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dc.contributor.authorWalpert, Madeleine Jane
dc.date.accessioned2018-04-17T16:12:30Z
dc.date.available2018-04-17T16:12:30Z
dc.date.issued2018-04-11
dc.date.submitted2017-12-13
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/274945
dc.description.abstractPeople with Down’s syndrome (DS) are known to experience premature ageing and have a high propensity for clinical diagnosis of dementia due to Alzheimer’s disease (AD). In DS there is a unique and natural model of over-expression of amyloid-beta (Aβ) protein, the accumulation of which is proposed to be the central early event in the pathogenesis of AD. In DS, AD neuropathology is universally seen in the brain from the fourth decade. Identifying biomarkers are essential to the evaluation of future treatment trials. The retina has been shown to experience changes in patients with AD, such as retinal thinning, compared to age-matched controls. As an extension of the brain, the retina can be quickly and non-invasively imaged and may provide a proxy measure of brain changes in AD. Using optical coherence tomography (OCT), cross-sectional retinal examinations were completed in 50 people with DS aged 18 years and over. Comparisons between retinal thickness of the DS and control groups were examined, as well as the effect of age on thickness in both groups. For the DS group, further investigations were made into the relationships between retinal thickness and (i) cognitive performance, (ii) diagnosis of dementia, (iii) cortical thickness and, (iv) presence of Aβ binding in the brain. Contrary to expectations, people with DS had thicker retina compared to age-matched controls. In addition, normal age-related retinal thinning was not seen in the DS group. People with DS have a life-long overproduction of Aβ, deposits of which have been previously imaged in the retina. Aβ may be responsible both directly, through physical mass, and indirectly through inflammation as a response to Aβ, for increased retinal thickness in people with DS. Consequently, retinal thickness in DS may be a proxy measure of Aβ deposition in the retina. As part of a collaborative study, brain Aβ binding was measured using positron emission tomography neuroimaging in a subset of the DS group. Individuals with positive Pittsburgh compound [11C]-PIB (PIB) binding to Aβ displayed a trend towards having thinner retina than those with negative PIB binding. These results indicate that a shift towards thinning retina in people DS may reflect changes in brain pathology. Future studies are discussed which aim to investigate Aβ and Aβ driven pathology in the retina.
dc.description.sponsorshipFunding provided by Stevenage Bioscience Catalyst and Alzheimer's Research UK
dc.language.isoen
dc.rightsAll rights reserved
dc.rightsAll Rights Reserveden
dc.rights.urihttps://www.rioxx.net/licenses/all-rights-reserved/en
dc.subjectDown's syndrome
dc.subjectAlzheimer's disease
dc.subjectRetina
dc.subjectDementia
dc.subjectOptical coherence tomography
dc.titleRetinal thickness in adults with Down's syndrome: Relationship with age, cognition and dementia
dc.typeThesis
dc.type.qualificationlevelDoctoral
dc.type.qualificationnameDoctor of Philosophy (PhD)
dc.publisher.institutionUniversity of Cambridge
dc.publisher.departmentPsychiatry
dc.date.updated2018-04-17T13:38:04Z
dc.identifier.doi10.17863/CAM.22096
dc.publisher.collegeMurray Edwards
dc.type.qualificationtitlePhD in Psychiatry
cam.supervisorHolland, Anthony John
cam.thesis.fundingfalse
rioxxterms.freetoread.startdate2018-04-17


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