A Planar Five-Membered Aromatic Ring Stabilized by Only Two π-Electrons.

Many chemicals known today are partially or fully aromatic, since a ring framework experiences additional stabilization through the delocalization of π-electrons. While aromatic rings with equal numbers of π-electrons and ring atoms such as benzene are particularly stable, those with the minimally required two π-electrons are very rare and yet remain limited to three- and four-membered rings if not stabilized in the coordination sphere of heavy metals. Here we report the facile synthesis of a dipotassium cyclopentagallene, a unique example of a five-membered aromatic ring stabilized by only two π-electrons. Single-crystal X-ray diffraction revealed a planar Ga5 ring with almost equal gallium-gallium bond lengths, which together with computational and spectroscopic data confirm its aromatic character. Our results prove that aromatic stabilization goes far beyond what has previously been assumed as minimum π-electron count in a five-atom ring fragment.

Slow-wave sleep and motor progression in Parkinson disease.

Growing evidence from Alzheimer disease supports a potentially beneficial role of slow-wave sleep in neurodegeneration. However, the importance of slow-wave sleep in Parkinson disease is unknown. In 129 patients with Parkinson disease, we retrospectively tested whether sleep slow waves, objectively quantified with polysomnography, relate to longitudinal changes in Unified Parkinson's Disease Rating Scale motor scores. We found that higher accumulated power of sleep slow waves was associated with slower motor progression, particularly of axial motor symptoms, over a mean time of 4.6 ± 2.3 years. This preliminary finding suggests that deeper sleep relates to slower motor progression in Parkinson disease. Ann Neurol 2019;85:765-770.

Gray matter gamma-hydroxy-butyric acid and glutamate reflect beta-amyloid burden at old age.

Gamma-hydroxy-butyric acid (GABA) and glutamate are neurotransmitters with essential importance for cognitive processing. Here, we investigate relationships between GABA, glutamate, and brain ß-amyloid (Aß) burden before clinical manifestation of Alzheimer's disease (AD). Thirty cognitively healthy adults (age 69.9 ± 6 years) received high-resolution atlas-based 1H-magnetic resonance spectroscopic imaging (MRSI) at ultra-high magnetic field strength of 7 Tesla for gray matter-specific assessment of GABA and glutamate. We assessed Aß burden with positron emission tomography and risk factors for AD. Higher gray matter GABA and glutamate related to higher Aß-burden (ß = 0.60, p < 0.05; ß = 0.64, p < 0.02), with positive effect modification by apolipoprotein-E-epsilon-4-allele (APOE4) (p = 0.01-0.03). GABA and glutamate negatively related to longitudinal change in verbal episodic memory performance (ß = -0.48; p = 0.02; ß = -0.50; p = 0.01). In vivo measures of GABA and glutamate reflect early AD pathology at old age, in an APOE4-dependent manner. GABA and glutamate may represent promising biomarkers and potential targets for early therapeutic intervention and prevention. Highlights: Gray matter-specific metabolic imaging with high-resolution atlas-based MRSI at 7 Tesla.Higher GABA and glutamate relate to ß-amyloid burden, in an APOE4-dependent manner.Gray matter GABA and glutamate identify older adults with high risk of future AD.GABA and glutamate might reflect altered synaptic and neuronal activity at early AD.

Trimethyltin(IV) Bearing 3-(4-Methyl-2-oxoquinolin-1(2H)-yl)propanoate Causes Lipid Peroxidation-Mediated Autophagic Cell Death in Human Melanoma A375 Cells.

A novel trimethyltin(IV) complex (Me3SnL), derived from 3-(4-methyl-2-oxoquinolin-1(2H)-yl)propanoate ligand, has been synthesized and characterized by elemental microanalysis, UV/Vis spectrophotometry, FT-IR and multinuclear (1H, 13C and 119Sn) NMR spectroscopies. Furthermore, the structure of the ligand precursor HL was solved using SC-XRD (single-crystal X-ray diffraction). The prediction of UV/Vis and NMR spectra by quantum-chemical methods was performed and compared to experimental findings. The protein binding affinity of Me3SnL towards BSA was determined by spectrofluorometric titration and subsequent molecular docking simulations. Me3SnL has been evaluated for its in vitro anticancer activity against three human cell lines, MCF-7 (breast adenocarcinoma), A375 (melanoma) and HCT116 (colorectal carcinoma), and three mouse tumor cell lines, 4T1 (breast carcinoma), B16 (melanoma) and CT26 (colon carcinoma), using MTT and CV assays. The strong inhibition of A375 cell proliferation, ROS/RNS upregulation and robust lipid peroxidation lead to autophagic cell death upon treatment with Me3SnL.

