Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume

The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes

Storage and Access procedures in Schizophrenia: Evidence for a Two Phase Model of Lexical Impairment

Original article can be found at: http://www.informaworld.com/smpp/title~content=t713657736 Copyright Informa / Taylor and Francis GroupEvidence has accumulated to show that schizophrenia is characterized by lexicalsemantic difficulties; however, questions remain about whether schizophrenics have problems in accessing intact representations or a loss of the representations themselves. Both access and storage types of disorder have been reported and it has been speculated that this may reflect a transition from the former to latter with increasing length of illness. This study investigated whether illness duration, age or estimated premorbid IQ predict the size and accessibility of the lexical store. Fifty-six schizophrenic patients (chosen to represent a wide range of illness duration from 3–40 years) and 24 matched healthy controls were asked to name 120 pictures on two occasions. Estimates of store size and retrieval probability were derived from a two parameter stochastic Markov chain model. This revealed that even early in the course of illness, schizophrenics appear to have suffered a reduction in lexical store size and that those with longer length of illness show deficits in both their store size and their ability to retrieve names from that store.Peer reviewe

An early marker for semantic memory impairment in patients with schizophrenia

Original article can be found at: http://www.informaworld.com Copyright Informa / Taylor and Francis Group [Full text of this article is not available in the UHRA]Introduction: Semantic memory impairment is now a well-documented phenomenon in patients with schizophrenia. Nevertheless, the characteristics of this deficit and any early markers remain contentious. Methods: In this preliminary study, 12 schizophrenic patients underwent longitudinal assessment using a battery of semantic memory tests. Patient performance was compared to 12 matched controls. Using set criteria (derived from Warrington & Shallice, 1979), we examined whether the patients had a disorder affecting access to intact representations, or a degradation/loss of the representations themselves. The criteria were: consistency across time and modality, level of attribute information, and responsiveness to cueing. Finally, we compared patient naming for the same items across two naming tests (naming-to-description and picture naming) to determine cross-modality consistency. Results: As expected, normal controls outperformed the patients on all tests. Naming-to-description was the most significant differentiator between patients and controls. Patients were inconsistent across both time and modality, showed minimal attributional knowledge impairment, and improved significantly with cueing on two naming tests. Conclusion: The profile of results indicates an access-type semantic deficit in this cohort of patients with schizophrenic. Finally, on a naming-to-description task, the patients failed to name up to 20% of items that they could name to picture. This suggests that naming-to-definition may act as an early marker of semantic memory impairment.Peer reviewe

Working memory in children and adolescents with Down syndrome: evidence from a colour memory experiment

This paper reports information on the visual and verbal short term memory of individuals with Down syndrome. Colour memory in 16 children and adolescents with Down syndrome was compared with that of 16 typically developing children matched for receptive vocabulary. It was suggested that focal colours should be remembered more successfully than non-focal colours on the basis that the former could be remembered using a verbal recoding strategy. However, children with Down syndrome, for whom a deficit in verbal short term memory makes the use of such a strategy unlikely, should remember focal and non-focal colours equally well. More importantly, if individuals with Down syndrome have more developed visual memory abilities than control children, they should out-perform them in recognising non-focal colours. Although the group with Down syndrome demonstrated significantly better Corsi blocks performance than controls, and displayed similar levels of colour knowledge, no advantage for colour memory was found. Non-focal colours were remembered by individuals with Down syndrome as successfully as focal colours but there was no indication of a visual memory advantage over controls. Focal colours were remembered significantly more successfully than non-focal colours by the typically developing children. Their focal colour memory was significantly related to digit span, but only Corsi span was related to focal colour memory in the group with Down syndrome