Selective visuoconstructional impairment following mild COVID-19 with inflammatory and neuroimaging correlation findings.

People recovered from COVID-19 may still present complications including respiratory and neurological sequelae. In other viral infections, cognitive impairment occurs due to brain damage or dysfunction caused by vascular lesions and inflammatory processes. Persistent cognitive impairment compromises daily activities and psychosocial adaptation. Some level of neurological and psychiatric consequences were expected and described in severe cases of COVID-19. However, it is debatable whether neuropsychiatric complications are related to COVID-19 or to unfoldings from a severe infection. Nevertheless, the majority of cases recorded worldwide were mild to moderate self-limited illness in non-hospitalized people. Thus, it is important to understand what are the implications of mild COVID-19, which is the largest and understudied pool of COVID-19 cases. We aimed to investigate adults at least four months after recovering from mild COVID-19, which were assessed by neuropsychological, ocular and neurological tests, immune markers assay, and by structural MRI and 18FDG-PET neuroimaging to shed light on putative brain changes and clinical correlations. In approximately one-quarter of mild-COVID-19 individuals, we detected a specific visuoconstructive deficit, which was associated with changes in molecular and structural brain imaging, and correlated with upregulation of peripheral immune markers. Our findings provide evidence of neuroinflammatory burden causing cognitive deficit, in an already large and growing fraction of the world population. While living with a multitude of mild COVID-19 cases, action is required for a more comprehensive assessment and follow-up of the cognitive impairment, allowing to better understand symptom persistence and the necessity of rehabilitation of the affected individuals.

Effects of yoga on impulsivity in patients with and without mental disorders: a systematic review.

BACKGROUND: Yoga can be used as a complementary intervention to conventional treatments, whether pharmacological or non-pharmacological. Sustained practice of yoga can generate a series of benefits for individuals' quality of life and improve their physical fitness. OBJECTIVE: To investigate the potential effects of yoga as an adjunct intervention in conditions involving impulse control issues, such as attention deficit hyperactivity disorder (ADHD), borderline personality disorder, bipolar affective disorder, and substance use disorders. METHODS: We performed a systematic review of placebo-controlled, randomized trials of yoga in patients with impulsivity. PubMed, Web of Science, and Science Direct databases were searched for trials published up to January, 2023. Data were extracted from published reports and quality assessment was performed per Cochrane recommendations. RESULTS: Out of 277 database results, 6 RCT were included in this systematic review. To assess the level of attention and impulsiveness, the following scales were analyzed: Barratt Impulsiveness, UPPS-P Impulsive Behavior scale, Conners' Continuous Performance Test IIª and Conners' Parent Rating Scale-Revised: Long. CONCLUSIONS: Yoga didn't have a significant improvement in impulsivity when compared to placebo. There are many tools to assess impulsivity, but they mean different concepts and domains consisting in a weakness on comparison of yoga effects. PROSPERO REGISTRATION: CRD42023389088.

The relationship between cognitive clusters and telomere length in bipolar-schizophrenia spectrum disorders.

BACKGROUND: Schizophrenia and bipolar disorder are complex mental illnesses that are associated with cognitive deficits. There is considerable cognitive heterogeneity that exists within both disorders. Studies that cluster schizophrenia and bipolar patients into subgroups based on their cognitive profile increasingly demonstrate that, relative to healthy controls, there is a severely compromised subgroup and a relatively intact subgroup. There is emerging evidence that telomere shortening, a marker of cellular senescence, may be associated with cognitive impairments. The aim of this study was to explore the relationship between cognitive subgroups in bipolar-schizophrenia spectrum disorders and telomere length against a healthy control sample. METHODS: Participants included a transdiagnostic group diagnosed with bipolar, schizophrenia or schizoaffective disorder (n = 73) and healthy controls (n = 113). Cognitive clusters within the transdiagnostic patient group, were determined using K-means cluster analysis based on current cognitive functioning (MATRICS Consensus Cognitive Battery scores). Telomere length was determined using quantitative PCRs genomic DNA extracted from whole blood. Emergent clusters were then compared to the healthy control group on telomere length. RESULTS: Two clusters emerged within the patient group that were deemed to reflect a relatively intact cognitive group and a cognitively impaired subgroup. Telomere length was significantly shorter in the severely impaired cognitive subgroup compared to the healthy control group. CONCLUSIONS: This study replicates previous findings of transdiagnostic cognitive subgroups and associates shorter telomere length with the severely impaired cognitive subgroup. These findings support emerging literature associating cognitive impairments in psychiatric disorders to accelerated cellular aging as indexed by telomere length.