Sleep spindle and slow wave activity in Parkinson disease with excessive daytime sleepiness.

STUDY OBJECTIVES: Excessive daytime sleepiness (EDS) is a common and devastating symptom in Parkinson disease (PD), but surprisingly most studies showed that EDS is independent from nocturnal sleep disturbance measured with polysomnography. Quantitative electroencephalography (EEG) may reveal additional insights by measuring the EEG hallmarks of non-rapid eye movement (NREM) sleep, namely slow waves and spindles. Here, we tested the hypothesis that EDS in PD is associated with nocturnal sleep disturbance revealed by quantitative NREM sleep EEG markers. METHODS: Patients with PD (n = 130) underwent polysomnography followed by spectral analysis to calculate spindle frequency activity, slow-wave activity (SWA), and overnight SWA decline, which reflects the dissipation of homeostatic sleep pressure. We used the Epworth Sleepiness Scale (ESS) to assess subjective daytime sleepiness and define EDS (ESS > 10). All examinations were part of an evaluation for deep brain stimulation. RESULTS: Patients with EDS (n = 46) showed reduced overnight decline of SWA (p = 0.036) and reduced spindle frequency activity (p = 0.032) compared with patients without EDS. Likewise, more severe daytime sleepiness was associated with reduced SWA decline (ß= -0.24 p = 0.008) and reduced spindle frequency activity (ß= -0.42, p < 0.001) across all patients. Reduced SWA decline, but not daytime sleepiness, was associated with poor sleep quality and continuity at polysomnography. CONCLUSIONS: Our data suggest that daytime sleepiness in PD patients is associated with sleep disturbance revealed by quantitative EEG, namely reduced overnight SWA decline and reduced spindle frequency activity. These findings could indicate that poor sleep quality, with incomplete dissipation of homeostatic sleep pressure, may contribute to EDS in PD.

No correlation of substantia nigra echogenicity and nigrostriatal degradation in Parkinson's disease.

BACKGROUND: Substantia nigra hyperechogenicity assessed by transcranial sonography is a typical finding in up to 90% of patients with idiopathic Parkinson's disease, although its value as a surrogate marker for disease progression in Parkinson's disease is controversial. (123) I-FP-CIT-single photon emission computed tomography (SPECT) represents an established paraclinical surrogate marker to quantify the nigrostriatal dopaminergic deficit in Parkinson's disease. Whereas most studies found no correlation between extent of substantia nigra echogenicity and the putaminal FP-CIT binding ratio, a more recent analysis reported opposite results. METHODS: In 92 patients with Parkinson's disease the substantia nigra echogenicity was compared with the putaminal FP-CIT binding ratio using an investigator-independent SPECT analysis protocol and with several clinical parameters. RESULTS: No correlation was found between the substantia nigra hyperechogenicity and the FP-CIT binding ratio or the disease severity. CONCLUSIONS: Substantia nigra hyperechogenicity does not reflect the degree of the nigrostriatal degeneration or the clinical state of the disease progression.

Onset of Postural Instability in Parkinson's Disease Depends on Age rather than Disease Duration.

Background: Postural instability and falls are considered a major factor of impaired quality of life in patients with advanced Parkinson's disease (PD). The knowledge of the time at which postural instability occurs will help to provide the evidence required to introduce fall-prevention strategies at the right time in PD. Objective: To investigate whether postural instability of patients with different age at disease onset is associated with age or with disease duration of PD. Methods: Patients diagnosed with sporadic PD between 1991 and 2017 and postural instability (according to the International Parkinson and Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III, item 3.12 postural instability) were included, with strict inclusion criteria including regular follow-ups, agreement on data use, and exclusion of comorbidities affecting the free stand. Results: Applying these strict inclusion criteria, we included 106 patients. Those younger than 50 years at PD onset took significantly longer to develop postural instability (n = 23 patients, median: 18.4 years) compared with patients with later onset of PD (50-70 years, n = 66, median: 14.2 years, p < 0.001; and >70 years, n = 17, median: 5.7 years, p < 0.001, Kruskal-Wallis test followed by Dunn's multiple comparisons test). There was no association between total MDS-UPDRS III (as a measure of motor symptom severity) at onset of postural instability. Conclusions: In PD, postural instability is primarily associated with the age of the patient and not with disease duration.

