Impairment in Proverb Interpretation as an Executive Function Deficit in Patients with Amnestic Mild Cognitive Impairment and Early Alzheimer's Disease

Background/Aims: Proverb interpretation is assumed to reflect executive functions. We hypothesized that proverb interpretation is impaired in patients with amnestic mild cognitive impairment (aMCI) diagnosed as single-domain impairment by common neuropsychological testing. Methods: We compared performance in a proverb interpretation test in single-domain aMCI patients and patients with early Alzheimer’s disease (EAD). Results: The groups with aMCI and EAD performed significantly worse than healthy controls. Both patient groups gave concrete answers with a similar frequency. However, patients with EAD tended to give senseless answers more frequently. Conclusions: Our data suggest that in patients diagnosed as single-domain aMCI, deterioration of executive functions is detectable with subtle and appropriate neuropsychological testing. Implementation of these procedures may improve the early prediction of AD

Altered Serum IgG Levels to a-Synuclein in Dementia with Lewy Bodies and Alzheimer’s Disease.

Natural self-reactive antibodies in the peripheral blood may play a considerable role in the control of potentially toxic proteins that may otherwise accumulate in the aging brain. The significance of serum antibodies reactive against asynuclein is not well known. We explored serum IgG levels to monomeric a-synuclein in dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD) with a novel and validated highly sensitive ELISA assay. Antibody levels revealed stark differences in patients compared to healthy subjects and were dependent on diagnosis, disease duration and age. Anti-asynuclein IgG levels were increased in both patient groups, but in early DLB to a much greater extent than in AD. Increased antibody levels were most evident in younger patients, while with advanced age relatively low levels were observed, similar to healthy individuals, exhibiting stable antibody levels independent of age. Our data show the presence of differentially altered IgG levels against a-synuclein in DLB and AD, which may relate to a disturbed a-synuclein homeostasis triggered by the disease process. These observations may foster the development of novel, possibly preclinical biomarkers and immunotherapeutic strategies that target a-synuclein in neurodegenerative disease.Fil: Koehler, Niklas. Department of Psychiatry and Psychotherapy. EBERHARD-KARLS-UNIVERSITY;Fil: Stransky, Elke. Department of Psychiatry and Psychotherapy. EBERHARD-KARLS-UNIVERSITY;Fil: Shing, Mona. Department of Psychiatry and Psychotherapy. EBERHARD-KARLS-UNIVERSITY;Fil: Gaertner, Susanne. Department of Psychiatry and Psychotherapy, EBERHARD-KARLS-UNIVERSITY;Fil: Meyer, Mirjam. Department of Psychiatry and Psychotherapy. EBERHARD-KARLS-UNIVERSITY;Fil: Schreitmueller, Brigitte. Department of Psychiatry and Psychotherapy. EBERHARD-KARLS-UNIVERSITY;Fil: Leyhe, Thomas. Department of Psychiatry and Psychotherapy. EBERHARD-KARLS-UNIVERSITY;Fil: Laske, Cristoph. Department of Psychiatry and Psychotherapy. EBERHARD-KARLS-UNIVERSITY;Fil: Maetzler, Walter. Department of Neurodegeneration. HERTIE INSTITUTE FOR CLINICAL BRAIN RESEARCH;Fil: Kahle, Philipp. FUNCTIONAL NEUROGENETICS. HERTIE INSTITUTE FOR CLINICAL;Fil: Celej, Maria Soleda. MAX-PLANCK-INSTITUTE FOR BIOPHYSICAL CHEMISTRY; Consejo Nacional de Invest.cientif.y Tecnicas. Centro Cientifico Tecnol.conicet - Cordoba. Centro de Invest.en Qca.biol.de Cordoba (p);Fil: Jovin, Thomas M.. MAX-PLANCK-INSTITUTE FOR BIOPHYSICAL CHEMISTRY;Fil: Fallgatter, Andreas. Department of Psychiatry and Psychotherapy. EBERHARD-KARLS-UNIVERSITY;Fil: Batra, Anil. Department of Psychiatry and Psychotherapy. EBERHARD-KARLS-UNIVERSITY;Fil: Buchkremer, Gherard. Department of Psychiatry and Psychotherapy. EBERHARD-KARLS-UNIVERSITY;Fil: Schott, Klauss. Department of Psychiatry and Psychotherapy. EBERHARD-KARLS-UNIVERSITY;Fil: Richartz-Salzburger, Elke. Department of Psychiatry and Psychotherapy. EBERHARD-KARLS-UNIVERSITY

Landscape of fear as an emergent property of heterogeneity: Contrasting patterns of predation risk in grassland ecosystems

