Elderly Controls Research Articles

Investigating the Effect of Resistance-Aerobic Training on the Absorption and Resorption Biomarkers of Bone Tissue in Young, Adult and Elderly Male Rats

Introduction: Exercise training is likely to be a non-pharmacological intervention to improve bone health in children and the elderly. The aim of this study was to investigate the effect of resistance-aerobic training on RUX2, CTX, RANKL and ALP biomarkers in rats of different ages. Methods: In the present experimental study, 30 male Wistar rats were obtained from Instituto Pasteur of Iran and were divided into three groups according to their age: immature (2 weeks old), mature (6 weeks old) and elderly (96 weeks old). In each age group, the mice were randomly divided into two training (n=5) and control (n=5) groups. Six weeks of combined training included three sessions of aerobic training and three sessions of resistance training per week. Extracting genes by PCR method was used. One-way analysis of variance and Tukey's post hoc test and SPSS16 software were used. The significance level P≥0.05 was considered. Results: One-way analysis of variance showed that resistance-aerobic training has had a significant effect on RUNX2, RANKL and ALP variables of rats in different age groups (P < 0.05). This significance was not observed in CTX variable (P > 0.05). On the other hand, the results of Tukey's RUNX2 test were significantly different between the adult training and elderly training groups (p=‌0.019) as well as between the elderly control groups (p = 0.01) and adult training (p = 0.002). Regarding the RANKL variable, it showed that there was a significant difference only between the adult exercise group and the elderly control group (p = 0.01). Conclusion: Resistance-endurance training probably increases absorption and reabsorption biomarkers such as RUX2, RANKL and ALP in immature, mature and elderly male rats.

Structural characteristics of gut microbiota in longevity from Changshou town, Hubei, China

The gut microbiota (GM) and its potential functions play a crucial role in maintaining host health and longevity. The aim of this study was to investigate the potential relationship between GM and longevity. We collected fecal samples from 92 healthy volunteers (middle-aged and elderly: 43–79 years old; longevity: ≥ 90 years old) from Changshou Town, Zhongxiang City, Hubei, China. In addition, we collected samples from 30 healthy middle-aged and elderly controls (aged 51–70 years) from Wuhan, Hubei. The 16S rDNA V3 + V4 region of the fecal samples was sequenced using high-throughput sequencing technology. Diversity analysis results showed that the elderly group with longevity and the elderly group with low body mass index (BMI) exhibited higher α diversity. However, no significant difference was observed in β diversity. The results of the microbiome composition indicate that Firmicutes, Proteobacteria, and Bacteroidota are the core phyla in all groups. Compared to younger elderly individuals, Akkermansia and Lactobacillus are significantly enriched in the long-lived elderly group, while Megamonas is significantly reduced. In addition, a high abundance of Akkermansia is a significant characteristic of elderly populations with low BMI values. Furthermore, the functional prediction results showed that the elderly longevity group had higher abilities in short-chain fatty acid metabolism, amino acid metabolism, and xenobiotic biodegradation. Taken together, our study provides characteristic information on GM in the long-lived elderly population in Changshou Town. This study can serve as a valuable addition to the current research on age-related GM.Key points• The gut microbiota of elderly individuals with longevity and low BMI exhibit higher alpha diversity• Gut microbiota diversity did not differ significantly between genders in the elderly population• Several potentially beneficial bacteria (e.g., Akkermansia and Lactobacillus) are enriched in long-lived individuals

Decreased oral function in Japanese inpatients with schizophrenia.

Oral function in patients with schizophrenia has not been well-characterized. To address this, we performed a cross-sectional study of oral function in Japanese inpatients with schizophrenia. We measured oral function, including occlusal force, tongue-lip motor function, tongue pressure, and masticatory function in 130 Japanese inpatients with schizophrenia. We then compared the frequency of clinical signs of oral hypofunction among 63 non-elderly and 67 elderly inpatients with schizophrenia, as well as data from 98 elderly control participants from a previous Japanese study. The frequency of reduced occlusal force was significantly higher in the elderly inpatients (76.2%) than in the non-elderly inpatients (43.9%) and elderly controls (43.9%). The frequency of decreased tongue-lip motor function in non-elderly inpatients (96.8%) and elderly inpatients (97.0%) was significantly higher than that in elderly controls (56.1%). The frequency of decreased tongue pressure in non-elderly inpatients (66.1%) and elderly inpatients (80.7%) was significantly higher than that in elderly controls (43.9%). Finally, the frequency of decreased masticatory function was highest in elderly inpatients (76.5%), followed by non-elderly inpatients (54.8%) and elderly controls (15.3%). Oral function was decreased in both non-elderly and elderly Japanese inpatients with schizophrenia compared with elderly controls.

