Normal Elderly Population Research Articles

Pre‐analytical and clinical validation on the highway to implementation of novel dementia blood tests

AbstractBackgroundBlood based biomarkers for Alzheimer’s disease and other dementias are now a reality. Results in large well‐defined research cohorts suggest high potential for implementation for diagnosis (pTau, amyloid isoforms, GFAP), prognosis (pTau, GFAP, NfL) or monitoring (pTau, NfL) in clinical practice and treatment development. Implementation of novel blood based biomarkers requires several aspects to be addressed, among which pre‐analytical sample handling, patient heterogeneity and the development of cut‐offs and computer‐assisted tools for interpretation.MethodTo mimic pre‐analytical variations occurring in current practice, systematic experiments were performed and effects on plasma Amyloid beta(42/40), (p)Tau, NfL and GFAP levels were measured using different technologies. To understand patient heterogeneity, these markers are measured in several cohorts of normal aging elderly using Simoa technology. To develop cut‐offs and tools for interpretation, these markers are measured in a retrospective cohort of patients with various dementias. Lastly, prospective analysis of these markers in the memory clinic setting has been started.ResultThe generated knowledge on the most important pre‐analytical factors affecting Amyloidbeta(42/40), (p)Tau, NfL and GFAP levels resulted in the construction of a standardized operating procedure for use in clinical practise and research (Figure). Results in the normal aging population followed longitudinally show that these biomarkers are higher in patients that are proven to be amyloid positive 10 year later. Detailed results of patient biomarker heterogeneity will be presented as well as a decision tool for use in clinical practice. Lastly, pilot data on experience with these novel blood based biomarkers and the decision tools for dementia diagnosis in the memory clinic setting will be presented.ConclusionTogether, the addressed are important steps towards smooth and widespread implementation of blood based biomarkers in clinical practise.

Plasma P‐tau181 levels predict amyloid pathology in cognitively unimpaired individuals after 10 years

AbstractBackgroundPlasma levels of phosphorylated‐tau (P‐tau) are able to identify core Alzheimer’s Disease (AD) pathologies, but its value in cognitively unimpaired individuals needs further study. We aimed to investigate the value of plasma P‐tau at threonine‐181 (P‐tau181) for predicting amyloid pathology in cognitively unimpaired individuals followed over 10 years.MethodFrom the EMIF‐AD PreclinAD study we selected 74 individuals, aged 60 years and older (Table 1) with normal cognition, that had plasma samples available that were collected at time of amyloid status assessment, as well as 10 years earlier (median (IQR) = ‐9.7 (2)). Amyloid status was defined using visual read of dynamic [18F]flutemetamol‐PET images or CSF amyloid‐β1‐42/1‐40<0.065 (Euroimmun). Simoa assays were applied to measure plasma P‐tau181 levels (Eli Lilly). ROC curve analysis was used to determine the value of plasma P‐tau181 in predicting amyloid status. Further, linear mixed models, adjusted for age and sex, were applied to assess longitudinal change in plasma P‐tau181, using time and the interaction between time and amyloid status as a predictor.ResultAmyloid‐positive individuals had higher plasma P‐tau181 levels compared to amyloid‐negative individuals, both at time of amyloid status assessment and 10 years earlier. Plasma P‐tau181 obtained 10 years prior to amyloid status assessment was able to discriminate amyloid status with similar high Area Under Curve, sensitivity and specificity as plasma P‐tau181 obtained at time of amyloid status assessment (Figure 1). Longitudinally, we observed a general increase in plasma P‐tau181 levels over time (β=0.10, p<.001). Interestingly, amyloid‐positive individuals showed a steeper increase in plasma P‐tau181 levels over 10 years compared to amyloid‐negative individuals (time*amyloid‐β‐interaction: β=0.16, p=.005 (Figure 2)).ConclusionOur data suggest that plasma P‐tau181 can be used to predict AD pathology in cognitively unimpaired individuals. The high discriminative value observed, even using plasma P‐tau181 collected 10 years prior to amyloid status assessment, indicates the potential of this marker as an early amyloid pathology pre‐screening tool in the normal aging population. The observed amyloid dependent longitudinal increases in plasma P‐tau181 levels indicates this marker to be eligible for disease monitoring.

Hyperbaric oxygen therapy induces transcriptome changes in elderly: a prospective trial.

