Name of Fellow


Dr Helena Watts

Institution


Funder


Alzheimer's Society

Contact information of fellow


Country


United Kingdom

Title of project/programme


‘Pleiotrophic Strategies to Prevent Surgery-induced Cognitive Decline in Normal and Vulnerable Aged Brain’.

Source of funding information


Alzheimer's Society

Total sum awarded (Euro)


€ 296,438

Start date of award


01/05/13

Total duration of award in years


3.0

The project/programme is most relevant to:


Alzheimer's disease & other dementias

Keywords


Research Abstract


The number of patients at risk of developing postoperative cognitive dysfunction (POCD) is set to rise dramatically as over 65-yr olds are predicted to become the largest consumers of surgery. We have shown that surgery in prodromal APP23 mice accelerates Alzheimer’s pathogenesis and is accompanied by aberrant cerebrovascular and microglial inflammation. Our work suggests the key to preventing the switch from self-limiting to chronic neuroinflammation will require pleiotropic interventions targeting multiple pathogenic cascades. This approach would not only limit the acute effects of systemic inflammation on the brain following surgery but also capitalize on the beneficial effects of peripheral-immune regulation to promote a protective gial phenotype and support synaptic flexibility. Utilizing in vivo imaging, cognitive testing and extensive biochemical analyses, the project will (1) determine whether orthopaedic surgery induces more persistent cerebrovascular alterations, neuroinflammatory responses and lasting cognitive deficits in aged versus adult mice (2) examine the influence of pre-existing pathology on POCD in aged mice using a high-fructose diet as a model of sporadic AD and (3) establish the efficacy of pleiotropic strategies (i) Atorvastatin + Q10, (ii) Celestrol or (iii) Tropisetron to protect aged mice +/- pre-existing pathology from aberrant surgery-induced neuroinflammation, synaptic impairment and progressive cognitive decline.

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