Benchmarking Real-Time Algorithms for In-Phase Auditory Stimulation of Low Amplitude Slow Waves With Wearable EEG Devices During Sleep.

OBJECTIVE: In-phase stimulation of EEG slow waves (SW) during deep sleep has shown to improve cognitive function. SW enhancement is particularly desirable in subjects with low-amplitude SW such as older adults or patients suffering from neurodegeneration. However, existing algorithms to estimate the up-phase of EEG suffer from a poor phase accuracy at low amplitudes and when SW frequencies are not constant. METHODS: We introduce two novel algorithms for real-time EEG phase estimation on autonomous wearable devices, a phase-locked loop (PLL) and, for the first time, a phase vocoder (PV). We compared these phase tracking algorithms with a simple amplitude threshold approach. The optimized algorithms were benchmarked for phase accuracy, the capacity to estimate phase at SW amplitudes between 20 and 60 µV, and SW frequencies above 1 Hz on 324 home-based recordings from healthy older adults and Parkinson disease (PD) patients. Furthermore, the algorithms were implemented on a wearable device and the computational efficiency and the performance was evaluated in simulation and with a PD patient. RESULTS: All three algorithms delivered more than 70% of the stimulation triggers during the SW up-phase. The PV showed the highest capacity on targeting low-amplitude SW and SW with frequencies above 1 Hz. The hardware testing revealed that both PV and PLL have marginal impact on microcontroller load, while the efficiency of the PV was 4% lower. Active stimulation did not influence the phase tracking. CONCLUSION: This work demonstrated that phase-accurate auditory stimulation can also be delivered during fully remote sleep interventions in populations with low-amplitude SW.

Low Subicular Volume as an Indicator of Dementia-Risk Susceptibility in Old Age.

Introduction: Hippocampal atrophy is an established Alzheimer's Disease (AD) biomarker. Volume loss in specific subregions as measurable with ultra-high field magnetic resonance imaging (MRI) may reflect earliest pathological alterations. Methods: Data from positron emission tomography (PET) for estimation of cortical amyloid ß (Aß) and high-resolution 7 Tesla T1 MRI for assessment of hippocampal subfield volumes were analyzed in 61 non-demented elderly individuals who were divided into risk-categories as defined by high levels of cortical Aß and low performance in standardized episodic memory tasks. Results: High cortical Aß and low episodic memory interactively predicted subicular volume [F(3,57) = 5.90, p = 0.018]. The combination of high cortical Aß and low episodic memory was associated with significantly lower subicular volumes, when compared to participants with high episodic memory (p = 0.004). Discussion: Our results suggest that low subicular volume is linked to established indicators of AD risk, such as increased cortical Aß and low episodic memory. Our data support subicular volume as a marker of dementia-risk susceptibility in old-aged non-demented persons.

Reduced Regional NREM Sleep Slow-Wave Activity Is Associated With Cognitive Impairment in Parkinson Disease.

Growing evidence implicates a distinct role of disturbed slow-wave sleep in neurodegenerative diseases. Reduced non-rapid eye movement (NREM) sleep slow-wave activity (SWA), a marker of slow-wave sleep intensity, has been linked with age-related cognitive impairment and Alzheimer disease pathology. However, it remains debated if SWA is associated with cognition in Parkinson disease (PD). Here, we investigated the relationship of regional SWA with cognitive performance in PD. In the present study, 140 non-demented PD patients underwent polysomnography and were administered the Montréal Cognitive Assessment (MoCA) to screen for cognitive impairment. We performed spectral analysis of frontal, central, and occipital sleep electroencephalography (EEG) derivations to measure SWA, and spectral power in other frequency bands, which we compared to cognition using linear mixed models. We found that worse MoCA performance was associated with reduced 1-4 Hz SWA in a region-dependent manner (F 2, 687 =11.67, p < 0.001). This effect was driven by reduced regional SWA in the lower delta frequencies, with a strong association of worse MoCA performance with reduced 1-2 Hz SWA (F 2, 687 =18.0, p < 0.001). The association of MoCA with 1-2 Hz SWA (and 1-4 Hz SWA) followed an antero-posterior gradient, with strongest, weaker, and absent associations over frontal (rho = 0.33, p < 0.001), central (rho = 0.28, p < 0.001), and occipital derivations, respectively. Our study shows that cognitive impairment in PD is associated with reduced NREM sleep SWA, predominantly in lower delta frequencies (1-2 Hz) and over frontal regions. This finding suggests a potential role of reduced frontal slow-wave sleep intensity in cognitive impairment in PD.