Can the inner eye canthus temperature be used as an alternative method to measure core temperature in sleep-deprived individuals?

Core temperature is used in several situations, including studies on biological rhythms and circadian markers of physical performance. Measuring the inner eye canthus (Tco) temperature is a method proposed to identify core temperature, but it has shown little concordance in physical exercise situations and has not yet been used in studies with measurements taken throughout the day. The objective of this study was to compare the measurements and daily behavior of Tco obtained by infrared thermography with rectal temperature (Tre) during a prolonged waking protocol. Eleven male individuals participated in the study, who remained in the laboratory for at least 38 h using an actigraph to determine the wakefulness time and were monitored during the entire period. The Tre and Tco measurements were performed every 3 h. The ANOVA was used for repeated measurements followed by Bonferroni's post-hoc test to find the limits of concordance/proximity, while the Bland and Altman method and the Intraclass Correlation Coefficient were used to establish the reliability between the pairs. The significance level adopted was p < 0.05. The results demonstrate significant differences, low levels of concordance and unsatisfactory reliability levels between Tco and Tre at all 13 analyzed moments, in addition to not showing measurement reliability when all data are used together with the 143 temperature measurements. Daily behavior analysis shows moments with similar behavior with an increase in Tco and Tre, but at other times the behavior was the opposite, with a decrease in one measurement and an increase in the other. Based on the results presented, it is not recommended to use the inner eye canthus temperature as a substitute for rectal temperature for measuring core temperature at different times of the day or in sleep-deprived individuals.

Influence of cortisol awakening response on telomere length: Trends for males and females.

Although telomere attrition is associated with the process of normal ageing, shorter telomere length (TL) has been associated with acute and chronic stressors. A neurobiological factor hypothesised to be responsible for this accelerated attrition is the dysregulation of the cortisol stress response, which can induce DNA damage affecting DNA telomeric caps. Marked sex differences are reported in both the cortisol stress response and telomere dynamics, yet no explicit investigation of sex specificity on the relationship between cortisol and TL exists. This study used mathematical equation modelling to describe the relationship between diurnal cortisol levels and telomere length within the context of sex, in a healthy population. Cortisol awakening responses (CAR) were measured via ELISA methodology in fifty-one healthy participants (28 males, 23 females). qPCRs determined TL from genomic DNA extracted from saliva. To assess the effect of free cortisol on relative TL ratio, a semi-log regression plot of the two variables trended for sex were fitted using spline curves. Results demonstrated significant differences between males and females in the relationship defining CAR and TL association (p = 0.03). These results suggest the relationship is not linear and can be represented as a complex arcsin function, and that the patterns are opposite in males and females. Males demonstrate a positive correlation, with higher levels of CAR being associated with longer telomere sequences. Females demonstrated a negative correlation. Future studies must carefully take into consideration moderating factors such as sex, and sex hormones across the lifespan when investigating telomere length.

Neural stem cell niche heterogeneity.

In mammals, new neurons can be generated from neural stem cells in specific regions of the adult brain. Neural stem cells are characterized by their abilities to differentiate into all neural lineages and to self-renew. The specific microenvironments regulating neural stem cells, commonly referred to as neurogenic niches, comprise multiple cell populations whose precise contributions are under active current exploration. Understanding the cross-talk between neural stem cells and their niche components is essential for the development of therapies against neurological disorders in which neural stem cells function is altered. In this review, we describe and discuss recent studies that identified novel components in the neural stem cell niche. These discoveries bring new concepts to the field. Here, we evaluate these recent advances that change our understanding of the neural stem cell niche heterogeneity and its influence on neural stem cell function.

Cognitive impairment in the HTLV-1 infection: a comparative study associated with functional performance.

