stilbenes and Dementia

Dementia is a collection of symptoms affecting a person's cognition. Dementia is debilitating, and therefore, finding an effective treatment is of utmost importance. Resveratrol, which exhibits neuroprotective effects, has low bioavailability. However, its glucoside polydatin is more bioavailable. Here, the evidence that supports the protective role of polydatin against dementia- related diseases such as Alzheimer's disease, vascular dementia, alcohol-related dementia, and Lewy body dementias is presented. The beneficial effects of polydatin from a mechanistic perspective are specifically emphasized in this review. Future directions in this area of research are also discussed.

Topics: Alzheimer Disease; Dementia; Glucosides; Humans; Lewy Body Disease; Stilbenes

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

Intake of dietary phytochemicals has frequently been associated with health benefits. Noninfectious diseases including cardiovascular disease (CVD), cancer and diabetes are major causes of death, whereas dementia cases are also increasing to 'epidemic' proportion. This review will focus on recent progress on mechanisms underlying the potential role of dietary phytochemicals in CVD, diabetes, cancer and dementia, with consideration of the latest clinical data.. The association of tea (Camellia sinensis), particularly catechins, with reported mechanistic effects for CVD, diabetes, cancer and cognition contributes to our understanding of the suggested benefits of tea consumption on health from limited and inconclusive clinical trial and epidemiological data. Resveratrol, which occurs in grapes (Vitis vinifera) and wine, and curcumin, a component of turmeric (Curcuma longa), are also emerging as potentially relevant to health, particularly for CVD and dementia, with some promising data also concluded for curcumin in cancer. Other phytochemicals mechanistically relevant for health include anthocyanins, isoflavones and glucosinolates, which are also discussed.. Evidence for the role of phytochemicals in health and disease is growing, but associations between phytochemicals and disease need to be more firmly understood and established from more robust clinical data using preparations that have been phytochemically characterized.

Topics: Cardiovascular Diseases; Catechin; Clinical Trials as Topic; Curcuma; Curcumin; Dementia; Diabetes Mellitus; Humans; Micronutrients; Neoplasms; Phytochemicals; Plant Extracts; Resveratrol; Stilbenes; Tea; Vitis; Wine

In contrast to many years of important research and clinical attention to the pathological effects of alcohol (ethanol) abuse, the past several decades have seen the publication of a number of peer-reviewed studies indicating the beneficial effects of light-moderate, nonbinge consumption of varied alcoholic beverages, as well as experimental demonstrations that moderate alcohol exposure can initiate typically cytoprotective mechanisms. A considerable body of epidemiology associates moderate alcohol consumption with significantly reduced risks of coronary heart disease and, albeit currently a less robust relationship, cerebrovascular (ischemic) stroke. Experimental studies with experimental rodent models and cultures (cardiac myocytes, endothelial cells) indicate that moderate alcohol exposure can promote anti-inflammatory processes involving adenosine receptors, protein kinase C (PKC), nitric oxide synthase, heat shock proteins, and others which could underlie cardioprotection. Also, brain functional comparisons between older moderate alcohol consumers and nondrinkers have received more recent epidemiological study. In over half of nearly 45 reports since the early 1990s, significantly reduced risks of cognitive loss or dementia in moderate, nonbinge consumers of alcohol (wine, beer, liquor) have been observed, whereas increased risk has been seen only in a few studies. Physiological explanations for the apparent CNS benefits of moderate consumption have invoked alcohol's cardiovascular and/or hematological effects, but there is also experimental evidence that moderate alcohol levels can exert direct "neuroprotective" actions-pertinent are several studies in vivo and rat brain organotypic cultures, in which antecedent or preconditioning exposure to moderate alcohol neuroprotects against ischemia, endotoxin, beta-amyloid, a toxic protein intimately associated with Alzheimer's, or gp120, the neuroinflammatory HIV-1 envelope protein. The alcohol-dependent neuroprotected state appears linked to activation of signal transduction processes potentially involving reactive oxygen species, several key protein kinases, and increased heat shock proteins. Thus to a certain extent, moderate alcohol exposure appears to trigger analogous mild stress-associated, anti-inflammatory mechanisms in the heart, vasculature, and brain that tend to promote cellular survival pathways.

