stilbenes and Cognitive-Dysfunction

Resveratrol is a natural phytoestrogen with neuroprotective properties. Polyphenolic compounds including resveratrol exert in vitro antioxidant, anti-inflammatory, and antiamyloid effects. Resveratrol and its derivative pterostilbene are able to cross the blood-brain barrier and to influence brain activity. The present short review summarizes the available evidence regarding the effects of these polyphenols on pathology and cognition in animal models and human subjects with dementia. Numerous investigations in cellular and mammalian models have associated resveratrol and pterostilbene with protection against dementia syndromes such as Alzheimer's disease (AD) and vascular dementia. The neuroprotective activity of resveratrol and pterostilbene demonstrated in in vitro and in vivo studies suggests a promising role for these compounds in the prevention and treatment of dementia. In comparison to resveratrol, pterostilbene appears to be more effective in combatting brain changes associated with aging. This may be attributed to the more lipophilic nature of pterostilbene with its two methoxyl groups compared with the two hydroxyl groups of resveratrol. The findings of available intervention trials of resveratrol in individuals with mild cognitive impairment or AD do not provide evidence of neuroprotective or therapeutic effects. Future clinical trials should be conducted with long-term exposure to preparations of resveratrol and pterostilbene with high bioavailability. © 2017 BioFactors, 44(1):83-90, 2018.

Topics: Alzheimer Disease; Animals; Antioxidants; Biological Transport; Blood-Brain Barrier; Brain; Clinical Trials as Topic; Cognitive Dysfunction; Dementia; Disease Models, Animal; Humans; Maze Learning; Neuroprotective Agents; Resveratrol; Stilbenes

Cognitive decline is among the most devastating age-related conditions and is rapidly becoming an important cause of disease burdens worldwide. New strategies for the prevention and management of cognitive decline are needed. Resveratrol, a polyphenolic compound, has been found to enhance brain health through multiple signaling pathways. Optimal SIRT1 activation is the most crucial step in the neuroprotection provided by resveratrol against cognitive impairment. This review discusses several recent developments in our understanding of the mechanisms by which resveratrol delay age-related cognitive decline through SIRT1. The regulatory mechanisms include anti-oxidative, anti-inflammatory, anti-apoptotic processes and autophagy regulation, as well as increases in cerebral blood flow and improvements in the plasticity of synaptic pathways. Resveratrol, as well as novel SIRT1 activators, is likely to provide promising therapeutic strategies for impeding cognitive decline, repairing brain functions, and supporting healthy aging.

Topics: Animals; Apoptosis; Autophagy; Cognition; Cognitive Dysfunction; Humans; Resveratrol; Sirtuin 1; Stilbenes

Mild cognitive impairment is characterized by a decline in cognitive performance without interference with activities of daily living. The amnestic subtype of mild cognitive impairment progresses to Alzheimer's disease at a rate of 10-15% per year and in the majority the neuropathology is intermediate between the neuropathological changes of typical ageing and Alzheimer's disease. Amyloid deposition occurs over a decade before the development of noticeable cognitive symptoms in a continuous process that starts in healthy elderly individuals. Newly developed PET amyloid imaging agents provide noninvasive biomarkers for the early in vivo detection of Alzheimer's pathology in healthy elderly individuals and those with mild cognitive impairment. Exclusion of amyloid pathology should allow a more accurate prognosis to be given and ensure appropriate recruitment into clinical trials testing the efficacy of new putative antiamyloid agents at an earlier disease stage. The development of (18)F-labelled amyloid imaging agents has increased the availability of this new technology for clinical and research use since they can be used in PET centres where a cyclotron and radiochemistry are not available. This review discusses the role of PET imaging for assessing the amyloid load in cognitively normal elderly subjects and subjects with mild cognitive impairment at risk of conversion to Alzheimer's disease.

Topics: Alzheimer Disease; Amyloid; Amyloid beta-Peptides; Aniline Compounds; Cognitive Dysfunction; Humans; Plaque, Amyloid; Positron-Emission Tomography; Prognosis; Radiopharmaceuticals; Stilbenes; Thiazoles

Based on the possibility that early-phase florbetaben (E-FBB) brain PET can be a surrogate for brain perfusion imaging, we conducted this study to investigate the clinical utility of E-FBB PET instead of F-FDG brain PET.. This prospective study included 35 patients with clinical suspicion of cognitive decline or dementia and 5 healthy controls. Brain MRI, E-FBB PET, late-phase FBB PET, and FDG PET were acquired. The regional SUV ratios (SUVRs) were calculated by cortical surface region of interest analysis using individual MRI, and relationship between E-FBB and FDG PET was analyzed. All PET scans were scored and analyzed as per visual scoring system, which represent tracer uptake abnormality. Moreover, uptake patterns were analyzed to determine the disease.. Among the 40 subjects, 19 were amyloid-positive and 21 were amyloid-negative on late-phase FBB PET. Cortical surface region of interest analysis conducted for comparing between E-FBB and FDG PET revealed significant correlations (P < 0.0001) for regional SUVR among all brain regions; however, the SUVR values of FDG PET were statistically higher than those of E-FBB PET. Similarly, although the visually rated scores for E-FBB and FDG PET showed significant correlation (P < 0.0001), it was considered that the tracer uptake was more severely decreased for FDG PET. The disease types, specified by E-FBB and FDG PET, were statistically correlated.. E-FBB PET could potentially be a useful biomarker for the diagnosis of dementia in place of FDG PET. Nevertheless, the severity of the disease was more accurately determined by FDG PET.

Topics: Aged; Amyloid; Aniline Compounds; Brain; Case-Control Studies; Cognitive Dysfunction; Dementia; Female; Fluorodeoxyglucose F18; Humans; Male; Neuroimaging; Positron-Emission Tomography; Prospective Studies; Stilbenes; Time Factors

Long-term longitudinal studies with multimodal biomarkers are needed to delve into the knowledge of preclinical AD. Subjective cognitive decline has been proposed as a risk factor for the development of cognitive impairment. Thus, including individuals with SCD in observational studies may be a cost-effective strategy to increase the prevalence of preclinical AD in the sample.. To describe the rationale, research protocols and baseline characteristics of participants in the Fundació ACE Healthy Brain Initiative (FACEHBI).. FACEHBI is a clinical trial (EudraCT: 2014-000798-38) embedded within a long-term observational study of individuals with SCD.. Participants have been recruited at the memory clinic of Fundació ACE (Barcelona) from two different sources: patients referred by a general practitioner and individuals from an Open House Initiative.. 200 individuals diagnosed with SCD with a strictly normal performance in a comprehensive neuropsychological battery.. Individuals will undergo an extensive neuropsychological protocol, risk factor assessment and a set of multimodal biomarkers including florbetaben PET, structural and functional MRI, diffusion tensor imaging, determination of amyloid species in plasma and neurophthalmologic assessment with optical coherence tomography.. Two hundred individuals have been recruited in 15 months. Mean age was 65.9 years; mean MMSE was 29.2 with a mean of 14.8 years of education.. FACEHBI is a long-term study of cognition, biomarkers and lifestyle that has been designed upon an innovative symptom-based approach using SCD as target population. It will shed light on the pathophysiology of preclinical AD and the role of SCD as a risk marker for the development of cognitive impairment.

Topics: Aged; Amyloid; Aniline Compounds; Biomarkers; Brain; Cognition; Cognitive Dysfunction; Diagnostic Self Evaluation; Humans; Life Style; Longitudinal Studies; Magnetic Resonance Imaging; Neuropsychological Tests; Positron-Emission Tomography; Radiopharmaceuticals; Research Design; Risk Factors; Stilbenes; Tomography, Optical Coherence

We assessed the clinical utility of β-amyloid (Aβ) imaging with (18)F-florbetaben (FBB) in mild cognitive impairment (MCI) by evaluating its prognostic accuracy for progression to Alzheimer's disease (AD), comparing semiquantitative with visual scan assessment, and exploring the relationships among Aβ, hippocampal volume (HV) and memory over time.. 45 MCI underwent FBB positron emission tomography, MRI and neuropsychological assessment at baseline and 2 years and clinical follow-up at 4 years. Positive FBB (FBB+), defined by a cortical to cerebellar cortex standardised uptake value ratio (SUVR) ≥ 1.45, was compared with visual assessment by five readers. Amnestic MCI (aMCI) was defined by a composite episodic memory (EM) Z-score of <-1.5.. At baseline, 24 (53%) MCI were FBB+. Majority reads agreed with SUVR classification (κ 0.96). In 2 years, 18 (75%) FBB+ progressed to AD compared with 2 (9.5%) FBB-, yielding a predictive accuracy of 83% (95% CI 61% to 94%). Four FBB- developed non-AD dementia. Predictive accuracies of HV (58% (95% CI 42% to 73%)) and aMCI status (73% (95% CI 58% to 81%)) were lower. Combinations did not improve accuracy. By 4 years, 21 (87.5%) FBB+ had AD whereas 5 (24%) FBB- had non-AD dementia yielding a predictive accuracy of 94% (95% CI 74% to 99%). While the strong baseline association between FBB SUVR and EM declined over 2 years, the association between EM and HV became stronger. FBB SUVR increased 2.2%/year in FBB+ with no change in FBB-.. (18)F-florbetaben Aβ imaging facilitates accurate detection of prodromal AD. As neurodegeneration progresses, and in contrast with the early stages of the disease, hippocampal atrophy and not Aβ, seems to drive memory decline.. NCT01138111.

Topics: Aged; Alzheimer Disease; Amyloid beta-Peptides; Aniline Compounds; Cognitive Dysfunction; Disease Progression; Female; Hippocampus; Humans; Magnetic Resonance Imaging; Male; Memory Disorders; Positron-Emission Tomography; Prospective Studies; Radiopharmaceuticals; Stilbenes

Assessment of disease biomarkers, particularly the in vivo assessment of amyloid-β (Aβ) burden with positron emission tomography (PET), is gradually becoming central to the diagnosis of mild cognitive impairment (MCI) due to Alzheimer's disease (AD). However, the incorporation of biomarker evidence to the diagnostic process is currently restricted mainly to research settings. The identification of memory measures that are associated with Aβ is of clinical relevance as this may enhance the confidence in making a diagnosis of MCI due to AD in clinical settings. Forty one persons with amnestic MCI underwent Aβ imaging with (18)F-Florbetaben PET, magnetic resonance imaging, and a comprehensive neuropsychological assessment. All measures of episodic memory were significantly correlated with Aβ burden, but regression analyses revealed a strong and selective association between story recall and Aβ over and beyond the effects of age, education, global cognition, hippocampal volume, or other memory tests. Analyses of sensitivity and specificity of memory measures to detect high versus low Aβ scans suggested that word-list recall performed better when high sensitivity was preferred, whereas story recall performed better when high specificity was preferred. In conclusion, a measure of story recall may increase the confidence in making a diagnosis of MCI due to AD in clinical settings.

