 111 eligible participants selected based on the availability of amyloid-β PET, tau-PET, MRI and APOEɛ4 genotyping. Among these participants, the mean standard deviation age was 70.1 (8.6) years; 20 (18%) were tau-PET-positive and 71 of 111 (63.9%) were women. A significant association between the baseline Braak Stages I-II [18F]-MK-6240 standardized uptake value ratio positivity and change in composite memory score were observed at the 12-month follow-up, after correcting for age, sex and years of education [logical memory and Rey Auditory Verbal Learning Test, standardized beta = -0.52 (-0.82-0.21), P < 0.001, for dichotomized tau-PET and -1.22 (-1.84-(-0.61)], P < 0.0001, for continuous tau-PET]. Moderate cognitive decline was observed for A + T + over the follow-up period, whereas no significant change was observed for A-T+, A + T- and A-T-, although it should be noted that the A-T + group was small. Our results indicate that baseline tau neurofibrillary tangle pathology is associated with longitudinal changes in memory function, supporting the use of [18F]-MK-6420 PET to predict the likelihood of asymptomatic elderly individuals experiencing future memory decline. Overall, [18F]-MK-6420 PET is a promising tool for predicting memory decline in older adults without cognitive impairment at baseline. This is of critical relevance as the field is shifting towards a biological model of Alzheimer's disease defined by the aggregation of pathologic tau. Therefore, early detection of tau pathology using [18F]-MK-6420 PET provides us with hope that living patients with Alzheimer's disease may be diagnosed during the preclinical phase before it is too late.

Higher rates of ultrasound synovial hypertrophy, bone erosion and power doppler signal in asymptomatic Brazilian elderly versus young adults: a cross-sectional study.

To evaluate the prevalence of musculoskeletal ultrasonography (MSUS) abnormalities in asymptomatic elderly individuals. A cross-sectional controlled study was conducted and MSUS of 23 joints (wrist, metacarpophalangeal-MCP, proximal interphalangeal-PIP, elbow, glenohumeral, hip, knee, ankle, and metatarsophalangeal-MTP joints) was performed in healthy individuals aged 18-29 (young, n = 32) and 60-80years-old (elderly, n = 32). Quantitative synovial hypertrophy (SH) was measured in mm and a semiquantitative scoring system (0-3) was used to grade SH, power doppler (PD) and bone erosion (BE). Young and elderly participants were 26.2 ± 3.2 and 65.9 ± 4.4years-old, respectively. As compared to the young participants, elderly individuals had higher SH values in 35% of the joint surfaces (P < 0.05), higher rates of scores 1-3 for SH at the dorsal surface of the 3rd MCP, palmar surface of the 2nd MCP, 2nd PIP, 3rd MCP and 3rd PIP and subtalar joints (17.2 vs. 1.6%, P = 0.002; 29.7 vs. 6.3%, P = 0.001; 12.5 vs. 1.6%, P = 0.016; 21.9 vs. 6.3%, P = 0.011; 21.9 vs. 7.8%, P = 0.025; and 24.2 vs. 6.3%, P = 0.005, respectively), BE at the radiocarpal, ulnocarpal, dorsal surface of the 2nd MCP and posterior area of the glenohumeral joints (10.9 vs. 1.6%, P = 0.028; 12.5 vs. 0%, P = 0.003; 9.4 vs. 0%, P = 0.012; and 29.7 vs. 10.9%, P = 0.008, respectively) and PD at the dorsal surface of the 2nd and 3rd MCP joints (9.4 vs. 0%; P = 0.012 and 7.8 vs. 0%; P = 0.023, respectively). BE scores ≥ 1 were more frequent in the elderly (P < 0.05) in 22 (88%) of the joint surfaces evaluated. MSUS abnormalities are more frequent in asymptomatic elderly individuals as compared to young subjects.