Ditopic bis(N,N',N'-substituted 1,2-ethanediamine) ligands: synthesis and coordination chemistry.

The synthesis of two different types of bis(N,N',N'-substituted 1,2-ethanediamine)s, bridged either through the secondary (type 1) or tertiary (type 2) amine groups is reported. Selected protio-ligands have been applied in subsequent metallation reactions using aluminium, magnesium, tin, and zinc sources allowing to isolate five mononuclear and eight dinuclear complexes. All complexes have been fully characterized and their solid-state structures have been studied by means of single-crystal X-ray diffraction analysis. Nine of the 13 complexes carry reactive alkyl, amide or hydride groups, which indicates their potential as catalysts or supports for (transition) metals.

Magnesium bis(amidinate) and bis(guanidinate) complexes: impact of the ligand backbone and bridging groups on the coordination behaviour.

A library of ten dinucleating bis(amidine) and bis(guanidine) ligands, in which the bridging groups, terminal rests, and backbone substituents were systematically altered, has been synthesized and subsequently applied in metallation reactions using three different magnesium sources. Eight Mg complexes could be isolated and fully characterized, and in seven cases their solid-state structure could be determined by means of single crystal X-ray diffraction analysis. The results evidence a versatile coordination behaviour, which ranges from the first dinuclear heteroleptic magnesium iodide complex to dinuclear homoleptic complexes. These findings indicate the crucial impact of both the ligand and the magnesium source not only on the accessibility of well-defined dinuclear complexes but also on the aggregation in solution and in the solid state.

Increased cerebral blood volume in small arterial vessels is a correlate of amyloid-ß-related cognitive decline.

The protracted accumulation of amyloid-ß (Aß) is a major pathologic hallmark of Alzheimer's disease and may trigger secondary pathological processes that include neurovascular damage. This study was aimed at investigating long-term effects of Aß burden on cerebral blood volume of arterioles and pial arteries (CBVa), possibly present before manifestation of dementia. Aß burden was assessed by 11C Pittsburgh compound-B positron emission tomography in 22 controls and 18 persons with mild cognitive impairment (MCI), [ages: 75(±6) years]. After 2 years, inflow-based vascular space occupancy at ultra-high field strength of 7-Tesla was administered for measuring CBVa, and neuropsychological testing for cognitive decline. Crushing gradients were incorporated during MR-imaging to suppress signals from fast-flowing blood in large arteries, and thereby sensitize inflow-based vascular space occupancy to CBVa in pial arteries and arterioles. CBVa was significantly elevated in MCI compared to cognitively normal controls and regional CBVa related to local Aß deposition. For both MCI and controls, Aß burden and follow-up CBVa in several brain regions synergistically predicted cognitive decline over 2 years. Orbitofrontal CBVa was positively associated with apolipoprotein E e4 carrier status. Increased CBVa may reflect long-term effects of region-specific pathology associated with Aß deposition. Additional studies are needed to clarify the role of the arteriolar system and the potential of CBVa as a biomarker for Aß-related vascular downstream pathology.

Value of 18F-FET PET in Patients With Suspected Tumefactive Demyelinating Disease-Preliminary Experience From a Retrospective Analysis.

PURPOSE: To investigate the diagnostic value of F-fluoroethyl-L-tyrosine (FET) positron emission tomography (PET) in patients with suspected tumefactive demyelinating disease. METHODS: We retrospectively examined FET-PET and MR imaging of 21 patients (12 female, 9 male) with known demyelinating disease and newly diagnosed tumefactive lesions. The maximum standardized uptake value (SUVmax), time activity curves (TAC) and lesion-to-background ratio (TBR) of these lesions were calculated. The standard of reference consisted of biopsy and/or follow-up imaging. FET parameters of true neoplastic lesions and tumefactive demyelinating lesions were compared using Mann-Whitney U-test and receiver operating characteristic (ROC) analysis. RESULTS: Nine patients (42.9%) had neoplastic lesions, 12 patients (57.1%) had tumefactive demyelinating lesions. TBRmax, SUVmax and TAC were significantly different between demyelinating lesions and neoplastic lesions: Tumors had a higher TBRmax (3.53 ± 1.09 vs. 1.48 ± 0.31, respectively; P < 0.001) and SUVmax (3.95 ± 1.59 vs. 1.86 ± 0.50, respectively; P < 0.001) than tumefactive demyelinating lesions. The TAC of tumors was significantly higher compared to tumefactive demyelinating lesions at all time points (P < 0.05). ROC analysis revealed that a TBRmax threshold of 2.2 and a SUVmax threshold of 2.5 could reliably differentiate tumor and tumefactive demyelination (area under the curve, 1.000 and 0.958, respectively). CONCLUSION: In patients with demyelinating disease, FET-PET parameters TBRmax (cut-off 2.2) and SUVmax (cut-off 2.5) are able to distinguish tumefactive demyelinations from true neoplastic lesions.