Topics: Alcohol Drinking; Animals; Antioxidants; Cardiotonic Agents; Cardiovascular Diseases; Central Nervous System Depressants; Dementia; Ethanol; Humans; Neuroprotective Agents; Nitric Oxide; Protein Kinase C; Resveratrol; Stilbenes

Several epidemiological studies indicate that moderate consumption of red wine is associated with a lower incidence of dementia and Alzheimer's disease. Red wine is enriched in antioxidant polyphenols with potential neuroprotective activities. Despite scepticism concerning the bioavailability of these polyphenols, in vivo data have clearly demonstrated the neuroprotective properties of the naturally occurring polyphenol resveratrol in rodent models for stress and diseases. Furthermore, recent work in cell cultures and animal models has shed light on the molecular mechanisms potentially involved in the beneficial effects of resveratrol intake against the neurodegenerative process in Alzheimer's disease.

Topics: Alzheimer Disease; Animals; Antioxidants; Dementia; Flavonoids; Humans; Nerve Degeneration; Phenols; Polyphenols; Resveratrol; Stilbenes; Wine

Aging is characterized by a progressive deterioration of physiological functions and metabolic processes. Healthy aging remains one of the ideals of modern society. In aging and in diseases associated with the elderly, such as Alzheimer's or Parkinson's, the loss of cells in vital structures or organs may be related to several factors, among which the production of reactive oxygen species (ROS) by mitochondria is a common denominator, one that leads to DNA damage, apoptosis and death. Although a diet rich in antioxidants seems to offer hope in delaying the onset of unhealthy disorders that accompany aging, no clinical treatment as such has yet been developed and anti-aging drugs are still unavailable. It is well established that reducing food intake (caloric restriction) extends the life-span in a wide range of species. The protein implicated in this protective process is the silent information regulator 2 (SIR2, SIRT1 in mammals), an enzyme that belongs to a nicotinamide adenine dinucleotide (NAD)+-dependent protein deacetylases. SIRs regulate gene silencing, DNA repair, rDNA recombination, and ageing, apart from regulating programmed cell death. In this context, increasing SIRT1 has been found to protect cells against amyloid-beta-induced ROS production and DNA damage, thereby reducing apoptotic death in vitro. Moreover, it has been demonstrated that Alzheimer's and Huntington's disease neurons are rescued by the over-expression of SIRT1, induced by either caloric restriction or administration of resveratrol, a potential activator of this enzyme. The therapeutic use of resveratrol (a polyphenol present in red wines) and other related compounds, which utilize SIRT1 pathway modulators, in treating aging-related brain disorders will be discussed in this review. Provided herein are novel new compound related with resveratrol or sirtinol that are able to modulate sirtuin activity that will be tested to treat and/or prevent a wide variety of diseases including, disorders related to aging or neurodegenerative diseases.

Topics: Aging; Animals; Dementia; Enzyme Inhibitors; Humans; Models, Biological; Reactive Oxygen Species; Resveratrol; Sirtuins; Stilbenes

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

Although some studies have previously addressed the clinical impact of amyloid positron emission tomography (PET), none has specifically addressed its selective and hierarchical implementation in relation to cerebrospinal fluid analysis in a naturalistic setting.. This multicenter study was performed at French tertiary memory clinics in patients presenting with most complex clinical situations (i.e., early-onset, atypical clinical profiles, suspected mixed etiological conditions, unexpected rate of progression), for whom cerebrospinal fluid analysis was indicated but either not feasible or considered as noncontributory (ClinicalTrials.gov: NCT02681172).. Two hundred five patients were enrolled with evaluable florbetaben PET scans; 64.4% of scans were amyloid positive. PET results led to changed diagnosis and improved confidence in 66.8% and 81.5% of patients, respectively, and altered management in 80.0% of cases.. High-level improvement of diagnostic certainty and management is provided by selective and hierarchical implementation of florbetaben PET into current standard practices for the most complex dementia cases.