Topics: Aged; Aged, 80 and over; Amnesia; Amyloidosis; Aniline Compounds; Arabidopsis Proteins; Biomarkers; Cognitive Dysfunction; Cyclophilins; Female; Fluorine Radioisotopes; Humans; Magnetic Resonance Imaging; Male; Memory, Episodic; Middle Aged; Neuropsychological Tests; Positron-Emission Tomography; Predictive Value of Tests; Protozoan Proteins; Regression Analysis; Reproducibility of Results; Sensitivity and Specificity; Stilbenes

To evaluate the performance characteristics of florbetapir F18 positron emission tomography (PET) in patients with Alzheimer's disease (AD), mild cognitive impairment (MCI), and healthy control subjects (HCs).. Florbetapir PET was acquired in 184 subjects (45 AD patients, 60 MCI patients, and 79 HCs) within a multicenter phase 2 study. Amyloid burden was assessed visually and quantitatively, and was classified as positive or negative.. Florbetapir PET was rated visually amyloid positive in 76% of AD patients, 38% of MCI patients, and 14% of HCs. Eighty-four percent of AD patients, 45% of MCI patients, and 23% of HCs were classified as amyloid positive using a quantitative threshold. Amyloid positivity and mean cortical amyloid burden were associated with age and apolipoprotein E ε4 carrier status.. : The data are consistent with expected rates of amyloid positivity among individuals with clinical diagnoses of AD and MCI, and indicate the potential value of florbetapir F18 PET as an adjunct to clinical diagnosis.

Topics: Aged; Aged, 80 and over; Aging; Alzheimer Disease; Amyloidogenic Proteins; Aniline Compounds; Apolipoprotein E4; Cognitive Dysfunction; Female; Fluorine Radioisotopes; Humans; Male; Mental Status Schedule; Middle Aged; Positron-Emission Tomography; Stilbenes

[(11)C]PIB and [(18)F]FDDNP are PET tracers for in vivo detection of the neuropathology underlying Alzheimer's disease (AD). [(18)F]FDG is a glucose analogue and its uptake reflects metabolic activity. The purpose of this study was to examine longitudinal changes in these tracers in patients with AD or mild cognitive impairment (MCI) and in healthy controls.. Longitudinal, paired, dynamic [(11)C]PIB and [(18)F]FDDNP (90 min each) and static [(18)F]FDG (15 min) PET scans were obtained in 11 controls, 12 MCI patients and 8 AD patients. The mean interval between baseline and follow-up was 2.5 years (range 2.0-4.0 years). Parametric [(11)C]PIB and [(18)F]FDDNP images of binding potential (BP(ND)) and [(18)F]FDG standardized uptake value ratio (SUVr) images were generated.. A significant increase in global cortical [(11)C]PIB BP(ND) was found in MCI patients, but no changes were observed in AD patients or controls. Subsequent regional analysis revealed that this increase in [(11)C]PIB BP(ND) in MCI patients was most prominent in the lateral temporal lobe (p < 0.05). For [(18)F]FDDNP, no changes in global BP(ND) were found. [(18)F]FDG uptake was reduced at follow-up in the AD group only, especially in frontal, parietal and lateral temporal lobes (all p < 0.01). Changes in global [(11)C]PIB binding (ρ = -0.42, p < 0.05) and posterior cingulate [(18)F]FDG uptake (ρ = 0.54, p < 0.01) were correlated with changes in Mini-Mental-State Examination score over time across groups, whilst changes in [(18)F]FDDNP binding (ρ = -0.18, p = 0.35) were not.. [(11)C]PIB and [(18)F]FDG track molecular changes in different stages of AD. We found increased amyloid load in MCI patients and progressive metabolic impairment in AD patients. [(18)F]FDDNP seems to be less useful for examining disease progression.

Topics: Aged; Alzheimer Disease; Aniline Compounds; Benzothiazoles; Case-Control Studies; Cognitive Dysfunction; Female; Humans; Longitudinal Studies; Male; Middle Aged; Nitriles; Positron-Emission Tomography; Stilbenes; Thiazoles; Time Factors

Topics: Animals; Brain-Gut Axis; Cognitive Dysfunction; Diabetes Mellitus; Inflammation; Mice; Neuroinflammatory Diseases; NF-kappa B; Stilbenes; Toll-Like Receptor 4

Traumatic brain injury (TBI) is the most common form of craniocerebral injury. Post-TBI neurological impairment is often accompanied by cognitive dysfunction. The potential molecular mechanisms of post-TBI cognitive impairment are not well characterized. Resveratrol, a natural polyphenolic agent, has been shown to improve cognitive function in neurological disorders and aging models through its anti-inflammatory activity. However, whether it can affect synapses to improve cognitive function and the potential mechanisms are not clear. Synapse plays an important role in cognitive function, and synaptophysin(SYN) is one of the important factors involved in synapse formation. Sirtuin 1 (SIRT1) has a neuroprotective effect via its effect on various biological processes, such as inflammation, metabolism, apoptosis, and autophagy. The results of this research suggest that resveratrol increases synaptophysin by activating the SIRT1/PGC-1 pathway and improves post-TBI cognitive function. Use of SIRT1 inhibitor (EX-527) and agonist (SRT1720) in the mice experiments verified the effect and mechanism of action of resveratrol in improving cognitive function. Our study identifies potential therapeutic targets for post-TBI cognitive dysfunction.

Topics: Animals; Brain Injuries, Traumatic; Cognitive Dysfunction; Mice; Neuroprotective Agents; Peroxisome Proliferator-Activated Receptors; Resveratrol; Sirtuin 1; Stilbenes; Synaptophysin

Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disease that is the most common cause of dementia in the elderly. Aβ1‑42 is significantly associated with memory deficits and it can increase the level of acetylcholine, promote the activity of acetylcholinesterase (AChE), and cause cognitive dysfunction. Isorhapontigenin (ISO) is a stilbene derivative that has antioxidant, anti‑tumor, and anti‑inflammatory effects. However, it is still unclear whether ISO can affect β‑amyloid‑associated cognitive impairments. In this study, we found that ISO improved cognitive dysfunction induced by Aβ1‑42 in rats. It inhibited the Aβ‑induced activation of M1 microglia and reduced the release of inflammatory cytokines. It alleviated amyloid beta‑induced oxidative stress and led to an overall improvement in AD symptoms. Cellularly, we found that ISO alleviated Aβ‑induced inflammation and oxidative stress by activating the PI3K/AKT/GSK‑3β pathway and ultimately improved cognitive dysfunction in AD rats.

Topics: Acetylcholine; Acetylcholinesterase; Alzheimer Disease; Amyloid beta-Peptides; Animals; Anti-Inflammatory Agents; Antioxidants; Cognitive Dysfunction; Cytokines; Disease Models, Animal; Glycogen Synthase Kinase 3 beta; Neurodegenerative Diseases; Oxidative Stress; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rats; Signal Transduction; Stilbenes

To assess the correlation between profile and severity deterioration in the neuropsychological assessment and the most affected regions in amyloid PET semiquantification. The influence of vascular risk and other potential confounding factors was also evaluated.. A retrospective, observational, and multicenter study including all patients referred for amyloid PET in daily practice was conducted. Patients underwent neuropsychological assessment, and cognitive decline severity and domain(s) affected were recorded. The patients were grouped according to cognitive impairment (CI) profile and severity: (A) no CI, single-domain amnestic CI, multiple-domain amnestic CI, and nonamnestic CI; and (B) mild CI, moderate and severe dementia. An adapted Framingham Stroke Risk Profile was calculated for each individual. Depression and parkinsonism were also recorded. Standardized quantitative analysis software was used to obtain standardized uptake value ratio (SUVR) values from PET/CT images. The corresponding associations were assessed with the most appropriate statistical tests.. One hundred twenty-nine patients were included (62 men, 67 women; 64.67 ± 7.47 years old). Significant differences in global and regional amyloid load were exclusively found in women between non-CI and moderate dementia ( P = 0.006, for total-cerebellum SUVR). Posterior and anterior cingulates and prefrontal cortex best represented CI severity ( P = 0.003, 0.006, and 0.006, respectively). No relationship between the CI profile and the regional amyloid load was shown. A significantly high positive correlation was found between age and vascular risk and between these variables and amyloid load in nearly all regions, especially in women with moderate dementia.. Semiquantitative analysis of amyloid PET by SUVR values revealed a significant correlation between amyloid burden and CI severity, although only in women.

