Markers Of Alzheimer Research Articles

Longitudinal changes in brain oxygen extraction fraction (OEF) in older adults: Relationship to markers of vascular and Alzheimer's pathology.

Oxygen extraction fraction (OEF) reflects the balance between oxygen delivery and consumption. We longitudinally measured OEF in older adults to examine the relationship with markers of Alzheimer's disease (AD) and vascular pathology. One hundred thirty-seven participants were studied at two time-points at an interval of 2.16 years. OEF was measured using T2 -relaxation-under-spin-tagging (TRUST) magnetic resonance imaging (MRI). The association between OEF and vascular risks, white matter hyperintensities (WMH), cerebrospinal fluid (CSF) measures of amyloid beta (Aβ), total tau (t-tau), and phosphorylated tau 181 (p-tau181) was examined. OEF increased from baseline to follow-up. The increase in OEF was more prominent in individuals with high vascular risks compared to those with low vascular risks, and was associated with progression of vascular risks and the growth in WMH volume. OEF change was not related to CSF markers of AD pathology or their progression. Longitudinal OEF change in older adults is primarily related to vascular pathology.

Altered visual entrainment in patients with Alzheimer's disease: magnetoencephalography evidence.

Recent research has indicated that rhythmic visual entrainment may be useful in clearing pathological protein deposits in the central nervous system of mouse models of Alzheimer’s disease. However, visual entrainment studies in human patients with Alzheimer’s disease are rare, and as such the degree to which these patients exhibit aberrations in the neural tracking of rhythmic visual stimuli is unknown. To fill this gap, we recorded magnetoencephalography during a 15 Hz visual entrainment paradigm in amyloid-positive patients on the Alzheimer’s disease spectrum and compared their neural responses to a demographically matched group of biomarker-negative healthy controls. Magnetoencephalography data were imaged using a beamformer and virtual sensor data were extracted from the peak visual entrainment responses. Our results indicated that, relative to healthy controls, participants on the Alzheimer’s disease spectrum exhibited significantly stronger 15 Hz entrainment in primary visual cortices relative to a pre-stimulus baseline period. However, the two groups exhibited comparable absolute levels of neural entrainment, and higher absolute levels of entertainment predicted greater Mini-mental Status Examination scores, such that those patients whose absolute entrainment amplitude was closer to the level seen in controls had better cognitive function. In addition, 15 Hz periodic activity, but not aperiodic activity, during the pre-stimulus baseline period was significantly decreased in patients on the Alzheimer’s disease spectrum. This pattern of results indicates that patients on the Alzheimer’s disease spectrum exhibited increased visual entrainment to rhythmic stimuli and that this increase is likely compensatory in nature. More broadly, these results show that visual entrainment is altered in patients with Alzheimer’s disease and should be further examined in future studies, as changes in the capacity to entrain visual stimuli may prove useful as a marker of Alzheimer’s disease progression.

Cholesterol and obesity: A marker for Alzheimer’s disease

Cholesterol and obesity: A marker for Alzheimer’s disease

Deficits in spontaneous and stimulus-dependent retrieval as an early sign of abnormal aging

Research on early cognitive markers of Alzheimer’s disease is primarily focused on episodic memory tests that involve deliberate retrieval. Our purpose was to provide clear evidence to support a novel Spontaneous Retrieval Deficit hypothesis, which predicts that people at pre-clinical stages of dementia, including those with amnestic Mild Cognitive Impairment (aMCI), are particularly impaired on tasks based on spontaneous retrieval. We compared 27 aMCI individuals and 27 healthy controls on mind-wandering while performing a task during which there were exposed to either highly meaningful or unmeaningful pictures. The substantial reduction in mind-wandering among individuals with aMCI was found with exposure to highly meaningful stimuli, but not to unmeaningful pictures, and it was most pronounced for past-oriented thoughts, i.e., involuntary autobiographical memories. Those findings provide strong support for this novel hypothesis, and show that it is the spontaneous, but bottom-up and cue-driven processes, for which meaningful environmental stimuli are crucial, that are very promising early markers of the disease.

Olfactory identification disorders due to Alzheimer's disease: A new test from France to Quebec.

