Normal Aging Changes Research Articles

Regional changes in cerebral perfusion with age when accounting for changes in gray-matter volume.

One possible contributing factor for cerebral blood flow (CBF) decline in normal aging is the increase in partial volume effects due to brain atrophy, as cortical thinning can exacerbate the contamination of gray-matter (GM) voxels by other tissue types. This work investigates CBF changes in normal aging of a large elderly cohort aged 54 to 84 and how correction for partial volume effects that would accommodate potential changes in GM might affect this. The study cohort consisted of 474 participants aged 54 to 84 years using pseudo-continuous arterial spin labeling MRI. A volumetric pipeline and a surface-based pipeline were applied to measure global and regional perfusion. Volumetric regions of interest (ROIs) included GM, cerebral white matter, vascular territories, and the brain atlas from the UK Biobank. The cortical parcellation was using Desikan-Killiany atlas. Non-partial volume effect correction (PVEc) and PVEc GM-CBF changes with aging were modeled using linear regressions. Global GM CBF decreased by 0.17 mL/100 g/min per year with aging before PVEc (p < 0.05) and was 0.18 mL/100 g/min after PVEc (p < 0.05). All cortical parcels exhibited CBF decreases with age before PVEc. After PVEc, seven parcels retained decreasing trends. However, GM CBF demonstrated increase with age after PVEc in three parcels. Although decreases in global perfusion are observed with aging before PVEc, perfusion variations appear to be more regionally selective after PVEc. This supports the understanding that variation in cerebral perfusion with age observed with imaging is influenced by regional changes in anatomy that can be accommodated with PVEc, but perfusion variation is still observable even after PVE is accounted for.

Age-related changes in the hair follicle and hair shaft in women in the parietal region

Introduction. Medical trichology is a promising and modern direction of cosmetology, engaged in the study of the scalp and hair, both in the state of health and various diseases. However, with all the variety of various scientific publications, there are very few works devoted to the study of morphological changes in normal physiological aging of a person.Aim. To reveal the dynamics of morphological changes in the hair bulb and hair shaft in women in the parietal region to elderly age.Materials and methods. The work is based on the results of microscopic examination of 80 women, the study sample consisted of conditionally healthy individuals. The examined women were divided into three groups depending on their age. The first group included 27 women of the first period of mature age (26.9 ± 0.70 years). The second group consisted of 30 women of the second period of mature age (47.1 ± 1.20 years). The third group was formed by 23 women of old age (62.1 ± 1.09 years). Hair sampling was performed in the parietal region of the head by combing out the hair that had already fallen out (without pulling it out of the skin!). The width of the hair bulb and hair shaft were measured. The percentage of bulbs containing an internal root sheath to the total number of bulbs was calculated.Results and discussion. With age, a decrease in the number of hair follicles with internal root sheath (p &lt; 0.01) along with a tendency to decrease the width of the hair follicle and hair shaft (p &gt; 0.05) was noted in women in the parietal region.Conclusions. The results of this study add to the information available in the scientific literature about age-related changes occurring in the hair bulb and hair shaft in women by old age. The data obtained will be useful for trichologists in medical practice to create clinical recommendations for the early prevention of age-related alopecia areata.

Mapping Student-Generated Learning Objectives Against USMLE Core Content

Purpose: To compare the content covered by student-generated, case-based, learning objectives with United States Medical Licensing Exams (USMLE) core-content guidelines, both in terms of range of topics covered and time spent with different topics. Secondarily, to examine the impact of online learning during the COVID-19 pandemic on the content covered by student generated learning objectives (SGLOs). Methods: The data used in this study was drawn from university records of SGLOs over the course of five years, including approximately 1,600 individual SGLOs, organized by semester and year. SGLOs were coded to correspond to topics on the USMLE core content guidelines. Two lists of core content provided by the USMLE were used in this study. The first consisted of 18 broad topics and 222 nesting subtopics tested on STEP 1. The second consisted of 11 broad topics with a corresponding percent range of how many questions on STEP 1 address that topic. Findings: Percent Coverage: 50-60% of USMLE core content topics are covered within the first year. Multiple regression analysis showed this number remaining consistent between first year classes, between semesters, and during COVID. Topic Weight: 7 out of 11 broad topics fell within the same ranges of the USMLE, with Social Sciences being the greatest outlier (significantly more coverage). 2 out of 11 topics were addressed less by SGLOs than by the USMLE. Gaps: 53 individual USMLE core content sub-topics were not addressed by a UP first year class in any learning objective. Notable trends in the identified content gaps included topics relating to congenital disorders, embryonic development, male and female reproductive systems, endocrine disorders (other than thyroid disorders and diabetes), normal ageing and age-related changes, psychiatric disorders and behavioral health, and drug adverse effects. Conclusions: SGLOs covered consistent amounts of material from year to year, suggesting curricular stability over time. The same standard of SGLO creation was also maintained during online COVID 19 activities. The agreement in weighting of topics between our student-driven curriculum and the USMLE core content indicate that students prioritize topics effectively. Identified gaps in coverage represent areas for improvement. This study further supports successful collaborations between faculty and medical students in regards to curriculum development and execution. Conflicts of Interest: None. This study (Study ID: STUDY00015600) was deemed exempt by the Institutional Review Board (IRB) at the Penn State College of Medicine.