Correlation between abnormal cellular immune and changes of magnetic resonance spectroscopy in patients with Alzheimer’s disease

BackgroundEvidence from previous studies indicates that neuroinflammation contributes to the onset of Alzheimer’s Disease (AD). Moreover, cellular dysfunction is induced by impaired signaling of neurotransmitters. This study aimed to explore the correlation between cellular immune dysfunction and neurotransmitter changes through cranial Magnetic Resonance Spectroscopy (MRS) in AD patients. MethodsHere, 32 AD, 40 Vascular Dementia (VD), and 35 Non-Dementia Elderly Control (NDE) cases were enrolled. Flow cytometry was performed to characterize lymphocyte subsets in plasma samples. The IL-1β and Caspase-1 levels were detected by ELISA. The NLRP3 expression level was measured by Western Blot (WB). The equivalence of N-acetylaspartate (NAA), Creatine (Cr), Choline (Cho), and Inositol (MI) in bilateral hippocampi of patients was examined by MRS. The association of NAA/Cr or MI/Cr ratios with the proportion of T lymphocyte subsets or NK cell subsets was determined through single-factor correlation analysis. ResultsThe proportion of T lymphocyte subsets was significantly lower in the AD group than in the NDE group (P < 0.01). On the other hand, the Caspase-1, NLRP3, and IL-1β protein expression levels were significantly higher in the AD group than in the other groups. Further analysis showed that the NAA/Cr ratio was lower in the AD group than in the NDE group. Additionally, a significant positive correlation was found between the NAA/Cr ratio and the MMSE score (r = 0.81, P < 0.01). Moreover, a significant positive correlation was observed between the NAA/Cr and T lymphocyte ratios. The NAA/Cr ratio was significantly negatively correlated with the proportion of NK cells in the blood (r = －0.83, P < 0.01). A significant negative correlation was also recorded between the MI/Cr and T cell ratios in blood samples. ConclusionsImpaired cellular immune dysfunction in AD patients was significantly correlated with abnormal MRS. Neuroimmune dysfunction may contribute to the pathogenesis of AD and alter the metabolism of neurotransmitters such as aspartic acid and MI in the brains of AD patients. Trial registrationNot applicable.

Relationship of plasma biomarkers to digital cognitive tests in Alzheimer's disease.

A major limitation in Alzheimer's disease (AD) research is the lack of the ability to measure cognitive performance at scale-robustly, remotely, and frequently. Currently, there are no established online digital platforms validated against plasma biomarkers of AD. We used a novel web-based platform that assessed different cognitive functions in AD patients (N=46) and elderly controls (N=53) who were also evaluated for plasma biomarkers (amyloid beta 42/40 ratio, phosphorylated tau ([p-tau]181, glial fibrillary acidic protein, neurofilament light chain). Their cognitive performance was compared to a second, larger group of elderly controls (N=352). Patients with AD were significantly impaired across all digital cognitive tests, with performance correlating with plasma biomarker levels, particularly p-tau181. The combination of p-tau181 and the single best-performing digital test achieved high accuracy in group classification. These findings show how online testing can now be deployed in patients with AD to measure cognitive function effectively and related to blood biomarkers of the disease. This is the first study comparing online digital testing to plasma biomarkers.Alzheimer's disease patients and two independent cohorts of elderly controls were assessed.Cognitive performance correlated with plasma biomarkers, particularly phosphorylated tau (p-tau)181.Glial fibrillary acidic protein and neurofilament light chain, and less so the amyloid beta 42/40 ratio, were also associated with performance.The best cognitive metric performed at par to p-tau181 in group classification.