Topics: Aged; Alzheimer Disease; Amyloid; Amyloid beta-Peptides; Amyloidosis; Aniline Compounds; Brain; Cognitive Dysfunction; Dementia; Female; Humans; Male; Middle Aged; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Retrospective Studies; Stilbenes

To compare visual and semi-quantitative analysis of brain [. After the consensus reading, 43/71 (60.6%) patients were considered positive. Cases that were interpreted as visually positive had higher SUVr than visually negative patients (1.48 ± 0.19 vs 1.11 ± 0.09) (P<0.05). Agreement between visual analysis and semi-quantitative analysis was excellent (k=0.86, P<0.05). Disagreement occurred in 7/71 patients (9.9%) (6 false positives and 1 false negative). Agreement between the two analyses was 90.0% (18/20) for SUVr < 1.1, 83% (24/29) for SUVr between 1.1 and 1.5, and 100% (22/22) for SUVr > 1.5 indicating lowest agreement for the group with intermediate amyloid burden.. Inter-rater agreement of visual analysis of amyloid PET images is high. Agreement between visual analysis and SUVr semi-quantitative analysis decreases in the range of 1.1

Topics: Aged; Aniline Compounds; Brain; Cognitive Dysfunction; Cross-Sectional Studies; Female; Fluorodeoxyglucose F18; Humans; Italy; Male; Positron-Emission Tomography; Prospective Studies; Radiopharmaceuticals; Stilbenes

The global growing rates of cognitive decline and dementia, together with the absence of curative therapies for these conditions, support the interest in researching potential primary prevention interventions, with particular focus on dietary habits. The aim was to assess the association between polyphenol intake and 6-year change in cognitive function in the 'Seguimiento Universidad de Navarra' (SUN) Project, a Spanish prospective cohort study. Changes (final - initial) in cognitive function were evaluated in a subsample of 806 participants (mean age 66 (sd 5) years, 69·7 % male) of the SUN Project using the validated Spanish Telephone Interview for Cognitive Status-modified score. Polyphenol intake was derived from a validated semi-quantitative FFQ and matching food composition data from the Phenol-Explorer database. Multivariable linear regression models were used to evaluate the association between total polyphenol intake, polyphenol subclasses and cognitive changes. No significant association between total polyphenol intake and changes in cognitive function was found. However, a higher intake of lignans (βQuintile (Q) 5 v. Q1 0·81; 95 % CI 0·12, 1·51; Ptrend = 0·020) and stilbenes (βQ5 v. Q1 0·82; 95 % CI 0·15, 1·49; Ptrend = 0·028) was associated with more favourable changes in cognitive function over time, particularly with respect to immediate memory and language domains. Olive oil and nuts were the major sources of variability in lignan intake, and wine in stilbene intake. The results suggest that lignan and stilbene intake was associated with improvements in cognitive function.

Topics: Aged; Cognitive Dysfunction; Diet; Female; Humans; Lignans; Male; Middle Aged; Polyphenols; Prospective Studies; Spain; Stilbenes

In the present study, effect of pterostilbene on β-amyloid 1-42 (Aβ. The behavior results show that pterostilbene alleviated Aβ. The present study reports that pterostilbene alleviated Aβ

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Behavior, Animal; Brain; Cell Line; Cognitive Dysfunction; Disease Models, Animal; Humans; Male; Memory, Short-Term; Mice; Neurons; Neuroprotective Agents; NF-E2-Related Factor 2; Oxidative Stress; Peptide Fragments; Signal Transduction; Stilbenes

Amyloid-β accumulation was found to alter precuneus-based functional connectivity (FC) in mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia, but its impact is less clear in subjective cognitive decline (SCD), which in combination with AD pathologic change is theorized to correspond to stage 2 of the Alzheimer's continuum in the 2018 NIA-AA research framework.. This study addresses how amyloid pathology relates to resting-state fMRI FC in SCD, especially focusing on the precuneus.. From the DELCODE cohort, two groups of 24 age- and gender-matched amyloid-positive (SCDAβ+) and amyloidnegative SCD (SCDβ-) patients were selected according to visual [18F]-Florbetaben (FBB) PET readings, and studied with resting-state fMRI. Local (regional homogeneity [ReHo], fractional amplitude of low-frequency fluctuations [fALFF]) and global (degree centrality [DC], precuneus seed-based FC) measures were compared between groups. Follow-up correlation analyses probed relationships of group differences with global and precuneal amyloid load, as measured by FBB standard uptake value ratios (SUVR=⫖FBB).. ReHo was significantly higher (voxel-wise p < 0.01, cluster-level p < 0.05) in the bilateral precuneus for SCDAβ+patients, whereas fALFF was not altered between groups. Relatively higher precuneus-based FC with occipital areas (but no altered DC) was observed in SCDAβ+ patients. In this latter cluster, precuneus-occipital FC correlated positively with global (SCDAβ+) and precuneus SUVRFBB (both groups).. While partial confounding influences due to a higher APOE ε4 carrier ratio among SCDAβ+ patients cannot be excluded, exploratory results indicate functional alterations in the precuneus hub region that were related to amyloid-β load, highlighting incipient pathology in stage 2 of the AD continuum.

Topics: Aged; Amyloid beta-Peptides; Aniline Compounds; Cognitive Dysfunction; Cohort Studies; Female; Humans; Magnetic Resonance Imaging; Male; Parietal Lobe; Stilbenes

Imaging with β-amyloid (Aβ) positron emission tomography (PET) has the potential to aid the diagnosis of the cause of cognitive impairment affecting people living with HIV (PLWH) when neurodegenerative disorders are considered. We evaluated the clinical utility of [18F]Florbetaben (FBB) in PLWH with cognitive symptoms.. Imaging with FBB PET was performed in 20 patients with cognitive concerns about dementia. Neuropsychological testing, plasma neurofilament light protein, plasma Aβ40, Aβ42, and cerebrospinal fluid Aβ42, tau, and HIV RNA were obtained. FBB PET images were assessed visually by 3 readers blinded to the clinical diagnosis and quantitatively by obtaining a composite cortical to cerebellar cortex standardized uptake value ratio (SUVR). FBB SUVR from 10 age-matched healthy controls was compared with SUVR of PLWH.. Most participants were men (90%) of white ethnicity (90%) with a median age (interquartile range) of 59 (43-79) years. Median CD4 count was 682 (74-1056). All patients were on combination antiretroviral therapy with plasma and cerebrospinal fluid HIV RNA <40 copies/mL. Fourteen patients had objective cognitive impairment including 2 who met clinical criteria for a diagnosis of dementia. No significant differences in composite SUVRs between PLWH and controls [mean (SD): 1.18 (0.03) vs. 1.16 (0.09); P = 0.37] were observed. Four patients were FBB+ with the highest SUVR in the posterior cingulate, superior temporal, and frontal superior lobe. Amyloid PET results contributed to a change in diagnosis and treatment for 10 patients.. [18F]Florbetaben PET has potential as an adjunctive tool in the diagnosis of PLWH with cognitive impairment, increasing diagnostic certainty and optimizing management.

Topics: Adult; Aged; Amyloid beta-Peptides; Aniline Compounds; Brain; CD4 Lymphocyte Count; Cognitive Dysfunction; Drug Therapy, Combination; Female; HIV Infections; Humans; Male; Middle Aged; Neurodegenerative Diseases; Neuropsychological Tests; Peptide Fragments; Positron-Emission Tomography; RNA, Viral; Stilbenes; tau Proteins

A low amount and extent of Aβ deposition at early stages of Alzheimer's disease (AD) may limit the use of previously developed pathology-proven composite SUVR cutoffs. This study aims to characterize the population with earliest abnormal Aβ accumulation using. The study population consisted of 686 subjects (n = 287 (cognitively normal healthy controls), n = 166 (subjects with subjective cognitive decline (SCD)), n = 129 (subjects with MCI), and n = 101 (subjects with AD dementia)). Three categories in the Aβ-deposition continuum were defined based on the developed SUVR cutoffs: Aβ-negative subjects, subjects with early Aβ deposition ("gray zone"), and subjects with established Aβ pathology.. SUVR using the whole cerebellum as the reference region and centiloid (CL) cutoffs for early and established amyloid pathology were 1.10 (13.5 CL) and 1.24 (35.7 CL), respectively. Cingulate cortices and precuneus, frontal, and inferior lateral temporal cortices were the regions showing the initial pathological tracer retention. Subjects in the "gray zone" or with established Aβ pathology accumulated more amyloid over time than Aβ-negative subjects. After a 4-year clinical follow-up, none of the Aβ-negative or the gray zone subjects progressed to AD dementia while 91% of the MCI subjects with established Aβ pathology progressed. Tau deposition was infrequent in those subjects without established Aβ pathology.. This study supports the utility of using two cutoffs for amyloid PET abnormality defining a "gray zone": a lower cutoff of 13.5 CL indicating emerging Aβ pathology and a higher cutoff of 35.7 CL where amyloid burden levels correspond to established neuropathology findings. These cutoffs define a subset of subjects characterized by pre-AD dementia levels of amyloid burden that precede other biomarkers such as tau deposition or clinical symptoms and accelerated amyloid accumulation. The determination of different amyloid loads, particularly low amyloid levels, is useful in determining who will eventually progress to dementia. Quantitation of amyloid provides a sensitive measure in these low-load cases and may help to identify a group of subjects most likely to benefit from intervention.. Data used in this manuscript belong to clinical trials registered in ClinicalTrials.gov ( NCT00928304 , NCT00750282 , NCT01138111 , NCT02854033 ) and EudraCT (2014-000798-38).

Topics: Alzheimer Disease; Amyloid beta-Peptides; Aniline Compounds; Cognitive Dysfunction; Humans; Positron-Emission Tomography; Stilbenes

Cognitive impairment is the main clinical manifestation of Alzheimer's disease (AD), and amyloid-β (Aβ) deposition and senile plaques are the characteristic neuropathological hallmarks in AD brains. This study aimed to explore the effect and mechanism of tetrahydroxy stilbene glucoside (TSG) on cognitive function in APP/PS1 mice during long-term administration. Here, we treated APP/PS1 model mice of AD with different doses of TSG (50 mg/kg and 100 mg/kg) for 5 to 17 months by gavage, and we further observed whether TSG could ameliorate the cognitive decline in APP/PS1 mice using behavioral tests, and investigated the possible mechanisms by immunohistochemistry and Western blotting. Our results showed that TSG treatment rescued the spatial and non-spatial learning and memory impairments of APP/PS1 mice at Morris water maze test and novel object recognition test. Furthermore, Aβ40/42 deposition in the cortex and hippocampus of APP/PS1 mice treated with TSG was significantly reduced compared to the wild type mice using the immunohistochemical technique. Finally, Western blotting showed that TSG primarily decreased the APP expression to avoid the Aβ plaque deposition in the cortex and hippocampus of mice. These results reveal the beneficial effects of TSG in APP/PS1-AD mice, which may be associated with the reduction of Aβ deposits in the brain.

