Psychological stress, cognitive decline and the development of dementia in amnestic mild cognitive impairment

To determine the relationship between psychological stress with cognitive outcomes in a multi-centre longitudinal study of people with amnestic mild cognitive impairment (aMCI) we assessed three parameters of psychological stress (Recent Life Changes Questionnaire (RLCQ); the Perceived Stress Scale (PSS) and salivary cortisol) and their relationship with rates of cognitive decline over an 18 month follow up period and conversion to dementia over a 5.5 year period. In 133 aMCI and 68 cognitively intact participants the PSS score was higher in the aMCI compared with control group but neither the RLCQ scores nor salivary cortisol measures were different between groups. In the aMCI group the RLCQ and the PSS showed no significant association with cognitive function at baseline, cognitive decline or with conversion rates to dementia but high salivary cortisol levels were associated with RLCQ scores and poorer cognitive function at baseline and lower rates of cognitive decline. No relationship was found between salivary cortisol levels and conversion rate to dementia. We conclude that psychological stress as measured by the RLCQ or PSS was not associated with adverse cognitive outcomes in an aMCI population and hypothesise that this may reflect diminished cortisol production to psychological stress as the disease progresses.</p

Borrowed scenery [Image no. 5470]

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Borrowed scenery : Detail [Image no. 5471]

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The materiality of truth : a universal language [Image no. 5477]

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The materiality of truth : a universal language [Image no. 5478]

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Face to face [Image no. 5480]

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In the mirror [Image no. 5476]

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Perceptions of space and realities

Beardmore describes her work as using three languages - the informative/textual layer, the photographic image and the material itself - each one presented with such fragility tat they cannot be collectively discerned. To engage fully with one involves relinquishing another. It is an unreliable experience in which no single language can be relied on to create coherence, and one which 'highlights the uneasy balance between experience and understanding; a fragile relationship in the body of knowledge currently being transformed by the pure possibility of access.' Source: Printmaking at the Edge by Richard Noyce, A&C Black, London, pp.91-94. ISBN: 0713667842.For more information about this item, browse to http://hdl.handle.net/102.100.100/308

Neuropathology of the Locus Coeruleus in Alzheimer's disease

The LocusCoeruleus (LC) undergoes extensive neuronal loss in Alzheimer’s Disease (AD)early in the disease process. Depletion of cortical noradrenaline (NA)concentration as a result of LC degeneration, has proinflammatory effects onmicroglia and likely contributes to the neuroinflammation observed in AD.Furthermore, abnormal intracellular tau aggregation associated with AD is firstobserved within the LC, decades prior to disease onset and LC neuron loss. Thissuggests neuropathology in AD originates in the LC, however this has been underappreciated and under-investigated because of a lack of non-invasive, directmeasures of LC activity.Using a high-resolution magnetic resonance imaging(MRI) technique, the LC can be visualised in vivo. This pilot study assessedthe feasibility of detecting signal intensity (SI) changes of the LC using adeveloped neuromelanin-sensitive imaging protocol in 24 participants with AD(12 mild AD, 12 moderate AD) and 24 age and gender matched cognitivelyunimpaired subjects. LC-SI was calculated by comparing maxima values in theanatomical location of the LC to a reference region in the adjacent pontinetegmentum to give a contrast ratio (LC-CR). LC-CR was lower in both the mildand moderate AD groups compared to controls (p&lt;0.05), however there was nodifference in LC signal between mild and moderate AD groups. This suggests LCsignal decreases occur early in the disease and that NM-MRI of the LC could beused as a biomarker for AD diagnosis. LC-CR correlated with SMMSE score(p=0.032) but did not correlate with peripheral inflammatory blood markers orindirect measures of LC activity including pupil size and task-evoked bloodpressure changes.Whilst LC cell loss and p-tau accumulation havebeen well studied in humans, surprisingly post-mortem studies have not examinedinflammatory changes occurring within the LC and how these relate to LC neuronloss, extracellular neuromelanin deposits and changes seen in LC projectionareas. Immunohistochemistry was used to examine markers for AD pathology, LCcell integrity, inflammation and neuromelanin in both the LC and temporalcortex of 60 post-mortem tissue samples grouped by disease severity determinedby Braak stage (0-II, III-IV and V-VI). In the LC, disease severity wasassociated with LC neuronal loss (p&lt;0.001), Aβ (p&lt;0.001) and p-tau(p&lt;0.001) accumulation, increased extraneuronal neuromelanin deposits(p&lt;0.001) and increased inflammation evidenced by increased motility of microglia(p&lt;0.001). This correlated with p-tau (p&lt;0.001) and Aβ pathology(p&lt;0.001) but not inflammatory markers in the temporal cortex.A better understanding of the role of the LC-NAsystem in AD may inform on whether the pharmacological elevation of NA would besuccessful in slowing disease progression and at which time-points it should beadministered. If NA manipulation was able to delay AD pathology, then earlydetection and monitoring of LC degeneration in vivo using NM-MRI as a biomarkerwould enable targeting of therapies </p

Face to face [Image no. 5481]

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