Higher levels of myelin are associated with higher resistance against tau pathology in Alzheimer’s disease

BackgroundIn Alzheimer’s disease (AD), fibrillar tau initially occurs locally and progresses preferentially between closely connected regions. However, the underlying sources of regional vulnerability to tau pathology remain unclear. Previous brain-autopsy findings suggest that the myelin levels—which differ substantially between white matter tracts in the brain—are a key modulating factor of region-specific susceptibility to tau deposition. Here, we investigated whether myelination differences between fiber tracts of the human connectome are predictive of the interregional spreading of tau pathology in AD.MethodsWe included two independently recruited samples consisting of amyloid-PET-positive asymptomatic and symptomatic elderly individuals, in whom tau-PET was obtained at baseline (ADNI: n = 275; BioFINDER-1: n = 102) and longitudinally in a subset (ADNI: n = 123, mean FU = 1.53 [0.69–3.95] years; BioFINDER-1: n = 39, mean FU = 1.87 [1.21–2.78] years). We constructed MRI templates of the myelin water fraction (MWF) in 200 gray matter ROIs and connecting fiber tracts obtained from adult cognitively normal participants. Using the same 200 ROI brain-parcellation atlas, we obtained tau-PET ROI values from each individual in ADNI and BioFINDER-1. In a spatial regression analysis, we first tested the association between cortical myelin and group-average tau-PET signal in the amyloid-positive and control groups. Secondly, employing a previously established approach of modeling tau-PET spreading based on functional connectivity between ROIs, we estimated in a linear regression analysis, whether the level of fiber-tract myelin modulates the association between functional connectivity and longitudinal tau-PET spreading (i.e., covariance) between ROIs.ResultsWe found that higher myelinated cortical regions show lower tau-PET uptake (ADNI: rho = − 0.267, p < 0.001; BioFINDER-1: rho = − 0.175, p = 0.013). Fiber-tract myelin levels modulated the association between functional connectivity and tau-PET spreading, such that at higher levels of fiber-tract myelin, the association between stronger connectivity and higher covariance of tau-PET between the connected ROIs was attenuated (interaction fiber-tract myelin × functional connectivity: ADNI: β = − 0.185, p < 0.001; BioFINDER-1: β = − 0.166, p < 0.001).ConclusionHigher levels of myelin are associated with lower susceptibility of the connected regions to accumulate fibrillar tau. These results enhance our understanding of brain substrates that explain regional variation in tau accumulation and encourage future studies to investigate potential underlying mechanisms.

Coronal knee moments of asymptomatic elderly individuals during gait: Preliminary study

IntroductionJoint moments are explained by the forces that occur during gait and generate a movement in the joint. The maximum peak adduction moment (MPM) of the knee has been associated with osteoarthritis (OA). In Colombia, however, there are no references to these values for clinical use in an asymptomatic population. ObjectiveTo describe the characteristics of joint moments in the coronal plane of the knee of asymptomatic elderly whilst walking. Materials and methodsThis is a descriptive study that included 50 participants of both genders and older than 60 years old. They were residents of the metropolitan area del Valle de Aburrá that had volunteered and were capable of following indications without any external aids while walking, and with no pain. Gait analysis was performed when walking at a normal speed on a 6m pathway on two force plates, and was registered by a system of 8 opto-electric 3D recording cameras. The statistical analysis was performed using SPSS 20. ResultsA mean BMI of 26.34kg/m2 was found, and the mean of the MPM was 0.26Nm/kg, generating a graph with two peaks, with the first being of greater magnitude that occurred in 17% of the gait cycle. ConclusionsThe MPM of 0.26Nm/kg found in this population is lower than that reported in the osteoarthritis population. A reference curve for gait analysis has been established in these asymptomatic elderly. It is essential that these values are available, in order to help the professional to make precise and quantitative diagnoses in gait alterations.