Comparison of Effects of Balance Training Exercise and Gaze Stability Exercises on Balance and Postural Control in Elderly With Fall Risk: A Randomized Controlled Trial

Aim To compare the changes in outcomes of balance and postural control after balance training exercise and gaze stability exercise in the elderly population with fall risk. Methods After the screening process, 44 subjects were randomized into three groups: Experimental Group A (Balance training exercises, BTE); Experimental Group B (Gaze stability exercises, GSE), and Control Group C (Fall prevention education only). The outcome measures were center of pressure (COP) range, COP sway, reaction time, proprioception, static balance, Clinical Test for Sensory Interaction in Balance (CTSIB), and Short Falls Efficacy Scale (SFES). The pre and post-data were recorded at baseline and after 8 weeks. The normality of the distribution was assessed using the Shapiro-Wilk test. Demographic data and baseline measures were compared using one-way ANOVA considering group as between factor and mixed model ANOVA was used to find out the group effect and time effect and time × group interaction effect. Statistical significance was indicated if p ≤ 0.05. Results GSE had significant changes only in CTSIB 4 whereas BTE had significant changes in CTSIB 4, 5, and 6. COP range showed a significant time effect in the front direction (p = 0.02). For proprioception, there was a significant time effect in the left (p = 0.018) and right direction (p = 0.005), whereas changes in front and back directions were found to be insignificant. SFES showed a significant time effect (p < 0.001), group effect (p = 0.21), and time × group interaction effect (p < 0.001). Conclusion Balance training exercises may be a more effective form of intervention to improve balance and postural control in the elderly population.

Microglia-neuron interactions in the caudate nucleus in different course of schizophrenia

To study the ultrastructure of microglia and neurons in contact with each other in the head of the caudate nucleus in continuous schizophrenia (CS) and paroxysmal-progressive schizophrenia (PPS) as compared to controls and to analyze correlations between the parameters of microglia and neurons in the control and schizophrenia groups. Post-mortem electron microscopic morphometric study of microglia and neurons in contact with each other was performed in the head of the caudate nucleus in 9 cases of CS, 10 cases of PPS and 20 controls without mental pathology. Group comparisons were made using analysis of covariance and Pearson correlation analysis. The PPS group showed increased numerical density of microglia in young (≤50 years old) patients compared to elderly (>50 years old) controls and increased area of endoplasmic reticulum vacuoles in microglia in young patients compared to young controls. Decreased numerical density of microglia was found in the CS group compared to the PPS group (p<0.05), and increased volume fraction (Vv) and the number of lipofuscin granules in microglia were found in the CS group in elderly patients compared with young and elderly controls. In this group, negative correlations were revealed between the numerical density of microglia, microglia nuclear area and the duration of disease (r= -0.72, p=0.03; r= -0.8; p=0.01). Decreased Vv and the number of mitochondria in microglia and increased area and perimeter of neurons were revealed in both groups compared to the control group. In neurons, increased vacuole area was found in the PPS group and mitochondrial area in the NTS group compared to the control group. Correlation violations were found between the parameters of mitochondria in microglia and neurons in both PPS and CS groups and between the area of mitochondria in neurons and the area of vacuoles in microglia in the CS group compared to the control group. Disturbed interactions between microglia and neurons in the caudate nucleus are associated with the types of course of schizophrenia and with microglial reactivity. They might be caused by the damage of energy metabolism in microglia in both types of schizophrenia course and by stress of endoplasmic reticulum in microglia in CS.

Effect of Customized Foot Insoles and Textured Insoles on the Balance and Postural Control in Elderly with Pes Planus: A Randomized Controlled Trial

Background An increase in age is associated with reduced postural stability and increased fall risk. Foot orthoses are the supplementary measure to enhance balance by activating mechanical receptors of the foot plantar thus amplifying somatosensory input.Objectives To compare and assess the effectiveness of two insoles customized insoles and textured insoles on balance and postural control in elderly. This study also aimed to identify the risk of fall prevention in elderly by using customized insoles and textured insoles.Methods This was a partially randomized controlled trial with patient preference protocol for evaluating the effect of two different insoles customized or textured on the balance of primary care elderly people compared with a control group without orthoses. The outcome measure were Berg balance scale and time up and go test conducted before and after the intervention. Data were analyzed after eight weeks of intervention period.Results Thirty participants 8 males and 22 females were enrolled. On comparison with the baseline scores the intervention group 2 textured insole showed moderately significant improvement in time up and go posttest P value- 0.041.Conclusion Improvements observed in balance and postural control in the subjects wearing customized or textured insoles. These approaches could serve as a cost-effective and widely accessible supplementary technique to enhance balance in the older adults living in the community. The use of insoles for eight weeks resulted in statistically significant improvements in balance functional mobility and pain.