Olfactory identification disorder is regarded as an early marker of Alzheimer’s disease (AD) and of similar diagnostic significance of biological or cognitive markers. Premature damage of the entorhinal olfactory cortex, the hippocampus and the orbitofrontal cortex characterize AD and suggest a specific impairment of olfactory identification. The use of psychophysical olfactory identification tests in clinical diagnostic practice is therefore strongly recommended, but not required. As these widespread tests are rarely used, an innovative test, adapted to this target group has been developed. It has been used and validated in a routine care protocol at different Memory Centers in France and in Quebec, Canada. A total of 157 participants were recruited: including 63 Alzheimer’s patients and 94 healthy controls. The test was composed of 14 odorants diluted into 4 different concentrations. A computer interface generated randomization of 6 odors per participant and the automatic calculation of identification scores, of perceptual thresholds and of composite scores. All participants underwent a Mini Mental Scale Examination within the previous three months or on the same day of the olfactory test. The Alzheimer’s patients had a score between 20 and 30 and healthy controls participants had a score above 28 without any loss of points on recalled items. The results show that our olfactory identification test is able to significantly differentiate Alzheimer’s patients from healthy controls (p < 0.001), and to distinguish the French population tested from the Quebec population (p < 0.001). This study highlights an olfactory identification disorder as a target for early diagnosis of AD. Its cultural qualities make it a potential candidate for differentiated calibration between France and Quebec.

Cerebrospinal fluid tau levels are associated with abnormal neuronal plasticity markers in Alzheimer’s disease

BackgroundIncreased total tau (t-tau) in cerebrospinal fluid (CSF) is a key characteristic of Alzheimer’s disease (AD) and is considered to result from neurodegeneration. T-tau levels, however, can be increased in very early disease stages, when neurodegeneration is limited, and can be normal in advanced disease stages. This suggests that t-tau levels may be driven by other mechanisms as well. Because tau pathophysiology is emerging as treatment target for AD, we aimed to clarify molecular processes associated with CSF t-tau levels.MethodsWe performed a proteomic, genomic, and imaging study in 1380 individuals with AD, in the preclinical, prodromal, and mild dementia stage, and 380 controls from the Alzheimer’s Disease Neuroimaging Initiative and EMIF-AD Multimodality Biomarker Discovery study.ResultsWe found that, relative to controls, AD individuals with increased t-tau had increased CSF concentrations of over 400 proteins enriched for neuronal plasticity processes. In contrast, AD individuals with normal t-tau had decreased levels of these plasticity proteins and showed increased concentrations of proteins indicative of blood–brain barrier and blood-CSF barrier dysfunction, relative to controls. The distinct proteomic profiles were already present in the preclinical AD stage and persisted in prodromal and dementia stages implying that they reflect disease traits rather than disease states. Dysregulated plasticity proteins were associated with SUZ12 and REST signaling, suggesting aberrant gene repression. GWAS analyses contrasting AD individuals with and without increased t-tau highlighted several genes involved in the regulation of gene expression. Targeted analyses of SNP rs9877502 in GMNC, associated with t-tau levels previously, correlated in individuals with AD with CSF concentrations of 591 plasticity associated proteins. The number of APOE-e4 alleles, however, was not associated with the concentration of plasticity related proteins.ConclusionsCSF t-tau levels in AD are associated with altered levels of proteins involved in neuronal plasticity and blood–brain and blood-CSF barrier dysfunction. Future trials may need to stratify on CSF t-tau status, as AD individuals with increased t-tau and normal t-tau are likely to respond differently to treatment, given their opposite CSF proteomic profiles.

Ophthalmological markers of Alzheimer's disease

Alzheimer's disease (AD) is the most common neurodegenerative disease-causing dementia. The severity of symptoms determines the diagnosis of AD, although an accurate diagnosis can only be made postmortem. Neuropsychological testing is the «gold standard» for early diagnosis of AD, but is time-consuming, does not allow a complete diagnosis with complete accuracy, is highly dependent on the correctness of the tests, and is rather an adjunct to the examination of the patient. Lumbar puncture and positron emission tomography are not available for routine screening of the population. Because the eye is an extension of the central nervous system, the study of its changes may lead to the development of a number of non-invasive differential diagnostic tests to identify patients with AD at an early stage. In recent years, the advent of quantifiable high-resolution imaging techniques that are non-invasive, rapid, and widely available has opened up a new field of ocular-neural imaging. In this paper, we review current foreign and domestic studies of some ocular biomarkers and the methods that could potentially be used in the early diagnosis of Alzheimer's disease.