Human T cell leukemia virus type-I (HTLV-1) infection courses with a myelopathy, the tropical spastic paraparesis (HAM/TSP). In a case-control study, we compared the neuropsychological profile and functional characteristics in two case HTLV-1-infected groups (asymptomatic and with HAM/TSP) with a control group negative for HTLV-1. Subjects were paired for age, sex, and educational features. The case group differed from control group in neuropsychological measures such as in episodic memory recall, executive functions, and fine motor dexterity measure. Individuals with HAM/TSP have more depressive symptoms and worst performance in activities of daily living (ADL) presenting a less functionality. In multivariate models, the fine motor performance, the executive functioning, the recognition memory, and the depressive symptoms explained part of the variance in functionality. Those findings may contribute to understand of everyday life impairments and limitations of HTLV-1-infected population and to organize the rehabilitation. Once more, based in neuropsychological and functional data, we can reaffirm that HTLV-1 is never a benign condition, but sometimes it is only in a stage coursing with less symptoms.

Nonlinear and vibrational microscopy for label-free characterization of amyloid-ß plaques in Alzheimer's disease model.

Given the long subclinical stage of Alzheimer's disease (AD), the study of biomarkers is relevant both for early diagnosis and the fundamental understanding of the pathophysiology of AD. Biomarkers provided by Amyloid-ß (Aß) plaques have led to an increasing interest in characterizing this hallmark of AD due to its promising potential. In this work, we characterize Aß plaques by label-free multimodal imaging: we combine two-photon excitation autofluorescence (TPEA), second harmonic generation (SHG), spontaneous Raman scattering (SpRS), coherent anti-Stokes Raman scattering (CARS), and stimulated Raman scattering (SRS) to describe and compare high-resolution images of Aß plaques in brain tissues of an AD mouse model. Comparing single-laser techniques images, we discuss the origin of the SHG, which can be used to locate the plaque core reliably. We study both the core and the halo with vibrational microscopy and compare SpRS and SRS microscopies for different frequencies. We also combine SpRS spectroscopy with SRS microscopy and present two core biomarkers unexplored with SRS microscopy: phenylalanine and amide B. We provide high-resolution SRS images with the spatial distribution of these biomarkers in the plaque and compared them with images of the amide I distribution. The obtained spatial correlation corroborates the feasibility of these biomarkers in the study of Aß plaques. Furthermore, since amide B enables rapid imaging, we discuss its potential as a novel fingerprint for diagnostic applications.

Micro-Raman spectroscopy of lipid halo and dense-core amyloid plaques: aging process characterization in the Alzheimer's disease APPswePS1ΔE9 mouse model.

The deposition of amyloid plaques is considered one of the main microscopic features of Alzheimer's disease (AD). Since plaque formation can precede extensive neurodegeneration and it is the main clinical manifestation of AD, it constitutes a relevant target for new treatment and diagnostic approaches. Micro-Raman spectroscopy, a label-free technique, is an accurate method for amyloid plaque identification and characterization. Here, we present a high spatial resolution micro-Raman hyperspectral study in transgenic APPswePS1ΔE9 mouse brains, showing details of AD tissue biochemical and histological changes without staining. First we used stimulated micro-Raman scattering to identify the lipid-rich halo surrounding the amyloid plaque, and then proceeded with spontaneous (conventional) micro-Raman spectral mapping, which shows a cholesterol and sphingomyelin lipid-rich halo structure around dense-core amyloid plaques. The detailed images of this lipid halo relate morphologically well with dystrophic neurites surrounding plaques. Principal Component Analysis (PCA) of the micro-Raman hyperspectral data indicates the feasibility of the optical biomarkers of AD progression with the potential for discriminating transgenic groups of young adult mice (6-month-old) from older ones (12-month-old). Frequency-specific PCA suggests that plaque-related neurodegeneration is the predominant change captured by Raman spectroscopy, and the main differences are highlighted by vibrational modes associated with cholesterol located majorly in the lipid halo.

Optogenetic Stimulation of the M2 Cortex Reverts Motor Dysfunction in a Mouse Model of Parkinson's Disease.