The likelihood of encountering a predator influences prey behavior and spatial distribution such that non-consumptive effects can outweigh the influence of direct predation. Prey species are thought to filter information on perceived predator encounter rates in physical landscapes into a landscape of fear defined by spatially explicit heterogeneity in predation risk. The presence of multiple predators using different hunting strategies further complicates navigation through a landscape of fear and potentially exposes prey to greater risk of predation. The juxtaposition of land cover types likely influences overlap in occurrence of different predators, suggesting that attributes of a landscape of fear result from complexity in the physical landscape. Woody encroachment in grasslands furnishes an example of increasing complexity with the potential to influence predator distributions. We examined the role of vegetation structure on the distribution of two avian predators, Red-tailed Hawk (Buteo jamaicensis) and Northern Harrier (Circus cyaneus), and the vulnerability of a frequent prey species of those predators, Northern Bobwhite (Colinus virginianus). We mapped occurrences of the raptors and kill locations of Northern Bobwhite to examine spatial vulnerability patterns in relation to landscape complexity. We use an offset model to examine spatially explicit habitat use patterns of these predators in the Southern Great Plains of the United States, and monitored vulnerability patterns of their prey species based on kill locations collected during radio telemetry monitoring. Both predator density and predation-specific mortality of Northern Bobwhite increased with vegetation complexity generated by fine-scale interspersion of grassland and woodland. Predation pressure was lower in more homogeneous landscapes where overlap of the two predators was less frequent. Predator overlap created areas of high risk for Northern Bobwhite amounting to 32% of the land area where landscape complexity was high and 7% where complexity was lower. Our study emphasizes the need to evaluate the role of landscape structure on predation dynamics and reveals another threat from woody encroachment in grasslands.Peer reviewedNatural Resource Ecology and Managemen

Empirical assessment of biases in cerebrospinal fluid biomarkers of Alzheimer's disease: an umbrella review and re-analysis of data from meta-analyses

OBJECTIVE: Alzheimer’s disease (AD) is a leading cause of years lived with disability in older age, and several cerebrospinal fluid (CSF) markers have been proposed in individual meta-analyses to be associated with AD but field-wide evaluation and scrutiny of the literature is not available. MATERIALS AND METHODS: We performed an umbrella review for the reported associations between CSF biomarkers and AD. Data from available meta-analyses were reanalyzed using both random and fixed effects models. We also estimated between-study heterogeneity, small-study effects, excess significance, and prediction interval. RESULTS: A total of 38 meta-analyses on CSF markers from 11 eligible articles were identified and reanalyzed. In 14 (36%) of the meta-analyses, the summary estimate and the results of the largest study showed non-concordant results in terms of statistical significance. Large heterogeneity (I2≥75%) was observed in 73% and small-study effects under Egger’s test were shown in 28% of CSF biomarkers. CONCLUSIONS: Our results suggest that there is an excess of statistically significant results and significant biases in the literature of CSF biomarkers for AD. Therefore, the results of CSF biomarkers should be interpreted with caution

Decision-making capacity evaluations: the role of neuropsychological assessment from a multidisciplinary perspective

Decision-making capacity (DMC) in aging adults has become increasingly salient as the number of older adults, life expectancy, and the amount of wealth to be transferred from older generations have all increased. The accurate and reliable determination of older adults’ DMC is a particularly important topic given its implication in legal, financial, and health decisions. Based upon the four-ability DMC model promulgated by Appelbaum and Grisso in the 1980’s, a number of MacArthur Competence Assessment Tools have been developed and widely utilized. However, these tools do not include cognitive testing or other sources of objective data and have limited validity in a medico-legal setting, necessitating additional options for the evaluation of DMC. This is significant from the perspective of the patient because they have a vested interest in accurate and objective assessment of their DMC across domains.Given the disparities in the assessment of DMC, the authors propose, through this debate article, that the evaluation of DMC in the aging adult population utilize a combination of traditional interview and domain specific instruments and neuropsychological testing. To achieve a consensus on the issue, medical experts in a number of fields related to capacity evaluation, including psychiatry, neurology, neuropsychology, and general medicine were consulted and recruited as authors. Experts in Swiss law and ethics were also consulted and provided input.A tendency to focus on a single capacity, and in particular, the ability to consent to medical treatment, arose in the literature. Similarly, there are many instruments purporting to evaluate a single capacity (e.g., consenting to medical treatment, managing finances), while other areas important to the evaluation of DMC received little attention (e.g., activities of daily living, the ability to live independently, to marry, to resist undue influence, and to make a will or advanced care directive). Medical and legal experts in the multidisciplinary group agreed that there is a clear need for more consistency across evaluation of DMC domains and that a combined approach of traditional methods and neuropsychological testing provides a more thorough evaluation and better serves the patient

Elevated Angiopoietin-1 Serum Levels in Patients with Alzheimer’s Disease

Background. Alzheimer's disease (AD) is the most common cause of dementia in the elderly. AD is characterized by the accumulation of amyloid plaques and neurofibrillary tangles and by massive neuronal loss in the brain. There is epidemiologic and pathologic evidence that AD is associated with vascular risk factors and vascular diseases, contributing to cerebral hypoperfusion with consecutive stimulation of angiogenesis and upregulation of proangiogenic factors such as Angiopoietin-1 (Ang-1). Methods. In the present study, we measured Ang-1 serum levels in 42 patients with AD, 20 patients with mild cognitive impairment (MCI), and in 40 healthy elderly controls by ELISA. Results. We found significantly increased Ang-1 serum levels in patients with AD compared to control subjects (P=0.003). There was no significant difference between MCI patients and healthy controls (P=0.553) or between AD and MCI patients (P=0.054). The degree of cognitive impairment as measured by the mini-mental status examination (MMSE) score was significantly correlated with the Ang-1 serum levels in all patients and healthy controls. Conclusions. We found significantly increased Ang-1 serum levels in AD patients. We could also show an association between Ang-1 serum levels and the cognitive status in all patients and healthy controls. Thus, serum Ang-1 could be a potential candidate for a biomarker panel for AD diagnosis