Intermittent hypoxia and sleep disruption in obstructive sleep apnea increase serum tau and amyloid-beta levels.

Obstructive sleep apnea is characterized by intermittent hypoxia and sleep disruption, leading to accelerated neurodegenerative changes and cognitive decline. Serum amyloid-beta and tau proteins, which are markers for Alzheimer's disease, have been reported to increase in patients with obstructive sleep apnea. This study compared the serum levels of amyloid-beta proteins and tau proteins in 46 cognitively normal obstructive sleep apnea patients and 30healthy controls. Sleep parameters and severity of obstructive sleep apnea were determined using overnight polysomnography. Serum levels of Aβ40, Aβ42, total tau and phosphorylated-tau were determined by enzyme-linked immunosorbent assay. Patients with obstructive sleep apnea had significantly higher median serum levels of Aβ40 (121.0 versus 78.3pg ml-1 ), Aβ42 (105.6 versus 18.6pg ml-1 ) and total tau (168.5 versus 10.9pg ml-1 ) than controls. Serum levels of phosphorylated-tau did not differ significantly between the two groups. Serum levels of amyloid and tau proteins correlated with parameters of nocturnal oxygen saturation. Rapid eye movement sleep was negatively correlated with total amyloid-beta proteins. We conclude that serum levels of amyloid-beta and total tau are higher in patients with obstructive sleep apnea and hypoxia as well as changes in sleep architecture associated with their increased levels. Patients with obstructive sleep apnea should be closely monitored for the signs of cognitive impairment. Obstructive sleep apnea is a modifiable risk factor, and its treatment may reverse neurodegenerative changes and prevent cognitive impairment.

Tin oxide nanoparticles trigger the formation of amyloid β oligomers/protofibrils and underlying neurotoxicity as a marker of Alzheimer's diseases

Alzheimer's disease (AD) is known as one of the most common forms of dementia, and oligomerization of amyloid β (Aβ42) peptides can result in the onset of AD. Tin oxide nanoparticles (SnO2 NPs) showed several applications in biomedical fields can trigger unwanted interaction with proteins and inducing protein aggregation. Herein, we synthesized SnO2 NPs via the hydrothermal method and characterized by UV–visible, XRD, FTIR, TEM, and DLS techniques. Afterward, the formation of Aβ42 amyloid oligomers/protofibrils treated alone and with SnO2 NPs was explored by ThT and Nile red fluorescence and CD spectroscopic methods along with TEM imaging. The neurotoxicity of different spices of Aβ42 samples against PC-12 cells was then explored by MTT and caspase-3 activity assays. The characterization of SnO2 NPs confirmed the successful synthesis of crystalline NPs (20–30 nm). Different biophysical and cellular analyses indicated that SnO2 NPs accelerated Aβ42 fibrillogenesis and promoted amyloid oligomers/protofibrils cytotoxicity. As compared to the Aβ42 samples grown alone, the ThT and ANS fluorescence intensity along with ellipticity results indicated the promotory effect of SnO2 NPs on the formation of oligomers/protofibrils. Also, the cellular results showed that the treated Aβ42 samples with SnO2 NPs further reduced cell viability through activation of caspase-3. In conclusion, SnO2 NPs greatly accelerate the fibrillation of Aβ42 peptides and lead to the formation of more toxic species. The present data may offer further warrants into nano-based systems for biomedical applications in the central nervous system.

Markers of Alzheimer’s disease in handwriting

The aim of the research. Alzheimer’s disease is the most common form of dementia. One of the potential tools for early detection of the onset of the disease is the handwriting analysis. It can be a warning signal for a serious medical investigation. The dynamics of handwriting changes are also a good indicator of the progression of the disease and the eff ectiveness of therapy. Methods. The authors have developed two corresponding tests. The fi rst (AD-HS) allows the assessment of handwriting markers of cognitive impairment and Alzheimer’s disease from an available handwriting sample. The second (ADHC) is designed to assess dynamics by comparing two handwritten documents written at diff erent times. Results. The pilot study includes 16 patients who were found to be at diff erent stages of the disease by medical examination. They all provided old handwriting samples dated 10–20 years ago and new handwriting samples specifi cally written as part of the experiment. Evaluation of 36 handwriting characteristics showed that both tests were eff ective in identifying Alzheimer’s disease and its stage. The correlation between the handwriting analysis and the medical test result was 0.62. Conclusion. Further refi nement of the proposed tests and expansion of the research base will enable handwriting exercises to be incorporated into supportive therapy to slow the progression of the disease.