Hippocampal Subregions Volume and Texture for the Diagnosis of Mild Cognitive Impairment

ABSTRACT The aim was to examine the diagnostic efficacy of hippocampal subregions volume and texture in differentiating amnestic mild cognitive impairment (MCI) from normal aging changes. Ninety MCI subjects and eighty-eight well-matched healthy controls (HCs) were selected. Twelve hippocampal subregions volume and texture features were extracted using Freesurfer and MaZda based on T1 weighted MRI. Then, two-sample t-test and Least Absolute Shrinkage and Selection Operator (LASSO) regression were developed to select a subset of the original features. Support vector machine (SVM) was used to perform the classification task and the area under the curve (AUC), sensitivity, specificity and accuracy were calculated to evaluate the diagnostic efficacy of the model. The volume features with high discriminative power were mainly located in the bilateral CA1 and CA4, while texture feature were gray-level non-uniformity, run length non-uniformity and fraction. Our model based on hippocampal subregions volume and texture features achieved better classification performance with an AUC of 0.90. The volume and texture of hippocampal subregions can be utilized for the diagnosis of MCI. Moreover, we found that the features that contributed most to the model were mainly textural features, followed by volume. These results may guide future studies using structural scans to classify patients with MCI.

RPE Curvature Can Screen for Early and Intermediate AMD.

Diagnosing AMD early optimizes clinical management. However, current diagnostic accuracy is limited by the subjectivity of qualitative diagnostic measures used in clinical practice. This study tests if RPE curvature could be an accurate, quantitative measure for AMD diagnosis. Consecutive patients without AMD or normal aging changes (n = 111), with normal aging changes (n = 107), early AMD (n = 102) and intermediate AMD (n = 114) were recruited. RPE curvature was calculated based on the sinuosity method of measuring river curvature in environmental science. RPE and Bruch's membrane were manually segmented from optical coherence tomography B-scans and then their lengths automatically extracted using customized MATLAB code. RPE sinuosity was calculated as a ratio of RPE to Bruch's membrane length. Diagnostic accuracy was determined from area under the receiver operator characteristic curve (aROC). RPE sinuosity of foveal B-scans could distinguish any eyes with AMD (early or intermediate) from those without AMD (non-AMD or eyes with normal aging changes) with acceptable diagnostic accuracy (aROC = 0.775). Similarly, RPE sinuosity could identify intermediate AMD from all other groups (aROC = 0.871) and distinguish between early and intermediate AMD (aROC = 0.737). RPE sinuosity was significantly associated with known AMD lesions: reticular pseudodrusen (P < 0.0001) and drusen volume (P < 0.0001), but not physiological variables such as age, sex, and ethnicity. RPE sinuosity is a simple, robust, quantitative biomarker that is amenable to automation and could enhance screening of AMD.

Vessel density mapping of small cerebral vessels on 3D high resolution black blood MRI

