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Faux N.G.,University of Melbourne | Faux N.G.,Cooperative Research Center for Mental Health | Rembach A.,University of Melbourne | Wiley J.,University of Melbourne | And 11 more authors.
Molecular Psychiatry | Year: 2014

Lower hemoglobin is associated with cognitive impairment and Alzheimer's disease (AD). Since brain iron homeostasis is perturbed in AD, we investigated whether this is peripherally reflected in the hematological and related blood chemistry values from the Australian Imaging Biomarker and Lifestyle (AIBL) study (a community-based, cross-sectional cohort comprising 768 healthy controls (HC), 133 participants with mild cognitive impairment (MCI) and 211 participants with AD). We found that individuals with AD had significantly lower hemoglobin, mean cell hemoglobin concentrations, packed cell volume and higher erythrocyte sedimentation rates (adjusted for age, gender, APOE-ε4 and site). In AD, plasma iron, transferrin, transferrin saturation and red cell folate levels exhibited a significant distortion of their customary relationship to hemoglobin levels. There was a strong association between anemia and AD (adjusted odds ratio (OR)=2.43, confidence interval (CI) (1.31, 4.54)). Moreover, AD emerged as a strong risk factor for anemia on step-down regression, even when controlling for all other available explanations for anemia (adjusted OR=3.41, 95% CI (1.68, 6.92)). These data indicated that AD is complicated by anemia, which may itself contribute to cognitive decline. © 2014 Macmillan Publishers Limited All rights reserved.

Guo L.-H.,TU Munich | Westerteicher C.,TU Munich | Wang X.-H.,University Utrecht | Kratzer M.,TU Munich | And 9 more authors.
European Archives of Psychiatry and Clinical Neuroscience | Year: 2012

The neuronal sortilin-related receptor with A-type repeats (SORL1, also called LR11 or sorLA) is involved in amyloidogenesis, and the SORL1 gene is a major risk factor for Alzheimer's disease (AD). We investigated AD-related CSF biomarkers for associations with SORL1 genetic variants in 105 German patients with mild cognitive impairment (MCI) and AD. The homozygous CC-allele of single nucleotide polymorphism (SNP) 4 was associated with increased Tau concentrations in AD, and the minor alleles of SNP8, SNP9, and SNP10 and the haplotype CGT of these SNPs were associated with increased SORL1 concentrations in MCI. SNP22 and SNP23, and the haplotypes TCT of SNP19-21-23, and TTC of SNP22-23-24 were correlated with decreased Ab42 levels in AD. These results strengthen the functional role of SORL1 in AD. © 2012 Springer-Verlag.

Creegan R.,Curtin University Australia | Hunt W.,Curtin University Australia | McManus A.,Curtin University Australia | Rainey-Smith S.R.,Edith Cowan University | Rainey-Smith S.R.,Sir James McCusker Alzheimers Disease Research Unit
British Journal of Nutrition | Year: 2015

Alzheimer's disease (AD), the most common form of dementia, is a chronic, progressive neurodegenerative disease that manifests clinically as a slow global decline in cognitive function, including deterioration of memory, reasoning, abstraction, language and emotional stability, culminating in a patient with end-stage disease, totally dependent on custodial care. With a global ageing population, it is predicted that there will be a marked increase in the number of people diagnosed with AD in the coming decades, making this a significant challenge to socio-economic policy and aged care. Global estimates put a direct cost for treating and caring for people with dementia at $US604 billion, an estimate that is expected to increase markedly. According to recent global statistics, there are 35.6 million dementia sufferers, the number of which is predicted to double every 20 years, unless strategies are implemented to reduce this burden. Currently, there is no cure for AD; while current therapies may temporarily ameliorate symptoms, death usually occurs approximately 8 years after diagnosis. A greater understanding of AD pathophysiology is paramount, and attention is now being directed to the discovery of biomarkers that may not only facilitate pre-symptomatic diagnosis, but also provide an insight into aberrant biochemical pathways that may reveal potential therapeutic targets, including nutritional ones. AD pathogenesis develops over many years before clinical symptoms appear, providing the opportunity to develop therapy that could slow or stop disease progression well before any clinical manifestation develops. Copyright © The Authors 2015.