Reduced awareness of cognitive decline is associated with brain amyloid load in asymptomatic elderly individuals at risk for AD: A longitudinal study

AbstractBackgroundIt has recently been proposed that the awareness of cognitive decline (ACD) may already be slightly reduced in the preclinical phase of AD, in the presence of subtle cognitive changes. This is a recent field of research, and the few studies available do not allow to appreciate the actual evolution of ACD in the pre‐dementia phases of AD. The present study describes the longitudinal trajectory of an index of ACD (ACDI) over 3 years in a cohort of cognitively‐normal elderly, its association to AD biomarkers, as well as its impact on cognitive scores’ evolution.Method314 elderly memory complainers, as just as many study‐partners, were followed‐up for 3 years. Brain glucose metabolism and amyloid load were assessed at baseline; screening cognitive tests were performed every 6 months, and a comprehensive neuropsychological evaluation every 12 months. The ACDI was based on the subject‐informant discrepancy on a questionnaire evaluating the subject’s cognitive decline. We performed a Latent Class Linear Mixed Model (LCLMM) to identify different trends of evolution of the ACDI over time, and Generalized Linear Mixed Models to analyse the impact of the baseline ACDI on the evolution of cognitive scores.ResultThe LCLMM identified three classes of subjects sharing similar longitudinal trajectories of the ACDI. Most subjects (76.8%) have accurate ACD (Class 2), and have been considered as the reference group. 18.95% of subjects showed heightened ACD (“worried‐well” individuals). They were comparable to subjects with accurate ACD in terms of AD biomarkers. 4.25% of the sample showing low ACD had higher amyloid burden than the reference group, and were mostly men. The GLMM found no overall effect of baseline ACDI on the evolution of the cognitive scores.ConclusionThe study of ACD in AD, its evolution and correlates is a topic of growing interest, as it is, notably, a piece of the larger understanding of the pre‐dementia phases of AD. This can be useful for a timely diagnosis of AD, and for the selection of populations to be included in clinical trials.

P98. Radiographic sagittal alignment in the asymptomatic elderly: what is normal for age?

BACKGROUND CONTEXT Over the past several years, there has been an increasing awareness of the impact of positive sagittal alignment in the overall health related quality of life (HRQOL). However, attempts to restore normal spino-pelvic parameters in the elderly population can introduce challenges with risk factors inherent in this age group, and complications such as proximal junctional failure are high. PURPOSE The purpose of this study was to help define ‘normal for age’ sagittal vertical axis (SVA) in asymptomatic individuals ranging 60 to 80 years in order to facilitate most appropriate care. STUDY DESIGN/SETTING This is a prospective cohort study. PATIENT SAMPLE One hundred and fifty-one volunteers were recruited and divided into age groups of 60, 65, 70, 75 and 80 years with equal numbers of men and women. Exclusion criteria included any history of back pain requiring medical attention within previous year, prior spinal surgery, neuromuscular condition, or compression fracture. OUTCOME MEASURES The primary outcome measure was the SVA and secondary measurements included thoracic kyphosis (T4-T12), total lumbar lordosis (L1-S1), lumbar lordosis (L4-S1), pelvic tilt (PT), pelvic incidence (PI), pelvic incidence lumbar lordosis mismatch (PI-LL), sacral slope (SS), and T1 spino-pelvic inclination (T1SPi) were made using Surgimap software. Oswestry Disability Index (ODI);Veterans Rand 12 (VR-12) HRQOL measures were completed. METHODS After informed consent, subjects completed PROMs and full-standing lateral radiographs were obtained. All statistical analysis was conducted with SAS/STAT version 9.4 (Carey, NC). Normality testing was performed and all radiographic measurements were normally distributed and the ODI and VR12 scores were not normally distributed. Measures of central tendency and variance were calculated. Kruskal Wallis tests were used to determine differences across age groups in the ODI and VR12 scores. An analysis of variance with a least square (LS) means test and a Tukey-Kramer adjustment was used to compare, unadjusted and adjusted by gender, differences in all radiographic measurements across age groups. RESULTS There was no significant (p=.07) difference in the gender adjusted LS mean SVA (mm) across age-groups. For the 60, 65, 70, 75 and 80-year old age groups were (20.2, 19.7, 27.7, 37.3, 37.9), respectively which are were in the normal range of CONCLUSIONS Elderly patients with ASD undergoing corrective surgery are vulnerable to increased complications which can negatively affect HRQL outcomes. Our study showed that asymptomatic elderly individuals maintain a normal sagittal profile with an average SVA FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

PM Association Between Silent Lacunar Infarcts And Muscle Strength: The Bunkyo Health Study