Caudal epidural, pericapsular nerve group block and lateral femoral cutaneous nerve block in hip fracture surgery: A case report

Background: Hip fractures are associated with significant morbidity and mortality in the elderly and optimal pain control is essential in improving postoperative outcomes. The sensory innervation of the hip is complex, and blocking the hip branches of the femoral, obturator and sciatic nerves is necessary to provide full sensory coverage of the hip joint. Objectives: This case report describes the use of a combination of three regional anesthesia techniques – caudal epidural, pericapsular nerve group block and lateral femoral cutaneous nerve block – in hip fracture surgery, and demonstrates its efficacy in minimizing pain and opioid requirements in a high cardiac risk geriatric patient. Results: Caudal epidural, pericapsular nerve group block and lateral femoral cutaneous nerve blocks were performed in a patient presenting for hip fracture surgery prior to general anaesthesia successfully without the need for further doses of opioids post operatively

MiRNA let-7d-5p Alleviates Inflammatory Responses by Targeting Map3k1 and Inactivating ERK/p38 MAPK Signaling in Microglia.

Alzheimer's disease (AD) is the most common form of dementia. Aberrant regulation of microRNAs (miRNAs) has been implicated in the pathogenesis of AD. In a large case-control study recruiting 208 patients with AD and 205 elderly control subjects, miRNA-let-7d-5p attracted our attention for its downregulated level in patients with AD. However, the biological functions of let-7d-5p in AD pathogenesis have not been investigated. This study emphasized the functions and mechanisms of let-7d-5p in the pathogenesis of AD. Mouse microglial BV2 cells treated with amyloid-β (Aβ)1-42 were used as in vitro AD inflammation models. We reported that let-7d-5p was downregulated in Aβ1-42-stimulated BV2 cells, and upregulation of let-7d-5p promoted the transversion of microglial cells from Ml phenotype to M2 phenotype. Then, the binding relationship between let-7d-5p and Map3k1 was verified by luciferase reporter assays. Mechanistically, let-7d-5p could target Map3k1 3'UTR to inactivate ERK/p38 MAPK signaling. Therefore, it was suggested that let-7d-5p might be a novel modulator of microglial neuroinflammation and serve as a novel target for diagnosis and treatment of AD.

The role of the tongue in post-stroke dysphagia and obstructive sleep apnea: Correlation with sonography measurement

ObjectiveObstructive sleep apnea (OSA) is a common risk factor for stroke, and dysphagia and pneumonia are both well-known complications of stroke. The development of these conditions is related to the oropharyngeal structures. We investigated whether specific structural features of the tongue may lead to the development of these complications. MethodsPatients with ischemic stroke who required admission and community-dwelling elderly controls were enrolled. The participants underwent tongue measurements by received hand-held ultrasound, and received questionnaires to evaluate sleep quality and daytime sleepiness. The patient group also underwent objective sleep measurement by actigraphy and the 3-Step Swallowing Test (3-SSS). Sleep parameters and outcomes were analyzed. ResultsPatient with ischemic stroke had significantly thicker tongue than controls (6.53 cm v. 6.05 cm, p = 0.002). Multiple logistic regression analysis revealed that the anatomical parameters of the tongue in patients with stroke were significantly correlated with parameters of OSA, and the thickness of the tongue was positively correlated with the development of OSA (p = 0.024) and pneumonia (p = 0.048). ConclusionsA thicker-than average tongue may be a risk factor for OSA and pneumonia in patient with stroke. Hand-held ultrasound can be used to identify these anatomical features. Further studies are warranted to clarify the role of the tongue in these post-stroke complications.

