Anatomy and Neuroscience - Research Publications
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ItemNo Preview AvailableMinimal Cognitive Impairment in UK HIV-Positive Men Who Have Sex With Men: Effect of Case Definitions and Comparison With the General Population and HIV-Negative Men(LIPPINCOTT WILLIAMS & WILKINS, 2014-10-01)BACKGROUND: To determine the prevalence of neurocognitive impairment (NCI) in UK HIV-positive and HIV-negative men who have sex with men (MSM). METHODS: HIV-positive and HIV-negative participants were recruited to a cross-sectional study from 2 London clinics and completed computer-assisted neuropsychological tests and questionnaires of depression, anxiety, and activities of daily living. Published definitions of HIV-associated neurocognitive disorders (HAND) and global deficit scores were used. Age- and education-adjusted neuropsychological test scores were directly compared with reference population data. RESULTS: A total of 248 HIV-positive and 45 HIV-negative MSM participated. In the HIV-positive group, median time since diagnosis was 9.4 years, median CD4 count was 550 cells per cubic millimeter, and 88% were on antiretroviral therapy. Prevalence of HAND was 21.0% in HIV-positive MSM (13.7% asymptomatic neurocognitive impairment, 6.5% mild neurocognitive disorder, and 0.8% HIV-associated dementia). Using a global deficit score threshold of 0.5, the prevalence of NCI was 31.5% (when averaged over 5 neuropsychological domains) and 40.3% (over 10 neuropsychological test scores). These results were not significantly different from the HIV-negative study sample. No consistent pattern of impairment was seen in HIV-positive patients relative to general male population data (n = 380). CONCLUSIONS: We found a prevalence of HAND and degree of impairment on neuropsychological testing of HIV-positive MSM that could represent a normal population distribution. These findings suggest that NCI may be overestimated in HIV-positive MSM, and that the attribution of NCI to HIV infection implied by the term HAND requires revision.
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ItemA combination of physical activity and computerized brain training improves verbal memory and increases cerebral glucose metabolism in the elderly(NATURE PUBLISHING GROUP, 2014-12)Physical exercise interventions and cognitive training programs have individually been reported to improve cognition in the healthy elderly population; however, the clinical significance of using a combined approach is currently lacking. This study evaluated whether physical activity (PA), computerized cognitive training and/or a combination of both could improve cognition. In this nonrandomized study, 224 healthy community-dwelling older adults (60-85 years) were assigned to 16 weeks home-based PA (n=64), computerized cognitive stimulation (n=62), a combination of both (combined, n=51) or a control group (n=47). Cognition was assessed using the Rey Auditory Verbal Learning Test, Controlled Oral Word Association Test and the CogState computerized battery at baseline, 8 and 16 weeks post intervention. Physical fitness assessments were performed at all time points. A subset (total n=45) of participants underwent [(18)F] fluorodeoxyglucose positron emission tomography scans at 16 weeks (post-intervention). One hundred and ninety-one participants completed the study and the data of 172 participants were included in the final analysis. Compared with the control group, the combined group showed improved verbal episodic memory and significantly higher brain glucose metabolism in the left sensorimotor cortex after controlling for age, sex, premorbid IQ, apolipoprotein E (APOE) status and history of head injury. The higher cerebral glucose metabolism in this brain region was positively associated with improved verbal memory seen in the combined group only. Our study provides evidence that a specific combination of physical and mental exercises for 16 weeks can improve cognition and increase cerebral glucose metabolism in cognitively intact healthy older adults.