Small cerebral blood vessels are largely inaccessible to existing clinical in vivo imaging technologies. This study aims to present a novel analysis pipeline for vessel density mapping of small cerebral blood vessels from high-resolution 3D black-blood MRI at 3T. Twenty-eight subjects (10 under 35 years old, 18 over 60 years old) were imaged with the T1-weighted turbo spin-echo with variable flip angles (T1w TSE-VFA) sequence optimized for black-blood small vessel imaging with iso-0.5 mm spatial resolution (interpolated from 0.51×0.51×0.64 mm3) at 3T. Hessian-based vessel segmentation methods (Jerman, Frangi and Sato filter) were evaluated by vessel landmarks and manual annotation of lenticulostriate arteries (LSAs). Using optimized vessel segmentation, large vessel pruning and non-linear registration, a semiautomatic pipeline was proposed for quantification of small vessel density across brain regions and further for localized detection of small vessel changes across populations. Voxel-level statistics was performed to compare vessel density between two age groups. Additionally, local vessel density of aged subjects was correlated with their corresponding gross cognitive and executive function (EF) scores using Montreal Cognitive Assessment (MoCA) and EF composite scores compiled with Item Response Theory (IRT). Jerman filter showed better performance for vessel segmentation than Frangi and Sato filter which was employed in our pipeline. Small cerebral blood vessels including small artery, arterioles, small veins, and venules on the order of a few hundred microns can be delineated using the proposed analysis pipeline on 3D black-blood MRI at 3T. The mean vessel density across brain regions was significantly higher in young subjects compared to aged subjects. In the aged subjects, localized vessel density was positively correlated with MoCA and IRT EF scores. The proposed pipeline is able to segment, quantify, and detect localized differences in vessel density of small cerebral blood vessels based on 3D high-resolution black-blood MRI. This framework may serve as a tool for localized detection of small vessel density changes in normal aging and cerebral small vessel disease.

Prevalence of risk of falls in a permanent geriatric stay

Aging or also called the normal process of changes that are related to the passage of time starts from when we are born and continues throughout life, and old age is the final phase of life. It is a gradual and adaptive process of a biological, psychological and social type, produced as a consequence of genetically programmed changes, history, lifestyles, environment and social conditions in which the elderly live. On the other hand, old age is a stage of life whose beginning is established by society, which is why the United Nations Organization agreed that, in developing countries, people aged 60 and over are classified as older adults. Within the present work, it is intended to obtain a diagnosis on the prevalence of falls in which the current situation of patients in a permanent geriatric stay located in Irapuato, Guanajuato is shown. This is considered important because during aging structural and functional changes occur in different organs and systems. For this reason, as health professionals, we must know the normal morphological and functional changes of physiological aging, and thus guide the elderly to adapt and improve their lifestyle.

Pressure ulcers in older adults in a permanent geriatric stay

We call human aging a gradual and adaptive process of a biological, psychological and social type, produced as a consequence of genetically programmed changes, history, lifestyles, environment and social conditions to which the person was exposed. On the other hand, old age is a stage of life whose beginning is established by society, which is why the United Nations Organization agreed that, in developing countries, people aged 60 and over are classified as older adults. In institutionalized older adults, the prevalence of pressure ulcers is a worrying issue in the development of nursing care plans. Prolonged bedridden, reduced mobility, malnutrition, physiological alterations, incontinence, among others, are causes that can cause pressure ulcers, as well as aspects related to current strategies and practices for their prevention in patients at a social health center. This is considered important because during aging structural and functional changes occur in different organs and systems. For this reason, as health professionals, we must know the normal morphological and functional changes of physiological aging, and thus guide the elderly to adapt and improve their lifestyle.

Blood-Brain Barrier Dysfunction in Normal Aging and Neurodegeneration: Mechanisms, Impact, and Treatments.

Cerebral endothelial cells and their linking tight junctions form a unique, dynamic and multi-functional interface, the blood-brain barrier (BBB). The endothelium is regulated by perivascular cells and components forming the neurovascular unit. This review examines BBB and neurovascular unit changes in normal aging and in neurodegenerative disorders, particularly focusing on Alzheimer disease, cerebral amyloid angiopathy and vascular dementia. Increasing evidence indicates BBB dysfunction contributes to neurodegeneration. Mechanisms underlying BBB dysfunction are outlined (endothelium and neurovascular unit mediated) as is the BBB as a therapeutic target including increasing the uptake of systemically delivered therapeutics across the BBB, enhancing clearance of potential neurotoxic compounds via the BBB, and preventing BBB dysfunction. Finally, a need for novel biomarkers of BBB dysfunction is addressed.

The Spectrum of Alzheimer-Type Pathology in Cognitively Normal Individuals.