A surrogate marker for very early-stage tau pathology is detectable by molecular magnetic resonance imaging.

The abnormal phosphorylation of tau is a necessary precursor to the formation of tau fibrils, a marker of Alzheimer's disease. We hypothesize that hyperphosphorylative conditions may result in unique cell surface markers. We identify and demonstrate the utility of such surrogate markers to identify the hyperphosphorylative state.Methods: Cell SELEX was used to identify novel thioaptamers specifically binding hyperphosphorylative cells. Cell surface vimentin was identified as a potential binding target of the aptamer. Novel molecular magnetic resonance imaging (M-MRI) probes using these aptamers and a small molecule ligand to vimentin were used for in vivo detection of this pre-pathological state.Results: In a mouse model of pathological tau, we demonstrated in vivo visualization of the hyperphosphorylative state by M-MRI, enabling the identification at a pre-pathological stage of mice that develop frank tau pathology several months later. In vivo visualization of the hyperphosphorylative state by M-MRI was further validated in a second mouse model (APP/PS1) of Alzheimer's disease again identifying the mutants at a pre-pathological stage.Conclusions: M-MRI of the hyperphosphorylative state identifies future tau pathology and could enable extremely early-stage diagnosis of Alzheimer's disease, at a pre-patholgical stage.

Primary progressive aphasias: clinical and genetic heterogeneity and diagnostic difficulties

This systematic review describes primary progressive aphasia (PPA) variants and includes the authors' own clinical observations. Over 20 genes have now been identified, with mutations that are directly involved in the development of the behavioural variant of frontotemporal dementia, as well as other forms of PPA. Pathomorphological markers of Alzheimer's disease were identified in 76% of cases of logopenic PPA, while signs of frontotemporal dementia associated with TDP-43 were identified in 80% of cases of the semantic variant, and those associated with TDP-43/tau were identified in 64% of cases of agrammatic PPA. The clinical diagnosis of PPA is based on a history of long-term, progressive speech disturbances and identifying a particular variant: agrammatic, semantic or logopenic. The primary variant of the speech disorder cannot be identified in approximately 30% of cases. The focus should be on the main and additional clinical signs (presence of agrammatism, object naming, word comprehension, preserved repetition), as well as neuroimaging (presence of asymmetrical frontal and/or temporal lobe atrophy).&#x0D; The article also provides key aspects of differential diagnosis of the PPA variants, and puts forth a stepwise diagnostic algorithm. It examines features of PPA progression, with possible development of corticobasal syndrome, illustrated by a clinical case. A dissociation between neuroimaging findings and clinical disease variant is also demonstrated to be possible. Different neuropsychological assessments of patients with aphasia and methods of determining the severity of speech dysfunction are presented. Standardized aphasia assessment tools and the adapted PPA severity scale are provided.

Networking analysis for neuroimaging and genetic markers in Alzheimer's disease

AbstractBackgroundThis paper examines late‐onset dementia‐related cognitive impairment and neuroimaging‐genetics biomarker association using the Alzheimer’s Disease Neuroimaging Initiative (ADNI) data archive.MethodThe demographics of the 1,026 ADNI 1, ADNI GO and ADNI 2 arms of the ADNI study included participants ages 65 to 85, 266 normal CN’s (CDR=0, Male:138, Female:128), 572 mild cognitively impaired MCI’s (CDR=0.5, Male:227, Female:245), and 188 AD patients (CDR=0.5/1, Male:102, Female:86).The extracted AD‐related imaging and genetic markers were employed in a subsequent network analysis. We used Plink, to model the genetics data, and the Pipeline environment, to develop an end‐to‐end neuroimaging‐genetics data analysis protocol that identified the neuroimaging associations with SNPs and the clinical diagnosis. The expected significant correlations between the SNPs and the neuroimaging phenotypes were confirmed using neuroimaging genetics networking analyses.Genotype dosage data for AD‐associated SNPs were extracted from the imputed ADNI genetics dosage data using sample‐major additive coding. 29 such SNPs were selected (Jansen, et al., 2019) that meet a minor allele frequency threshold (MAF&gt;0.5%).ResultThere were 9 ROIs (7 thicknesses, 1 volume, and 1 gauscurve) which were associated with 6 genomic markers in the level of ‘p&lt;0.001’ in the CN cohort. There were 43 ROIs (31 thicknesses, 11 volume, and 1 pct) which were associated with 5 genomic markers in the level of ‘p&lt;0.001’. There were 10 ROIs (9 thicknesses and 1 volumes) which were associated with 3 genomic markers in the level of ‘p&lt;0.0001 in the MCI cohort. There were 3 ROIs (1 thicknesses, 1 volume, and 1 pct) which were associated with 3 genomic markers in the level of ‘p&lt;0.001’ in the AD cohort. The 29 genes were influencing on the 200 neuroimaging markers with some networking patterns using WGCNA R‐package for the CN, MCI and AD groups, even though we could not find any networking the 29 genes themselves.ConclusionStructural brain changes are important indicators of dementia progression. Network analysis pairing morphometric biomarkers with genetic indicators allows investigation of clinical and phenotypic associations that facilitate deep systematic understanding of genetic and environmental influences on aging and cognitive decline.