Topics: Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Cognitive Dysfunction; Glucosides; Hippocampus; Memory Disorders; Mice, Transgenic; Peptide Fragments; Presenilin-1; Stilbenes

Patients with early-onset Alzheimer's disease (EOAD) are commonly excluded from large-scale observational and therapeutic studies due to their young age, atypical presentation, or absence of pathogenic mutations. The goals of the Longitudinal EOAD Study (LEADS) are to (1) define the clinical, imaging, and fluid biomarker characteristics of EOAD; (2) develop sensitive cognitive and biomarker measures for future clinical and research use; and (3) establish a trial-ready network. LEADS will follow 400 amyloid beta (Aβ)-positive EOAD, 200 Aβ-negative EOnonAD that meet National Institute on Aging-Alzheimer's Association (NIA-AA) criteria for mild cognitive impairment (MCI) or AD dementia, and 100 age-matched controls. Participants will undergo clinical and cognitive assessments, magnetic resonance imaging (MRI), [

Topics: Alzheimer Disease; Aniline Compounds; Autopsy; Biomarkers; Brain; Cognitive Dysfunction; Early Diagnosis; Female; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Middle Aged; National Institute on Aging (U.S.); Positron-Emission Tomography; Stilbenes; United States

We developed a machine learning-based classifier for in vivo amyloid positron emission tomography (PET) staging, quantified cortical uptake of the PET tracer by using a machine learning method, and investigated the impact of these amyloid PET parameters on clinical and structural outcomes.. A total of 337. The classification accuracy was 97.3% for cortical amyloid positivity and 91.1% for striatal positivity. The left frontal and precuneus/posterior cingulate regions, as well as the anterior portion of the striatum, were important in determination of stages. The clinical scores and magnetic resonance imaging parameters showed negative associations with PET stage. However, except for the hippocampal volume, most outcomes were associated with the stage through the complete mediation effect of pRCTU.. Using a machine learning algorithm, we achieved high accuracy for in vivo amyloid PET staging. The in vivo amyloid stage was associated with cognitive function and cerebral atrophy mostly through the mediation effect of cortical amyloid.

Topics: Alzheimer Disease; Aniline Compounds; Brain; Cognitive Dysfunction; Humans; Machine Learning; Positron-Emission Tomography; Stilbenes

Free and Cued Selective Reminding Test (FCSRT) is a reliable cognitive marker for Alzheimer's disease (AD), and the identification of neuropsychological tests sensitive to the early signs of AD pathology is crucial both in research and clinical practice.. The study aimed to ascertain the ability of FCSRT in predicting the amyloid load as determined from amyloid PET imaging (Amy-PET) in patients with cognitive disorders.. For our purpose, 79 patients (71 MCI, 8 mild dementia) underwent a complete workup for dementia, including the FCSRT assessment and a [18F]florbetaben PET scan. FCSRT subitem scores were used as predictors in different binomial regression models.. Immediate free recall and delayed free recall were the best predictors overall in the whole sample; whereas in patients <76 years, all models further improved with immediate total recall (ITR) and Index of Sensitivity of Cueing (ISC) resulting the most accurate in anticipating Amy-PET results, with a likelihood of being Amy-PET positive greater than 85% for ITR and ISC scores of less than 25 and 0.5, respectively.. FCSRT proved itself to be a valid tool in dementia diagnosis, also being able to correlate with amyloid pathology. The possibility to predict Amy-PET results through a simple and reliable neuropsychological test might be helpful for clinicians in the dementia field, adding value to a paper and pencil tool compared to most costly biomarkers.

Topics: Adult; Aged; Aged, 80 and over; Aniline Compounds; Body Burden; Cerebral Amyloid Angiopathy; Cognitive Dysfunction; Cues; Dementia; Disease Progression; Female; Humans; Male; Mental Recall; Mental Status and Dementia Tests; Middle Aged; Neuropsychological Tests; Positron-Emission Tomography; Predictive Value of Tests; Prospective Studies; Psychomotor Performance; Radiopharmaceuticals; Reproducibility of Results; Stilbenes

The impact of maternal nutrition on neurodevelopment and neonatal neuroprotection is a research topic with increasing interest. Maternal diet can also have deleterious effects on fetal brain development. Fetal exposure to alcohol is responsible for poor neonatal global development, and may increase brain vulnerability to hypoxic-ischemic encephalopathy, one of the major causes of acute mortality and chronic neurological disability in newborns. Despite frequent prevention campaigns, about 10% of women in the general population drinks alcohol during pregnancy and breastfeeding. This study was inspired by this alarming fact. Its aim was to evaluate the beneficial effects of maternal supplementation with two polyphenols during pregnancy and breastfeeding, on hypoxic-ischemic neonate rat brain damages, sensorimotor and cognitive impairments, in a context of moderate maternal alcoholism. Both stilbenoid polyphenols, trans-resveratrol (RSV - 0.15 mg/kg/day), and its hydroxylated analog, trans-piceatannol (PIC - 0.15 mg/kg/day), were administered in the drinking water, containing or not alcohol (0.5 g/kg/day). In a 7-day post-natal rat model of hypoxia-ischemia (HI), our data showed that moderate maternal alcoholism does not increase brain lesion volumes measured by MRI but leads to higher motor impairments. RSV supplementation could not reverse the deleterious effects of HI coupled with maternal alcoholism. However, PIC supplementation led to a recovery of all sensorimotor and cognitive functions. This neuroprotection was obtained with a dose of PIC corresponding to the consumption of a single passion fruit per day for a pregnant woman.

Topics: Alcohol Drinking; Alcoholism; Animals; Animals, Newborn; Brain; Brain Injuries; Cognitive Dysfunction; Female; Hypoxia; Hypoxia-Ischemia, Brain; Ischemia; Male; Maternal Nutritional Physiological Phenomena; Maternal-Fetal Exchange; Neuroprotection; Neuroprotective Agents; Polyphenols; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar; Resveratrol; Stilbenes

Topics: Alzheimer Disease; AMP-Activated Protein Kinases; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Anti-Inflammatory Agents; Cell Line, Tumor; Cognitive Dysfunction; Disease Models, Animal; Gene Expression Regulation; Glucosides; Humans; Inflammasomes; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microglia; Mitochondria; Mitophagy; Neurons; Neuroprotective Agents; NLR Family, Pyrin Domain-Containing 3 Protein; Primary Cell Culture; Protein Kinases; RNA, Small Interfering; Signal Transduction; Stilbenes; Ubiquitin-Protein Ligases

18F-florbetaben (FBB) and 18F-flutemetamol (FMM) amyloid PET have been developed and approved for clinical use. It is important to understand the distinct features of these ligands to compare and correctly interpret the results of different amyloid PET studies.. We performed a head-to-head comparison of FBB and FMM to compare with regard to imaging characteristics, including dynamic range of retention, and differences in quantitative measurements between the two ligands in cortical, striatal, and white matter (WM) regions.. Paired FBB and FMM PET images were acquired in 107 participants. Correlations of FBB and FMM amyloid deposition in the cortex, striatum, and WM were investigated and compared in different reference regions (cerebellar gray matter (CG), whole cerebellum (WC), WC with brainstem (WC + B), and pons).. The cortical SUVR (R2 = 0.97) and striatal SUVR (R2 = 0.95) demonstrated an excellent linear correlation between FBB and FMM using a WC as reference region. There was no difference in the cortical SUVR ratio between the two ligands (p = 0.90), but the striatal SUVR ratio was higher in FMM than in FBB (p < 0.001). Also, the effect size of differences in striatal SUVR seemed to be higher with FMM (2.61) than with FBB (2.34). These trends were similarly observed according to four different reference regions (CG, WC, WC + B, and pons).. Our findings suggest that FMM might be better than FBB to detect amyloid burden in the striatum, although both ligands are comparable for imaging AD pathology in vivo.

Topics: Adult; Aged; Aged, 80 and over; Alzheimer Disease; Aniline Compounds; Benzothiazoles; Cerebral Cortex; Cognitive Dysfunction; Corpus Striatum; Female; Fluorine Radioisotopes; Humans; Male; Middle Aged; Positron-Emission Tomography; Stilbenes

We aimed to quantitatively and qualitatively assess whether there is a discrepancy in detecting amyloid beta (Aβ) positivity between 18F-florbetaben (FBB) and 18F-flutemetamol (FMM) positron emission tomography (PET). We obtained paired FBB and FMM PET images from 107 participants. Three experts visually quantified the Aβ deposition as positive or negative. Quantitative assessment was performed using global cortical standardized uptake value ratio (SUVR) with the whole cerebellum as the reference region. Inter-rater agreement was excellent for FBB and FMM. The concordance rates between FBB and FMM were 94.4% (101/107) for visual assessment and 98.1% (105/107) for SUVR cut-off categorization. Both FBB and FMM showed high agreement rates between visual assessment and SUVR positive or negative categorization (93.5% in FBB and 91.2% in FMM). When the two ligands were compared based on SUVR cut-off categorization as standard of truth, although not statistically significant, the false-positive rate was higher in FMM (9.1%) than in FBB (1.8%) (p = 0.13). Our findings suggested that both FBB and FMM had excellent agreement when used to quantitatively and qualitatively evaluate Aβ deposits, thus, combining amyloid PET data associated with the use of different ligands from multi-centers is feasible.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Amyloid beta-Peptides; Aniline Compounds; Benzothiazoles; Case-Control Studies; Cognitive Dysfunction; Dementia, Vascular; False Negative Reactions; False Positive Reactions; Female; Fluorine Radioisotopes; Humans; Male; Middle Aged; Plaque, Amyloid; Positron-Emission Tomography; Radiopharmaceuticals; Stilbenes

Amyloid PET allows for the assessment of amyloid β status in the brain, distinguishing true Alzheimer's disease from Alzheimer's disease-mimicking conditions. Around 15-20% of patients with clinically probable Alzheimer's disease have been found to have no significant Alzheimer's pathology on amyloid PET. However, a limited number of studies had been conducted on this subpopulation in terms of clinical progression.. We investigated the risk factors that could affect the progression to dementia in patients with amyloid-negative amnestic mild cognitive impairment (MCI).. This study was a single-institutional, retrospective cohort study of patients over the age of 50 with amyloid-negative amnestic MCI who visited the memory clinic of Asan Medical Center with a follow-up period of more than 36 months. All participants underwent brain magnetic resonance imaging (MRI), detailed neuropsychological testing, and fluorine-18[F18]-florbetaben amyloid PET.. During the follow-up period, 39 of 107 patients progressed to dementia from amnestic MCI. In comparison with the stationary group, the progressed group had a more severe impairment in verbal and visual episodic memory function and hippocampal atrophy, which showed an Alzheimer's diseaselike pattern despite the lack of evidence for significant Alzheimer's disease pathology. Voxel-based morphometric MRI analysis revealed that the progressed group had a reduced gray matter volume in the bilateral cerebellar cortices, right temporal cortex, and bilateral insular cortices.. Considering the lack of evidence of amyloid pathology, clinical progression of these subpopulation may be caused by other neuropathologies such as TDP-43, abnormal tau or alpha synuclein that lead to neurodegeneration independent of amyloid-driven pathway. Further prospective studies incorporating biomarkers of Alzheimer's disease-mimicking dementia are warranted.