The cortical thickness of tricenarian cocaine users assembles features of an octogenarian brain.

It has been suggested that substance use disorders could lead to accelerated biological aging, but only a few neuroimaging studies have investigated this hypothesis so far. In this cross-sectional study, structural neuroimaging was performed to measure cortical thickness (CT) in tricenarian adults with cocaine use disorder (CUD, n1 = 30) and their age-paired controls (YC, n1 = 30), and compare it with octogenarian elder controls (EC, n1 = 20). We found that CT in the right fusiform gyrus was similar between CUD and EC, thinner than the expected values of YC. We also found that regarding CT of the right inferior temporal gyrus, right inferior parietal cortex, and left superior parietal cortex, the CUD group exhibited parameters that fell in between EC and YC groups. Finally, CT of the right pars triangularis bordering with orbitofrontal gyrus, right superior temporal gyrus, and right precentral gyrus were reduced in CUD when contrasted with YC, but those areas were unrelated to CT of EC. Despite the 50-year age gap between our age groups, CT of tricenarian cocaine users assembles features of an octogenarian brain, reinforcing the accelerated aging hypothesis in CUD.

Plasma neuron specific enolase (NSE), tumour necrosis factor-alpha (TNF-α) and soluble IL-2 receptor alpha (sIL-2Rα) levels in children with developmental delay (DD): Use of combined ROC curves to increase their diagnostic value

BackgroundDevelopmental delay (DD) occurs when children fail to reach developmental milestones in comparison to peers of the same age range. However, there are no valuable biomarkers for the early diagnosis of DD. Since there is no specific marker for screening the disease, we evaluated plasma NSE, TNF-α and sIL2-Rα as potential markers for this purpose. MethodsIn this cross-sectional randomized case-control study, a total of 174 DD patients and 49 matched elderly controls aged between 2 months and 60 months were recruited. A sensitive enzyme-linked immunosorbent assay and an immunoradiometric assay were used to evaluate the levels of plasma IL-1, IL-6, IL-8, IL-10, sIL2-Rα, TNF-α, and NSE. Statistical analyses using t test, χ2, ANOVA, ROC curves and binary logistic regression models were performed. ResultsIn comparison to the control group, the DD group had greater levels of NSE, TNF-α, and sIL2-Rα(p < 0.05). In the binary logistic regression analysis of DD, NSE had an odds ratio (OR) of 1.783 (95 % CI 1.297 to 2.451, p = 0.000), indicating that NSE was an independent risk factor for DD. The plasma TNF-α level was positively correlated with plasma NSE and sIL2-Rα levels in the DD group (r = 0.366 and 0.433, respectively), and the DQ score and plasma sIL2-Rα level in the DD group were positively correlated. The ROC curve revealed that the respective areas under the NSE, TNF-α, and sIL2-Rα ROC curves were 0.9797, 0.9365, and 0.8533, respectively. Moreover, a significant increase in AUC was observed using combined ROC curve analysis. ConclusionsChildren with DD have significantly altered plasma concentrations of sIL2-Rα, NSE, and TNF-α. NSE, TNF-α and sIL2-Rα can be used as DD blood biomarkers. This information may be helpful in early diagnosis and intervention.

Clinical Significance of Nutritional Status, Inflammation, and Body Composition in Elderly Hemodialysis Patients-A Case-Control Study.