The strongest risk factor for the development of Alzheimer's disease (AD) is age. The progression of Braak stage and Thal phase with age has been demonstrated. However, prior studies did not include cognitive status. We set out to define normative values for Alzheimer-type pathologic changes in individuals without cognitive decline, and then define levels that would qualify them to be resistant to or resilient against these changes. Utilizing neuropathology data obtained from the National Alzheimer's Coordinating Center (NACC), we demonstrate the age-related progression of Alzheimer-type pathologic changes in cognitively normal individuals (CDR = 0, n = 542). With plots generated from these data, we establish standard lines that may be utilized to measure the extent to which an individual's Alzheimer-type pathology varies from the estimated normal range of pathology. Although Braak stage and Thal phase progressively increase with age in cognitively normal individuals, the Consortium to Establish a Registry for Alzheimer's Disease neuritic plaque score and Alzheimer's disease neuropathologic change remain at low levels. These findings suggest that an increasing burden of neuritic plaques is a strong predictor of cognitive decline, whereas, neurofibrillary degeneration and amyloid-β (diffuse) plaque deposition, both to some degree, are normal pathologic changes of aging that occur in almost all individuals regardless of cognitive status. Furthermore, we have defined the amount of neuropathologic change in cognitively normal individuals that would qualify them to be "resilient" against the pathology (significantly above the normative values for age, but still cognitively normal) or "resistant" to the development of pathology (significantly below the normative values for age).

DeepParcellation: A novel deep learning method for robust brain magnetic resonance imaging parcellation in older East Asians.

Accurate parcellation of cortical regions is crucial for distinguishing morphometric changes in aged brains, particularly in degenerative brain diseases. Normal aging and neurodegeneration precipitate brain structural changes, leading to distinct tissue contrast and shape in people aged >60 years. Manual parcellation by trained radiologists can yield a highly accurate outline of the brain; however, analyzing large datasets is laborious and expensive. Alternatively, newly-developed computational models can quickly and accurately conduct brain parcellation, although thus far only for the brains of Caucasian individuals. To develop a computational model for the brain parcellation of older East Asians, we trained magnetic resonance images of dimensions 256 × 256 × 256 on 5,035 brains of older East Asians (Gwangju Alzheimer's and Related Dementia) and 2,535 brains of Caucasians. The novel N-way strategy combining three memory reduction techniques inception blocks, dilated convolutions, and attention gates was adopted for our model to overcome the intrinsic memory requirement problem. Our method proved to be compatible with the commonly used parcellation model for Caucasians and showed higher similarity and robust reliability in older aged and East Asian groups. In addition, several brain regions showing the superiority of the parcellation suggest that DeepParcellation has a great potential for applications in neurodegenerative diseases such as Alzheimer's disease.

&lt;I&gt;In vivo&lt;/I&gt; vascular mapping of the human hippocampus using MICRO imaging

BACKGROUND: There is an urgent need for better detection and understanding of vascular abnormalities at the micro-level, where critical vascular nourishment and cellular metabolic changes occur. This is especially the case for structures such as the midbrain and hippocampus, where both the feeding and draining vessels are quite small. The hippocampus is a complex grey matter structure that plays an important role in spatial and episodic memory. It can be affected by a wide range of pathologies including vascular abnormalities. Being able to monitor vascular changes in normal aging in various hippocampal subfields will allow us to better understand vascular vulnerability across the hippocampus.&#x0D; METHODS: We recently introduced the concept of microvascular in-vivo contrast revealed origins (MICRO) protocol to image micro-cerebral vessels.1-3 MICRO uses ferumoxytol, an ultra-small superparamagnetic iron oxides (USPIO) agent, to induce susceptibility in the arteries and veins; and by imaging with high resolution (0.22×0.44×1 mm3) susceptibility weighted imaging sequence (SWI) at 3 T. Although the increased vascular susceptibility enhances the visibility of small sub-voxel vessels, the accompanying strong signal loss of the large vessels deteriorates the local tissue contrast. Hence, data are collected at different time points during a gradual administration (final concentration = 4 mg/kg) of ferumoxytol. Dynamically acquired SWI data were co-registered and combined (phase gradient-based adaptive combination or SWIPGAC) to reduce the blooming artifacts from large vessels, preserving the small-vessel contrast.&#x0D; RESULTS: The presence of ferumoxytol helped to enhance the microvasculature, something that has previously only been demonstrated in cadaver brain studies. Figure 1 shows the difference between the pre-contrast SWI and SWIPGAC data in visualizing the micro-vasculature across four healthy subjects. The intra-hippocampal and superficial major arteries (obtained through a non-linear subtraction method) and veins (obtained by averaging the T1-shortening map, pre-contrast quantitative susceptibility mapping (QSM) and pre-contrast R2* maps) are used as an overlay in the third column to better visualize the major vessels penetrating and draining the hippocampus. The hippocampal fissure, along with the fimbria, granular cell layer of the dentate gyrus and cornu ammonis layers (except for CA1), showed higher micro-vascular density than the other parts of hippocampus. The CA1 region exhibited a significant correlation with age (R=−0.37, p&lt;0.05, n=37). demonstrating an overall loss of hippocampal vascularity in the normal aging process. Moreover, the vascular density reduction was more prominent than the age correlation with the volume reduction (R=−0.1, p&gt;0.05, n=37) of the CA1 subfield.&#x0D; CONCLUSIONS: With this USPIO-induced increase in susceptibility comes the potential to study the cerebral micro-vasculature using high-resolution SWI. There was a strong negative correlation between hippocampal functional vessel density (FVD) (especially in CA1) and age. This FVD reduction was more prominent than volume reduction vs age, suggesting that vascular atrophy may precede reductions in tissue volume. Mapping the hippocampal vasculature has immediate implications for understanding the effects of normal aging and the etiology of many neurovascular diseases. MICRO imaging brings us into the decade of imaging the microvasculature of the entire human body.

