Pathology - Research Publications

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    Effect of BDNF Val66Met on Memory Decline and Hippocampal Atrophy in Prodromal Alzheimer's Disease: A Preliminary Study
    Lim, YY ; Villemagne, VL ; Laws, SM ; Ames, D ; Pietrzak, RH ; Ellis, KA ; Harrington, K ; Bourgeat, P ; Bush, AI ; Martins, RN ; Masters, CL ; Rowe, CC ; Maruff, P ; Fan, Y (PUBLIC LIBRARY SCIENCE, 2014-01-27)
    OBJECTIVE: Cross-sectional genetic association studies have reported equivocal results on the relationship between the brain-derived neurotrophic factor (BDNF) Val66Met and risk of Alzheimer's disease (AD). As AD is a neurodegenerative disease, genetic influences may become clearer from prospective study. We aimed to determine whether BDNF Val66Met polymorphism influences changes in memory performance, hippocampal volume, and Aβ accumulation in adults with amnestic mild cognitive impairment (aMCI) and high Aβ. METHODS: Thirty-four adults with aMCI were recruited from the Australian, Imaging, Biomarkers and Lifestyle (AIBL) Study. Participants underwent PiB-PET and structural MRI neuroimaging, neuropsychological assessments and BDNF genotyping at baseline, 18 month, and 36 month assessments. RESULTS: In individuals with aMCI and high Aβ, Met carriers showed significant and large decline in episodic memory (d = 0.90, p = .020) and hippocampal volume (d = 0.98, p = .035). BDNF Val66Met was unrelated to the rate of Aβ accumulation (d = -0.35, p = .401). CONCLUSIONS: Although preliminary due to the small sample size, results of this study suggest that high Aβ levels and Met carriage may be useful prognostic markers of accelerated decline in episodic memory, and reductions in hippocampal volume in individuals in the prodromal or MCI stage of AD.
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    Clinical utility of the cogstate brief battery in identifying cognitive impairment in mild cognitive impairment and Alzheimer's disease.
    Maruff, P ; Lim, YY ; Darby, D ; Ellis, KA ; Pietrzak, RH ; Snyder, PJ ; Bush, AI ; Szoeke, C ; Schembri, A ; Ames, D ; Masters, CL (BioMed Central, 2013-12-23)
    Background: Previous studies have demonstrated the utility and sensitivity of the CogState Brief Battery (CBB) in detecting cognitive impairment in Alzheimer's disease (AD) and mild cognitive impairment (MCI) and in assessing cognitive changes in the preclinical stages of AD. Thus, the CBB may be a useful screening tool to assist in the management of cognitive function in clinical settings. In this study, we aimed to determine the utility of the CBB in identifying the nature and magnitude of cognitive impairments in MCI and AD.; Methods: Healthy adults (n = 653) adults with amnestic MCI (n = 107), and adults with AD (n = 44) who completed the CBB participated in this study. Composite Psychomotor/Attention and Learning/Working Memory scores were computed from the individual CBB tests. Differences in composite scores were then examined between the three groups; and sensitivity and specificity analyses were conducted to determine cut scores for the composite scores that were optimal in identifying MCI- and AD-related cognitive impairment.; Results: Large magnitude impairments in MCI (g = 2.2) and AD (g = 3.3) were identified for the learning/working memory composite, and smaller impairments were observed for the attention/psychomotor composite (g's = 0.5 and 1, respectively). The cut-score associated with optimal sensitivity and specificity in identifying MCI-related cognitive impairment on the learning/working memory composite was -1SD, and in the AD group, this optimal value was -1.7SD. Both composite scores showed high test-retest reliability (r = 0.95) over four months. Poorer performance on the memory composite was also associated with worse performance on the Mini Mental State Exam and increasing severity on the Clinical Dementia Rating Scale sum of boxes score.; Conclusions: Results of this study suggest that the CogState learning/working memory composite score is reduced significantly in CI and AD, correlate well with measures of disease classification and are useful in identifying memory impairment related to MCI- and AD.;
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    Monitoring change requires a rethink of assessment practices in voice and speech
    Vogel, AP ; Maruff, P (TAYLOR & FRANCIS LTD, 2014-07)
    Assessment for the purpose of monitoring change over time requires a different practical and statistical approach to that of assessment for diagnosing impairment. Sophisticated methods exist for identifying strengths and weaknesses in a patient's voice/speech profile, yet our understanding of the impact of repeated assessment is limited. Monitoring change necessitates that stimuli are stable in the absence of any true change in functioning, while remaining sensitive to influences that are considered to alter functioning (degeneration, therapy). The current paper discusses the issues relating to stimuli selection, identifying error within the sample and appropriate statistical models for identifying intra-individual change in the context of clinical and experimental speech or voice examinations.