Topics: Aged; Amyloid; Aniline Compounds; Brain; Dementia; Diagnosis, Differential; Female; France; Humans; Male; Positron-Emission Tomography; Radiopharmaceuticals; Stilbenes

This methodological paper presents both a scientific rationale and a methodological approach for investigating the effects of resveratrol supplementation on mood and cognitive performance in postmenopausal women. Postmenopausal women have an increased risk of cognitive decline and dementia, which may be at least partly due to loss of beneficial effects of estrogen on the cerebrovasculature. We hypothesise that resveratrol, a phytoestrogen, may counteract this risk by enhancing cerebrovascular function and improving regional blood flow in response to cognitive demands. A clinical trial was designed to test this hypothesis.. Healthy postmenopausal women were recruited to participate in a randomised, double-blind, placebo-controlled (parallel comparison) dietary intervention trial to evaluate the effects of resveratrol supplementation (75 mg twice daily) on cognition, cerebrovascular responsiveness to cognitive tasks and overall well-being. They performed the following tests at baseline and after 14 weeks of supplementation: Rey Auditory Verbal Learning Test, Cambridge Semantic Memory Battery, the Double Span and the Trail Making Task. Cerebrovascular function was assessed simultaneously by monitoring blood flow velocity in the middle cerebral arteries using transcranial Doppler ultrasound.. This trial provides a model approach to demonstrate that, by optimising circulatory function in the brain, resveratrol and other vasoactive nutrients may enhance mood and cognition and ameliorate the risk of developing dementia in postmenopausal women and other at-risk populations.

Topics: Affect; Aged; Aged, 80 and over; Cerebrovascular Circulation; Clinical Protocols; Cognition; Cognition Disorders; Dementia; Dietary Supplements; Double-Blind Method; Female; Health Status; Humans; Mental Health; Middle Aged; Neuropsychological Tests; New South Wales; Phytoestrogens; Postmenopause; Regional Blood Flow; Research Design; Resveratrol; Risk Factors; Stilbenes; Time Factors; Treatment Outcome; Ultrasonography, Doppler, Transcranial

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

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 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

Previous studies have evaluated the diagnostic effect of amyloid positron emission tomography (PET) in selected research cohorts. However, these research populations do not reflect daily practice, thus hampering clinical implementation of amyloid imaging.. To evaluate the association of amyloid PET with changes in diagnosis, diagnostic confidence, treatment, and patients' experiences in an unselected memory clinic cohort.. Amyloid PET using fluoride-18 florbetaben was offered to 866 patients who visited the tertiary memory clinic at the VU University Medical Center between January 2015 and December 2016 as part of their routine diagnostic dementia workup. Of these patients, 476 (55%) were included, 32 (4%) were excluded, and 358 (41%) did not participate. To enrich this sample, 31 patients with mild cognitive impairment from the University Medical Center Utrecht memory clinic were included. For each patient, neurologists determined a preamyloid and postamyloid PET diagnosis that existed of both a clinical syndrome (dementia, mild cognitive impairment, or subjective cognitive decline) and a suspected etiology (Alzheimer disease [AD] or non-AD), with a confidence level ranging from 0% to 100%. In addition, the neurologist determined patient treatment in terms of ancillary investigations, medication, and care. Each patient received a clinical follow-up 1 year after being scanned.. Primary outcome measures were post-PET changes in diagnosis, diagnostic confidence, and patient treatment.. Of the 507 patients (mean [SD] age, 65 (8) years; 201 women [39%]; mean [SD] Mini-Mental State Examination score, 25 [4]), 164 (32%) had AD dementia, 70 (14%) non-AD dementia, 114 (23%) mild cognitive impairment, and 159 (31%) subjective cognitive decline. Amyloid PET results were positive for 242 patients (48%). The suspected etiology changed for 125 patients (25%) after undergoing amyloid PET, more often due to a negative (82 of 265 [31%]) than a positive (43 of 242 [18%]) PET result (P < .01). Post-PET changes in suspected etiology occurred more frequently in patients older (>65 years) than younger (<65 years) than the typical age at onset of 65 years (74 of 257 [29%] vs 51 of 250 [20%]; P < .05). Mean diagnostic confidence (SD) increased from 80 (13) to 89 (13%) (P < .001). In 123 patients (24%), there was a change in patient treatment post-PET, mostly related to additional investigations and therapy.. This prospective diagnostic study provides a bridge between validating amyloid PET in a research setting and implementing this diagnostic tool in daily clinical practice. Both amyloid-positive and amyloid-negative results had substantial associations with changes in diagnosis and treatment, both in patients with and without dementia.