Introduction: Aging is characterized by the progressive loss of physiological capacity. Changes in gene expression can alter activity in defined age-related molecular pathways leading to cellular aging and increased aging disease susceptibility. The aim of the current study was to evaluate whether hyperbaric oxygen therapy (HBOT) affects gene expression in normal, non-pathological, aging adults.Methods: Thirty-five healthy independently living adults, aged 64 and older, were enrolled to receive 60 daily HBOT exposures. Whole blood samples were collected at baseline, at the 30th and 60th HBOT session, and 1–2 weeks following the last session. Differential gene expression analysis was performed.Results: Following 60 sessions of HBOT, 1342 genes and 570 genes were differently up- and downregulated (1912 total), respectively (p < 0.01 FDR), compared to baseline. Out of which, five genes were downregulated with a >1.5-fold change: ABCA13 (FC = −2.28), DNAJ6 (FC = −2.16), HBG2 (FC = −1.56), PDXDC1 (FC = −1.53), RANBP17 (FC = −1.75). Two weeks post-HBOT, ABCA13 expression was significantly downregulated with a >1.5fold change (FC = −1.54, p = 0.008).In conclusion, for the first time in humans, the study provides direct evidence of HBOT is associated with transcriptome changes in whole-blood samples. Our results demonstrate significant changes in gene expression of normal aging population.

Amide Proton Transfer-Weighted MRI Might Help Distinguish Amnestic Mild Cognitive Impairment From a Normal Elderly Population.

Objectives: To evaluate whether 3D amide proton transfer weighted (APTw) imaging based on magnetization transfer analysis can be used as a novel imaging marker to distinguish amnestic mild cognitive impairment (aMCI) patients from the normal elderly population by measuring changes in APTw signal intensity in the hippocampus and amygdala.Materials and Methods: Seventy patients with aMCI and 74 age- and sex-matched healthy volunteers were recruited for routine MRI and APT imaging examinations. Magnetic transfer ratio asymmetry (MTRasym) of the amide protons (at 3.5 ppm), or APTw values, were measured in the bilateral hippocampus and amygdala on three consecutive cross-sectional APT images and were compared between the aMCI and control groups. The independent sample t-test was used to evaluate the difference in APTw values of the bilateral hippocampus and amygdala between the aMCI and control groups. Receiver operator characteristic analysis was used to assess the diagnostic performance of the APTw. The paired t-test was used to assess the difference in APTw values between the left and right hippocampus and amygdala, in both the aMCI and control groups.Results: The APTw values of the bilateral hippocampus and amygdala in the aMCI group were significantly higher than those in the control group (left hippocampus 1.01 vs. 0.77% p < 0.001; right hippocampus 1.02 vs. 0.74%, p < 0.001; left amygdala 0.98 vs. 0.70% p < 0.001; right amygdala 0.94 vs. 0.71%, p < 0.001). The APTw values of the left amygdala had the largest AUC (0.875) at diagnosis of aMCI. There was no significant difference in APTw values between the left and right hippocampus and amygdala, in either group. (aMCI group left hippocampus 1.01 vs. right hippocampus 1.02%, p = 0.652; healthy control group left hippocampus 0.77 vs. right hippocampus 0.74%, p = 0.314; aMCI group left amygdala 0.98 vs. right amygdala 0.94%, p = 0.171; healthy control group left amygdala 0.70 vs. right amygdala 0.71%, p = 0.726).Conclusion: APTw can be used as a new imaging marker to distinguish aMCI patients from the normal elderly population by indirectly reflecting the changes in protein content in the hippocampus and amygdala.

Population-Based Evaluation of Indirect Signs of Increased Intracranial Pressure.