Nutritional and inflammatory disorders are factors that increase the risk of adverse clinical outcomes and mortality in elderly hemodialysis (HD) patients. This study aimed to examine nutritional and inflammation status as well as body composition in older adults on HD compared to matched controls. A case-control study was conducted on 168 older participants (84 HD patients (cases) and 84 controls) age- and sex-matched. Demographic, clinical, anthropometric, and laboratory parameters were collected from medical records. The primary outcome was nutritional status assessment using a combination of nutritional and inflammatory markers along with the geriatric nutritional risk index (GNRI). Sarcopenic obesity (SO) was studied by the combined application of anthropometric measures. Body composition and hydration status were assessed by bioelectrical impedance analysis (BIA). Univariate and multivariate regression analyses were performed to identify nutritional and inflammatory independent risk indicators in elderly HD patients and controls. A significantly high prevalence of nutritional risk measured by the GNRI was found in HD patients (32.1%) compared to controls (6.0%) (p < 0.001). Elderly HD patients were overweight and had lower percent arm muscle circumference, phase angle (PA), serum albumin (s-albumin), as well as higher percent extracellular body water (ECW%) and serum C-reactive protein (s-CRP) than controls (all at least, p < 0.01). SO was higher in HD patients (15.50%) than in controls (14.30%). By multi-regression analyses, age < 75 years (OR: 0.119; 95%CI: 0.036 to 0.388), ECW% (OR: 1.162; 95%CI: 1.061 to 1.273), PA (OR: 0.099; 95%CI: 0.036 to 0.271), as well as BMI, s-albumin ≥ 3.8 g/dL, and lower s-CRP were independently related between cases and controls (all at least, p < 0.05). Elderly HD patients had increased nutritional risk, SO, inflammation, overhydration, and metabolic derangements compared to controls. This study highlights the importance of identifying nutritional risk along with inflammation profile and associated body composition disorders in the nutritional care of elderly HD patients. Further studies are needed to prevent nutritional disorders in elderly HD patients.

White matter hyperintensity burden does not differentiate SuperAgers from average cognitive agers

AbstractBackgroundThe amount of white matter hyperintensity (WMH) found on T2‐weighted imaging has shown a strong relationship with age and is thought to be a marker of ischemia‐associated demyelination or secondary axonal degeneration associated with neurodegenerative disease. Previous healthy older aging studies have shown increased WMH are associated with poorer episodic memory performance and decreased volume of medial temporal lobe regions. Here, we examine if lower WMH are associated with a phenotype of successful cognitive aging, SuperAging. SuperAgers are participants over the age 80 with episodic memory at least as good as that of average middle‐aged adults.MethodWe quantified the WMH volume from T2‐FLAIR imaging with a pre‐trained Bayesian 3D U‐Net convolutional neural network in SuperAgers and cognitively healthy elderly controls (EC) of a similar age and education. All participants underwent the ADNI‐3 FLAIR on the same 3T Prisma MRI. WMH volume was square root transformed to account for the skewed distribution. A 2‐tail independent samples t‐test evaluated the difference in WMH volume between SuperAgers and EC. Additionally, we examined if there were differences within SA and EC groups by sex.Result46 SuperAgers (average age 86.3 ± 1.86; average years of education 16.9 ± 1.9) and 25 EC (average age 87.1 ± 5.17; average years of education 17.1 ± 3.1) met criteria and were included in the study. There was no significant difference in the volume of WMH between SuperAgers and ECs (t = 1.01, p = 0.32). Further, there was no significant difference in WMH by sex within the SuperAging group (t = 0.10, p = 0.92) or EC group (t = 0.82, p = 0.42).ConclusionResistance to the development of WMH, a cross‐sectional marker of cerebrovascular disease and demyelination, does not appear to be a strong discriminating factor in 80+ year‐olds with superior memory function compared to cognitively average agers. Future analyses will include longitudinal changes in WMH and examining regional WMH. Cognitive aging is associated with several underlying brain‐based etiologies, and SuperAging may be better explained by a more sophisticated multi‐modal approach.

White matter hyperintensity burden does not differentiate SuperAgers from average cognitive agers

