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Randwick, Australia

Gates N.J.,University of New South Wales | Kochan N.A.,University of New South Wales | Kochan N.A.,Neuropsychiatric Institute
Current Opinion in Psychiatry | Year: 2015

Cost-effective, valid, efficient and accessible tests for the detection of late-life neurocognitive disorders are crucial, as early identification facilitates appropriate early intervention. Proponents of computerized neuropsychological assessment devices (CNADs) assert that technology-based assessments improve upon traditional neuropsychological tests. However, there remain fundamental questions of validity, reliability, normative data and administration, raising the question of whether CNADs are appropriate alternatives. RECENT FINDINGS: Since publication of the 2012 American Academy of Clinical Neuropsychology and National Academy of Neuropsychology joint position paper outlining appropriate standards for CNAD development, the field has not significantly advanced, with the majority of recommendations inadequately addressed. SUMMARY: Whilst there is a pressing need for innovative and readily applicable cognitive tests, these requirements do not outweigh the necessity for valid measures. Overall, the psychometric quality, standardization, normative data and administration advice of CNADs for neurocognitive disorders are lacking. Therefore, the risk of diagnostic errors is potentially high and poor clinical decisions could potentially arise, having significant impact upon individuals in terms of their well being and access to treatment. We recommend clinicians and researchers make informed decisions about CNAD suitability for their clients and their individual requirements based upon published psychometric and other test information. © 2015 Wolters Kluwer Health, Inc. Source

Braidy N.,University of New South Wales | Jayasena T.,University of New South Wales | Poljak A.,University of New South Wales | Sachdev P.S.,University of New South Wales | Sachdev P.S.,Neuropsychiatric Institute
Current Opinion in Psychiatry | Year: 2012

Purpose of Review: Sirtuins are a family of enzymes highly conserved in evolution and involved in mechanisms known to promote healthy ageing and longevity. This review aims to discuss recent advances in understanding the role of sirtuins, in particular mammalian SIRT1, in promoting longevity and its potential molecular basis for neuroprotection against cognitive ageing and Alzheimer's disease pathology. Recent Findings: Accumulative increase in oxidative stress during ageing has been shown to decrease SIRT1 activity in catabolic tissue, possibly by direct inactivation by reactive oxygen. SIRT1 overexpression prevents oxidative stress-induced apoptosis and increases resistance to oxidative stress through regulation of the FOXO family of forkhead transcription factors. In addition, resveratrol strongly stimulates SIRT1 deacetylase activity in a dose-dependent manner by increasing its binding affinity to both the acetylated substrate and NAD. Recently, SIRT1 has been shown to affect amyloid production through its influence over the ADAM10 gene. Upregulation of SIRT1 can also induce the Notch pathway and inhibit mTOR signalling. Summary: Recent studies have revealed some of the mechanisms and pathways that are associated with the neuroprotective effects of SIRT1. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source

Zheng J.J.J.,University of New South Wales | Delbaere K.,University of New South Wales | Close J.C.T.,University of New South Wales | Sachdev P.S.,University of New South Wales | And 2 more authors.
Stroke | Year: 2011

Background and Purpose- White matter lesions (WMLs) are common findings on neuroimaging in older people. This review systematically evaluates the published literature on the associations between WMLs and balance, gait, mobility, and falls in older people. Methods- Studies were identified with searches of the MEDLINE databases. Articles reporting associations between WMLs and balance, gait, mobility, and falls in older people in cross-sectional and longitudinal studies were included. Results- Thirty-one articles reporting data from 19 studies met the inclusion criteria. There were consistent findings from both cross-sectional and longitudinal studies indicating greater WML volumes are associated with impaired balance, slower gait, and reduced mobility. Most studies addressing regional WML distributions have reported that WMHs in the frontal lobe and periventricular regions show the strongest relationships with balance, gait, and mobility impairments. In relation to falls, a threshold effect was apparent in that only those with severe WML volumes were found to be at increased risk of falling. Conclusions- The findings of this systematic review indicate that WMLs are common and are significantly associated with impaired balance, gait, mobility, and falls in older people. In many studies, however, impaired mobility and increased fall risk are only evident in people who have the most severe degree of WMLs. Copyright © 2011 American Heart Association. All rights reserved. Source

Gates N.J.,University of New South Wales | Gates N.J.,Neuropsychiatric Institute | Sachdev P.,University of New South Wales | Sachdev P.,Neuropsychiatric Institute
Journal of Alzheimer's Disease | Year: 2014

There is much interest in early intervention for the prevention or postponement of dementia in Alzheimer's disease (AD). The results of drug trials in this regard have thus far been disappointing, and non-pharmacological interventions are receiving increased attention. One such intervention is complex cognitive activity. Evidence from epidemiological studies suggests that participation in stimulating mental activities is associated with lowered dementia risk. The introduction of novel and complex cognitive interventions to healthy adults and those with cognitive impairment may represent an efficacious treatment option to improve cognition, lower dementia incidence, and slow rate of decline. This review examines the evidence for restorative cognitive training (CT) and addresses a number of clinically relevant issues regarding cognitive benefit and its transfer and persistence. Although the number of randomized controlled trials is limited, preliminary evidence suggests that CT may provide immediate and longer term cognitive benefits which generalize to non-trained domains and non-cognitive functions, with supervised small group multi-domain training providing greatest benefits. Possible neuroplastic mechanisms are discussed, and recommendations for further research and clinical implementation provided. © 2014 - IOS Press and the authors. All rights reserved. Source

Yang Z.,Center for Healthy Brain Ageing | Yang Z.,Neuropsychiatric Institute | Slavin M.J.,Dementia Collaborative Research Center Assessment and Better Care | Slavin M.J.,Neuropsychiatric Institute | And 2 more authors.
Nature Reviews Neurology | Year: 2013

People over the age of 90 years-the oldest old-are the fastest growing sector of the population. A substantial proportion of these individuals are affected by dementia, with major implications for the individual as well as society. Research on dementia in the oldest old is important for service planning, and the absence of dementia at this exceptional old age may serve as a model of successful ageing. This Review summarizes population-based epidemiological studies of dementia and its underlying neuropathology in nonagenarians and centenarians. The available data, although somewhat limited, show an age-specific and sex-specific profile of dementia status in very late life, resulting from a variety of neuropathologies that often co-occur. Extensive overlap in neuropathology between cognitively normal and cognitively impaired individuals is evident despite challenges to gathering data particular to this population. A complex picture is emerging of multiple pathogenetic mechanisms underlying dementia, and of the potential risk and protective factors for dementia that interact with genetics and lifestyle in normal and exceptional cognitive ageing. © 2013 Macmillan Publishers Limited. All rights reserved. Source

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