Silent lacunar infarcts by definition, lack clinically overt stroke-like symptom, are occasionally found by brain magnetic resonance imaging (MRI) scan in asymptomatic elderly individuals. A previous study revealed that more than 25% of elderly people have silent lacunar infarcts. The main risk factors for lacunar infarcts and stroke were reported as aging, hypertension, and smoking. While a recent study showed that low muscle strength is also a risk factor for cerebrovascular events, it remains unclear whether low muscle strength is a risk factor for silent lacunar infarcts. PURPOSE: To investigate the association between muscle strength and silent lacunar infarcts in the elderly people living in urban community. METHODS: This study included 1,536 elderly people without past history of cerebral vascular events, aged 65-84 years living in an urban area of Tokyo, Japan (Bunkyo Health Study). All participants underwent brain MRI scan and silent lacunar infarcts were defined as the presence of 1 or more lacunar infarcts. Isokinetic muscle strength of knee extensors was evaluated at angular velocity of 60 degree per seconds using dynamometer. Subjects was categorized tertiles (high, medium, and low) by muscle strength, and compared the prevalence of silent lacunar infarcts. RESULTS: Mean age of subjects was 73.0±5.4 years old and 58.9% were female. Two hundred fifty-two (16.4%) subjects were diagnosed as silent lacunar infarcts, and the subjects categorized as lower muscle strength showed higher prevalence of silent lacunar infarcts (high: 12.3%, medium: 17.7%, and low: 19.3%, p for trend 0.003), while skeletal muscle indices among the groups were similar. After multivariate adjustment by age, sex, body mass index, smoking status, physical activity, hypertension, diabetes, and dyslipidemia, the trend was still significant and the odds ratio for having silent lacunar infarcts was significantly higher in the lowest muscle strength tertile compared to the highest tertile [(High: 1.00 (reference), medium: 1.42 (95%CI: 0.98-2.04), Low: 1.48 (1.02-2.14), p for trend 0.043]. CONCLUSIONS: In the elderly people living in urban community, lower muscle strength of knee extensors was associated with higher prevalence of silent lacunar infarcts independent of other established risk factors.

Expression of degenerative markers in intervertebral discs of young and elderly asymptomatic individuals.

Intervertebral disc (IVD) degeneration is a remodeling process mediated by several growth factors and cytokines. This process has been extensively studied in vitro and with pathologic specimens obtained during surgery for scoliosis or back pain. However, the occurrence and temporal evolution of these molecules during normal aging, particularly in the cervical segment, is not known. Our objective was to study and compare the presence of putative mediators in the IVD of young (<35 years, G1) and elderly (>65 years, G2) presumably asymptomatic individuals. Thirty C4-5 and C5-6 discs and thirty L4-5 and L5-S1 discs per group were collected during the autopsy of individuals whose family members denied a history of neck or back pain. Discs were divided into anterior, central (lumbar only) and posterior sectors for analysis. Immunohistochemistry for TNF-α, IL-1β, VEGF, NGF-β, BDNF, TIMP-1, MMP-1, -2 and -3 was performed and reactivity compared between groups and sectors. All of these molecules were detected in every disc sector of both G1 and G2. Most statistical comparisons (25/45, 55.6%) revealed an increase in mediator expression in G2 in relation to G1. Regional differences in the expression of remodeling enzymes were rare; NGF-β and BDNF had slightly higher expression in the cervical segment of elderly individuals. A senescent profile with elevated VEGF, MMP-2 and MMP-3 was observed across most G2 disc regions and were generally elevated from G1. In conclusion, the mere presence of any of the studied molecules inside the IVD cannot be considered pathologic. Expression of remodeling enzymes and inflammatory mediators is relatively similar across different vertebral segments and disc regions leading to a common degenerated pattern, while neurotrophins have slightly higher expression in cervical discs. These findings support the concept that disc remodeling in different segments follows a similar pathway that can be potentially mediated to avoid structural failure.

Mild behavioral impairment is associated with β-amyloid but not tau or neurodegeneration in cognitively intact elderly individuals.