Improving the estimation of subtle blood-brain barrier permeability changes in aging using a deep learning approach

Background: Increasing evidence suggests detecting the subtle changes in blood-brain barrier (BBB) permeability in normal aging and in Alzheimer’s disease by using dynamic contrast-enhanced MRI (DCE-MRI) (Figure 1).1,2 However, measuring these subtle changes poses a great challenge for accurate measurement, resulting in inconsistent results among previous studies.1,2 Two major challenges are long scan times, as suggested by other studies, and the selection of the arterial input function (AIF). In this study, we aim to estimate the capillary level input function (CIF) using a deep learning network to overcome these two challenges.&#x0D; Methods: Healthy volunteers (n=12, age 21-78) were recruited for DCE-MRI scan for 28 min. Golden-angle radial sampling parallel (GRASP) sequence was used to obtain the dynamic images at ~5s/frame. Individual AIF was sampled from the superior sagittal sinus of the brain. FSL3 was used to segment the gray and white matter. Each voxel was fitted using the graphical Patlak model4 to assess the vascular permeability-surface area product (PS) for both 28-min data and 10-min truncated data. We used a 3x3 kernel sliding through the images, and feed each voxel’s dynamic as the input to our vision-transformer.5 Training data were generated using individual AIFs with a mathematical model and used to simulate dynamic patches using the extended Patlak model.4&#x0D; Results: The conventional approach with AIF results in the majority of voxels exhibiting negative PS, regardless of scan time. This is not physiologically valid, as this indicates the contrast agent extravasates into the vessel. However, the proposed approach with the network-predicted CIF results in most voxels in positive PS, even with a scan-time of 10 min. The estimated PS levels are in good accordance with the previous studies.1 Due to the limited sample size, we could not find the difference in BBB permeability between young and old groups.&#x0D; Conclusions: Our approach showed promising quantification of subtle permeability. The results in this study suggest that our proposed CIF-based approach provides an appropriate input function for DCE analysis, allowing assessment of subtle permeability changes in the BBB even with a reduced scan time of 10 min. Future studies will include larger cohorts to investigate the BBB permeability changes in normal aging.

Cognitive decline is associated with frequency-specific resting state functional changes in normal aging.

Resting state low-frequency brain activity may aid in our understanding of the mechanisms of aging-related cognitive decline. Our purpose was to explore the characteristics of the amplitude of low-frequency fluctuations (ALFF) in different frequency bands of fMRI to better understand cognitive aging. Thirty-seven cognitively normal older individuals underwent a battery of neuropsychological tests and MRI scans at baseline and four years later. ALFF from five different frequency bands (typical band, slow-5, slow-4, slow-3, and slow-2) were calculated and analyzed. A two-way ANOVA was used to explore the interaction effects in voxel-wise whole brain ALFF of the time and frequency bands. Paired-sample t-test was used to explore within-group changes over four years. Partial correlation analysis was performed to assess associations between the altered ALFF and cognitive function. Significant interaction effects of time × frequency were distributed over inferior frontal gyrus, superior frontal gyrus, right rolandic operculum, left thalamus, and right putamen. Significant ALFF reductions in all five frequency bands were mainly found in the right hemisphere and the posterior cerebellum; whereas localization of the significantly increased ALFF were mainly found in the cerebellum at typical band, slow-5 and slow-4 bands, and left hemisphere and the cerebellum at slow-3, slow-2 bands. In addition, ALFF changes showed frequency-specific correlations with changes in cognition. These results suggest that changes of local brain activity in cognitively normal aging should be investigated in multiple frequency bands. The association between ALFF changes and cognitive function can potentially aid better understanding of the mechanisms underlying normal cognitive aging.