Topics: Aged; Amyloid beta-Peptides; Aniline Compounds; Brain; Clinical Decision-Making; Cohort Studies; Dementia; Female; Humans; Male; Mental Status and Dementia Tests; Middle Aged; Positron-Emission Tomography; Prospective Studies; 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

To this day the definite diagnosis of Alzheimer's disease still relies on post-mortem histopathological detection of neurofibrillary tangles and beta-amyloid deposits. Amyloid positron emission tomography (PET) is a new diagnostic tool that enables the in vivo quantification of pathological beta-amyloid deposits. The aim of the current study was to evaluate to what extent. Imaging with FBB-PET was performed on 33 patients from our outpatient department for cognitive neurology. Beforehand all patients underwent a comprehensive clinical, neuropsychiatric and laboratory examination as well as imaging by means of magnetic resonance imaging (MRI) and fluorodeoxyglucose-PET. The working diagnoses before and after FBB-PET imaging were compared.. 17 out of 33 patients were scored as FBB-PET positive. In four cases the initial diagnosis had to be changed to Alzheimer's disease (three cases) and cerebral amyloid angiopathy (one case) due to the positive FBB-PET scan. 16 patients showed a negative FBB-PET scan. In three patients the initial diagnosis of Alzheimer's disease could be ruled out due to the negative FBB-PET scan. Overall, in 7 out of 33 examined patients the initial diagnosis had to be changed because of the findings of the FBB-PET scan. In 24 patients the initial diagnosis was confirmed by the results of the FBB-PET scan.. Amyloid-PET is currently no standard procedure in the diagnosis of dementia; however, it can be a helpful additional diagnostic tool when used according to the "Appropriate Use Criteria" and the S3 guidelines on dementia in cases of unclear clinical presentation, atypically early age of onset as well as in patients with persistent or progressive unexplained mild cognitive impairment. By facilitating early diagnosis amyloid-PET imaging allows patient selection for therapeutic drug trials.

Topics: Adult; Aged; Amyloid beta-Peptides; Aniline Compounds; Biomarkers; Brain; Dementia; Female; Humans; Male; Middle Aged; Molecular Imaging; Positron-Emission Tomography; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Stilbenes; Tissue Distribution

In recent years several [. All subjects were recruited with clinical suspicion of dementia due to neurodegenerative disease. FDG PET was undertaken by conventional methods, and amyloid PET was performed with FBB, with early recordings for the initial 10 min (early-phase FBB), and late recordings at 90-110 min p.i. (late-phase FBB). Regional SUVR with cerebellar and global mean normalization were calculated for early-phase FBB and FDG PET. Pearson correlation coefficients between FDG and early-phase FBB were calculated for predefined cortical brain regions. Furthermore, a visual interpretation of disease pattern using 3-dimensional stereotactic surface projections (3D-SSP) was performed, with assessment of intra-reader agreement.. Among a total of 33 patients (mean age 67.5 ± 11.0 years) included in the study, 18 were visually rated amyloid-positive, and 15 amyloid-negative based on late-phase FBB scans. Correlation coefficients for early-phase FBB vs. FDG scans displayed excellent agreement in all target brain regions for global mean normalization. Cerebellar normalization gave strong, but significantly lower correlations. 3D representations of early-phase FBB visually resembled the corresponding FDG PET images, irrespective of the amyloid-status of the late FBB scans.. Early-phase FBB acquisitions correlate on a relative quantitative and visual level with FDG PET scans, irrespective of the amyloid plaque density assessed in late FBB imaging. Thus, early-phase FBB uptake depicts a metabolism-like image, suggesting it as a valid surrogate marker for synaptic dysfunction, which could ultimately circumvent the need for additional FDG PET investigation in diagnosis of dementia.