IntroductionMild behavioral impairment (MBI) is characterized by the emergence of neuropsychiatric symptoms in elderly persons. Here, we examine the associations between MBI and Alzheimer's disease (AD) biomarkers in asymptomatic elderly individuals.MethodsNinety‐six cognitively normal elderly individuals underwent MRI, [18F]AZD4694 β‐amyloid‐PET, and [18F]MK6240 tau‐PET. MBI was assessed using the MBI Checklist (MBI‐C). Pearson's correlations and voxel‐based regressions were used to evaluate the relationship between MBI‐C score and [18F]AZD4694 retention, [18F]MK6240 retention, and gray matter (GM) volume.ResultsPearson correlations revealed a positive relationship between MBI‐C score and global and striatal [18F]AZD4694 standardized uptake value ratios (SUVRs). Voxel‐based regression analyses revealed a positive correlation between MBI‐C score and [18F]AZD4694 retention. No significant correlations were found between MBI‐C score and [18F]MK6240 retention or GM volume.ConclusionWe demonstrate for the first time a link between MBI and early AD pathology in a cognitively intact elderly population, supporting the use of the MBI‐C as a metric to enhance clinical trial enrolment.

Multi-omics signature of brain amyloid deposition in asymptomatic individuals at-risk for Alzheimer's disease: The INSIGHT-preAD study.

BackgroundOne of the biggest challenge in Alzheimer's disease (AD) is to identify pathways and markers of disease prediction easily accessible, for prevention and treatment. Here we analysed blood samples from the INveStIGation of AlzHeimer's predicTors (INSIGHT-preAD) cohort of elderly asymptomatic individuals with and without brain amyloid load.MethodsWe performed blood RNAseq, and plasma metabolomics and lipidomics using liquid chromatography-mass spectrometry on 48 individuals amyloid positive and 48 amyloid negative (SUVr cut-off of 0·7918). The three data sets were analysed separately using differential gene expression based on negative binomial distribution, non-parametric (Wilcoxon) and parametric (correlation-adjusted Student't) tests. Data integration was conducted using sparse partial least squares-discriminant and principal component analyses. Bootstrap-selected top-ten features from the three data sets were tested for their discriminant power using Receiver Operating Characteristic curve. Longitudinal metabolomic analysis was carried out on a subset of 22 subjects.FindingsUnivariate analyses identified three medium chain fatty acids, 4-nitrophenol and a set of 64 transcripts enriched for inflammation and fatty acid metabolism differentially quantified in amyloid positive and negative subjects. Importantly, the amounts of the three medium chain fatty acids were correlated over time in a subset of 22 subjects (p < 0·05). Multi-omics integrative analyses showed that metabolites efficiently discriminated between subjects according to their amyloid status while lipids did not and transcripts showed trends. Finally, the ten top metabolites and transcripts represented the most discriminant omics features with 99·4% chance prediction for amyloid positivity.InterpretationThis study suggests a potential blood omics signature for prediction of amyloid positivity in asymptomatic at-risk subjects, allowing for a less invasive, more accessible, and less expensive risk assessment of AD as compared to PET studies or lumbar puncture.FundInstitut Hospitalo-Universitaire and Institut du Cerveau et de la Moelle Epiniere (IHU-A-ICM), French Ministry of Research, Fondation Alzheimer, Pfizer, and Avid.

Regional Cerebral Perfusion and Cerebrovascular Reactivity in Elderly Controls With Subtle Cognitive Deficits.