Topics: Aged; Alzheimer Disease; Amnesia; Aniline Compounds; Brain; Cognitive Dysfunction; Disease Progression; Female; Fluorine Radioisotopes; Humans; Image Processing, Computer-Assisted; Male; Middle Aged; Neuropsychological Tests; Positron-Emission Tomography; Republic of Korea; Retrospective Studies; Risk Factors; Stilbenes; tau Proteins

Alzheimer's disease (AD) pathology precedes the onset of clinical symptoms by several decades. Thus, biomarkers are required to identify prodromal disease stages to allow for the early and effective treatment. The methoxy-X04-derivative BSC4090 is a fluorescent ligand which was designed to target neurofibrillary tangles in AD. BSC4090 staining was previously detected in post-mortem brains and olfactory mucosa derived from AD patients. We tested BSC4090 as a potential diagnostic marker of prodromal and early AD using olfactory mucosa biopsies from 12 individuals with AD, 13 with mild cognitive impairment (MCI), and 10 cognitively normal (CN) controls. Receiver-operating curve analysis revealed areas under the curve of 0.78 for AD versus CN and of 0.86 for MCI due to AD versus MCI of other causes. BSC4090 labeling correlated significantly with cerebrospinal fluid levels of tau protein phosphorylated at T181. Using NMR spectroscopy, we find that BSC4090 binds to fibrillar and pre-fibrillar but not to monomeric tau. Thus, BSC4090 may be an interesting candidate to detect AD at the early disease stages.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Benzylidene Compounds; Biopsy; Case-Control Studies; Cognitive Dysfunction; Female; Fluorescent Dyes; Humans; Magnetic Resonance Spectroscopy; Male; Mental Status and Dementia Tests; Microscopy, Confocal; Microscopy, Electron, Transmission; Middle Aged; Olfactory Mucosa; Prodromal Symptoms; Pyrimidines; Stilbenes

The aim of this study was to identify white matter structural networks of amnestic mild cognitive impairment (aMCI) dichotomized by β amyloid (Aβ) status and compare them using network-based statistics (NBS).. Patients underwent whole-brain diffusion-weighted magnetic resonance imaging, detailed neuropsychological test and [. One hundred sixteen participants (Aβ- cognitively normal [CN], n = 35; Aβ- aMCI, n = 42; Aβ+ aMCI, n = 39) were included. There was no subnetwork showing significant difference between Aβ+ aMCI and Aβ- aMCI. However, by comparing each aMCI group with control group, we found that supplementary motor areas were common hub regions. Intriguingly, Aβ+ aMCI showed reduced connectivity mainly in the medial frontal regions, while Aβ- aMCI showed somewhat uniform disruption when compared to CN.. Structural network analysis using network-based approach in aMCI may shed light on further understanding of white matter disruption in the prodromal stage of Alzheimer's disease.

Topics: Aged; Alzheimer Disease; Amnesia; Amyloid; Aniline Compounds; Brain; Brain Mapping; Cerebral Cortex; Cognitive Dysfunction; Diffusion Tensor Imaging; Female; Humans; Male; Neuropsychological Tests; Positron-Emission Tomography; Stilbenes; White Matter

Topics: Aged; Alzheimer Disease; Amyloid; Aniline Compounds; Brain Diseases; Cognitive Dysfunction; Deep Learning; Female; Humans; Lewy Body Disease; Magnetic Resonance Imaging; Male; Middle Aged; Multimodal Imaging; Parkinsonian Disorders; Positron-Emission Tomography; Retrospective Studies; Stilbenes

Subjective cognitive decline (SCD) may herald the first symptoms of Alzheimer's disease (AD) whereas individuals with beta-amyloid (Aβ) deposition are regarded as a high-risk group for AD. Recently, amyloid positron emission tomography (PET) studies have demonstrated clinical and cognitive feature differences between Aβ-positive and negative SCD, but details of their differences remain unclear. We aimed to investigate the relationships among Aβ deposition, clinical, and cognitive features in patients with SCD.. Forty-two patients with SCD (22 women, 74.5 ± 4.7 years) were examined using fluorine-18 florbetaben PET and were divided into Aβ-positive (n = 10) and negative (n = 32) groups. We compared cognitive and psychological outcomes, and single photon emission computed tomography (SPECT) imaging data between the two groups. In addition, a linear regression analysis was performed to assess relationships between the severity of SCD and neuropsychological tests, affective scores, and demographic factors.. The rate of score changes from the immediate recall to delayed recall in the logical memory subtest of the Wechsler's Memory Scale Revised were different between the groups (P = 0.04). However, the binary logistic regression analysis showed no significant differences between the two. In addition, the severity of SCD was significantly strong in women (P = 0.002). Furthermore, within the Aβ-negative group, subjective memory loss correlated with word fluency category score (P = 0.023) and apathy scale (P = 0.037).. No significant differences were observed between Aβ-positive and -negative SCD on any of the neuropsychological measures, clinical measures, or SPECT imaging. Further, the severity of SCD was not predicted by the symptoms of anxiety, depression, or neuropsychological examination.

Topics: Aged; Aged, 80 and over; Amyloid beta-Peptides; Aniline Compounds; Cerebrovascular Circulation; Cognitive Dysfunction; Diagnostic Self Evaluation; Female; Humans; Male; Memory Disorders; Positron-Emission Tomography; Severity of Illness Index; Stilbenes; Tomography, Emission-Computed, Single-Photon

Amyloid pathology is a key feature of Alzheimer's disease (AD) and can be assessed in vivo with amyloid positron emission tomography (PET) imaging.. The objective of this study was to evaluate the incremental value of a PET scan with [18F]florbetaben, in terms of changes of diagnosis, diagnostic confidence, and treatment plan when added to a standardized diagnostic workup for cognitive disorders, with particular focus on the role of the neuropsychological assessment, including the Free and Cued Selective Reminding Test (FCSRT).. A total of 104 patients (69 mild cognitive impairment, 35 dementia), with diagnostic uncertainty after diagnostic workup, were recruited from our memory clinic. [18F]florbetaben PET scans were interpreted as amyloid negative or positive on the basis of a semi-quantitative visual rating. Clinical diagnosis and diagnostic confidence for AD or non-AD dementia were rated before and after PET result disclosure, as was the impact of PET on the patient management plan.. There were 69/104 (66%) [18F]florbetaben positive scans, 51/62 (82%) patients were suspected as having AD before the PET scan and 18/42 (43%) were not. Overall, the data obtained at PET changed 18/104 diagnoses (17%) and increased diagnostic confidence from 69.1±8.1% to 83.5±9.1 (p < 0.001), with the greatest impact on diagnosis and confidence in PET negative patients with an initial diagnosis of AD (p < 0.01) and in early-onset patients (p = 0.01).. Amyloid PET represents a source of added value in dementia diagnosis, with a significant effect on diagnosis and diagnostic confidence. However, the use of a complete neuropsychological assessment has an add-on value on limiting the amyloid PET influence on change of diagnosis, and the real impact of amyloid PET should always be weighed up together with an accurate standardized diagnostic workup.

Topics: Aged; Alzheimer Disease; Amyloid; Aniline Compounds; Cognitive Dysfunction; Diagnosis, Differential; Female; Fluorine Radioisotopes; Humans; Male; Neuropsychological Tests; Positron-Emission Tomography; Radioactive Tracers; Reproducibility of Results; Stilbenes

Pterostilbene (Pt; trans-3,5-dimethoxy-4'-hydroxystilbene) is a natural phenol found in blueberries and grapevines. It shows remarkable biomedical activities similar to those of resveratrol. Its high bioavailability is a major advantage for possible biomedical applications. The goal of the study was to evaluate the effects of chronic pterostilbene administration on cognitive performance in aged rats with mild cognitive impairment.. 18-month-old animals were subjected to behavioral tests to establish the "baseline", then divided into treatment and control groups. The former were chronically fed Pt (22.5 mg/kg-day) for 20 consecutive days. At the end of this period all animals were tested again and sacrificed. The dentate gyrus, the hippocampus and the prefrontal and perirhinal cortices were then collected, and RT-qPCR and/or Western blot analyses were performed on a few transcripts/proteins involved in synaptic remodeling. Mitochondrial content was also assessed.. Pt administration improved performance in behavioral tests and positively affected memory consolidation. We found increased levels of REST, PSD-95 and mitochondrial porin1 in the dentate gyrus and a positive correlation between T-maze test score and levels of cAMP responsive element binding protein (CREB) phosphorylation.. These results underscore the therapeutic potential of Pt supplementation for age-related cognitive decline.

Topics: Aging; Animals; Behavior, Animal; Cognition; Cognitive Dysfunction; CREB-Binding Protein; Dentate Gyrus; Disks Large Homolog 4 Protein; Maze Learning; Rats; Repressor Proteins; Stilbenes

Brain amyloid deposition is one of the main hallmarks of Alzheimer's disease (AD) and two approaches are available for assessing amyloid pathology in vivo: cerebrospinal fluid (CSF) biomarkers levels and amyloid load visualized by amyloid beta positron emission tomography imaging (Amy-PET) probes. We aimed to investigate the concordance between CSF biomarkers and Amy-PET in a memory clinic cohort. Moreover, using a proper clinical follow-up, we wanted to assess the diagnostic accuracy of CSF and PET biomarkers in predicting the progression of patients with mild cognitive impairment (MCI) to AD dementia. We included 31 MCI patients who underwent [18F]florbetaben PET and CSF sampling (Aβ1-42, t-Tau, p-Tau). A semiquantitative visual scan assessment was used to quantify amyloid deposition in 5 brain regions, rating from 1 (negative), to 2 and 3 (positive). CSF biomarkers were considered abnormal if: Aβ1-42 < 600 pg/ml, p-Tau/Aβ1-42 > 0.08 and t-Tau/Aβ1-42 > 0.52. We also applied less lenient cutoffs of 550 pg/ml and 450 pg/ml for Aβ1-42. The concordance rate was 77% between Amy-PET and CSF Aβ1-42 levels, and 89% between Amy-PET and p-Tau/Aβ1-42 and t-Tau/Aβ1-42. According to the clinical follow-up, Amy-PET (sensitivity [SE] 93.7%, specificity [SP] 80%) exhibited the best diagnostic accuracy in discriminating AD from non-AD, followed by p-Tau/Aβ1-42 ratio and t-Tau/Aβ1-42 ratio (SE 93.7%, SP 66.6%), and Aβ1-42 levels (SE 81%, SP 60%). The regional uptake of [18F]florbetaben PET in the precuneus and the striatum showed the best SP (86.6%). In discordant cases, the clinical diagnosis was most often in agreement with PET results. In general, concordance between CSF biomarkers and Amy-PET was good, especially when the ratios between CSF amyloid and Tau biomarkers were used. However, Amy-PET proved to be superior to CSF Aβ1-42 in terms of diagnostic accuracy for AD, with the possibility to further increase its specificity by focusing the analysis in specific areas such as the precuneus/posterior cingulate cortex and the striatum.

