GABA and glutamate moderate beta-amyloid related functional connectivity in cognitively unimpaired old-aged adults.

BACKGROUND: Effects of beta-amyloid accumulation on neuronal function precede the clinical manifestation of Alzheimer's disease (AD) by years and affect distinct cognitive brain networks. As previous studies suggest a link between beta-amyloid and dysregulation of excitatory and inhibitory neurotransmitters, we aimed to investigate the impact of GABA and glutamate on beta-amyloid related functional connectivity. METHODS: 29 cognitively unimpaired old-aged adults (age = 70.03 ±â€¯5.77 years) were administered 11C-Pittsburgh Compound B (PiB) positron-emission tomography (PET), and MRI at 7 Tesla (7T) including blood oxygen level dependent (BOLD) functional MRI (fMRI) at rest for measuring static and dynamic functional connectivity. An advanced 7T MR spectroscopic imaging (MRSI) sequence based on the free induction decay acquisition localized by outer volume suppression' (FIDLOVS) technology was used for gray matter specific measures of GABA and glutamate in the posterior cingulate and precuneus (PCP) region. RESULTS: GABA and glutamate MR-spectra indicated significantly higher levels in gray matter than in white matter. A global effect of beta-amyloid on functional connectivity in the frontal, occipital and inferior temporal lobes was observable. Interactive effects of beta-amyloid with gray matter GABA displayed positive PCP connectivity to the frontomedial regions, and the interaction of beta-amyloid with gray matter glutamate indicated positive PCP connectivity to frontal and cerebellar regions. Furthermore, decreased whole-brain but increased fronto-occipital and temporo-parietal dynamic connectivity was found, when GABA interacted with regional beta-amyloid deposits in the amygdala, frontal lobe, hippocampus, insula and striatum. CONCLUSIONS: GABA, and less so glutamate, may moderate beta-amyloid related functional connectivity. Additional research is needed to better characterize their interaction and potential impact on AD.

Simultaneous quantitative susceptibility mapping and Flutemetamol-PET suggests local correlation of iron and ß-amyloid as an indicator of cognitive performance at high age.

The accumulation of ß-amyloid plaques is a hallmark of Alzheimer's disease (AD), and recently published data suggest that increased brain iron burden may reflect pathologies that synergistically contribute to the development of cognitive dysfunction. While preclinical disease stages are considered most promising for therapeutic intervention, the link between emerging AD-pathology and earliest clinical symptoms remains largely unclear. In the current study we therefore investigated local correlations between iron and ß-amyloid plaques, and their possible association with cognitive performance in healthy older adults. 116 older adults (mean age 75 ±â€¯7.4 years) received neuropsychological testing to calculate a composite cognitive score of performance in episodic memory, executive functioning, attention, language and communication. All participants were scanned on a combined PET-MRI instrument and were administered T1-sequences for anatomical mapping, quantitative susceptibility mapping (QSM) for assessing iron, and 18F-Flutemetamol-PET for estimating ß-amyloid plaque load. Biological parametric mapping (BPM) was used to generate masks indicating voxels with significant (p < 0.05) correlation between susceptibility and 18F-Flutemetamol-SUVR. We found a bilateral pattern of clusters characterized by a statistical relationship between magnetic susceptibility and 18F-Flutemetamol-SUVR, indicating local correlations between iron and ß-amyloid plaque deposition. For two bilateral clusters, located in the frontal and temporal cortex, significant relationships (p<0.05) between local ß-amyloid and the composite cognitive performance score could be observed. No relationship between whole-cortex ß-amyloid plaque load and cognitive performance was observable. Our data suggest that the local correlation of ß-amyloid plaque load and iron deposition may provide relevant information regarding cognitive performance of healthy older adults. Further studies are needed to clarify pathological correlates of the local interaction of ß-amyloid, iron and other causes of altered magnetic susceptibility.

Size Matters! Differences in Nutritional Care between Small, Medium and Large Nursing Homes in Germany.