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ItemInfluence of BDNF Val66Met on the relationship between physical activity and brain volume(LIPPINCOTT WILLIAMS & WILKINS, 2014-10-07)OBJECTIVE: To investigate the association between habitual physical activity levels and brain temporal lobe volumes, and the interaction with the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism. METHODS: This study is a cross-sectional analysis of 114 cognitively healthy men and women aged 60 years and older. Brain volumes quantified by MRI were correlated with self-reported physical activity levels. The effect of the interaction between physical activity and the BDNF Val66Met polymorphism on brain structure volumes was assessed. Post hoc analyses were completed to evaluate the influence of the APOE ε4 allele on any found associations. RESULTS: The BDNF Val66Met polymorphism interacted with physical activity to be associated with hippocampal (β = -0.22, p = 0.02) and temporal lobe (β = -0.28, p = 0.003) volumes. In Val/Val homozygotes, higher levels of physical activity were associated with larger hippocampal and temporal lobe volumes, whereas in Met carriers, higher levels of physical activity were associated with smaller temporal lobe volume. CONCLUSION: The findings from this study support higher physical activity levels in the potential attenuation of age- and disease-related hippocampal and temporal lobe volume loss in Val/Val homozygotes.
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ItemBehavior at the Choice Point: Decision Making in Hidden Pathway Maze Learning(SPRINGER, 2014-12)Hidden pathway maze learning tasks (HPMLTs) have been used in neuropsychological research and practice for more than 80 years. These tasks require the use of visual and auditory task feedback signals to learn the order and direction of a pathway, typically within a grid of stepping-stones, or alleys. Hidden pathway maze learning tasks are purported to assess both visuospatial learning and executive processes. The original motivation for the HPMLT paradigm for humans was to reduce a complex tactual planning task to one in which decisions could be directly measured by discrete actions at choice points guided by visual cues. Hidden maze learning paradigms were used extensively throughout the 20th century, initially to study exploratory, anticipatory, and goal-related behavior within the context of memory research, and later as an experimental tool in neuropsychology. Computerization of HPMLTs have allowed for the measurement of different move categories according to the rule structure and ipso facto, clinically meaningful differences in memory and monitoring functions during spatial search and learning. Hidden pathway maze learning tests have been used to understand the cognitive effects of ageing, neurological disorders, and psychopharmacological challenges. We provide a review of historical antecedents relevant to contemporary applications of HPMLTs in neuropsychology. It is suggested that contemporary applications of HPMLTs could be advanced by analysis of component operations necessary for efficient performance that can inform theoretical interpretations of this class of tests in clinically meaningful terms.
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ItemNo Preview AvailableThe impact of task automaticity on speech in noise(Elsevier Science, 2014)In the control of skeleto-motor movement, it is well established that the less complex, or more automatic a motor task is, the less variability and uncertainty there is in its performance. It was hypothesized that a similar relationship exists for integrated cognitive-motor tasks such as speech where the uncertainty with which actions are initiated may increase when the feedback loop is interrupted or dampened. To investigate this, the Lombard effect was exploited to explore the acoustic impact of background noise on speech during tasks increasing in automaticity. Fifteen healthy adults produced five speech tasks bearing different levels of automaticity (e.g., counting, reading, unprepared monologue) during habitual and altered auditory feedback conditions (Lombard effect). Data suggest that speech tasks relatively free of meaning or phonetic complexity are influenced to a lesser degree by a compromised auditory feedback than more complex paradigms (e.g., contemporaneous speech) on measures of timing. These findings inform understanding of the relative contribution speech task selection plays in measures of speech. Data also aid in understanding the relationship between task automaticity and altered speech production in neurological conditions where dual impairments of movement and cognition are observed (e.g., Huntington’s disease, progressive aphasia).
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ItemPersonal Memory Function in Mild Cognitive Impairment and Subjective Memory Complaints: Results from the Australian Imaging, Biomarkers, and Lifestyle (AIBL) Study of Ageing(IOS PRESS, 2014)BACKGROUND: Autobiographical memory (ABM) refers to the recollection of individual experiences, while personal semantic memory (PSM) refers to personally relevant, but shared, facts. Mild cognitive impairment (MCI) is routinely diagnosed with the aid of neuropsychological tests, which do not tap the ABM and PSM domains. OBJECTIVE: We aimed to characterize the nature of ABM and PSM retrieval in cognitively healthy (HC) memory complainers, non-memory complainers, and MCI participants, and to investigate the relationship between neuropsychological tests and personal memory. METHODS: Gender- and education-matched participants (HC = 80 and MCI = 43) completed the Episodic ABM Interview (EAMI) and a battery of neuropsychological tests. RESULTS: ABM and PSM did not differ between complainers and non-complainers, but were poorer in MCI participants, after accounting for age and depressive symptomatology. There were significant associations between personal memory and objective memory measures were found in MCI participants, but standard cognitive measures were more sensitive to MCI. CONCLUSION: Personal memory was compromised in MCI, reflected by lower scores on the EAMI. Memory complaining, assessed by current approaches, did not have an impact on personal memory. Standard subjective questionnaires might not reflect the sorts of concerns that bring individuals to clinical attention. Understanding personal memory function in the elderly may aid in the development of a more sensitive measure of subjective memory concerns.