Brain amyloid burden and cerebrovascular disease are synergistically associated with neurometabolism in cognitively unimpaired older adults.

Alzheimer's disease (AD) is the most common cause of cognitive dysfunction in older adults. The pathological hallmarks of AD such as beta amyloid (Aß) aggregation and neurometabolic change, as indicated by altered myo-inositol (mI) and N-acetylaspartate (NAA) levels, typically precede the onset of cognitive dysfunction by years. Furthermore, cerebrovascular disease occurs early in AD, but the interplay between vascular and neurometabolic brain change is largely unknown. Thirty cognitively normal older adults (age = 70 ± 5.6 years, Mini-Mental State Examination = 29.2 ± 1) received 11-C-Pittsburgh Compound B positron emission tomography for estimating Aß-plaque density, 7 Tesla fluid-attenuated inversion recovery magnetic resonance imaging for quantifying white matter hyperintensity volume as a marker of small vessel cerebrovascular disease and high-resolution magnetic resonance spectroscopic imaging at 7 Tesla, based on free induction decay acquisition localized by outer volume suppression to investigate tissue-specific neurometabolism in the posterior cingulate and precuneus. Aß (ß = 0.45, p = 0.018) and white matter hyperintensities (ß = 0.40, p = 0.046) were independently and interactively (ß = -0.49, p = 0.026) associated with a higher ratio of mI over NAA (mI/NAA) in the posterior cingulate and precuneus gray matter but not in the white matter. Our data suggest that cerebrovascular disease and Aß burden are synergistically associated with AD-related gray matter neurometabolism in older adults.

Memory performance-related dynamic brain connectivity indicates pathological burden and genetic risk for Alzheimer's disease.

BACKGROUND: The incidence of Alzheimer's disease (AD) strongly relates to advanced age and progressive deposition of cerebral amyloid-beta (Aß), hyperphosphorylated tau, and iron. The purpose of this study was to investigate the relationship between cerebral dynamic functional connectivity and variability of long-term cognitive performance in healthy, elderly subjects, allowing for local pathology and genetic risk. METHODS: Thirty seven participants (mean (SD) age 74 (6.0) years, Mini-Mental State Examination 29.0 (1.2)) were dichotomized based on repeated neuropsychological test performance within 2 years. Cerebral Aß was measured by 11C Pittsburgh Compound-B positron emission tomography, and iron by quantitative susceptibility mapping magnetic resonance imaging (MRI) at an ultra-high field strength of 7 Tesla (7T). Dynamic functional connectivity patterns were investigated by resting-state functional MRI at 7T and tested for interactive effects with genetic AD risk (apolipoprotein E (ApoE)-ε4 carrier status). RESULTS: A relationship between low episodic memory and a lower expression of anterior-posterior connectivity was seen (F(9,27) = 3.23, p < 0.008), moderated by ApoE-ε4 (F(9,27) = 2.22, p < 0.005). Inherent node-strength was related to local iron (F(5,30) = 13.2; p < 0.022). CONCLUSION: Our data indicate that altered dynamic anterior-posterior brain connectivity is a characteristic of low memory performance in the subclinical range and genetic risk for AD in the elderly. As the observed altered brain network properties are associated with increased local iron, our findings may reflect secondary neuronal changes due to pathologic processes including oxidative stress.

Low episodic memory performance in cognitively normal elderly subjects is associated with increased posterior cingulate gray matter N-acetylaspartate: a 1H MRSI study at 7 Tesla.

Low episodic memory performance characterizes elderly subjects at increased risk for Alzheimer's disease (AD) and may reflect neuronal dysfunction within the posterior cingulate cortex and precuneus (PCP) region. To investigate a potential association between cerebral neurometabolism and low episodic memory in the absence of cognitive impairment, tissue-specific magnetic resonance spectroscopic imaging at ultrahigh field strength of 7 Tesla was used to investigate the PCP region in a healthy elderly study population (n = 30, age 70 ± 5.7 years, Mini-Mental State Examination 29.4 ± 4.1). The Verbal Learning and Memory Test (VLMT) was administered as part of a neuropsychological battery for assessment of episodic memory performance. Significant differences between PCP gray and white matter could be observed for glutamate-glutamine (p = 0.001), choline (p = 0.01), and myo-inositol (p = 0.02). Low Verbal Learning and Memory Test performance was associated with high N-acetylaspartate in PCP gray matter (p = 0.01) but not in PCP white matter. Our data suggest that subtle decreases in episodic memory performance in the elderly may be associated with increased levels of N-acetylaspartate as a reflection of increased mitochondrial energy capacity in PCP gray matter.