OBJECTIVES: The aim of this study is to comprehensively describe nutritional care in German nursing homes (NHs) and to examine if nutritional care differs between small, medium and large NHs. DESIGN: Nationwide cross-sectional postal survey. SETTING: Nursing homes. PARTICIPANTS: 541 NHs across Germany. MEASUREMENTS: Information on structural NH characteristics and nutritional care (food provision and menu planning, nursing care, and management and quality assurance) was collected by means of a questionnaire addressed to the management of a random sample of German NHs. NHs were grouped by size as small (≤ 50 beds), medium (50 - 100 beds) or large (> 100 beds) institutions. Frequencies were used to describe nutritional care, and Chi2-test to identify differences in nutritional care by NH size. RESULTS: Aspects in the domain of food provision and menu planning regarding food variety and choice were widely implemented in German NHs (77 - 100 %). Best results were achieved in the domain of nursing care, where all aspects were implemented in at least 68 % of the NHs. Aspects regarding management and quality assurance, especially those concerning staffing, i.e. the availability of an interface manager (14 %), an interdisciplinary nutrition team (12 %) and a dietician (42 %), were only rarely implemented. Differences by NH size were found between small and medium or large NHs. On the one hand, small NHs stated more often to consider individual capabilities of the residents with texture-modified food (81 % vs. 60 %, p<0.05) and produce more often hot meals at ward level on a regular base (46 % vs. 32 %, p<0.05) than large NHs. On the other hand, several aspects regarding food provision and menu planning, and management and quality assurance were significantly more often implemented in larger than smaller NHs. CONCLUSION: Whereas kitchen and nursing-related aspects of nutritional care seem to be widely implemented in German NHs, management and quality assurance demands are often not met. The differences found by NH size support the hypothesis that the number of residents living in a NH has an impact on how nutritional care is performed.

Colocalization of cerebral iron with Amyloid beta in Mild Cognitive Impairment.

Quantitative Susceptibility Mapping (QSM) MRI at 7 Tesla and 11-Carbon Pittsburgh-Compound-B PET were used for investigating the relationship between brain iron and Amyloid beta (Aß) plaque-load in a context of increased risk for Alzheimer's disease (AD), as reflected by the Apolipoprotein E ε4 (APOE-e4) allele and mild cognitive impairment (MCI) in elderly subjects. Carriers of APOE-e4 with normal cognition had higher cortical Aß-plaque-load than non-carriers. In MCI an association between APOE-e4 and higher Aß-plaque-load was observable both for cortical and subcortical brain-regions. APOE-e4 and MCI was also associated with higher cortical iron. Moreover, cerebral iron significantly affected functional coupling, and was furthermore associated with increased Aß-plaque-load (R2-adjusted = 0.80, p < 0.001) and APOE-e4 carrier status (p < 0.001) in MCI. This study confirms earlier reports on an association between increased brain iron-burden and risk for neurocognitive dysfunction due to AD, and indicates that disease-progression is conferred by spatial colocalization of brain iron deposits with Aß-plaques.

Association of anger-related traits with SNPs in the TPH gene.

Since both aggression-related traits and serotonergic activity are partially heritable and correlate inversely, variations in genes of the serotonergic system might then, to some extent, account for variations in aggression-related behavior. Tryptophan hydroxylase (TPH) is the rate limiting biosynthetic enzyme in the serotonin pathway and regulates levels of serotonin. Recently, a genetic variation in TPH has been associated with aggression and anger-related traits in volunteers. We investigated a sample of community-based healthy volunteers (n = 154) and suicide attempters (n = 86), a clinical population with a high risk for elevated impulsive aggression and related traits. The subjects were genotyped for a A218C and a A779C single nucleotide polymorphism (SNP) located in the TPH gene. All subjects were administered standard psychiatric interviews as well as self-report questionnaires for aggression, irritability and anger-related traits. For anger-related traits, a multivariate effect of the tryptophan hydroxylase genotype and an interaction effect for genotype and diagnosis was observed in healthy volunteers and suicide attempters after controlling for age and educational level. U-carriers in both groups showed higher scores for State Anger, Trait Anger and Angry Temperament. These findings support the hypothesis that the A218C and the A779C SNP in the TPH gene may be associated with anger-related traits in German samples.

Association study of suicidal behavior and affective disorders with a genetic polymorphism in ABCG1, a positional candidate on chromosome 21q22.3.

The gene that codes for the ABC transporter ABCG1 is located in a chromosomal susceptibility region (21q22.3) for affective disorders. Genetic variations in ABCG1 have been associated with affective disorders in Japanese males. In this study, we investigated the distribution of a G2457A polymorphism in patients with affective disorders, suicide attempters with various psychiatric diagnoses and healthy subjects. We initially found a trend towards a modest association with affective disorders in males (p = 0.046 for allele frequencies and p = 0.046 for AA versus GG). We conducted a replication study with independent patients and controls. There was no association with affective disorders, either in the replication or in the combined group. Furthermore, we found no association with suicidal behavior. These findings do not support the hypothesis that ABCG1 is a susceptibility gene for affective disorders or suicidal behavior.