Background: Recent studies suggested that arterial spin labeling (ASL)-based measures of cerebral blood flow (CBF) as well as cerebral vasoreactivity to CO2 (CVR CO2) show significant alterations mainly in posterior neocortical areas both in mild cognitive impairment (MCI) and Alzheimer disease. It remains, however, unknown whether similar changes occur in at risk healthy elders without clinically overt symptoms. This longitudinal study investigated patterns of ASL perfusion and CVR CO2 as a function of the cognitive trajectories in asymptomatic elderly individuals.Methods: Seventy-nine community-dwelling subjects (mean age: 78.7 years, 34 male) underwent three neuropsychological assessments during a subsequent 3-year period. Individuals were classified as stable-stable (SS), variable (V), or progressive-progressive (PP). Between-group comparisons were conducted for ASL CBF and transit-time delay maps and β-maps of CO2 response. Spearman’s rho maps assessed the correlation between ASL (respectively, CVR CO2 measures) and Shapes test for working memory, as well as Verbal fluency test for executive functions. Three group-with-continuous-covariate-interaction designs were implemented to investigate group-based differences on the association between neuropsychological scores and ASL or CO2 measures.Results: Comparison of CBF maps demonstrates significantly lower perfusion in the V-group as to PP-cases predominantly in parietal regions, including the precuneus and, to a lesser degree, in temporal and frontal cortex. A stronger CVR CO2 response was found in the PP-group in left parietal areas compared to the V-group. V-cases showed a stronger ASL-Shape value relationship than V-group in right temporoparietal junction and superior parietal lobule. CO2-Shape value correlation was significantly higher in both SS and PP-groups compared to the V-group in right insular and superior perisylvian regions.Conclusion: Our data indicate the presence of decreased ASL and CVR CO2 values mainly in parietal and fronto-temporal areas in cases with the first signs of cognitive instability (V-group). Importantly, the PP-group, at high risk for MCI transition, displays an increase of both parameters in the same areas. Clinicoradiologic correlations also indicate a clear distinction between the V-group and both PP and SS-cases. These data imply the presence of an inverted U-shape pattern of regional blood flow and CVR in old age that might predict subsequent cognitive fate.

Long-Term Prognostic Value of Coronary Computed Tomography Angiography in Asymptomatic Elderly Population Including Diabetic Patients

Objectives: There is still controversy about the long-term prognostic value of coronary computed tomography angiography (CCTA) for coronary heart disease (CHD) in asymptomatic individuals including diabetic patients. Also, long term CCTA’s role among elderly population has not been established. We investigated the long-term prognostic value of CCTA in asymptomatic elderly patients with or without diabetes. Methods: A community based-cohort study of 470 asymptomatic elderly individuals (mean age 75.1 ± 7.3 years) who underwent CCTA was conducted. Among them, there were 156 [33.2%] diabetic patients and 55 [11.7%] patients with HbA1c of more than 7% (HbA1c &amp;gt;7%). Major adverse cardiac events (MACE) defined as composite of cardiac death, nonfatal myocardial infarction, unstable angina requiring hospitalization and coronary revascularization were measured. CCTA findings were categorized by various means including the presence of proximal LAD or left main disease (pLAD/LM). Coronary calcium score (CACS) and Framingham risk score (FRS) were adjusted for analysis. Results: There were 57 individuals (12.1%) with pLAD/LM finding for overall population and 8 (14.5%) for diabetic patients with HbA1c &amp;gt;7%. During median follow-up of 8.1 years (interquartile range: 7.7-8.2), MACE occurred in 28 (6%) subjects among overall population and 6 (10.9%) among diabetic patients with HbA1c &amp;gt;7%. Compared to individuals with negative pLAD/LM finding, positive group was significantly associated with MACE for overall population (HR 2.817 [95% CI 1.044-7.601], p = 0.041). Among diabetic patients with HbA1c &amp;gt;7%, there is more significant association between pLAD/LM finding and MACE (HR 6.525 [95% CI 1.147-37.121], p = 0.034). Conclusion: Among asymptomatic elderly population, CCTA showed considerable prognostic value additive on CACS and FRS over 8 years. And this result was more significant in elderly diabetic patients with poor glycemic control. Disclosure S. Moon: None. D. Lee: None. T. Oh: None. K. Kim: None. S. Choi: None. H. Jang: None. S. Lim: None.