Topics: Aged; Alzheimer Disease; Amyloid beta-Peptides; Aniline Compounds; Biomarkers; Cerebrospinal Fluid; Cognitive Dysfunction; Disease Progression; Female; Follow-Up Studies; Humans; Male; Middle Aged; Peptide Fragments; Positron-Emission Tomography; Predictive Value of Tests; Sensitivity and Specificity; Stilbenes; tau Proteins

Hypoxia-ischemia (HI) remains a major cause of perinatal mortality and chronic disability in newborns worldwide (1-6 for 1000 births) with a high risk of future motor, behavioral and neurological deficits. Keeping newborns under moderate hypothermia is the unique therapeutic approach but is not sufficiently successful as nearly 50% of infants do not respond to it. In a 7-day post-natal rat model of HI, we used pregnant and breastfeeding female nutritional supplementation with piceatannol (PIC), a polyphenol naturally found in berries, grapes and passion fruit, as a neuroprotective strategy. Maternal supplementation led to neuroprotection against neonate brain damage and reversed their sensorimotor deficits as well as cognitive impairments. Neuroprotection of per os maternal supplementation with PIC is a preventive strategy to counteract brain damage in pups induced by HI. This nutritional approach could easily be adopted as a preventive strategy in humans.

Topics: Animals; Animals, Newborn; Behavior, Animal; Brain; Brain Injuries; Cognitive Dysfunction; Dietary Supplements; Disease Models, Animal; Female; Hypoxia; Hypoxia-Ischemia, Brain; Ischemia; Maternal Nutritional Physiological Phenomena; Neurons; Neuroprotection; Neuroprotective Agents; Pregnancy; Rats; Stilbenes

The threshold for amyloid positivity by visual assessment on PET has been validated by comparison to amyloid load measured histopathologically and biochemically at post mortem. As such, it is now feasible to use qualitative visual assessment of amyloid positivity as an in-vivo gold standard to determine those factors which can modify the quantitative threshold for amyloid positivity. We calculated quantitative amyloid load, measured as Standardized Uptake Value Ratios (SUVRs) using [18-F]florbetaben PET scans, for 159 Hispanic and non-Hispanic participants, who had been classified clinically as Cognitively Normal (CN), Mild Cognitive Impairment (MCI) or Dementia (DEM). PET scans were visually rated as amyloid positive (A+) or negative (A-), and these judgments were used as the gold standard with which to determine (using ROC analyses) the SUVR threshold for amyloid positivity considering factors such as age, ethnicity (Hispanic versus non-Hispanic), gender, cognitive status, and apolipoprotein E ε4 carrier status. Visually rated scans were A+ for 11% of CN, 39.0% of MCI and 70% of DEM participants. The optimal SUVR threshold for A+ among all participants was 1.42 (sensitivity = 94%; specificity = 92.5%), but this quantitative threshold was higher among E4 carriers (SUVR = 1.52) than non-carriers (SUVR = 1.31). While mean SUVRs did not differ between Hispanic and non-Hispanic participants;, a statistically significant interaction term indicated that the effect of E4 carrier status on amyloid load was greater among non-Hispanics than Hispanics. Visual assessment, as the gold standard for A+, facilitates determination of the effects of various factors on quantitative thresholds for amyloid positivity. A continuous relationship was found between amyloid load and global cognitive scores, suggesting that any calculated threshold for the whole group, or a subgroup, is artefactual and that the lowest calculated threshold may be optimal for the purposes of early diagnosis and intervention.

Topics: Age Factors; Aged; Aged, 80 and over; Amyloid beta-Peptides; Aniline Compounds; Apolipoprotein E4; Cognitive Dysfunction; Dementia; Female; Hispanic or Latino; Humans; Male; Middle Aged; Neuroimaging; Positron-Emission Tomography; Sensitivity and Specificity; Sex Factors; Stilbenes

The rate of clinical progression of cognitive impairment in subjects with early amyloid deposition is unknown. The primary aim of the study was to follow the rate of cognitive decline over 1 year in patients with amnestic mild cognitive impairment (aMCI) by determining amyloid retention levels in terms of standardized uptake value ratios (SUVr) that ranged from 0.85 to 1.57. The secondary objective was to compare the rate of cognitive decline between subjects with and without early amyloid positivity.. Of 66 aMCI subjects evaluated with [. Of the 41 aMCI subjects, 38 completed the assessment according to the study protocol. Amyloid-positive (Aβ+ ) subjects (N = 18, age 75.6 ± 5.8 years, six men, 12 women) showed greater clinical deterioration according to the Mattis Dementia Rating Scale (MDRS) score (p = 0.006). Amyloid-negative (Aβ-) subjects (N = 20, age 72.4 ± 5.8 years, 11 men, 6 women) showed no significant changes in MDRS score over 1 year. MDRS score significantly decreased (MDRS+) in 37% of the aMCI subjects, and remained stable (MDRS-) in the remaining 63%. Among subjects with cognitive deterioration, 86% were Aβ+ and 14% were Aβ-, while 25% of the MDRS- subjects were Aβ+ and 75% were Aβ- (χ. This study demonstrated that early amyloid deposition predicts cognitive decline in subjects with aMCI, with a higher rate of decline in those with SUVr above a threshold of 1.21. Detection of early amyloid positivity may help in selecting the target population for preventive therapeutic interventions and in designing treatment trials (Trial number, EudraCT 2015-001184-39).

Topics: Aged; Aged, 80 and over; Amyloid; Aniline Compounds; Cognitive Dysfunction; Early Diagnosis; Female; Humans; Male; Mental Status and Dementia Tests; Middle Aged; Neocortex; Positron-Emission Tomography; Radiopharmaceuticals; Stilbenes

Topics: Aging; Alzheimer Disease; Amyloid beta-Peptides; Animal Feed; Animals; Biomarkers; Brain; Cognitive Dysfunction; Cytokines; Disease Models, Animal; Flavonoids; Fruit; Glycogen Synthase Kinase 3 beta; Male; Mice; Molecular Structure; Peptide Fragments; Phosphorylation; Protein Aggregates; Psoralea; Resveratrol; Stilbenes; tau Proteins

BACKGROUND Traumatic brain injury (TBI) is characterized by cognitive deficits, which was associated with brain oxidative stress and apoptosis. Resveratrol (RSV) is an anti-apoptotic and anti-oxidative. This study aimed to investigate neuroprotective effects and involved molecular mechanisms in TBI. MATERIAL AND METHODS RSV and p38 inhibitor were administrated to TBI rats. Cognitive deficits were evaluated by Morris water maze assay. Reactive oxygen species (ROS) and apoptosis were detected in rat brains by fluorescent staining. Western blotting was used to assess the phosphorylation of p38 and the expression levels of Nrf2, HO1, and activated caspase-3. RESULTS RSV administration attenuated cognitive deficits of TBI rats. The ROS generation and apoptosis in the brain of TBI rats were suppressed by RSV treatment. Moreover, RSV treatment recovered activation of p38/Nrf2/HO1 signaling pathway. The co-administration of p38 inhibitor impaired RSV's attenuating effects on cognitive deficits, brain apoptosis, and ROS generation. CONCLUSIONS RSV attenuated cognitive deficits of TBI by inhibiting oxidative stress-mediated apoptosis via targeting p38/Nrf2 signaling.

Topics: Animals; Antioxidants; Apoptosis; Brain; Brain Injuries, Traumatic; Cognition; Cognitive Dysfunction; Female; Male; MAP Kinase Signaling System; Neuroprotective Agents; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Resveratrol; Stilbenes

Chronic unpredictable mild stress (CUMS) leads to neuropsychiatric disorders, such as depression, anxiety and cognitive impairment. Resveratrol is a natural polyphenol existed in polygonum cuspidatum and has been demonstrated to be a potent activator of Sirtuin 1 (Sirt1). Previous studies reported that resveratrol treatment ameliorated CUMS-induced depressive-like behavior and cognitive deficits through upregulating cAMP response element-binding protein (CREB) and brain derived neurotrophic factor (BDNF) expression. However, the upstream signalling pathway mediating CREB/BDNF expression and then exerting a protective role on cognitive function remains unclear. The present study aims to investigate the possible mechanism of resveratrol on CUMS-induced cognitive deficits. Male Sprague Dawley rats were adminstrated resveratrol (40 and 80 mg/kg) every day for 4 consecutive weeks before exposure to CUMS procedure. Morris Water Maze test was used to appraise spatial learing and memory of rats. Sirt1/miR-134 signalling pathway and CREB/BDNF expression in hippocampus of rats were measured. We also explored Sirt1/miR-134 signalling pathway and CREB/BDNF expression in primary cultured hippocampus neurons with resveratrol (25, 50 and 100 μmol/L) treatment. We found that resveratrol treatment prevented spatial learing and memory impairment induced by CUMS. Meanwhile the potential mechanism of resveratrol was associated with increased levels of Sirt1, CREB phosphorylation (p-CREB), CREB, BDNF and decreased levels of miR-134 in vivo and in vitro. In conclusion, our study showed that the neuroprotective effect of resveratrol on CUMS-induced cognitive impairment may rely on activating Sirt1/miR-134 pathway and then upregulating its downstream CREB/BDNF expression in hippocampus.