Normal Aging Induces Changes in the Brain and Neurodegeneration Progress: Review of the Structural, Biochemical, Metabolic, Cellular, and Molecular Changes.

Aging is accompanied by many changes in brain and contributes to progressive cognitive decline. In contrast to pathological changes in brain, normal aging brain changes have relatively mild but important changes in structural, biochemical and molecular level. Representatively, aging associated brain changes include atrophy of tissues, alteration in neurotransmitters and damage accumulation in cellular environment. These effects have causative link with age associated changes which ultimately results in cognitive decline. Although several evidences were found in normal aging changes of brain, it is not clearly integrated. Figuring out aging related changes in brain is important as aging is the process that everyone goes through, and comprehensive understanding may help to progress further studies. This review clarifies normal aging brain changes in an asymptotic and comprehensive manner, from a gross level to a microscopic and molecular level, and discusses potential approaches to seek the changes with cognitive decline.

To evaluate histopathological changes in placenta of IUGR

The present study entitled “To evaluate Histopathological changes in Placenta of IUGR” was conducted in the Department of Obstetrics and Gynaecology. A total of 400 patients were studied. Out of them 200 were normal patients without IUGR and 200 with IUGR. These patients were evaluated with the help of semistructured proforma consisting of various socio-demographic and clinical variables.Number of LSCS deliveries in IUGR patients (59) is significantly more than control group (33).The number of syncytial knot formation (&amp;#62;10) in IUGR is 169 compared to 153 of control and hence is statistically insignificant. Cytotrophoblastic proliferation (&amp;#62;10) in IUGR (126) is significantly more than (92) in the control group. Number Of area fibrinoid necrosis in villi &amp;#62; 5 in IUGR group is 57 compared to control group (29) (significantly higher) No. of hylinized areas (&amp;#62; 5) in IUGR (101) is significantly higher than in control group (68). Histopathological findings in low power field like syncytial knot formation, cytotrophoblastic cellular proliferation, calcification and hyalinisation of villi are also found as normal aging changes in placenta but it occur early and more frequently per low power field in IUGR group. To conclude, these morphological &amp; histological findings of placenta are the etiological basis for Intra uterine growth restriction.

Attitudes of children towards the elderly - children between of 3 and 10 years old

Objective: to identify attitudes of children towards the elderly. Methods: a quantitative, descriptive, exploratory, and correlational study was conducted. Results: the population studied were children between the ages of 3 to 10 years. Data collection incorporated some sociodemographic data and application of the "Galvão" scale validated for the Portuguese population. The convenience sample of 109 children between 3 and 10 years old, of Portuguese nationality and resident in Portugal. The results have shown on average children presented (24%) positive attitude towards the elderly. This value was close to the midpoint of the scale (28%), which places them in a moderate attitude. Conclusion: children presented more positive attitudes towards the elderly, although with some inconsistency in some dimensions. This research could become an important contribution to analyse stereotypes about aging. It is important to be able to intervene in children's attitudes towards the elderly, helping children to understand the normal changes of aging.

Normal aging, motor neurone disease, and Alzheimer's disease are characterized by cortical changes in inflammatory cytokines.

The role of increased brain inflammation in the development of neurodegenerative diseases is unclear. Here, we have compared cytokine changes in normal aging, motor neurone disease (MND), and Alzheimer's disease (AD). After an initial analysis, six candidate cytokines, interleukin (IL)- 4, 5, 6, 10, macrophage inhibitory protein (MIP)-1α, and fibroblast growth factor (FGF)-2, showing greatest changes were assayed in postmortem frozen human superior frontal gyri (n=12) of AD patients, aging and young adult controls along with theprecentral gyrus (n=12) of MND patients. Healthy aging was associated with decreased anti-inflammatory IL-10 and FGF-2 levels. AD prefrontal cortex was associated with increased levels of IL-4, IL-5, and FGF-2, with the largest increase seen for FGF-2. Notwithstanding differences in the specific frontal lobe gyrus sampled, MND patients' primary motor cortex (precentral gyrus) was associated with increased levels of IL-5, IL-6, IL-10, and FGF-2 compared to the aging prefrontal cortex (superior frontal gyrus). Immunocytochemistry showed that FGF-2 is expressed in neurons, astrocytes, and microglia in normal aging prefrontal cortex, AD prefrontal cortex, and MND motor cortex. We report that healthy aging and age-related neurodegenerative diseases have different cortical inflammatory signatures that are characterized by increased levels of anti-inflammatory cytokines and call into question the view that increased inflammation underlies the development of age-related neurodegenerative diseases.