AbstractBackgroundThe amount of white matter hyperintensity (WMH) found on T2‐weighted imaging has shown a strong relationship with age and is thought to be a marker of ischemia‐associated demyelination or secondary axonal degeneration associated with neurodegenerative disease. Previous healthy older aging studies have shown increased WMH are associated with poorer episodic memory performance and decreased volume of medial temporal lobe regions. Here, we examine if lower WMH are associated with a phenotype of successful cognitive aging, SuperAging. SuperAgers are participants over the age 80 with episodic memory at least as good as that of average middle‐aged adults.MethodWe quantified the WMH volume from T2‐FLAIR imaging with a pre‐trained Bayesian 3D U‐Net convolutional neural network in SuperAgers and cognitively healthy elderly controls (EC) of a similar age and education. All participants underwent the ADNI‐3 FLAIR on the same 3T Prisma MRI. WMH volume was square root transformed to account for the skewed distribution. A 2‐tail independent samples t‐test evaluated the difference in WMH volume between SuperAgers and EC. Additionally, we examined if there were differences within SA and EC groups by sex.Result46 SuperAgers (average age 86.3 ± 1.86; average years of education 16.9 ± 1.9) and 25 EC (average age 87.1 ± 5.17; average years of education 17.1 ± 3.1) met criteria and were included in the study. There was no significant difference in the volume of WMH between SuperAgers and ECs (t = 1.01, p = 0.32). Further, there was no significant difference in WMH by sex within the SuperAging group (t = 0.10, p = 0.92) or EC group (t = 0.82, p = 0.42).ConclusionResistance to the development of WMH, a cross‐sectional marker of cerebrovascular disease and demyelination, does not appear to be a strong discriminating factor in 80+ year‐olds with superior memory function compared to cognitively average agers. Future analyses will include longitudinal changes in WMH and examining regional WMH. Cognitive aging is associated with several underlying brain‐based etiologies, and SuperAging may be better explained by a more sophisticated multi‐modal approach.

Chinese ADNI study:Characteristic AD biomarkers precisely predicts Alzheimer’s dementia: China Aging and Neurodegenerative Initiative (CANDI) study

AbstractBackgroundTo test the utility of the “A/T/N” system in the Chinese population, we study core Alzheimer’s disease (AD) biomarkers in a newly established Chinese cohort.MethodA total of 411 participants were selected, including 96 cognitively normal individuals, 94 patients with mild cognitive impairment (MCI) patients, 173 patients with AD, and 48 patients with non‐AD dementia. Fluid biomarkers were measured with single molecule array. Amyloid beta (Aβ) deposition was determined by 18F‐Flobetapir positron emission tomography (PET), and brain atrophy was quantified using magnetic resonance imaging (MRI).ResultAβ42/Aβ40 was decreased, whereas levels of phosphorylated tau (p‐tau) were increased in cerebrospinal fluid (CSF) and plasma from patients with AD. CSF Aβ42/Aβ40, CSF p‐tau, and plasma p‐tau showed a high concordance in discriminat‐ ing between AD and non‐AD dementia or elderly controls. A combination of plasma p‐tau, apolipoprotein E (APOE) genotype, and MRI measures accurately predicted amyloid PET status.ConclusionThese results revealed a universal applicability of the “A/T/N” framework in a Chinese population and established an optimal diagnostic model consisting of cost‐ effective and non‐invasive approaches for diagnosing AD.

Relation between cortical thickness and frontal lobe P50 response in neurotypical aging: MEG study

AbstractBackgroundThe auditory Event Related Potential (ERP) with latency at peak at 50 ms is a potential biomarker of prodromal Alzheimer’s disease (AD). However, the relation between P50 ERP and the thickness of the gray matter over frontal brain regions in healthy individuals over 55 y.o is not well studied. We examined the relation between frontal lobe generator of auditory P50 and degree of the gray matter volume lost in healthy individuals. We hypothesized that reduced thickness in the cingulate cortex is associated with aberrant function of the frontal lobe generator of the P50 response.MethodSeven healthy subjects (ages 58‐72 years, 4 women) participated in the ongoing study. P50 response was calculated from magnetoencephalographic and electroencephalographic data during presentation of 7 tones (30 ms duration) ranging from 500 to 986 Hz. Each tone was preceded by 850 ms period of silence. Free‐surfer computed the cortical thickness for each subject as the distance between the gray/white matter boundary and the pial surface for each pair of vertices. 110 T1‐MPRAGE scans of elderly healthy controls (over 65 yo) from a Neurocognitive aging dataset were used as an average‐control group. To calculate the difference in thickness between averaged control and individual subject, the z‐value was applied. The template of 110‐averaged data was transformed into the subject’s space, and for each vertices we subtracted the mean and divide by the standard deviationResultIn this study we show, that in subjects with less thickness in the cingulate cortex the amplitude of P50 response was enhanced with respect to those subjects who had more cortical thickness (Z value &gt;5 vs. Z value &lt;2). The aberrant function of the frontal lobe generator of P50 response was associated with enchanted amplitude of the P50 in MEG and EEG data.ConclusionOur results suggest that age‐related deficiency in frontal lobe generators of auditory P50 in healthy aging participants is associated with a reduction of gray matter volume in cingulate cortex. Present results support the notion about age‐related changes in modulatory role of frontal lobe generator of auditory P50 that are located at the cingulate cortex.