Prevalence of asymptomatic malaria and anaemia among elderly population in Osun state Southwestern, Nigeria

Background: Malaria has remained a global burden for many centuries. It remains a major public health disease particularly in the tropic despite several interventional efforts targeted at its elimination. Malaria if not treated early enough could result in patients becoming anaemic. In Nigeria, elderly (60 years and above) represent a vulnerable group of individuals, they enjoy very little attention in terms of specific health related interventions and facilities. This study aimed to assess the prevalence and proportion of asymptomatic malaria infections and anaemia among the geriatric population in Osun state, Southwestern Nigeria.Methods: A community-based cross-sectional study was conducted among 396 elderly with average age of 69.14±7.27 years. Blood samples were collected for the preparation of Giemsa stained blood films for the detection and quantification of malaria parasites microscopically. Packed cell volume (PCV) was assessed using hematocrit.Results: Malaria parasites were present in the peripheral blood of 16.2% of the population and only 9.3% of the elderly were found to be anaemic. The ‘Very old’ age group of &gt;85 years years had highest prevalence of malaria (33.3%) but this was not statistically significant (p=0.17). Male respondents (24.4%) were more infected than females (13.7%) and this was found statistically significant (p=0.015). Having malaria parasite and living in the rural areas were significantly associated with being anaemic, p&lt;0.05 in each case.Conclusions: Considerable proportion of asymptomatic elderly individuals with parasitaemia were found anaemic. This group also represents a silent reservoir for malaria transmission in the country, if not addressed.

Highly Accurate Analysis of the Cervical Neural Tract of the Elderly Using ZOOM DTI.

Background/AimsTo investigate the fractional anisotropy (FA) values of the cervical spinal cord in elderly individuals using zonally magnified oblique multislice (ZOOM) diffusion tensor imaging (DTI). MethodsFourteen healthy elderly volunteers (group E) and 10 young volunteers (group Y) were enrolled. We assessed the FA, apparent diffusion coefficient (ADC), and λ1–λ3 values using 3-T magnetic resonance imaging. The region of interest was contoured entirely inside the spinal cord, with no gray/white matter distinction, in order to avoid including the cerebrospinal fluid. ResultsAs lower cervical levels were approached, the FA values gradually decreased, while the ADC values increased. The mean FA values at each cervical level were as follows in groups E and Y: 0.71 and 0.70 at the C2/3 level, 0.66 and 0.66 at the C3/4 level, 0.63 and 0.62 at the C4/5 level, 0.57 and 0.57 at the C5/6 level, and 0.58 and 0.57 at the C6/7 level, respectively. The mean ADC values in groups E and Y were 1.06 and 0.99 at the C2/3 level, 1.05 and 1.06 at the C3/4 level, 1.14 and 1.06 at the C4/5 level, 1.18 and 1.21 at the C5/6 level, and 1.39 and 1.46 at the C6/7 level, respectively. There were no significant differences between the elderly and young participants. ConclusionIn both asymptomatic elderly and young individuals, the FA values gradually decreased and the ADC values increased moving towards lower cervical levels. Age did not affect the FA values, even though mild cord compression was evident due to spondylotic changes. ZOOM DTI has the potential to provide more information than conventional DTI.

Consequences of mutant TET2 on clonality and subclonal hierarchy.

Somatic mutations in TET2 are common in myelodysplastic syndromes (MDS), myeloproliferative, and overlap syndromes. TET2 mutant (TET2MT) clones are also found in asymptomatic elderly individuals, a condition referred to as clonal hematopoiesis of indeterminate potential (CHIP). In various entities of TET2MT neoplasia, we examined the phenotype in relation to the strata of TET2 hits within the clonal hierarchy. Using deep sequencing, 1781 mutations were found in 1205 of 4930 patients; 40% of mutant cases were biallelic. Hierarchical analysis revealed that of TET2MT cases >40% were ancestral, e.g., representing 8% of MDS. Higher (earlier) TET2 lesion rank within the clonal hierarchy (greater clonal burden) was associated with impaired survival. Moreover, MDS driven by ancestral TET2MT is likely derived from TET2MT CHIP with a penetrance of ~1%. Following ancestral TET2 mutations, individual disease course is determined by secondary hits. Using multidimensional analyses, we demonstrate how hits following the TET2 founder defect induces phenotypic shifts toward dysplasia, myeloproliferation, or progression to AML. In summary, TET2MT CHIP-derived MDS is a subclass of MDS that is distinct from de novo disease.