Neuromodulation of deep brain structures (deep brain stimulation) is the current surgical procedure for treatment of Parkinson's disease (PD). Less studied is the stimulation of cortical motor areas to treat PD symptoms, although also known to alleviate motor disturbances in PD. We were able to show that optogenetic activation of secondary (M2) motor cortex improves motor functions in dopamine-depleted male mice. The stimulated M2 cortex harbors glutamatergic pyramidal neurons that project to subcortical structures, critically involved in motor control, and makes synaptic contacts with dopaminergic neurons. Strikingly, optogenetic activation of M2 neurons or axons into the dorsomedial striatum increases striatal levels of dopamine and evokes locomotor activity. We found that dopamine neurotransmission sensitizes the locomotor behavior elicited by activation of M2 neurons. Furthermore, combination of intranigral infusion of glutamatergic antagonists and circuit specific optogenetic stimulation revealed that behavioral response depended on the activity of M2 neurons projecting to SNc. Interestingly, repeated M2 stimulation combined with l-DOPA treatment produced an unanticipated improvement in working memory performance, which was absent in control mice under l-DOPA treatment only. Therefore, the M2-basal ganglia circuit is critical for the assembly of the motor and cognitive function, and this study demonstrates a therapeutic mechanism for cortical stimulation in PD that involves recruitment of long-range glutamatergic projection neurons.SIGNIFICANCE STATEMENT Some patients with Parkinson's disease are offered treatment through surgery, which consists of delivering electrical current to regions deep within the brain. This study shows that stimulation of an area located on the brain surface, known as the secondary motor cortex, can also reverse movement disorders in mice. Authors have used a brain stimulation technique called optogenetics, which allowed targeting a specific type of surface neuron that communicates with the deep part of the brain involved in movement control. The study also shows that a combination of this stimulation with drug treatment might be useful to treat memory impairment, a kind of cognitive problem in Parkinson's disease.

Pericytes Act as Key Players in Spinal Cord Injury.

Spinal cord injury results in locomotor impairment attributable to the formation of an inhibitory fibrous scar, which prevents axonal regeneration after trauma. The scarcity of knowledge about the molecular and cellular mechanisms involved in scar formation after spinal cord lesion impede the design of effective therapies. Recent studies, by using state-of-the-art technologies, including genetic tracking and blockage of pericytes in combination with optogenetics, reveal that pericyte blockage facilitates axonal regeneration and neuronal integration into the local neural circuitry. Strikingly, a pericyte subset is essential during scarring after spinal cord injury, and its arrest results in motor performance improvement. The arising knowledge from current research will contribute to novel approaches to develop therapies for spinal cord injury. We review novel advances in our understanding of pericyte biology in the spinal cord.

A fingerprint of amyloid plaques in a bitransgenic animal model of Alzheimer's disease obtained by statistical unmixing analysis of hyperspectral Raman data.

The global prevalence of Alzheimer's disease (AD) points to endemic levels, especially considering the increase of average life expectancy worldwide. AD diagnosis based on early biomarkers and better knowledge of related pathophysiology are both crucial in the search for medical interventions that are able to modify AD progression. In this study we used unsupervised spectral unmixing statistical techniques to identify the vibrational spectral signature of amyloid ß aggregation in neural tissues, as early biomarkers of AD in an animal model. We analyzed spectral images composed of a total of 55 051 Raman spectra obtained from the frontal cortex and hippocampus of five bitransgenic APPswePS1ΔE9 mice, and colocalized amyloid ß plaques by other fluorescence techniques. The Raman signatures provided a multifrequency fingerprint consistent with the results of synthesized amyloid ß fibrils. The fingerprint obtained from unmixed analysis in neural tissues is shown to provide a detailed image of amyloid plaques in the brain, with the potential to be used as biomarkers for non-invasive early diagnosis and pathophysiology studies in AD on the retina.

Protein synthesis is associated with high-speed dynamics and broad-band stability of functional hubs in the brain.

L-[1-11C]leucine PET can be used to measure in vivo protein synthesis in the brain. However, the relationship between regional protein synthesis and on-going neural dynamics is unclear. We use a graph theoretical approach to examine the relationship between cerebral protein synthesis (rCPS) and both static and dynamical measures of functional connectivity (measured using resting state functional MRI, R-fMRI). Our graph theoretical analysis demonstrates a significant positive relationship between protein turnover and static measures of functional connectivity. We compared these results to simple measures of metabolism in the cortex using [18F]FDG PET). Whilst some relationships between [18F]FDG binding and graph theoretical measures was present, there remained a significant relationship between protein turnover and graph theoretical measures, which were more robustly explained by L-[1-11C]Leucine than [18F]FDG PET. This relationship was stronger in dynamics at a faster temporal resolution relative to dynamics measured over a longer epoch. Using a Dynamic connectivity approach, we also demonstrate that broad-band dynamic measures of Functional Connectivity (FC), are inversely correlated with protein turnover, suggesting greater stability of FC in highly interconnected hub regions is supported by protein synthesis. Overall, we demonstrate that cerebral protein synthesis has a strong relationship independent of tissue metabolism to neural dynamics at the macroscopic scale.