Effect of CSF biomarkers on cortical thickness in males and females

AbstractBackgroundThe level of elevated Tau, phosphorylated Tau, and aggregated Amyloid β in the cerebrospinal fluid (CSF) are markers of Alzheimer’s pathology in the brain. In this study, we analyzed how these CSF biomarkers are related to the cortical thickness in males and females, for subjects who are cognitively normal (CN), with mild cognitive impairment (MCI), and diagnosed as Alzheimer’s disease (AD).MethodWe studied the CN (305), MCI (264) and AD (230) subjects from the ADNI dataset at baseline. We first studied the CSF biomarker level differences between males and females in all three groups. The effect of age was controlled using general linear models (GLM) We also looked at the effect of the CSF biomarkers on cortical thickness maps generated separately for males and females for all three groups, also with GLM‐based covariate regression to control the effect of age, ICV, and field strength of the scan.ResultFor the CSF biomarker levels, we observed Tau to be significantly higher in females in the AD group. No other significant sex difference in the biomarker levels were observed. We found MCI males [Figure 1] and AD [Figure 2] females showing a negative relationship between Tau and thickness. When comparing CSF pTau levels to cortical thickness, a negative correlation was found only in males [Figure 3] for the AD group. When comparing Aβ and cortical thickness, negative correlations were found for males in the CN [Figure 4] and AD group [Figure 5], and for females [Figure 6] in the MCI group.ConclusionThe results suggest that the relationship between cortical thickness and CSF biomarkers is different in males and females in CN, MCI, and AD groups. We found that there is a negative relationship between CSF biomarkers and cortical thickness.

Gamma phase synchronization during olfactory stimulation as a marker for Alzheimer’s disease

AbstractBackgroundAltered gamma oscillations have been observed in patients of Alzheimer’s disease (AD). A large number of studies have linked the quality of gamma oscillations in the frontal cortex to the performance of memory retrieval tasks. Synchronization of gamma oscillations has a strong correlation with cognitive functions (Fell et al., Nature Reviews Neuroscience 2011), and deficit in gamma synchronization in the frontal cortex has been reported as a marker for AD (Sedghizadeh et al., PLOS One 2020). In this study, we examine the phase synchronization of gamma oscillations in the EEG data recorded from the frontal cortex during olfactory stimulation as a marker for AD.MethodTwenty‐four elderly participants (13 Normal and 11 mild AD patients) participated in this study. The cognitive status of the participants was quantified using the MMSE test. Then, each participant underwent an olfactory stimulation session consisting of 120 trials of 2s stimuli presentation with a random selection of two odors (lemon as the frequent and rose as the rare odor) followed by 8s of rest. EEG data were simultaneously recorded and pre‐processed for artifact and noise removal and trial averaging. To analyze gamma band synchronization, the phase‐locking value (PLV) for lower gamma oscillations (35‐45Hz) was calculated between the Fz and Cz electrodes. Fig. 1 illustrates the measurement and processing flow.ResultOur study shows that the PLV is significantly higher for normal participants compared to AD patients (Fig. 2). Also, the phase difference between the Fz and Cz electrodes in the lower gamma band remains unchanged across trials for normal participants while it widely varies between ‐180 and 180 degrees for AD patients (Fig. 3).ConclusionThis study shows that there is a significant difference between normal participants and AD patients in terms of the synchronization of gamma oscillations in the frontal cortex in response to olfactory stimulation. These results suggest that the PLV between the Fz and Cz electrodes under olfactory stimulation can be used as a marker for AD diagnosis.