Topics: Animals; Brain-Derived Neurotrophic Factor; Cognitive Dysfunction; Cyclic AMP Response Element-Binding Protein; Disease Models, Animal; Hippocampus; Male; Maze Learning; MicroRNAs; Nootropic Agents; Random Allocation; Rats, Sprague-Dawley; Resveratrol; Sirtuin 1; Spatial Memory; Stilbenes; Stress, Psychological; Uncertainty

Depression is a risk factor for mild cognitive impairment (MCI) and for the conversion from MCI to Alzheimer's disease (AD). This study investigated regional cerebral glucose metabolism (rCMglc) in older adults with depression and MCI, either with or without amyloidopathy.. We recruited 31 older adults diagnosed with depression and MCI, and 21 older adults with normal cognition (NC). All participants completed demographic questionnaires and were examined with a standardized neuropsychological battery, F-18 fluorodeoxyglucose positron emission tomography (PET), and F-18 florbetaben PET. We classified subjects with depression and MCI into amyloid-β-positive (CDAP; n = 16) and amyloid-β-negative (CDAN; n = 15) groups. Pairwise rCMglc analyses were conducted between all three groups (CDAP vs. NC, CDAN vs. NC, and CDAP vs. CDAN).. In comparison with the NC group, the CDAP group showed reduced rCMglc predominantly in temporoparietal regions, whereas the CDAN group showed lower rCMglc in regions of the frontal lobe, in addition to the temporoparietal regions. The CDAN group also showed lower rCMglc in right anterior cingulate and left inferior orbitofrontal regions, in a comparison between the CDAP and CDAN groups.. The generalizability of the findings is limited because this study has a relatively small number of participants. In addition, this study used cross-sectional design rather than longitudinal design.. Our findings may provide a reference to assess the risk of future cognitive deterioration. Consequently, this study is expected to contribute to prevention and early identification of dementia associated with AD.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Amyloid; Aniline Compounds; Cerebral Cortex; Cognitive Dysfunction; Cross-Sectional Studies; Depressive Disorder; Female; Fluorodeoxyglucose F18; Glucose; Humans; Male; Middle Aged; Positron-Emission Tomography; Radiopharmaceuticals; Stilbenes

Biomarkers of neurodegeneration play a major role in the diagnosis of Alzheimer's disease (AD). Information on both amyloid-β accumulation, e.g., from amyloid positron emission tomography (PET), and downstream neuronal injury, e.g., from 18F-fluorodeoxyglucose (FDG) PET, would ideally be obtained in a single procedure.. On the basis that the parallelism between brain perfusion and glucose metabolism is well documented, the objective of this work is to evaluate whether brain perfusion estimated in a dual-point protocol of 18F-florbetaben (FBB) PET can be a surrogate of FDG PET in appropriate use criteria (AUC) for amyloid PET.. This study included 47 patients fulfilling international AUC for amyloid PET. FDG PET, early FBB (pFBB) PET (0-10 min post injection), and standard FBB (sFBB) PET (90-110 min post injection) scans were acquired. Results of clinical subjective reports and of quantitative region of interest (ROI)-based analyses were compared between procedures using statistical techniques such as Pearson's correlation coefficients and t-tests.. pFBB and FDG visual reports on the 47 patients showed good agreement (k  >  0.74); ROI quantitative analysis indicated that both data modalities are highly correlated; and the t-test analysis does not reject the null hypothesis that data from pFBB and FDG examinations comes from independent random samples from normal distributions with equal means and variances.. A good agreement was found between pFBB and FDG data as obtained by subjective visual and quantitative analyses. Dual-point FBB PET scans could offer complementary information (similar to that from FDG PET and FBB PET) in a single procedure, considering pFBB as a surrogate of FDG.

Topics: Amyloid; Aniline Compounds; Brain; Cognitive Dysfunction; Dementia; Fluorodeoxyglucose F18; Follow-Up Studies; Humans; Mental Disorders; Positron-Emission Tomography; Prospective Studies; Radiopharmaceuticals; Stilbenes

The maladaptive response of aged microglia to surgery and consequent neuroinflammation plays a key pathogenic role in postoperative cognitive dysfunction (POCD). Here, we assessed the preventive effect of resveratrol (RESV) for POCD in aged rats. The emulsified form of RESV (e-RESV) was selected to improve its oral and brain bioavailability. Animals were assigned to one of four groups: e-RESV (80 mg/kg) versus vehicle treatment by abdominal surgery versus isoflurane anesthesia alone (n = 8 in each group). The dose-dependent effects of e-RESV were also assessed in dose range of 0-60 mg/kg. Either vehicle or e-RESV was administered intragastrically 24 h before surgery. Seven days after procedure, cognitive function was evaluated using a novel object recognition test, followed by measurement of hippocampal pro-inflammatory cytokine levels. Our results showed that pre-treatment with e-RESV attenuated the surgery-induced cognitive impairment and related hippocampal neuroinflammation at 40 mg/kg or higher doses. Additionally, the ex-vivo experiments revealed that the preemptive e-RESV regimen reduced the hippocampal microglial immune reactivity to lipopolysaccharide. Furthermore, e-RESV induced neuroprotective benefits were inhibited by the concomitant administration of sirtinol, a specific SIRT1 inhibitor. Our findings imply the preventive potential of e-RESV for POCD via the SIRT1 signaling pathway.

Topics: Administration, Oral; Aging; Animals; Biological Availability; Cognitive Dysfunction; Cytokines; Dose-Response Relationship, Drug; Emulsions; Hippocampus; Inflammation; Inflammation Mediators; Male; Microglia; Postoperative Complications; Rats, Wistar; Resveratrol; Signal Transduction; Sirtuin 1; Stilbenes

Most clinical trials focus on amyloid-β positive (Aβ+) amnestic mild cognitive impairment (aMCI), but screening failures are high because only a half of patients with aMCI are positive on Aβ PET. Therefore, it becomes necessary for clinicians to predict which patients will have Aβ biomarker.. We aimed to compare clinical factors, neuropsychological (NP) profiles, and apolipoprotein E (APOE) genotype between Aβ+ aMCI and Aβ-aMCI and to develop a clinically useful prediction model of Aβ positivity on PET (PET-Aβ+) in aMCI using a nomogram.. We recruited 523 aMCI patients who underwent Aβ PET imaging in a nation-wide multicenter cohort. The results of NP measures were divided into following subgroups: 1) Stage (Early and Late-stage), 2) Modality (Visual, Verbal, and Both), 3) Recognition failure, and 4) Multiplicity (Single and Multiple). A nomogram for PET-Aβ+ in aMCI patients was constructed using a logistic regression model.. PET-Aβ+ had significant associations with NP profiles for several items, including high Clinical Dementia Rating Scale Sum of Boxes score (OR 1.47, p = 0.013) and impaired memory modality (impaired both visual and verbal memories compared with visual only, OR 3.25, p = 0.001). Also, presence of APOEɛ4 (OR 4.14, p < 0.001) was associated with PET-Aβ+. These predictors were applied to develop the nomogram, which showed good prediction performance (C-statistics = 0.79). Its prediction performances were 0.77/0.74 in internal/external validation.. The nomogram consisting of NP profiles, especially memory domain, and APOEɛ4 genotype may provide a useful predictive model of PET-Aβ+ in patients with aMCI.

Topics: Aged; Aged, 80 and over; Amyloid beta-Peptides; Aniline Compounds; Apolipoproteins E; Cognitive Dysfunction; Cohort Studies; Female; Humans; Male; Neuropsychological Tests; Nomograms; Positron-Emission Tomography; Reproducibility of Results; Stilbenes

Current research diagnostic criteria for Alzheimer's disease (AD) and mild cognitive impairment (MCI) due to AD include biomarkers to supplement clinical testing. Recently, we demonstrated that dual time-point [18F]FBB PET is able to deliver both blood flow and amyloid-β (Aβ) load surrogates.. The aim of this study was to investigate whether these surrogates can be utilized as AD biomarkers.. 112 subjects (41 with MCI, 50 with probable/possible AD, 21 with other dementias) underwent dual time-point [18F]FBB PET. Data were visually and relative quantitatively (Herholz scores for the early and composite SUVRs for the late PET data) analyzed.. In the early images AD-typical patterns were present in 42% /27% /33% of probable/possible AD/MCI/other dementia cases. In late [18F]FBB PET, 42% /29% /38% of probable/possible AD/ MCI/other dementia cases were Aβ-positive. 17% of the MCIs were categorized as "MCI due to AD-high likelihood", 44% of the probable ADs as "probable AD with high evidence of AD pathophysiological process" and 28% of the possible ADs as "possible AD with evidence of AD pathophysiological process". 27% of all subjects showed a positive diagnostic and progression biomarker. Herholz scores were lower (0.85±0.05 versus 0.88±0.04, p = 0.015) for probable/possible AD versus MCI. Composite late phase SUVRs were significantly higher (1.65±0.23 versus 1.15±0.17, p < 0.005) in Aβ-positive versus Aβ-negative patients. Herholz and MMSE scores were positively correlated (R = 0.30 p = 0.006).. Dual time-point [18F]FBB PET provides dual biomarker information which enables to categorize MCI and AD dementia patients according to established diagnostic criteria. Thus, dual time-point [18F]FBB PET has great potential to supplement diagnostic dementia workups.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Aniline Compounds; Biomarkers; Brain; Cognitive Dysfunction; Diagnosis, Differential; Female; Fluorine Radioisotopes; Humans; Male; Middle Aged; Neuroimaging; Positron-Emission Tomography; Retrospective Studies; Stilbenes

Disease-modifying treatments for Alzheimer's disease (AD) may require implementation during early stages of β-amyloid accumulation, well before patients have objective cognitive decline. In this study we aimed to assess the clinical value of subjective cognitive impairment (SCI) by examining the cross-sectional relationship between β-amyloid load and SCI. Cerebral β-amyloid and SCI was assessed in a cohort of 112 cognitively normal subjects. Subjective cognition was evaluated using specific questions on memory and cognition and the MAC-Q. Participants had cerebral β-amyloid load measured with

Topics: Affect; Aged; Aging; Amyloid beta-Peptides; Aniline Compounds; Apolipoprotein E4; Brain; Cognitive Dysfunction; Cohort Studies; Confusion; Cross-Sectional Studies; Diagnostic Self Evaluation; Educational Status; Female; Humans; Longitudinal Studies; Perception; Positron-Emission Tomography; Radiopharmaceuticals; Self Report; Stilbenes

Inflammation and oxidative stress (OS) are key points in age progression. Both processes impact negatively in cognition and in brain functions. Resveratrol (RV) has been postulated as a potent antioxidant natural compound, with rejuvenating properties. Inducing a metabolic stress by high-fat (HF) diet in aged C56/BL6 (24 months) led to cognitive disturbances compared with control age mated and with young mice. These changes were prevented by RV. Molecular determinations demonstrated a significant increase in some inflammatory parameters (TNF-α, Cxcl10, IL-1, IL-6, and Ccl3) in old mice, but slight changes in OS machinery. RV mainly induced the recovery of the metabolically stressed animals. The study of key markers involved in senescence and rejuvenation (mitochondrial biogenesis and Sirt1-AMPK-PGC1-α) demonstrated that RV is also able to modulate the changes in these cellular metabolic pathways. Moreover, changes of epigenetic marks (methylation and acetylation) that are depending on OS were demonstrated. On the whole, results showed the importance of integrative role of different cellular mechanisms in the deleterious effects of age in cognition and the beneficial role of RV. The work presented in this study showed a wide range of processes modified in old age and by metabolic stress, weighting the importance of each one and the role of RV as a possible strategy for fighting against.