The Mayo Clinic Study of Aging (MCSA) is a unique prospective study that systematically evaluates the normal aging population and includes many participants undergoing both MRI and lumbar puncture (LP). Using MCSA date, we aimed to determine the prevalence of indirect signs of raised intracranial pressure (ICP) on MRI and whether these correlate with LP opening pressure (OP). This is a large-scale study that evaluates how often indirect signs of increased ICP occur in a normal population. MCSA participants who had an MRI within 3 months of an LP with recorded OP were included in the study. MRIs were reviewed for indirect signs of raised ICP, including pituitary to sella (P/S) ratio, cerebellar tonsillar ectopia, and optic nerve sheath diameter (ONSD). These signs were evaluated for correlations with OP and influences from body mass index (BMI) and obstructive sleep apnea (OSA). Five hundred ninety-seven MCSA patients were identified who underwent both LP and MRI. Two hundred sixty (43.6%) were women. The median age was 70.7 years (range 32.6-92.7). Median OP was 152 mm H2O (range 60-314 mm H2O), with 91 (15.2%) participants having an OP ≥ 200 mm H2O. Empty or partially empty sella was seen in 81 (12.8%) of the cohort. The P/S ratio decreased with increasing OP (r = -0.3, P < 0.001). There was a weak correlation between OP and average ONSD (r = 0.184, P = 0.01), which was no longer significant when accounting for age, gender, and BMI (partial r2 = 0.014, P = 0.097). There was no correlation between OP and cerebellar tonsillar ectopia. OSA was associated with increased ONSD (P = 0.004), but this did not remain statistically significant after accounting for age, gender, and BMI (P = 0.085). Smaller pituitary gland size correlated with increasing OP. This suggests that ICP is a continuum with some normal individuals demonstrating asymptomatic radiologic signs of raised ICP.

Effects of Virtual Reality-Based Cognitive Training in the Elderly with and without Mild Cognitive Impairment.

ObjectiveThis study aimed to introduce a 4-week long fully immersive virtual reality-based cognitive training (VRCT) program that could be applied for both a cognitively normal elderly population and patients with mild cognitive impairment (MCI). In addition, we attempted to investigate the neuropsychological effects of the VRCT program in each group. MethodsA total of 56 participants, 31 in the MCI group and 25 in the cognitively normal elderly group, underwent eight sessions of VRCT for 4 weeks. In order to evaluate the effects of the VRCT, the Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease Assessment Packet was administered before and after the program. The program’ s safety was assessed using a simulator sickness questionnaire (SSQ), and availability was assessed using the presence questionnaire. ResultsAfter the eighth session of the VRCT program, cognitive improvement was observed in the ability to learn new information, visuospatial constructional ability, and frontal lobe function in both groups. At the baseline evaluation, based on the SSQ, the MCI group complained of disorientation and nausea significantly more than the cognitively normal elderly group did. However, both groups showed a reduction in discomfort as the VRCT program progressed. ConclusionWe conclude that our VRCT program helps improve cognition in both the MCI group and cognitively normal elderly group. Therefore, the VRCT is expected to help improve cognitive function in elderly populations with and without MCI.

Effect of neurodynamic sliding technique on bilateral hamstring flexibility and balance in normal elderly population

The objective of this study was to determine the effectiveness of Neurodynamic sliding technique on hamstring flexibility and postural balance in elderly population. This study was randomized experimental trial. A total of 30 subjects (14 females and16 males), confirmed by the subject specialist were selected on the basis of exclusion and inclusion criteria. All subjects began with a single measure of passive SLR on their dominant leg. Range of motion was less than 75° and balance was assessed by Berg Balance Scale. Measurements were performed on very first day of the intervention. Subjects were then treated with Neurodynamic Sliding Technique on 6 different days over two weeks. Results were noted and compared on the 1 day (pre) and after 2 weeks (post). Data was analysed using MS EXCEL. Student’s test was applied for the comparison of all variable in elderly population treated with Neurodynamic Sliding Technique in improving balance and straight leg raise. The evaluation of results was done pre and post intervention on the two parameters which were balance by BBS and passive range of motion of SLR by Goniometer. It showed improvement in PROM (SLR) test and berg balance score on the subsequent days i.e. day 1 (Before) and 2 weeks (After). Results from this study show that an isolated Neurodynamic Intervention provides a greater immediate increase in Passive Straight Leg Raise. The results confirmed our initial hypothesis that an isolated neurodynamic sliding technique would provide a greater immediate improvement in hip flexion, assessed by Passive Straight Leg Raise. Limitation of the study was Small sample size and lack of control group. It was concluded that Neurodynamic sliding technique was effective in increasing the hamstring flexibility and improving postural balance in elderly population.