Loss of a neural AMP-activated kinase mimics the effects of elevated serotonin on fat, movement, and hormonal secretions.

AMP-activated protein kinase (AMPK) is an evolutionarily conserved master regulator of metabolism and a therapeutic target in type 2 diabetes. As an energy sensor, AMPK activity is responsive to both metabolic inputs, for instance the ratio of AMP to ATP, and numerous hormonal cues. As in mammals, each of two genes, aak-1 and aak-2, encode for the catalytic subunit of AMPK in C. elegans. Here we show that in C. elegans loss of aak-2 mimics the effects of elevated serotonin signaling on fat reduction, slowed movement, and promoting exit from dauer arrest. Reconstitution of aak-2 in only the nervous system restored wild type fat levels and movement rate to aak-2 mutants and reconstitution in only the ASI neurons was sufficient to significantly restore dauer maintenance to the mutant animals. As in elevated serotonin signaling, inactivation of AAK-2 in the ASI neurons caused enhanced secretion of dense core vesicles from these neurons. The ASI neurons are the site of production of the DAF-7 TGF-ß ligand and the DAF-28 insulin, both of which are secreted by dense core vesicles and play critical roles in whether animals stay in dauer or undergo reproductive development. These findings show that elevated levels of serotonin promote enhanced secretions of systemic regulators of pro-growth and differentiation pathways through inactivation of AAK-2. As such, AMPK is not only a recipient of hormonal signals but can also be an upstream regulator. Our data suggest that some of the physiological phenotypes previously attributed to peripheral AAK-2 activity on metabolic targets may instead be due to the role of this kinase in neural serotonin signaling.

The In Vitro and In Vivo Antiangiogenic Effects of Flavokawain B.

Angiogenesis is implicated in the development of a variety of pathological processes, most commonly cancer. It is essential for tumor growth and metastasis, making it an important cancer therapeutic target. Naturally occurring substances have led to the discovery of anticancer agents. Flavokawain B (FKB), a chalcone isolated from the root extracts of kava-kava plant, inhibits proliferation and causes apoptosis in vitro and in vivo of various cancer cell lines. The antimetastatic potential of FKB has also been suggested. In our study, we confirm the antiangiogenic action of FKB in vitro and, for the first time, demonstrate its strong antiangiogenic activity in vivo, using a zebrafish model. Our data show that FKB inhibits human brain endothelial cell (HUVEC) migration and tube formation even at very low and non-toxic concentrations. Moreover, FKB blocks angiogenesis process in zebrafish, with a dramatic reduction of subintestinal vein formation in a dose-dependent manner. Flavokawain B at the concentration of 2.5 µg/mL did not exhibit any toxic effects in zebrafish larvae and caused a markedly or complete obliteration of subintestinal vein formation. Our findings along with previously published data confirm that FKB may form the basis for creating an additional tool in the treatment of cancer and other neovascularization-related diseases. Copyright © 2017 John Wiley & Sons, Ltd.

Association between DCHS2 gene and mild cognitive impairment and Alzheimer's disease in an elderly Brazilian sample.

OBJECTIVES: In 2012, Kamboh and colleagues published a genome-wide association study that identified the DCHS2 gene (rs1466662 T/A) influencing the age at onset of Alzheimer's disease (AD). We aimed to investigate if there is association between the DCHS2 gene and amnestic mild cognitive impairment (aMCI) and AD in a sample of the Brazilian population. METHODS: 143 controls, 79 aMCI and 299 AD patients were selected and submitted to the same protocol of tests. Genotyping was performed using the Real Time PCR RESULTS: Amnestic MCI patients showed a higher prevalence of AA than controls and a lower frequency of TT when compared with controls. We also stratified the sample according to the APOE ε4 status. No difference in DCHS2 genotype or allelic frequency occurred in the APOE ε4 allele carrier subgroup. Amnestic MCI patients showed a higher frequency of AA genotype and a lower frequency of TA and TT when compared with controls in APOE ε4 allele non-carrier subgroup. The allelic distribution followed the same pattern. In AD group, we observed a significant difference with a higher A allelic frequency in AD in this subgroup. A multiple logistic regression demonstrated that in APOE ε4 non-carriers, allele rs1466662 was associated to aMCI group. Different variables were associated with aMCI and AD according to APOE ε4 status in our sample. Low level of education was associated with AD, while diabetes mellitus type 2 was associated with aMCI. Copyright © 2016 John Wiley & Sons, Ltd. CONCLUSIONS: Our findings suggest a possible role for DCHS2 gene in aMCI and AD.