Frost S.,University of Western Australia | Frost S.,CSIRO | Martins R.N.,University of Western Australia | Martins R.N.,Sir James McCusker Alzheimers Disease Research Unit | And 3 more authors.
Journal of Alzheimer's Disease | Year: 2010

Alzheimer's disease (AD) is the most common form of dementia and is clinically characterized by a progressive decline in memory, learning, and executive functions, and neuropathologically characterized by the presence of cerebral amyloid deposits. Despite a century of research, there is still no cure or conclusive premortem diagnosis for the disease. A number of symptom-modifying drugs for AD have been developed, but their efficacy is minimal and short-lived. AD cognitive symptoms arise only after significant, irreversible neural deterioration has occurred; hence there is an urgent need to detect AD early, before the onset of cognitive symptoms. An accurate, early diagnostic test for AD would enable current and future treatments to be more effective, as well as contribute to the development of new treatments. While most AD related pathology occurs in the brain, the disease has also been reported to affect the eye, which is more accessible for imaging than the brain. AD-related proteins exist in the normal human eye and may produce ocular pathology in AD. There is some homology between the retinal and cerebral vasculatures and the retina also contains nerve cells and fibers that form a sensory extension of the brain. The eye is the only place in the body where vasculature or neural tissue is available for non-invasive optical imaging. This article presents a review of current literature on ocular morphology in AD and discusses the potential for an ocular-based screening test for AD. © 2010 IOS Press and the authors. All rights reserved.

Lim Y.Y.,University of Melbourne | Lim Y.Y.,Brown University | Villemagne V.L.,University of Melbourne | Laws S.M.,Edith Cowan University | And 16 more authors.
Molecular Psychiatry | Year: 2015

Accumulation of β-amyloid (Aβ) in the brain is associated with memory decline in healthy individuals as a prelude to Alzheimer's disease (AD). Genetic factors may moderate this decline. We examined the role of apolipoprotein E (ε4 carrier ε4 + , ε4 non-carrier ε4) and brain-derived neurotrophic factor (BDNF Val/Val, BDNF Met) in the extent to which they moderate Aβ-related memory decline. Healthy adults (n=333, M age =70 years) enrolled in the Australian Imaging, Biomarkers and Lifestyle study underwent Aβ neuroimaging. Neuropsychological assessments were conducted at baseline, 18-, 36- and 54-month follow-ups. Aβ positron emission tomography neuroimaging was used to classify participants as Aβ - or Aβ +. Relative to Aβ - ε4 -, Aβ + ε4 + individuals showed significantly faster rates of cognitive decline over 54 months across all domains (d=0.40-1.22), while Aβ + ε4 - individuals showed significantly faster decline only on verbal episodic memory (EM). There were no differences in rates of cognitive change between Aβ - ε4 - and Aβ - ε4 + groups. Among Aβ + individuals, ε4 + /BDNF Met participants showed a significantly faster rate of decline on verbal and visual EM, and language over 54 months compared with ε4 - /BDNF Val/Val participants (d=0.90-1.02). At least two genetic loci affect the rate of Aβ-related cognitive decline. Aβ + ε4 + /BDNF Met individuals can expect to show clinically significant memory impairment after 3 years, whereas Aβ + ε4 + /BDNF Val/Val individuals can expect a similar degree of impairment after 10 years. Little decline over 54 months was observed in the Aβ - and Aβ + ε4 - groups, irrespective of BDNF status. These data raise important prognostic issues in managing preclinical AD, and should be considered in designing secondary preventative clinical trials. © 2015 Macmillan Publishers Limited Molecular Psychiatry.

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