Three-dimensional morphology of the distal femur based on surgical epicondylar axis in the normal elderly population

BackgroundWe aimed to analyze the surface morphology of the distal femur in three dimensions for the healthy elderly, based on the concept that the surgical epicondylar axis (SEA) is a better surrogate for the flexion–extension axis of the knee joint. MethodsWe studied 77 healthy elderly volunteers (40 males and 37 females; age, 68 ± 6 years). The medial and lateral contact lines were calculated three-dimensionally, using the highest points of the medial and lateral condyles in 201 cross-sectional planes around the SEA (every 1°, −60° (hyperextension) to 140° (flexion)). A piecewise fitting function consisting of two linear segments was applied to detect the inflection point of the constant radii in the sagittal plane. The main assessment parameters were knee flexion angle at the inflection point of the radius (inflection angle), mean radius from 0° to the inflection angle (constant radius), and coronal tilt angle of the contact line. ResultsThe inflection angles, constant radii, and coronal tilt angles were 78.2 ± 8.6°, 26.1 ± 2.3 mm, and −0.6 ± 3.2° and 65.6 ± 9.2°, 23.9 ± 2.2 mm, and 6.2 ± 3.2° in the medial and lateral condyles, respectively (all, P < 0.001). The coronal alignment was 88.7 ± 2.2°. ConclusionsThe medial and lateral femoral condyles showed asymmetrical morphologies with the almost ‘constant’ radius of sagittal curvature from 0° to around 80° and 65° of knee flexion, respectively.

Early neuroinflammation is associated with lower amyloid and tau levels in cognitively normal older adults

CNS inflammation is a key factor in Alzheimer’s Disease (AD), but its relation to pathological Aβ, tau, and APOE4 is poorly understood, particularly prior to the onset of cognitive symptoms. To better characterize early relationships between inflammation, APOE4, and AD pathology, we assessed correlations between cerebrospinal fluid (CSF) inflammatory markers and brain levels of Aβ and tau in cognitively normal older adults.Each participant received a lumbar puncture to collect and quantify CSF levels of TNFα, IL-6, IL-8, and IL-10, a T1-weighted MRI, and PET scanning with [18F]flortaucipir (FTP; n = 57), which binds to tau tangles and/or [18F]florbetapir (FBP; n = 58), which binds to Aβ. Parallel voxelwise regressions assessed relationships between each CSF inflammatory marker and FTP and FBP SUVR, as well as APOE4*CSF inflammation interactions.Unexpectedly, we detected significant negative associations between regional Aβ and tau PET uptake and CSF inflammatory markers. For Aβ PET, we detected negative associations with CSF IL-6 and IL-8 in regions known to show early accumulation of Aβ (i.e. lateral and medial frontal lobes). For tau PET, negative relationships were observed with CSF TNFα and IL-8, predominantly in regions known to exhibit early tau accumulation (i.e. medial temporal lobe). In subsequent analyses, significant interactions between APOE4 status and IL-8 on Aβ and tau PET levels were observed in spatially distinct regions from those showing CSF–Aβ/tau relationships.Results from the current cross-sectional study support previous findings that neuroinflammation may be protective against AD pathology at a given stage of the disease, and extend these findings to a cognitively normal aging population. This study provides new insight into a dynamic relationship between neuroinflammation and AD pathology and may have implications for whom and when neuroinflammatory therapies may be appropriate.

Torg ratio in normal ageing population: no risk of stenosis

Torg ratio in normal ageing population: no risk of stenosis

No panacea? Tai Chi enhances motoric but not executive functioning in a normal aging population

ABSTRACT Tai Chi Chuan (TCC) is a promising intervention against age-related decline. Though previous studies have shown benefits in motoric and cognitive domains, it is unclear how these effects are functionally related. Therefore, a randomized controlled trial was conducted in an aging population (53–85). Two measures of motor functioning – motor speed and functional balance – and three cognitive control measures – shifting, updating and inhibition – were included. The TCC condition consisted of an online 10 week 20 lessons video program of increasing level and control condition of educational videos of similar length and frequency. All analyses were done with Bayesian statistics. Counter to expectation no differences were found in cognition between TCC and control pre-to-posttest. However, there was extreme evidence for TCC benefits on functional balance and moderate evidence for increased motoric speed. After weighing the evidence and limitations of the intervention we conclude that TCC does not enhance cognitive control.