Detection of subclinical epileptiform discharges in Alzheimer’s disease using long‐term out‐patient EEG monitoring

AbstractBackgroundIn patients with Alzheimer’s disease (AD) without clinical seizures, up to half have epileptiform discharges in long‐term in‐patient electroencephalography (EEG) recordings. Long‐term in‐patient monitoring is obtrusive, and expensive as compared to out‐patient monitoring. No studies have so far investigated if long‐term out‐patient EEG monitoring is able to identify epileptiform discharges in AD. To investigate if epileptiform discharges as measured with ear‐EEG are more common in patients with AD compared to healthy elderly controls (HC). To understand the association with AD, we investigated the variability across multiple recordings.MethodIn this longitudinal observational study, 24 patients with mild to moderate AD and 15 age‐matched HC were included in the analysis. Patients with AD underwent up to three ear‐EEG recordings, each lasting up to two days, within 6 months. The first recording was defined as the baseline recording.ResultAt baseline, epileptiform discharges were detected in 75.0% of patients with AD and in 46.7% of HC (p‐value = 0.073). The spike frequency (spikes or sharp waves/24 hours) was significantly higher in patients with AD as compared to HC with a risk ratio of 2.90 (CI: 1.77‐5.01, p&lt;0.001). Most patients with AD (91.7%) showed epileptiform discharges when combining all ear‐EEG recordings.ConclusionLong‐term ear‐EEG monitoring detects epileptiform discharges in most patients with AD with a three‐fold increased spike frequency compared to HC, which most likely originates from the temporal lobes. Since most patients showed epileptiform discharges with multiple recordings, elevated spike frequency should be considered a marker of hyperexcitability in AD.

How Do Event‐Related Gamma Oscillations Differ in Alzheimer’s Disease From Other Types of Dementia ?

AbstractBackgroundAlthough recent studies showed that gamma frequency entrainment might have therapeutic effects on Alzheimer’s Disease (AD) (Iaccarino et al. 2016), the gamma band abnormalities in AD patients are still poorly understood, while some studies presented increased gamma responses in AD, others showed reduced gamma responses (Güntekin et al., 2022). The differentiation of gamma responses between different dementia types is also not known. The present study aims to analyze the event‐related gamma responses in AD patients and to find out how the event‐related gamma responses differentiate between AD, Parkinson’s disease dementia (PDD), and Lewy Body dementia (DLB).MethodEEG of 17 DLB, 19 PDD, 20 AD patients, and 20 healthy controls was recorded with a 32‐channel EEG device. Subjects had performed visual oddball paradigm during EEG recordings. Event‐related phase locking and Event‐related power were analyzed in three gamma frequency bands (25‐30 Hz, 30‐35 Hz, 35‐48 Hz) in three different time windows (0 200 ms, 200 400 ms, 400‐600 ms) for target and non‐target stimuli. Repeated measures of ANOVA were used with the between‐subjects and within‐subjects factors.ResultTarget responses elicited higher gamma phase locking than the non‐target responses (p&lt;0.05). Healthy subjects had higher gamma phase locking than AD, PDD, and DLB patients (p&lt;0.05). The healthy control group had increased gamma power in the 0‐200 ms time window at frontal and central locations (p&lt;0.05); however, patient groups did not have this early time window increase of gamma responses. Furthermore, although it was non‐significant, gamma phase locking values of PDD and DLB patients were worse than AD.ConclusionThe present study showed that AD, PDD, and DLB patients had reduced event‐related gamma phase locking and power in the early time window compared to healthy elderly controls. The gamma phase locking values of PDD and DLB patients were worse than those of AD patients. The present study showed that similar to AD patients and other dementia types could also have deficits in the gamma frequency band. Since the PDD and DLB patients had even more abnormal gamma band activities, the gamma entrainment could also have positive effects in these groups of patients.