Topics: 5-Methylcytosine; Animals; Biomarkers; Body Weight; Cognitive Dysfunction; Energy Intake; Gene Expression Regulation; Glucose Tolerance Test; Inflammation; Male; Maze Learning; Memory; Mice, Inbred C57BL; Neuroprotective Agents; Oxidative Phosphorylation; Oxidative Stress; Resveratrol; Stilbenes; Stress, Physiological

Resveratrol, a polyphenol phytoalexine, has been shown to play a neuroprotective role in the neurodegenerative process in Alzheimer's disease (AD) and improve memory function in dementia. However, the in vivo effect of resveratrol in normal aging models of learning and memory has not yet been evaluated. Therefore, the present neurobehavioral study was undertaken to evaluate the effect of resveratrol on cognitive impairment induced by aging in passive avoidance and Morris water maze (MWM) tests. Male Wistar albino rats were divided into four groups: young control (4month), young resveratrol (4month+RESV), old control (24month) and old resveratrol (24month+RESV). Resveratrol (50mg/kg/day) was given to the 4month+RESV and 24month+RESV groups orally for 12weeks. There was no significant difference between the groups for the first day of latency, while in aged rats, the second day of latency was significantly shortened compared to the young group in the passive avoidance test (p<0.05). Additionally, in the MWM test, the results showed a decrease in the time spent in the escape platform's quadrant in the probe test in aged rats (p<0.05). The administration of resveratrol at 50mg/kg/day increased the retention scores in the passive avoidance test and the time spent in the escape platform's quadrant in the MWM task (p<0.05). Furthermore resveratrol attenuated the protein levels of TNFα and IL1β in the 24-month group. These findings indicate that aging impairs emotional and spatial learning-memory and resveratrol reverses the effect of age-related learning and memory impairment. The results of this study suggest that resveratrol is effective in preventing cognitive deficit in aged rats by inhibiting the production of inflammatory cytokines.

Topics: Aging; Animals; Anti-Inflammatory Agents, Non-Steroidal; Avoidance Learning; Behavior, Animal; Cognitive Dysfunction; Cytokines; Disease Models, Animal; Inflammation; Male; Rats, Wistar; Resveratrol; Spatial Learning; Stilbenes

To investigate the topographical distribution of tau pathology and its effect on functional and structural changes in patients with Alzheimer disease (AD) and mild cognitive impairment (MCI) by using (18)F-AV-1451 PET.. We included 20 patients with AD, 15 patients with MCI, and 20 healthy controls, and performed neuropsychological function tests, MRI, as well as (18)F-florbetaben (for amyloid) and (18)F-AV-1451 (for tau) PET scans. By using the regional volume-of-interest masks extracted from MRIs, regional binding values of standardized uptake value ratios and volumes were measured. We compared regional binding values among 3 diagnostic groups and identified correlations among the regional binding values, performance in each cognitive function test, and regional atrophy.. (18)F-AV-1451 binding was increased only in the entorhinal cortex in patients with MCI, while patients with AD exhibited greater binding in most cortical regions. In the 35 patients with MCI and AD, (18)F-AV-1451 binding in most of the neocortex increased with a worsening of global cognitive function. The visual and verbal memory functions were associated with the extent of (18)F-AV-1451 binding, especially in the medial temporal regions. The (18)F-AV-1451 binding also correlated with the severity of regional atrophy of the cerebral cortex.. Tau PET imaging with (18)F-AV-1451 could serve as an in vivo biomarker for the evaluation of AD-related tau pathology and monitoring disease progression. The accumulation of pathologic tau is more closely related to functional and structural deterioration in the AD spectrum than β-amyloid.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Amyloid beta-Peptides; Aniline Compounds; Atrophy; Cognitive Dysfunction; Disease Progression; Entorhinal Cortex; Female; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Memory; Neuropsychological Tests; Positron-Emission Tomography; Prospective Studies; Radiopharmaceuticals; Stilbenes; tau Proteins; Vision, Ocular

Many patients with diabetes are at increased risk of cognitive dysfunction and dementia. Resveratrol, a polyphenol found mainly in grapes and red wine, has antioxidant, anti-inflammatory, and neuroprotective activities. Studies demonstrated that resveratrol could prevent memory deficits and the increase in acetylcholinesterase activity in streptozotocin-induced diabetic rats. However, whether administration of resveratrol could modulate the structural synaptic plasticity in diabetic rats remains unknown. Therefore, we tested its influence against cognitive dysfunction as well as on hippocampal structural synaptic plasticity in streptozotocin-induced diabetic rats. Our results showed that the cognitive performances in diabetic group were markedly deteriorated, accompanied by noticeable alterations in oxidative as well as inflammation parameters, SYN and GAP-43 expression were reduced in the hippocampus. In contrast, chronic treatment with resveratrol (10, 20mg/kg) improved neuronal injury and cognitive performance by attenuating oxidative stress and inflammation as well as inhibiting synapse loss in diabetic rats. In conclusion, the present study suggested that oral supplementation of resveratrol might be a potential therapeutic strategy for the treatment and/or prevention of diabetic encephalopathy.

Topics: Animals; Antioxidants; Blood Glucose; Cognition; Cognition Disorders; Cognitive Dysfunction; Diabetes Complications; Diabetes Mellitus, Experimental; Hippocampus; Inflammation; Male; Maze Learning; Memory; Neuronal Plasticity; Oxidative Stress; Rats; Rats, Sprague-Dawley; Resveratrol; Stilbenes; Superoxide Dismutase; Synapses

We investigated the effects of 4-17 month supplementation with ω-3 fatty acids and antioxidants (Smartfish drink; Smartfish AS, Oslo, Norway) in 12 patients with minor cognitive impairment (MCI) [minimental state examination (MMSE) ≥19], 2 patients with pre-MCI (normal MMSE), and 7 patients with Alzheimer disease (AD) (MMSE <19). We measured the phagocytosis of amyloid-β 1-42 (Aβ) by flow cytometry and microscopy, the transcription of inflammatory genes by RT-PCR, the production of resolvin D1 (RvD1) by enzyme immunoassay, and the cognitive status by MMSE. In patients with MCI and pre-MCI, phagocytosis of Aβ by monocytes increased from 530 to 1306 mean fluorescence intensity units (P = 0.016). The increase in patients with AD was not significant (N.S.). The lipidic mediator RvD1, which stimulates Aβ phagocytosis in vitro, increased in macrophages in 80% of patients with MCI and pre-MCI (mean increase 9.95 pg/ml) (N.S.). Transcription of inflammatory genes' mRNAs was increased in a subgroup of patients with low transcription at baseline, whereas it was not significantly changed in patients with high transcription at baseline. The mean MMSE score of patients with MCI and pre-MCI was 25.9 at baseline and 25.7 after 4-17 months (N.S.). Our study is the first to show significant immune and biochemical effects of ω-3 fatty acids with antioxidants in patients with MCI. Cognitive benefits of ω-3 supplementation in patients with MCI should be tested in a clinical trial.

Topics: Adult; Aged; Aged, 80 and over; Alzheimer Disease; Amyloid beta-Peptides; Antioxidants; Cholecalciferol; Cognitive Dysfunction; Dietary Supplements; Docosahexaenoic Acids; Fatty Acids, Omega-3; Female; Humans; Inflammation; Macrophages; Male; Mental Status Schedule; Middle Aged; Monocytes; Phagocytosis; Resveratrol; RNA, Messenger; Stilbenes

Prenatal stress induces cognitive functional impairment in offspring, an eventuality in which mitochondrial dysfunction and oxidative stress are believed to be closely involved. In this study, the involvement of the AMP-activated protein kinase (AMPK) pathway was investigated. A well-known activator, resveratrol (Res), was used to induce AMPK activation in SH-SY-5Y cells. Significant mitochondrial biogenesis and phase II enzyme activation, accompanied by decreased protein oxidation and GSSG content, were observed after Res treatment, and inhibition of AMPK with Compound c abolished the induction effects of Res. Further study utilizing a prenatal restraint stress (PRS) animal model indicated that maternal supplementation of Res may activate AMPK in the hippocampi of both male and female offspring, and that PRS-induced mitochondrial loss in the offspring hippocampus was inhibited by Res maternal supplementation. In addition, Res activated Nrf2-mediated phase II enzymes and reduced PRS-induced oxidative damage in both male and female offspring. Moreover, PRS markedly decreased mRNA levels of various neuron markers, as well as resultant offspring cognitive function, based on spontaneous alternation performance and Morris water maze tests, the results of which were significantly improved by maternal Res supplementation. Our results provide evidence indicating that AMPK may modulate mitochondrial content and phase II enzymes in neuronal cells, a process which may play an essential role in preventing PRS-induced cognitive impairment. Through the coupling of mitochondrial biogenesis and the Nrf2 pathway, AMPK may modulate oxidative stress and be a promising target against neurological disorders.

Topics: AMP-Activated Protein Kinases; Animals; Antioxidants; Cell Line; Cognition; Cognitive Dysfunction; Enzyme Activation; Female; Glutathione; Hippocampus; Humans; Male; Mitochondria; NF-E2-Related Factor 2; Oxidation-Reduction; Oxidative Stress; Pregnancy; Rats; Rats, Sprague-Dawley; Resveratrol; Stilbenes; Stress, Psychological