Topics: Aged; Amyloidogenic Proteins; Aniline Compounds; Dementia; Female; Humans; Imaging, Three-Dimensional; Male; Middle Aged; Neurodegenerative Diseases; Positron-Emission Tomography; Statistics as Topic; Stereotaxic Techniques; Stilbenes; Time Factors

Amyloid imaging with (18)F-labeled radiotracers will allow widespread use, facilitating research, diagnosis, and therapeutic development for Alzheimer disease. The purpose of the study program was to compare cortical amyloid deposition using (18)F-florbetaben and PET in controls and subjects with mild cognitive impairment (MCI), frontotemporal lobar degeneration (FTLD), dementia with Lewy bodies (DLB), vascular dementia (VaD), Parkinson disease (PD), and Alzheimer disease (AD).. One hundred nine subjects in 3 clinical studies at Austin Health were reviewed: 32 controls, 20 subjects with MCI, and 30 patients with AD, 11 with FTLD, 7 with DLB, 5 with PD, and 4 with VaD underwent PET after intravenous injection of 300 MBq of (18)F-florbetaben. Standardized uptake value ratios (SUVR) using the cerebellar cortex as a reference region were calculated between 90 and 110 min after injection.. When compared with the other groups, AD patients demonstrated significantly higher SUVRs (P < 0.0001) in neocortical areas. Most AD patients (96%) and 60% of MCI subjects showed diffuse cortical (18)F-florbetaben retention. In contrast, only 9% of FTLD, 25% of VaD, 29% of DLB, and no PD patients and 16% of controls showed cortical binding. Although there was a correlation between Mini Mental State Examination and β-amyloid burden in the MCI group, no correlation was observed in controls, FTLD or AD.. (18)F-florbetaben had high sensitivity for AD, clearly distinguished patients with FTLD from AD, and provided results comparable to those reported with (11)C-Pittsburgh Compound B in a variety of neurodegenerative diseases.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Amyloid beta-Peptides; Aniline Compounds; Case-Control Studies; Cerebellum; Dementia; Female; Fluorine Radioisotopes; Frontotemporal Dementia; Humans; Image Processing, Computer-Assisted; Lewy Bodies; Male; Middle Aged; Neurodegenerative Diseases; Positron-Emission Tomography; Radioisotopes; Stilbenes; Treatment Outcome

Amyloid-beta (Abeta) plaque formation is a hallmark of Alzheimer's disease (AD) and precedes the onset of dementia. Abeta imaging should allow earlier diagnosis, but clinical application is hindered by the short decay half-life of current Abeta-specific ligands. (18)F-BAY94-9172 is an Abeta ligand that, due to the half-life of (18)F, is suitable for clinical use. We thus studied the effectiveness of this ligand in identifying patients with AD.. 15 patients with mild AD, 15 healthy elderly controls, and five individuals with frontotemporal lobar degeneration (FTLD) were studied. (18)F-BAY94-9172 binding was quantified by use of the standardised uptake value ratio (SUVR), which was calculated for the neocortex by use of the cerebellum as reference region. SUVR images were visually rated as normal or AD.. (18)F-BAY94-9172 binding matched the reported post-mortem distribution of Abeta plaques. All AD patients showed widespread neocortical binding, which was greater in the precuneus/posterior cingulate and frontal cortex than in the lateral temporal and parietal cortex. There was relative sparing of sensorimotor, occipital, and medial temporal cortex. Healthy controls and FTLD patients showed only white-matter binding, although three controls and one FTLD patient had mild uptake in frontal and precuneus cortex. At 90-120 min after injection, higher neocortical SUVR was observed in AD patients (2.0 [SD 0.3]) than in healthy controls (1.3 [SD 0.2]; p<0.0001) or FTLD patients (1.2 [SD 0.2]; p=0.009). Visual interpretation was 100% sensitive and 90% specific for detection of AD.. (18)F-BAY94-9172 PET discriminates between AD and FTLD or healthy controls and might facilitate integration of Abeta imaging into clinical practice.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Amyloid beta-Peptides; Aniline Compounds; Brain; Dementia; Diagnosis, Differential; Female; Humans; Image Interpretation, Computer-Assisted; Isotope Labeling; Male; Middle Aged; Plaque, Amyloid; Positron-Emission Tomography; Radiopharmaceuticals; Stilbenes