Cortical Amyloid Beta in Cognitively Normal Elderly Adults is Associated with Decreased Network Efficiency within the Cerebro-Cerebellar System.

BACKGROUND: Deposition of cortical amyloid beta (Aß) is a correlate of aging and a risk factor for Alzheimer disease (AD). While several higher order cognitive processes involve functional interactions between cortex and cerebellum, this study aims to investigate effects of cortical Aß deposition on coupling within the cerebro-cerebellar system. METHODS: We included 15 healthy elderly subjects with normal cognitive performance as assessed by neuropsychological testing. Cortical Aß was quantified using (11)carbon-labeled Pittsburgh compound B positron-emission-tomography late frame signals. Volumes of brain structures were assessed by applying an automated parcelation algorithm to three dimensional magnetization-prepared rapid gradient-echo T1-weighted images. Basal functional network activity within the cerebro-cerebellar system was assessed using blood-oxygen-level dependent resting state functional magnetic resonance imaging at the high field strength of 7 T for measuring coupling between cerebellar seeds and cerebral gray matter. A bivariate regression approach was applied for identification of brain regions with significant effects of individual cortical Aß load on coupling. RESULTS: Consistent with earlier reports, a significant degree of positive and negative coupling could be observed between cerebellar seeds and cerebral voxels. Significant positive effects of cortical Aß load on cerebro-cerebellar coupling resulted for cerebral brain regions located in inferior temporal lobe, prefrontal cortex, hippocampus, parahippocampal gyrus, and thalamus. CONCLUSION: Our findings indicate that brain amyloidosis in cognitively normal elderly subjects is associated with decreased network efficiency within the cerebro-cerebellar system. While the identified cerebral regions are consistent with established patterns of increased sensitivity for Aß-associated neurodegeneration, additional studies are needed to elucidate the relationship between dysfunction of the cerebro-cerebellar system and risk for AD.

Regional Fluid-Attenuated Inversion Recovery (FLAIR) at 7 Tesla correlates with amyloid beta in hippocampus and brainstem of cognitively normal elderly subjects.

BACKGROUND: Accumulation of amyloid beta (Aß) may occur during healthy aging and is a risk factor for Alzheimer Disease (AD). While individual Aß-accumulation can be measured non-invasively using Pittsburgh Compund-B positron emission tomography (PiB-PET), Fluid-attenuated inversion recovery (FLAIR) is a Magnetic Resonance Imaging (MRI) sequence, capable of indicating heterogeneous age-related brain pathologies associated with tissue-edema. In the current study cognitively normal elderly subjects were investigated for regional correlation of PiB- and FLAIR intensity. METHODS: Fourteen healthy elderly subjects without known history of cognitive impairment received 11C-PiB-PET for estimation of regional Aß-load. In addition, whole brain T1-MPRAGE and FLAIR-MRI sequences were acquired at high field strength of 7 Tesla (7T). Volume-normalized intensities of brain regions were assessed by applying an automated subcortical segmentation algorithm for spatial definition of brain structures. Statistical dependence between FLAIR- and PiB-PET intensities was tested using Spearman's rank correlation coefficient (rho), followed by Holm-Bonferroni correction for multiple testing. RESULTS: Neuropsychological testing revealed normal cognitive performance levels in all participants. Mean regional PiB-PET and FLAIR intensities were normally distributed and independent. Significant correlation between volume-normalized PiB-PET signals and FLAIR intensities resulted for Hippocampus (right: rho = 0.86; left: rho = 0.84), Brainstem (rho = 0.85) and left Basal Ganglia vessel region (rho = 0.82). CONCLUSIONS: Our finding of a significant relationship between PiB- and FLAIR intensity mainly observable in the Hippocampus and Brainstem, indicates regional Aß associated tissue-edema in cognitively normal elderly subjects. Further studies including clinical populations are necessary to clarify the relevance of our findings for estimating individual risk for age-related neurodegenerative processes such as AD.