Neuro4Neuro: A neural network approach for neural tract segmentation using large-scale population-based diffusion imaging

Subtle changes in white matter (WM) microstructure have been associated with normal aging and neurodegeneration. To study these associations in more detail, it is highly important that the WM tracts can be accurately and reproducibly characterized from brain diffusion MRI. In addition, to enable analysis of WM tracts in large datasets and in clinical practice it is essential to have methodology that is fast and easy to apply. This work therefore presents a new approach for WM tract segmentation: Neuro4Neuro, that is capable of direct extraction of WM tracts from diffusion tensor images using convolutional neural network (CNN). This 3D end-to-end method is trained to segment 25 WM tracts in aging individuals from a large population-based study (N ​= ​9752, 1.5T MRI). The proposed method showed good segmentation performance and high reproducibility, i.e., a high spatial agreement (Cohen’s kappa, κ=0.72−0.83) and a low scan-rescan error in tract-specific diffusion measures (e.g., fractional anisotropy: ε=1%−5%). The reproducibility of the proposed method was higher than that of a tractography-based segmentation algorithm, while being orders of magnitude faster (0.5s to segment one tract). In addition, we showed that the method successfully generalizes to diffusion scans from an external dementia dataset (N ​= ​58, 3T MRI). In two proof-of-principle experiments, we associated WM microstructure obtained using the proposed method with age in a normal elderly population, and with disease subtypes in a dementia cohort. In concordance with the literature, results showed a widespread reduction of microstructural organization with aging and substantial group-wise microstructure differences between dementia subtypes. In conclusion, we presented a highly reproducible and fast method for WM tract segmentation that has the potential of being used in large-scale studies and clinical practice.

Reduced Retinal Thickness Predicts Age-Related Changes in Cognitive Function.

Currently, there is a lack of biomarkers to identify individuals in the early stages of Alzheimer’s disease (AD). A preponderance of evidence suggests that neurodegenerative processes that affect the brain, may also affect the retina. Using optical coherence tomography (OCT), a non-invasive approach, many have shown thinning of the retina in AD and the developmental precursor to AD, mild cognitive impairment (MCI). However, the relationship between retinal thickness and cognitive function is not entirely clear. This is likely due to the disparity in diagnostic criteria used to determine MCI that does not fully probe the cognitive domains that are particularly vulnerable to aging. This study used a comprehensive neuropsychological assessment involving multiple domains of cognition to determine if retinal thickness correlates with cognitive performance in a normal aged population. In this study, 20 healthy individuals between 60 and 90 years of age were administered neuropsychological assessments probing various domains of cognitive function, and OCT to measure peripapillary retinal nerve fiber layer (RNFL) thickness. We found that RNFL thickness is correlated with neuropsychological performance in multiple cognitive domains (e.g., working memory, psychomotor speed, and executive function). Our work demonstrates a positive correlation between RNFL thickness and several, but not all, domains of cognitive function in a normative aging population. By determining which cognitive domains retinal thickness can predict, this work can help identify individuals at risk or in preclinical stages of AD and other neurodegenerative diseases.

A TREML2 missense variant influences specific hippocampal subfield volumes in cognitively normal elderly subjects.

IntroductionTriggering receptor expressed on myeloid cells‐like transcript 2 gene (TREML2) is a newly identified AD susceptibility gene. Its missense variant rs3747742‐C substantially decreases AD risk in both Caucasians and Han Chinese, but the underlying mechanisms remain elusive. In the present study, to uncover the possible mechanisms by which TREML2 rs3747742‐C reduces AD risk, we investigated the possible relation of this variant with AD‐related brain structures using a cognitively normal elderly population from Alzheimer's Disease Neuroimaging Initiative (ADNI) database.MethodsIn total, 158 cognitively normal elders from ADNI database with complete data for brain structures and TREML2 rs3747742 genotype were included in this study. The association of TREML2 rs3747742 genotype with the structures of three cerebral cortices (entorhinal cortex, middle temporal gyrus, and parahippocampal gyrus), two subcortical regions (amygdala and hippocampus), and three subfields of hippocampus (CA1, CA2 + CA3, and CA4 + dentate gyrus) was investigated.ResultsA significant difference was noted in the volume of right CA1 subfield among three genotypes of TREML2 rs3747742 (p = .0364). In the multivariate analysis, TREML2 rs3747742‐C significantly increased right CA1 subfield volume after adjusting for age, gender, education years, APOE ε4 status, and intracranial volume under the recessive genetic model (Bonferroni corrected p = .003586).ConclusionThe present study provides the first evidence that TREML2 rs3747742‐C carriers have larger volumes of hippocampal CA1 subfield in a cognitively normal elderly population. These findings imply that enhancement of brain reserve may contribute to the protection of TREML2 rs3747742‐C in AD susceptibility.