The GAB2 and BDNF polymorphisms and the risk for late-onset Alzheimer's disease in an elderly Brazilian sample.

BACKGROUND: Evidences suggest that GAB2 and BDNF genes may be associated with Alzheimer's disease (AD). We aimed to investigate the GAB2 rs2373115 and BDNF rs6265 polymorphisms and the risk of AD in a Brazilian sample. METHODS: 269 AD patients and 114 controls were genotyped with Real-time PCR. Multifactor dimensionality reduction (MDR) was employed to explore the effects of gene-gene interactions. RESULTS: GAB2 and BDNF were not associated with AD in our sample. Nevertheless BDNF Val allele (rs6265) presented a synergic association with the APOE ε4 allele. A multiple logistic regression demonstrated that the APOE ε4 allele and years of education were the best predictors for AD. In ε4 non-carriers sex, education and hypertension were independently correlated with AD, while in ε4 carriers we did not observe any association. The findings were further confirmed by bootstrapping method. CONCLUSIONS: Our data suggest that the interaction of BDNF and APOE has significant effect on AD. Moreover in absence of ε4, female sex, low level of education and hypertension are independently associated with AD. Interventions aimed to prevent AD should focus on these factors and also taking into account the APOE alleles.

Evaluation of NCS-1, DARPP-32, and neurotrophins in hippocampus and prefrontal cortex in rats submitted to sepsis.

Sepsis is defined as the host's reaction to infection and it is characterized by a systemic inflammatory response with important clinical implications. Central nervous system dysfunction secondary to sepsis is associated with local generation of pro- and anti-inflammatory cytokines, impaired cerebral microcirculation, disturbance of neurotransmitters, apoptosis, and cognitive impairment. It is known that during the process of learning and memory formation several pathways are involved such as dopaminergic and cholinergic systems. Thus, the objective of this study is to evaluate the neuronal calcium sensor (NCS-1) and dopamine-cAMP regulated phosphoprotein of 32,000 kDa (DARPP-32) expression as well as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) levels in prefrontal cortex and hippocampus of rats 12, 24, and 48 h after sepsis induction. To this aim, we used sham-operated Wistar rats or submitted to the cecal ligation and perforation procedure. After 12 and 24 h, there was an increase of NGF levels in hippocampus; and up to 48 h, a decrease of NCS-1 expression in prefrontal cortex, a decrease of BDNF levels in hippocampus and an increase of NGF levels in hippocampus. In conclusion, we believe that the low expression of NCS-1 in prefrontal cortex and low levels of BDNF in hippocampus may be associated with the pathophysiology of cognitive impairment during sepsis and a putative role of the dopaminergic system.

Increased frequency of cluster of differentiation 14 (CD14+) monocytes expressing interleukin 1 beta (IL-1ß) in Alzheimer's disease patients and intermediate levels in late-onset depression patients.

OBJECTIVE: Depression might be a prodromal stage of dementia. Many factors contribute to the etiology of depression and dementia, being inflammation one of those. The present work measured and analyzed immune molecules involved in the innate immunity on cluster of differentiation 14 (CD14+) monocytes trying to investigate any relationship among late-onset depression (LOD) and Alzheimer's disease (AD). METHODS: Immune molecules were evaluated in monocytes of AD, LOD patients, and controls using flow cytometry. RESULTS: Interestingly, interleukin 1 beta (IL-1ß) expressing CD14+ monocytes were increased in AD patients compared with controls. LOD presented intermediate frequency of CD14+ monocytes expressing IL-1ß between controls and AD patients. CONCLUSION: Results suggest that an increased frequency of CD14+ monocytes expressing IL-1ß level could be a stage marker related to the pathophysiology of dementia process between normal aging and AD.