Association of neighborhood-level disadvantage with neurofibrillary tangles.

Neighborhood disadvantage, a social exposome measure reflecting income, education, employment, and housing in a census-block group, is associated with markers of Alzheimer's disease brain health such as brain volume and amyloid plaque presence. Yet it is not known whether this association extends to neurofibrillary degeneration, signaling a stronger link to neuropathology confirmed Alzheimer's disease. A cross sectional analysis was conducted using a sample of decedents from two Alzheimer's Disease Research Center brain banks with known Braak stage and neighborhood disadvantage ranking from 1990-2016 (n=428). Neurofibrillary tangle Braak stage was abstracted from data collected via the Neuropathology Data Set form or autopsy reports for earlier donations. The main exposure was neighborhood-level disadvantage measured by the Area Deprivation Index. Generalized ordered logistic regression with site-level clustered standards errors was used to model the ordinal neurofibrillary B score adjusting for age, sex, rurality, geographic proximity to the Alzheimer center, and year of death. Living in a disadvantaged neighborhood at the time of death was associated with more severe neurofibrillary degeneration: for every decile increase in neighborhood disadvantage, there was a 2% increase in the odds of having a more severe B score (OR=1.02, 95% CI, 1.01-1.03) after adjustment. This 2% increase was proportional when comparing the odds at each increasing level of the neurofibrillary tangle B score-when comparing the odds of B score (1,2,3,) vs (0), B score (2,3) vs (0,1), and B score (3) vs (0,1,2). With these new findings, neighborhood disadvantage has been associated with both of the hallmarks signs of Alzheimer's disease neuropathology. Given that Alzheimer's is a life course problem with neuropathologic changes accumulating over decades, future work should apply a life course approach to understand how lifetime exposure accumulation impacts brain health. Taking such a perspective can move the field closer to uncovering and disrupting the social-to-biological pathways impacting Alzheimer's disease brain health and related disparities.

Self‐reflection is associated with markers of Alzheimer’s disease in cognitively unimpaired older adults

AbstractBackgroundSelf‐reflection is conceptualised as an introspective process that involves active evaluation of one’s thoughts, feelings and behaviours. Engagement in self‐reflection is thought to yield more adaptive stress responses, that in turn result in better short‐term (e.g., reduced inflammatory responses to stressors) and long‐term (e.g., recovery from major depression) outcomes. Despite self‐reflection’s known protective effect against adverse health outcomes, the association between self‐reflection and Alzheimer’s disease (AD) risk is unknown.MethodBaseline data from 134 healthy older adults (mean age=69.3) enrolled in the Age‐Well clinical trial and 125 older adults with subjective cognitive decline (mean age=72.5) from the SCD‐Well clinical trial were included. All participants completed an assessment of self‐reflection. Modified versions of the Preclinical Alzheimer’s Cognitive Composite 5 were used to measure global cognition in both cohorts. Additionally, in Age‐Well, glucose metabolism and amyloid deposition were assessed with PET scans, and the Lifestyle‐for‐Brain‐Health (LIBRA) AD‐risk index computed to assess health and lifestyle behaviours. Separate linear regressions were run to determine associations between self‐reflection levels and AD markers (i.e., global cognition, glucose metabolism, and amyloid deposition). Analyses adjusted for available prognostic characteristics associated with AD (e.g., age, sex, education and APOE4 status) and levels of psychological distress (i.e., depression and rumination). Furthermore, to explore the potential mechanism linking self‐reflection with AD markers, the relationship between self‐reflection and LIBRA scores was investigated.ResultSelf‐reflection was positively associated with global cognition in both cohorts (Age‐Well: β=0.18, p=0.023; SCD‐Well: β=0.20, p=0.024) and glucose metabolism (Age‐Well: β=0.29, p=0.027; see Figure). No relationship, however, was found with amyloid deposition (Age‐Well: β=0.13, p=0.198). Self‐reflection was associated with LIBRA scores (Age‐Well: β=‐0.31, p=0.002), with lower self‐reflection levels associated with poorer health and lifestyle behaviours.ConclusionSelf‐reflection was associated with higher glucose metabolism, and with better global cognition in two independent older adult cohorts. For the first time, we introduce preliminary support for self‐reflection as a potential protective factor against AD‐related decline. Furthermore, the results suggest that self‐reflection may affect AD risk by influencing health and lifestyle behaviours. Both Age‐Well and SCD‐Well are clinical trials. Future work will investigate whether modifying self‐reflection via interventions affects AD markers.