Gender difference in health issues and cognitive functions among an Egyptian normal elderly population

BackgroundAging is associated with changes in cognitive functions. However, many other factors may affect cognitive functions and this interaction needs further assessment.ObjectivesTo detect gender differences in sleep quality, nutritional status, and health-related quality of life and their impact on performance in verbal fluency tasks among apparently healthy elderly.Subjects and methodsThe study was conducted on 102 normal aged subjects, 51 males and 51 females. Subjects were divided according to age into group ≥ 60 years and group < 60 years as a control. They were subjected to clinical assessment, Medical outcome study Short-Form 36-item Health Survey, Pittsburgh sleep quality index, mini nutritional assessment and Category Verbal fluency for animals and girls’ names.ResultsAmong the older group, females had significantly poorer physical and mental health, sleep quality and nutritional status than males (p value 0.001, 0.003, 0.012, and 0.014, respectively). Older females had significantly lower performance in verbal fluency (girls’ names) compared to younger females (p value 0.013), but no significant gender difference was found among the older group. Verbal fluency tasks are correlated to the level of education in both males and females (r 0.392 and 0.42, p value 0.029 and 0.019, respectively), However, in older males, it is also correlated to sleep latency (r 0.41 and p value 0.021).ConclusionOlder females had poorer sleep quality, lower health-related quality of life and lower nutritional status. No gender difference was found in verbal fluency tasks. Although no single variable could independently affect verbal fluency, education remains the main player in the difference in performance.

Health-related quality of life in elderly patients with bronchiectasis

Background: Chronic lung diseases such as bronchiectasis (BR) can adversely affect health-related quality of life (HRQOL), but there are limited studies conducted to investigate HRQOL in elderly BR patients. This study aims to investigate the HRQOL in elderly patients with BR and to assess its relationship with clinical outcomes and radiological findings. Materials and Methods: A total of 74 elderly BR patients involved in the study. BR was diagnosed using high-resolution computed tomography, and all patients were evaluated with the Short Form-36 (SF-36) questionnaire. Symptoms, pulmonary function tests, BR Severity Index (BSI), Reiff's score, and medical treatments were recorded. Results: The mean age of the patients was 70.1 ± 5.0 (range: 65–89) years, and 41 (55.4%) were men. The mean SF-36 Physical Component Summary (PCS) and Mental Health Component Summary (MCS) scores of the 74 elderly patients with BR were 36.6 ± 11.2 (range: 16.3–70) and 44.8 ± 8.9 (range: 23–59.6), respectively. All of the SF-36 subscale results except physical functioning subscale were lower in elderly patients with BR than in the normal Turkish elderly population. There was a major difference in the pain domain between males and females (57.9 ± 27.7 vs. 43.9 ± 27.6, respectively; P = 0.035), but there was no other significant difference between SF-36 domains by gender. The BSI was strongly correlated with all SF-36 subscales. There were statistically significant correlations between Reiff's score, forced expiratory volume in 1 s percent predicted value, forced vital capacity percent predicted value, and number of admissions to the emergency room in the previous year and some SF-36 subscales (P Conclusion: Our study demonstrated that elderly patients with BR had poorer HRQOL scores. The BSI, Reiff's score, and pulmonary function tests were correlated with the SF-36 domains.

Dentate Gyrus Peroxiredoxin 6 Levels Discriminate Aged Unimpaired From Impaired Rats in a Spatial Memory Task.

Similar to humans, the normal aged rat population is not homogeneous in terms of cognitive function. Two distinct subpopulations of aged Sprague–Dawley rats can be identified on the basis of spatial memory performance in the hole-board paradigm. It was the aim of the study to reveal protein changes relevant to aging and spatial memory performance. Aged impaired (AI) and unimpaired (AU) male rats, 22–24 months old were selected from a large cohort of 160 animals; young animals served as control. Enriched synaptosomal fractions from dentate gyrus from behaviorally characterized old animals were used for isobaric tags labeling based quantitative proteomic analysis. As differences in peroxiredoxin 6 (PRDX6) levels were a pronounced finding, PRDX6 levels were also quantified by immunoblotting. AI showed impaired spatial memory abilities while AU performed comparably to young animals. Our study demonstrates substantial quantitative alteration of proteins involved in energy metabolism, inflammation and synaptic plasticity during aging. Moreover, we identified protein changes specifically coupled to memory performance of aged rats. PRDX6 levels clearly differentiated AI from AU and levels in AU were comparable to those of young animals. In addition, it was observed that stochasticity in protein levels increased with age and discriminate between AI and AU groups. Moreover, there was a significantly higher variability of protein levels in AI. PRDX6 is a member of the PRDX family and well-defined as a cystein-1 PRDX that reduces and detoxifies hydroxyperoxides. It is well-known and documented that the aging brain shows increased active oxygen species but so far no study proposed a potential target with antioxidant activity that would discriminate between impaired and unimpaired memory performers. Current data, representing so far the largest proteomics data set in aging dentate gyrus (DG), provide the first evidence for a probable role of PRDX6 in memory performance.