Spontaneous blinking and brain health: Can blink‐related oscillations capture brain changes in aging?

AbstractBackgroundBlink‐related oscillations (BROs) are recently discovered neurophysiological responses that follow spontaneous blinking, and represent environmental monitoring and awareness processes as the brain evaluates new visual information after eye reopening. BROs strongly activate the precuneus which is one of the earliest brain regions impacted by Alzheimer’s disease (AD) neuropathology, and as such may provide an important avenue for assessing and monitoring brain health in aging. In this study, we conducted the first investigation of BRO effects in normal aging to determine whether these responses can capture aging‐related brain changes.MethodThis research used data from the Cambridge Centre for Aging and Neuroscience (Cam‐CAN) repository, which comprises magnetocenphalography (MEG) and structural magnetic resonance imaging (MRI) from 700 healthy adults aged 18‐88. The MEG paradigm consists of a target detection task with simultaneous auditory and visual stimulation. MEG data were first denoised using independent component analysis, then BRO responses were derived by segmenting the cleaned data into 3s epochs time‐locked to spontaneous blinking. Participants were divided into 4 age groups comprising the youngest (18‐30), middle‐young (31‐50), middle‐old (51‐70), and oldest (71‐90), and analyses were performed using global field power (GFP) and minimum norm estimates to examine BRO effects at the sensor‐ and source‐levels, respectively.ResultResults showed that BRO responses were present in all age groups. GFP amplitude increased with age during intervals spanning post‐blink BRO peaks, but not the pre‐blink baseline (p&lt;0.05). BROs also activated brain regions spanning the occipital, temporal, and parietal cortices in all age groups (p&lt;0.05 FWE), with the extent of activation increasing with age. Moreover, the activation extent of precuneus and hippocampus regions showed inverted U‐shape with age, increasing towards the middle‐old group but decreasing in the oldest.ConclusionThese results demonstrate for the first time that BRO responses can capture brain changes in normal aging, with increased neural activation for processing blink‐related information as one ages. Results suggest that BROs may represent a simple yet powerful avenue for measuring aging‐related brain function changes, providing a potential tool for early detection of neurodegeneration – particularly with respect to the precuneus and hippocampus regions highly implicated in AD.

Characteristics of Neural Network Changes in Normal Aging and Early Dementia.

To understand the mechanisms underlying preserved and impaired cognitive function in healthy aging and dementia, respectively, the spatial relationships of brain networks and mechanisms of their resilience should be understood. The hub regions of the brain, such as the multisensory integration and default mode networks, are critical for within- and between-network communication, remain well-preserved during aging, and play an essential role in compensatory processes. On the other hand, these brain hubs are the preferred sites for lesions in neurodegenerative dementias, such as Alzheimer’s disease. Disrupted primary information processing networks, such as the auditory, visual, and sensorimotor networks, may lead to overactivity of the multisensory integration networks and accumulation of pathological proteins that cause dementia. At the cellular level, the brain hub regions contain many synapses and require a large amount of energy. These regions are rich in ATP-related gene expression and had high glucose metabolism as demonstrated on positron emission tomography (PET). Importantly, the number and function of mitochondria, which are the center of ATP production, decline by about 8% every 10 years. Dementia patients often have dysfunction of the ubiquitin-proteasome and autophagy-lysosome systems, which require large amounts of ATP. If there is low energy supply but the demand is high, the risk of disease can be high. Imbalance between energy supply and demand may cause accumulation of pathological proteins and play an important role in the development of dementia. This energy imbalance may explain why brain hub regions are vulnerable to damage in different dementias. Here, we review (1) the characteristics of gray matter network, white matter network, and resting state functional network changes related to resilience in healthy aging, (2) the mode of resting state functional network disruption in neurodegenerative dementia, and (3) the cellular mechanisms associated with the disruption.