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ItemNo Preview AvailableEffect of amyloid on memory and non-memory decline from preclinical to clinical Alzheimer's disease(OXFORD UNIV PRESS, 2014-01)High amyloid has been associated with substantial episodic memory decline over 18 and 36 months in healthy older adults and individuals with mild cognitive impairment. However, the nature and magnitude of amyloid-related memory and non-memory change from the preclinical to the clinical stages of Alzheimer's disease has not been evaluated over the same time interval. Healthy older adults (n = 320), individuals with mild cognitive impairment (n = 57) and individuals with Alzheimer's disease (n = 36) enrolled in the Australian Imaging, Biomarkers and Lifestyle study underwent at least one positron emission tomography neuroimaging scan for amyloid. Cognitive assessments were conducted at baseline, and 18- and 36-month follow-up assessments. Compared with amyloid-negative healthy older adults, amyloid-positive healthy older adults, and amyloid-positive individuals with mild cognitive impairment and Alzheimer's disease showed moderate and equivalent decline in verbal and visual episodic memory over 36 months (d's = 0.47-0.51). Relative to amyloid-negative healthy older adults, amyloid-positive healthy older adults showed no decline in non-memory functions, but amyloid-positive individuals with mild cognitive impairment showed additional moderate decline in language, attention and visuospatial function (d's = 0.47-1.12), and amyloid-positive individuals with Alzheimer's disease showed large decline in all aspects of memory and non-memory function (d's = 0.73-2.28). Amyloid negative individuals with mild cognitive impairment did not show any cognitive decline over 36 months. When non-demented individuals (i.e. healthy older adults and adults with mild cognitive impairment) were further dichotomized, high amyloid-positive non-demented individuals showed a greater rate of decline in episodic memory and language when compared with low amyloid positive non-demented individuals. Memory decline does not plateau with increasing disease severity, and decline in non-memory functions increases in amyloid-positive individuals with mild cognitive impairment and Alzheimer's disease. The combined detection of amyloid positivity and objectively-defined decline in memory are reliable indicators of early Alzheimer's disease, and the detection of decline in non-memory functions in amyloid-positive individuals with mild cognitive impairment may assist in determining the level of disease severity in these individuals. Further, these results suggest that grouping amyloid data into at least two categories of abnormality may be useful in determining the disease risk level in non-demented individuals.
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ItemNo Preview AvailableAnxiety symptoms, cerebral amyloid burden and memory decline in healthy older adults without dementia: 3-year prospective cohort study(ROYAL COLLEGE OF PSYCHIATRISTS, 2014-05)Although beta-amyloid, anxiety and depression have linked cross-sectionally to reduced memory function in healthy older adults without dementia, prospective data evaluating these associations are lacking. Using data an observational cohort study of 178 healthy older adults without dementia followed for 3 years, we found that anxiety symptoms significantly moderated the relationship between beta-amyloid level and decline in verbal (Cohen's d = 0.65) and episodic (Cohen's d = 0.38) memory. Anxiety symptoms were additionally linked to greater decline in executive function, irrespective of beta-amyloid and other risk factors. These findings suggest that interventions to mitigate anxiety symptoms may help delay memory decline in otherwise healthy older adults with elevated beta-amyloid.
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ItemEffect of BDNF Val66Met on Memory Decline and Hippocampal Atrophy in Prodromal Alzheimer's Disease: A Preliminary Study(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.