The Endothelium in Acromegaly.

Growth hormone (GH) and insulin like growth factor-1 (IGF-1) excess induce well-known deleterious effects on the cardiovascular system, especially after long-term exposition. Acromegaly, a condition of chronic GH and IGF-1 hypersecretion, is frequently associated to cardiovascular complications, although recent studies have shown a reduction in the prevalence of these comorbidities in well-controlled patients and a mortality risk similar to normal aging population. Many factors could contribute to the increased cardiovascular risk of acromegaly patients. Among these factors, the endothelium plays a key role in the pathogenesis of atherosclerotic plaques and could be considered an early marker of atherosclerosis and cardiovascular dysfunction. In this review we examined the relationship between GH/IGF-1 excess and the endothelium, from basic studies to clinical evidence. Many studies involving various arterial districts (microvascular arteries of retina, kidney and brain, and major vessels as carotid and aorta) showed that GH/IGF-1 excess promotes endothelial dysfunction via several different mechanisms. Increased endothelial proliferation, dysfunction of endothelial progenitor cells, increased oxidative stress, and compromised oxidative defenses are the main factors that are associated with endothelial dysfunction. In the general population, these alterations are associated with the development of atherosclerosis with an increased incidence of coronary artery disease and cerebrovascular complications. However, in acromegaly this is still a debated issue, despite the presence of many pro-atherogenic factors and comorbidities, such as hypertension, diabetes, sleep apnoea, and metabolic syndrome. Preclinical markers of atherosclerosis as arterial intima media thickness, pulse wave velocity and flow mediated dilation seem to be impaired in acromegaly and partly mediated by the endothelium dysfunction. In conclusion, the pathophysiology of endothelial dysfunction in the condition of GH and IGF-1 excess remains a crucial area of investigation to fully dissect the association of acromegaly with cardiovascular disease complications.

0707 Factors Associated with Sleepiness and Vigilance in a Cognitively Normal Elderly Population

0707 Factors Associated with Sleepiness and Vigilance in a Cognitively Normal Elderly Population

Prevalence and determinants of subjective cognitive decline in a representative Greek elderly population.

We studied the prevalence of subjective cognitive decline (SCD) and its determinants in a sample of 1456 cognitively normal Greek adults ≥65years old. Subjects were evaluated by a multidisciplinary team on their neurological, medical, neuropsychological, and lifestyle profile to reach consensus diagnoses. We investigated various types of SCD, including single-question, general memory decline, specific subjective memory decline based on a list of questions and three types of subjective naming, orientation, and calculation decline. In a single general question about memory decline, 28.0% responded positively. The percentage of our sample that reported at least one complaint related to subjective memory decline was 76.6%. Naming difficulties were also fairly common (26.0%), while specific deficits in orientation (5.4%) and calculations/currency handling (2.6%) were rare. The majority (84.2%) of the population reported subjective deficits in at least one cognitive domain. Genetic predisposition to dementia increased the odds for general memory decline by more than 1.7 times. For each one-unit reduction in the neuropsychological composite score (a mean of memory, executive, language, visuospatial, and attention-speed composite scores), the odds for decline in orientation increased by 40.3%. Depression/anxiety and increased cerebrovascular risk were risk factors for almost all SCD types. SCD regarding memory is more frequent than non-memory decline in the cognitively normal Greek elderly population. Genetic predisposition to dementia, lower cognitive performance, affective symptoms, and increased cerebrovascular risk are associated with prevalent SCD. Further prospective research is needed to improve understanding of the evolution of SCD over time.