Visit-to-visit blood pressure variability in mild cognitive impairment: A possible marker of Alzheimer's disease in the SPRINT study?

Visit-to-visit blood pressure variability in mild cognitive impairment: A possible marker of Alzheimer's disease in the SPRINT study?

Salivary Uric Acid: A Noninvasive Wonder for Clinicians?

This review is a summary of the modern-day approach and recent trend in the determination of uric acid in the saliva of humans and its use in diagnosis by clinicians. Uric acid, which is the end product obtained from the breakdown of purine nucleotides, is an important biomarker associated with various conditions. Uric acid is found in various body fluids, such as serum, plasma, and urine. It can be used as an important tool for various diseases, such as gout and hyperuricemia, or conditions that are associated with increased oxidative stress. Recently, there has been an emergence of studies that have utilized uric acid concentrations measured in the saliva and studied its association with various diseases. Salivary uric acid can prove to be a noninvasive method to provide a diagnosis of serious illness. A raised uric acid level in the saliva can be associated with cancer, human immunodeficiency virus (HIV) infection, gout, and hypertension. A reduced level of salivary uric acid on the other hand can be a marker for Alzheimer’s disease, progression of multiple sclerosis, and impairment of cognition.Online search databases, including Google Scholar, Scopus, PubMed, and Web of Science, were searched, and articles that were published before September 2021 based on salivary uric acid analysis were analyzed for this review.Uric acid is an essential biomarker that has antioxidant properties. Assessment of salivary uric acid levels was found to be essential in conditions such as cancer, metabolic syndrome, neurological conditions, psychiatric conditions, human immunodeficiency virus, and gout and in monitoring treatment of hyperuricemia.Although having importance in diagnosis and therapeutic monitoring, salivary uric acid analysis has not gained enough popularity due to limitations such as saliva collection and sample processing issues. With proper education and standardization, salivary uric acid analysis can be used as a cost-effective and noninvasive tool for getting a clue about antioxidant biomarker concentration in saliva and hence various diseases associated with oxidative stress.

Plasma phosphorylated-tau181 as a predictive biomarker for Alzheimer\u2019s amyloid, tau and FDG PET status

Plasma phosphorylated-tau181 (p-tau181) showed the potential for Alzheimer’s diagnosis and prognosis, but its role in detecting cerebral pathologies is unclear. We aimed to evaluate whether it could serve as a marker for Alzheimer’s pathology in the brain. A total of 1189 participants with plasma p-tau181 and PET data of amyloid, tau or FDG PET were included from ADNI. Cross-sectional relationships of plasma p-tau181 with PET biomarkers were tested. Longitudinally, we further investigated whether different p-tau181 levels at baseline predicted different progression of Alzheimer’s pathological changes in the brain. We found plasma p-tau181 significantly correlated with brain amyloid (Spearman ρ = 0.45, P < 0.0001), tau (0.25, P = 0.0003), and FDG PET uptakes (−0.37, P < 0.0001), and increased along the Alzheimer’s continuum. Individually, plasma p-tau181 could detect abnormal amyloid, tau pathologies and hypometabolism in the brain, similar with or even better than clinical indicators. The diagnostic accuracy of plasma p-tau181 elevated significantly when combined with clinical information (AUC = 0.814 for amyloid PET, 0.773 for tau PET, and 0.708 for FDG PET). Relationships of plasma p-tau181 with brain pathologies were partly or entirely mediated by the corresponding CSF biomarkers. Besides, individuals with abnormal plasma p-tau181 level (>18.85 pg/ml) at baseline had a higher risk of pathological progression in brain amyloid (HR: 2.32, 95%CI 1.32–4.08) and FDG PET (3.21, 95%CI 2.06–5.01) status. Plasma p-tau181 may be a sensitive screening test for detecting brain pathologies, and serve as a predictive biomarker for Alzheimer’s pathophysiology.